CHAPTER 22
Primary Care
KEY POINTS
1 Respiratory infections in adults are commonly viral and do not require antibiotics.
For good antibiotic stewardship, one needs to use them only for bacterial infections
that require them. If empiric therapy is used, it should be based on the specific
patient and the severity of the infection. All patients with possible communityacquired pneumonia should have a chest radiograph to establish the diagnosis and
presence of complications.
2 Effective screening for hypertension and hyperlipidemia is critical to reduce the
occurrence of cardiac disease (a primary cause of death). When hypertension or
significant risks for hypertension are found, active lifestyle intervention needs to be
initiated. If this is not adequate, pharmaceutical intervention is used to achieve a
goal of less than 140/90. In patients with comorbidities such as diabetes or renal
disease, the goal should be less than 130/80.
3 The role of diet in hyperlipidemia is still unclear although a low-fat diet along with
weight loss and exercise do reduce lipids. Current recommendations strongly
encourage the use of statins as first line pharmaceutical therapy with clear guidelines
for use and optimal goals as targets.
11474 Type 2 diabetes is increasing as the incidence of obesity increases. Screening highrisk individuals allows early diagnosis and intervention prior to development of
complications. Lifestyle modifications including diet, weight loss, and exercise are
the first steps in management.
5 Given the frequency of thyroid pathology in women, providers need to understand
risk factors that merit screening and the proper physical examination to identify
masses. The sensitive thyroid-stimulating hormone (TSH) assay is the single best
screening test for hyperthyroidism and hypothyroidism.
As health care providers for women, gynecologists are responsible for providing
care that extends beyond diseases of the reproductive organs to include much of
the general medical care of their patients. Broadening the spectrum of care
requires adjustments in practice, with less emphasis placed on the surgical aspects
of the specialty. Early diagnosis and treatment of medical illnesses can have a
major impact on a woman’s health. Although timely referral is important for
complex and advanced diseases, many conditions can be screened for,
recognized, and potentially treated initially by gynecologists.
Respiratory problems are the most common reasons patients seek care
from a physician, so gynecologists should be aware of their pathophysiology.
Cardiovascular disease has a significant impact on the overall morbidity and
is the main cause of death in women. Cardiovascular disease is associated
with cigarette smoking, hypertension, hypercholesterolemia, and diabetes
mellitus (DM). These conditions are responsive to screening, behavior
modification, and control to lower risk factors. Thyroid disease is a major
cause of morbidity for women. Because of the interaction of hormones and
the overall effect on the endocrine system, thyroid disease can be of special
significance in women. The gynecologist should provide screening and initial
therapy for these conditions and assess the need for referral.
RESPIRATORY INFECTIONS
Infections of the respiratory system can range from the common cold to lifethreatening illness. Those with risk factors should be counseled about preventive
measures. Vaccines against flu and pneumonia should be offered as indicated.
Upper Respiratory Infections (URIs)
This term can encompass a number of diagnoses including the “common cold.”
“Cold” is a term often used for a variety of virus-induced mild URIs that typically
have the symptoms of stuffy nose, sore scratchy throat, cough, no or low-grade
fever, and fatigue or malaise (1). Ear pain can be part of the cluster. Despite
1148thoughts that “colds” are more common in certain times of the year, there is no
seasonal variation in their incidence—only in the virus causing the cold.
Adenovirus, rhinoviruses, coronaviruses, and respiratory syncytial viruses are
common etiologies of “colds.” Although patients will frequently equate colds and
“flu,” the viruses that cause influenza tend to have more body aches, fever, and
systemic symptoms as well as being seasonal.
Differentiating which virus is causing a cold does not impact treatment, so
cultures are not indicated unless there is concern for an influenza virus that might
benefit from antiviral medication. The diagnosis of a cold tends to be a process of
exclusion. The presence of temperature >100, facial pain, prolonged (>2 weeks)
barking cough, exudate on pharynx/tonsils, abnormal breath sounds, or poor
oxygen saturation would indicate that other diagnoses need to be considered, such
as sinusitis, pertussis, strep throat, bronchitis, monospot, or influenza. In the
presence of these findings, strep culture, pertussis screen, viral screen for
influenza, or chest x-ray might be indicated.
The treatment of a cold is basically symptomatic. This includes aspirin/NSAID
for any body aches or low-grade temperature, hydration, decongestant (topical or
oral), and good hand hygiene. In an otherwise healthy person a cold will last 7 to
10 days and occasionally up to 2 weeks. Spread is by droplets (both small from
cough/sneeze and large on hands/environmental) and contact (hands or
contaminated surfaces). Antibacterial wipes and cleaners do NOT impact the
transmission of cold viruses (2). The use of decongestants such as
pseudoephedrine or oxymetazoline HCl should not be used for more than 2 or 3
days because of a risk of a rebound effect.
The risk of acquiring a cold is increased in individuals who are sleep deprived,
stressed, have children in day care settings, have chronic diseases, smoke, or have
poor nutrition and immune deficiency. The last four situations increase the risk of
a more severe “cold” and having it progress into a bacterial complication.
Seasonal changes do NOT change the incidence of “colds” but only the virus that
caused it.
Sinusitis
A problem frequently encountered in women is self-diagnosed “sinus
problems.” Many medical problems—headaches, dental pain, postnasal drainage,
halitosis, and dyspepsia—may be related to sinus conditions. The sinuses are not
an isolated organ, and diseases of the sinuses are often related to conditions that
affect other portions of the respiratory system (i.e., the nose, bronchial tree, and
lungs). Therefore, during the evaluation of symptoms attributable to sinusitis, the
presence of other infections should be investigated.
Multiple infectious and chemical agents or reactions to nervous, physical,
1149emotional, or hormonal stimuli may cause an inflammatory response in the
respiratory system (3). Systemic diseases such as connective tissue syndromes
and malnutrition may contribute to chronic sinusitis. Environmental factors in the
workplace and geographic conditions (e.g., cold and damp weather) may
aggravate or accelerate the development of sinusitis. Factors contributing to the
development of sinus disease include atmospheric pollutants, allergy, tobacco
smoke, skeletal deformities, dental conditions, barotrauma from scuba diving or
airline travel, and neoplasms.
[1] Most acute infections (lasting less than 4 weeks) begin with a viral agent
(acute viral rhinosinusitis [AVRS]) in the nose or nasopharynx that causes
inflammation, blocking the draining ostia (3). The location of the symptoms
varies by the anatomic site of infection—maxillary sinus over the cheeks, ethmoid
sinus across the nose, frontal sinus in the supraorbital area, and sphenoid sinus to
the vertex of the head—and typically last 7 to 10 days, clearing with nothing
more than a decongestant. Viral agents impede the sweeping motion of ciliary
function in the sinus and, in combination with edema from inflammation,
may occasionally lead to superinfection with bacteria (acute bacterial
rhinosinusitis [ABRS]). The most common bacterial agents infecting sinuses
are Streptococcus pneumoniae and Haemophilus influenzae. Gram-negative
organisms are usually limited to compromised hosts in intensive care units. [1]
Although less than 2% of acute sinusitis cases transition from viral to bacterial
infections requiring antibiotics, more than 85% of patients receive antibiotic
prescriptions. Chronic sinusitis (lasting more than 12 weeks) develops from either
inadequate drainage or compromised local defense mechanisms. The flora usually
is polymicrobial, consisting of aerobic and anaerobic organisms.
Sinus ailments frequently occur in middle-age individuals. Acute infection
is usually located in the maxillary and frontal sinuses. Classically, infection in the
maxillary sinus results from obstruction of the ostia found in the medial wall of
the nose. Fever, malaise, a vague headache, and pain in the maxillary teeth are
early symptoms. Reports of “fullness” in the face or exploding pressure behind
the eyes often are elicited as well as increasing pain with bending over. Pressure
and percussion over the malar areas can cause severe pain. Purulent exudates in
the middle meatus of the nose or in the nasopharynx often are present. To
differentiate between a “cold” and sinusitis the following can be helpful. Viral
URI typically peak rapidly in 3 to 4 days and they consistently decline in severity
of symptoms with full resolution in 7 to 14 days. Sinusitis in contrast will often
persistent without improvement for over a week. A pattern of initial improvement
with sudden worsening may represent a transition to a bacterial infection. Initial
episodes of sinusitis do not require imaging studies; however, when persistent
infections occur, studies and referral are indicated. Radiographic changes do not
1150reliably identify sinusitis secondary to bacteria. Unless culture samples are
obtained by direct needle drainage, they are contaminated by oropharyngeal flora
and are thus of no value. For this reason, therapy usually is empiric.
Systemic decongestants containing pseudoephedrine are useful in shrinking
the obstructive ostia and promoting sinus drainage and ventilation. Topical
decongestants should be used for no longer than 3 days because prolonged use
may lead to rebound vasodilation and worsening of symptoms. Mucolytics like
guaifenesin may help thin sinus secretions and promote drainage. Antihistamines
should be avoided in acute sinusitis because of their drying effects, which can
lead to thickened secretions and poor drainage of the sinuses. Analgesics are
recommended for pain relief. Therapies to relieve symptoms include facial hot
packs and analgesics. Topical nasal steroids may accelerate the recovery in
patients with viral sinusitis and those with a history of chronic rhinitis or recurrent
sinusitis who seek treatment of acute rhinosinusitis (4,5). Improvement should be
apparent within 48 hours of treatment, but 10 days may be necessary for complete
resolution of symptoms. If antibiotics are used, broad antibiotic coverage of
common aerobes and anaerobes is necessary but should be limited to patients
with acute pain, especially unilateral maxillary tooth, facial, or sinus pain,
and purulent discharge, particularly if the symptoms initially improved and
then worsened. This cluster of symptoms is more suggestive of bacterial
rather than viral acute sinusitis. It should be noted that the majority of acute
bacterial sinusitis cases resolve in 7 to 10 days without antibiotics, similarly
to the viral form. [1] For this reason, in an otherwise healthy adult, the use of
antibiotics is not recommended. In the setting of comorbidities such as diabetes,
chronic respiratory disease, congestive failure or immunodeficiency state, the use
of antibiotics for ABRS may be warranted. For acute bacterial sinus infections,
amoxicillin (1,000 mg three times a day) remains the treatment of choice.
Amoxicillin is inexpensive, penetrates the sinus tissues well, and can be changed
to another antibiotic if symptoms have not improved in 48 to 72 hours. If these
give only a minimal or no response after 7 days, consider broader-spectrum
antibiotics. If beta-lactam resistance is likely, amoxicillin/clavulanic acid (875 mg
twice daily) may be used. Other second-line drugs include, levofloxacin (500 mg
qd), and doxycycline (200 mg qd for 5 to 10 days). The usual treatment course is
5 to 10 days, and patients should be informed that relapses might occur if the full
course of treatment is not completed. [1] Trimethoprim/sulfamethoxazole and
azithromycin are no longer recommended as a result of high rates of microbial
resistance (3).
No clinical criteria can reliably identify those patients who might benefit
from treatment with antibiotics. It is reasonable to treat women with presumed
bacterial sinusitis if they have high fever, systemic toxicity, immune deficiency,
1151or possible orbital or intracranial involvement (5). Although very rare, untreated
sinus infections may have dire consequences, such as orbital cellulitis, leading to
orbital abscess, subperiosteal abscess formation of the facial bones, cavernous
sinus thrombosis, and acute meningitis. Brain and dural abscesses are rare; when
they occur, it usually is the result of direct spread from a sinus. A patient
complaining of abnormal vision such as diplopia, changes in mental status, and
periorbital edema should prompt a referral to the emergency room for evaluation
of intracranial or orbital extension. Computed tomography scanning is the most
accurate diagnostic tool. The use of aggressive surgical approaches with broadspectrum antibiotics is necessary for adequate drainage.
Otitis Media
Otitis media remains primarily a disease of children, but may affect adults,
often secondary to a concurrent viral infection of the upper respiratory tract.
Diagnosis in most cases reveals fluid behind the tympanic membrane. Treatment
is directed to symptoms and involves the use of antihistamines and decongestants,
despite few data to support their use for acute serous otitis, as this is typically
caused by a blocked eustachian tube. Acute suppurative otitis media is usually a
bacterial infection; S. pneumoniae and H. influenzae are the most common
pathogens. [1] Symptoms include acute purulent otorrhea, fever, hearing loss,
severe deep throbbing ear pain, and leukocytosis. Physical examination of the ear
reveals a red, bulging, or perforated membrane with possible pre- and
postauricular nodes. Indicated treatment is broad-spectrum antibiotics such as
amoxicillin, amoxicillin/clavulanic acid, cefuroxime, erythromycin, or
azithromycin (6,7).
Bronchitis
Acute bronchitis is an inflammatory condition of the tracheobronchial tree.
Most often it is viral in origin and occurs in winter. It accounts for up to 10%
of ambulatory care visits. Common cold viruses (rhinovirus and coronavirus),
adenovirus, influenza virus, and Mycoplasma pneumoniae (a nonviral pathogen)
are the most common pathogens involved. Bacterial infections occur less
commonly and may be secondary pathogens. Cough, hoarseness, and mild fever
are the usual presenting symptoms. In the initial 3 to 4 days, the symptoms of
rhinitis and sore throat are prominent; coughing may last as long as 3 weeks.
Presence of tachycardia or tachypnea raises concern for pneumonia (8,9). The
prolonged nature of these infections promotes the use of antibiotics to “clear up
the infection” (8). Sputum production commonly occurs and may be prolonged in
cigarette smokers. [1] Most serious bacterial infections occur in cigarette
1152smokers, who have damage to the lining of the upper respiratory tree and changes
in the host flora. Differential diagnosis includes the following: postnasal drip,
asthma, pneumonia, gastroesophageal reflex disease (GERD), use of angiotensinconverting enzyme (ACE) inhibitors, and heart failure.
Physical examination discloses a variety of upper airway sounds, usually
coarse rhonchi. Rales are usually not present on auscultation, and signs of
consolidation and alveolar involvement are absent. During auscultation of the
chest, signs of pneumonia such as fine rales, decreased breath sounds, and
euphonia (“E to A changes”) should be sought. If the results of the physical
examination are uncertain or the patient’s condition appears to be in respiratory
distress chest radiography should be performed to detect the presence of
parenchymal disease. Paradoxically, as the initial acute syndrome subsides,
sputum production may become more purulent. Sputum cultures are of limited
value because of the polymicrobial nature of infections. In the absence of
complications, treatment is directed to relief of symptoms. [1] The use of
antibiotics is reserved for patients in whom chest radiography findings are
consistent with pneumonia (10,11). Cough is usually the most aggravating
symptom and may be treated with antitussive preparations containing either
dextromethorphan or guaifenesin. The use of codeine as a cough suppressant is
discouraged. The efficacy of any expectorant is not proved. If the cough persists
longer than 2 weeks the patient may have pertussis. This is treated with
azithromycin or other macrolides (8).
Chronic bronchitis is defined as a productive cough from excessive
secretions for at least 3 months in a year for 2 consecutive years. Prevalence is
estimated to be between 10% and 25% of the adult population who are smokers.
Previously the incidence was lower in women than men, but as the prevalence of
cigarette smoking in women increased, so too has the incidence of bronchitis in
women. Chronic bronchitis is classified as a form of chronic obstructive
pulmonary disease (COPD; e.g., “blue bloaters”). Other causes include chronic
infections and environmental pathogens found in dust. The cardinal manifestation
of disease is an incessant cough, usually in the morning, with expectoration of
sputum. Because of frequent exacerbations, the hospitalizations involved and the
complexity of medical management, these patients should be referred to an
internist.
Pneumonia
Pneumonia is defined as inflammation of the distal lung that includes
terminal airways, alveolar spaces, and the interstitium. Pneumonia may have
multiple causes, including viral and bacterial infections or aspiration. Aspiration
pneumonia is usually the result of depressed awareness commonly associated
1153with the use of drugs and alcohol or anesthesia. Viral pneumonias are caused by
multiple infectious agents, including influenza A or B, parainfluenza virus, or
respiratory syncytial virus. Most viral syndromes are spread by aerosolization
associated with coughing, sneezing, and even conversation. Incubation is short,
requiring only 1 to 3 days before the acute onset of fever, chills, headache,
fatigue, and myalgias. Symptom intensity is directly related to intensity of the
host febrile reaction. Pneumonia develops in only 1% of patients who have a viral
syndrome, but mortality rates may reach 30% in immunocompromised
individuals and the elderly. An additional risk is the development of secondary
bacterial pneumonias after the initial viral insult. These infections are more
common in elderly patients and may explain the high fatality in this group (12).
Staphylococcal pneumonias, which often arise from a previous viral infection, are
extremely lethal regardless of patient age. [1] The best treatment for viral
pneumonia is prevention by immunization. Treatment is supportive and consists
mostly of administration of antipyretics and fluids.
Bacterial pneumonia is classified as either community-acquired (CAP) or
nosocomial, and in many cases the classification determines prognosis and
antibiotic therapy. [1] Risk factors that contribute to mortality are chronic
cardiopulmonary diseases, alcoholism, diabetes, renal failure, malignancy, and
malnutrition. Prognostic features associated with poor outcome include greater
than two lobe involvement, respiratory rate greater than 30 breaths per minute on
presentation, severe hypoxemia (<60 mm Hg on room air), hypoalbuminemia,
and septicemia. Pneumonia is a common cause of adult respiratory distress
syndrome (ARDS), with a mortality rate between 50% and 70% (12,13). CAP is
the most common cause of severe sepsis and a leading cause of death from
infection in the United States.
Signs and symptoms of pneumonia vary depending on the infecting
organism and the patient’s immune status. In typical pneumonias, the usual
presentation is a patient with high fever, rigors, productive cough, chills, and
pleuritic chest pain. Chest radiography often will show infiltrates (11). The
following agents, listed in decreasing order, cause two-thirds of all bacterial
pneumonias: S. pneumoniae, H. influenzae, Klebsiella pneumoniae, gramnegative organisms, and anaerobic bacteria. Atypical pneumonias are more
insidious in onset than typical pneumonias. Patients have moderate fever without
the characteristic rigors and chills. Additional symptoms include a nonproductive
cough, headache, myalgias, and mild leukocytosis. Chest radiography reveals
bronchopneumonia with a diffuse interstitial pattern; characteristically, the patient
does not appear to be as ill as the x-ray suggests. Common causes of atypical
pneumonia include viruses, M. pneumoniae, Legionella pneumophila, Chlamydia
pneumoniae (also called the TWAR agent), and other rare agents.
1154A strong index of suspicion is required for diagnosis, especially in the
elderly and immunocompromised individuals, who have altered response
mechanisms. Subtle clues in the elderly include changes in mentation, confusion,
and exacerbation of other illnesses. The febrile response may be entirely absent,
and the results of the physical examination are not predictive of pneumonia. In
high-risk groups, an increased respiratory rate of greater than 25 breaths per
minute remains the most reliable sign of infection. Mortality in these high-risk
groups of patients is strongly correlated with the ability of the host to mount
normal defenses to the symptoms of fever, chills, and tachycardia.
All women suspected of having pneumonia should undergo chest
radiography to establish the diagnosis and to detect alternate diagnoses such
as congestive heart failure and tumors. [1] The chest radiograph can detect
complications like pleural effusions and multilobar disease. In the setting of CAP
in a markedly ill patient, a referral to a pulmonary specialist or to the local
emergency room may be indicated because of the high rate of severe
complications. The appropriate laboratory studies, including sputum cultures,
Gram stains, etc., can be obtained.
The American Thoracic Society updated their original guidelines in 2007 and
these are currently in the process of being revised again (12). These clinical
recommendations use an evidence-based approach for the diagnosis and
management of community-acquired pneumonia. Therapy should be directed at
the responsible or most likely pathogen (13), but in many cases of pneumonia, the
exact cause cannot be determined, and empiric therapy should be initiated. [1]
The American Thoracic Society recommends empiric therapy based on four
groups of specific patient profiles, the presence of modifying factors, and
pneumonia severity (Table 22-1):
Group I: Outpatients with no cardiopulmonary disease (congestive
heart failure or COPD) and no modifying factors. These patients are in
the lowest-risk group and are usually infected by pathogens such as C.
pneumoniae, M. pneumoniae, or S. pneumoniae. Patients should be treated
with an advanced-generation macrolide such as azithromycin,
clarithromycin, or doxycycline.
Group II: Outpatients with cardiopulmonary disease or modifying
factors. Patients in this group usually have some comorbidities and are
older than 50 years of age. Aerobic gram-negative bacilli, mixed infections
with atypical pathogens, and drug-resistant S. pneumoniae (DRSP) should
be considered in this patient population. Drug recommendations include a
respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin)
or beta-lactam PLUS macrolide.
1155Group III: Inpatients who are not in the intensive care unit and have
cardiopulmonary or modifying factors. Drugs for these patients include
intravenous fluoroquinolone monotherapy or a combination of an
intravenous beta-lactam agent plus either intravenous or oral administration
of an advanced macrolide or doxycycline.
Group IV: Inpatients in the intensive care unit. These patients usually
have the most severe pneumonia, and all antibiotics are given
intravenously. Immediate consultation with an internist, hospitalist, or
infectious disease specialist is recommended.
Table 22-1 Modifying Factors that Increase the Risk of Infection with Specific
Pathogens
Penicillin-resistant and Drug-resistant Pneumococci
Age >65 yrs
Beta-lactam therapy within the past 3 mo
Alcoholism
Immune-suppressive illness (including therapy with corticosteroids)
Multiple medical comorbidities
Exposure to a child in a day-care center
Enteric gram-negatives
Residence in a nursing home
Underlying cardiopulmonary disease
Multiple medical comorbidities
Recent antibiotic therapy
Pseudomonas aeruginosa
Structural lung disease (bronchiectasis)
Corticosteroid therapy (>10 mg of prednisone per day)
Broad-spectrum antibiotic therapy for >7 days in the past month
Malnutrition
1156Adapted from American Thoracic Society. Guidelines for the management of adults with
community-acquired pneumonia. Am J Respir Crit Care Med 2001;163:1730–1754.
Oxygen therapy and hydration should be initiated in addition to antibiotic
therapy. Given issues of bacterial resistance and development of severe lifethreatening compromise, patients in groups III, IV, and the sicker patients in
group II may benefit from consultation with a pulmonary specialist or an internist.
Most patients will have an adequate clinical response within 3 days of treatment.
Oral antibiotics may be given when patients meet the following criteria: ability to
eat and drink, improvement in cough and dyspnea, afebrile (<100°F) on two
occasions 8 hours apart, and a decreasing white blood cell count. If other clinical
features are favorable, patients may be switched to oral antibiotics even if febrile.
They may be discharged on the same day that oral antibiotics are started if other
medical and social factors are favorable.
Vaccination
There are numerous vaccines that need to be administered to adults
depending on age, comorbidities, and presence of young children. All primary
care providers should be familiar with the recommended immunizations and urge
their patients to have them. Many are available at pharmacies by prescription if a
practice has not undertaken the cost of providing vaccines at the office. The
Centers for Disease Control and Prevention (CDC) has a comprehensive chart
outlining the vaccines for adults (14). See Figure 22-1. The influenza vaccine
should be given every fall to high-risk groups: individuals 50 years of age or
older; anyone with serious long-term health problems such as heart disease,
lung disease, kidney disease, diabetes, and weak immune systems as with
HIV and AIDS; individuals on long-term steroids or receiving cancer
treatment; women who are pregnant during the flu season (November
through April); and anyone coming in close contact with people at risk of
serious influenza like physicians, nurses, and family members. Vaccination is
best given from October to mid-November. Antiviral agents should not be used as
a substitute for vaccination but may be a useful adjunct. The four agents approved
for use in the United States are amantadine, rimantadine, zanamivir, and
oseltamivir. These drugs should be given within 2 days of the onset of symptoms
to shorten the duration of uncomplicated illness caused by influenza (15).
CARDIOVASCULAR DISEASE
The risk factors for coronary artery disease are presented in Table 22-2.
Central to treating cardiovascular disease is the control of contributing
1157diseases and risk factors through lifestyle modifications (Table 22-3). Aerobic
exercise protects against cardiovascular disease (16). Additional aspects of
prevention of myocardial disease, renal disease, and stroke include control of
hypertension, identification and control of diabetes and obesity, and control of
dietary fats, especially cholesterol, in susceptible individuals (Fig. 22-2).
Table 22-2 Major Risk Factors for Coronary Artery Disease
Age >55 for men and >65 for women
Family history of cardiovascular disease (men <55 yrs; women <65 yrs)
Physical inactivity
Diabetes mellitus
Cigarette smoking
Dyslipidemia
Obesity (body mass index ≥30)
Hypertension
Microalbuminuria or estimated glomerular filtration rate <60 mL/min
Adapted from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC VII). JAMA 2003;289:2560–2572.
1158FIGURE 22-1 Recommended immunizations for adults by health condition 2017.
(Adapted from U.S. Department of Health and Human Services, Center for Disease
Control and Prevention. Recommended immunizations for adults by age. Available online
at https://www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule-easy-read.pdf.
Accessed September 28, 2017.)
1159FIGURE 22-2 Disease and risk factors contributing to cardiovascular disease.
Table 22-3 Lifestyle Adjustments to Manage Hypertension
Weight reduction to maintain a body mass index of 18.5–24.9
Limit alcohol use to two drinks per day for men (24 oz beer, 10 oz of wine, 3 oz of
80-proof whiskey) and no more than one drink per day for women and lighter-weight
persons
Regular aerobic exercise (at least 30 min per day of brisk walking most days of the
week)
Decrease salt intake to less than 2.4 g of sodium or 6 g of sodium chloride per day
Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced
content of saturated and total fat
Adapted from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC VII). JAMA 2003;289:2560–2572.
Hypertension
The relationship between hypertension and cardiovascular events such as
stroke, coronary artery disease, congestive heart disease, and renal disease is
well known. More than 50 million people in the United States have
1160hypertension. It is found in 15% of the population between the ages of 18 and 74
years; the incidence increases with age and varies with race. Recognition and
treatment of hypertension may decrease the development of renal and cardiac
disease.
Epidemiology
The incidence of hypertension is twice as high in African Americans than in
whites. Geographic variations exist: the southeastern United States has a higher
prevalence of hypertension and stroke, regardless of race (17). Preventive
measures can be most effective in those at highest risk, such as in African
American women and individuals from the lowest socioeconomic level (18). The
influence of genetic predisposition is poorly understood. Classically,
hypertension is defined as blood pressure levels higher than 140/90 when
measured on two separate occasions. Life insurance risk tables indicate that
when blood pressure is controlled to lower than 140/90, normal survival occurs
over a 10- to 20-year follow-up, regardless of gender. Recommendations are
based on sustained blood pressures higher than 140/90 (see Fig. 22-3) (19).
Table 22-4 Laboratory Tests and Procedures Recommended in the Evaluation of
Uncomplicated Hypertensiona
Urinalysis
Complete blood count
Potassium
Creatinine or estimated glomerular filtration rate
Calcium
Fasting glucose
Lipid profile that includes HDL, LDL, and triglycerides after a 9- to 12-hr fast
12-lead electrocardiogram
aIf any of the above are abnormal, consultation or referral to an internist is indicated.
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Adapted from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC VII). JAMA 2003;289:2560–2572.
1161Table 22-5 Blood Pressure (BP) Classification (Adults 18 Yrs and Older)
Category Systolic BP (mm Hg) Diastolic BP (mm Hg)
Normal <120 and <80
Prehypertension 120–139 or 80–89
Stage 1 hypertension 140–159 or 90–99
Stage 2 hypertension >160 or >100
Modified from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC VII). JAMA 2003;289:2560–2572.
More than 95% of individuals with hypertension have primary or essential
hypertension (cause unknown), whereas fewer than 5% have secondary
hypertension resulting from another disorder. [2] Key factors to be determined
in the history and physical examination include presence of prior elevated
readings including a history of pre-eclampsia, previous use of antihypertensive
agents, a family history of cardiovascular death before age 55, use of weight-loss
supplements and excessive intake of alcohol or sodium (Tables 22-2 and 22-3).
Lifestyle modification is considered important in the therapy of hypertension;
thus, a detailed history of diet and physical activity should be obtained (16).
Baseline laboratory evaluations to rule out reversible causes of hypertension
(secondary hypertension) are listed in Table 22-4. Diagnosis and management are
based on the classification of blood pressure readings, as presented in Table 22-5.
The Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure (JNC7) released their seventh report in 2003.
The purpose was to provide an evidence-based approach to the prevention and
management of hypertension. [2] Following are some of the key points of this
report:
Systolic blood pressure in those older than 50 years is a more
important cardiovascular risk factor than diastolic blood pressure.
Beginning at 115/75 mm Hg, the risk of cardiovascular disease doubles
for each increment of 20/10 mm Hg.
Individuals who are normotensive at 55 years of age will have a 90%
lifetime risk of developing hypertension.
Patients with prehypertension (systolic blood pressure 120 to 139 mm
Hg or diastolic blood pressure 80 to 89 mm Hg) require health-
1162promoting lifestyle modifications to prevent the progressive rise in
blood pressure and cardiovascular disease.
For uncomplicated hypertension, thiazide diuretic should be used in
most cases for medical treatment, either alone or combined with drugs
from other classes.
Other antihypertensive drug classes (ACE inhibitors, angiotensinreceptor blockers, beta blockers, calcium channel blockers) should be
used in the presence of specific high-risk conditions (Fig. 22-3).
These recommendations were supplemented in the 2014 JNC8 meeting
with the following (19):
In the general population aged 60+, initiate pharmacologic treatment at
systolic pressures ≥150 mm Hg or diastolic blood pressure ≥90 mm Hg to
reach treatment goal of less than 150/90 mm Hg.
In the general population aged less than 60, initiate pharmacologic
treatment to lower blood pressure at a diastolic of 90 mm Hg or greater.
In the general population aged less than 60, initiate pharmacologic
treatment to lower blood pressures at a systolic of 140 mm Hg or greater.
In population aged 18 or more with chronic kidney disease or diabetes,
initiate pharmacologic treatment to lower blood pressure at systolic blood
pressure of 140 mm Hg or greater or diastolic blood pressure of 90 mm Hg
or greater.
In the general black population including those with diabetes, initial
antihypertensive treatment should include a thiazide-type diuretic or
calcium channel blocker.
The main objective of hypertensive treatment is to attain and maintain a
goal BP. If the goal BP is not reached within a month of treatment, increase
the dose of the first drug or add a second agent. Referral to a hypertension
specialist may be indicated for patients in whom goal BP cannot be attained
using the above strategies or for the management of complicated patients.
[2] Regardless of therapy or care, hypertension will be controlled only if patients
are motivated to maintain their treatment plan. If blood pressure control is not
easily achieved, if the systolic blood pressure is higher than 180 mm Hg, or if the
diastolic reading is higher than 110 mm Hg, referral to an internist is
recommended. Referral is indicated if secondary hypertension is suspected or
evidence of end-organ damage (renal insufficiency or congestive heart failure) is
present.
Measurement of Blood Pressure
1163Essential variables in the evaluation of hypertension are the acquisition of
measurements and the need to standardize measurements (20). “White coat”
or office hypertension (i.e., elevated just by seeing a physician) may occur in
up to 30% of patients. For patients who have repeated normal measures outside
of the office, it is reasonable to use ambulatory or home monitoring devices.
Given the variation of accuracy and patient interpretation, it is advisable for the
patient to bring their blood pressure unit into the office to calibrate it against the
office-based measurements.
Blood pressure protocols for measurement should be standardized. The
following steps will optimize the accuracy of the reading:
The patient should rest for 5 minutes in a seated position with legs
uncrossed.
Use the right arm for measurements (for unknown reasons, the right arm
has higher readings).
The cuff should be applied 2 cm above the bend of the elbow.
The cuff should be inflated to 30 mm Hg above the disappearance of the
brachial pulse, or 220 mm Hg.
The cuff should be deflated slowly. The cuff size is important, and most
cuffs are marked with “normal limits” for the relative size they can
accommodate. The most common clinical problem encountered is small
cuffs used with obese patients, resulting in “cuff hypertension.”
Phase-V Korotkoff is when sounds completely disappear. Most experts in
hypertension advocate the use of phase-V Korotkoff sounds.
The use of automated devices may help eliminate discrepancies in
measurements. Regardless of the method or device used, two measurements
should be obtained with less than a 10 mm Hg disparity to be judged adequate.
When repeated measures are performed, there should be a 2-minute rest period
between readings. Blood pressure has a diurnal pattern, so determinations
preferably should be done at the same time.
Therapy
[2] Nonpharmacologic interventions or lifestyle modifications should be
attempted before initiation of medication. Drug therapy should be initiated
for systolic blood pressure greater than 140 mm Hg or diastolic blood
pressure greater than 90 mm Hg. An important element in lifestyle
modifications is to modify all contributors to cardiovascular disease. In obese
patients, weight loss, especially in individuals with truncal and abdominal
obesity, can play a significant role in the prevention of atherosclerosis (16). A
1164loss of just 10 lb was reported to lower blood pressure. Enquiries into dietary
practices should be made to eliminate excess salt, cholesterol, and fats in the diet.
Dietary interventions that use calcium, magnesium, and potassium
supplementation did not make a clinically significant reduction in pressure (21).
[2] An exercise program, weight loss, and moderating alcohol intake (to no
more than two alcoholic beverages per day) contribute to overall
cardiovascular health. Aerobic exercise alone may prevent hypertension in
20% to 50% of normotensive individuals (16).
[2] The goal of therapy is for the patient to lower blood pressure into the
“normal range”: a systolic reading less than or equal to 120 mm Hg and a
diastolic reading less than or equal to 80 mm Hg. If lifestyle modifications
are not sufficient to control blood pressure, then pharmacologic intervention
is indicated (Fig. 22-3).
Diuretics
The most commonly used medication for initial blood pressure reduction is a
thiazide diuretic. The mechanism of action is to reduce plasma and extracellular
fluid volume. This lowering of volume is thought to decrease peripheral
resistance. Cardiac output initially decreases and then normalizes (19). The
important long-term effect is a slight decrease in extracellular fluid volume.
Potassium-sparing diuretics (spironolactone, triamterene, or amiloride) are
available in fixed doses and should be prescribed to prevent the development of
hypokalemia. Potassium supplementation is less effective than the use of
potassium-sparing agents. Thiazide diuretics are best used in patients with
creatinine levels less than 2.5 g/L. Control of hypertension with concurrent renal
insufficiency is difficult and is probably best handled by an internist or
nephrologist. Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs)
limits the effectiveness of this class of drugs. Other side effects of thiazide
diuretics include hyperuricemia, which may contribute to acute gout attacks,
glucose intolerance, and hyperlipidemias (19).
Angiotensin-Converting Enzyme Inhibitors
The ACE inhibitors are first-line drugs in the treatment of hypertension.
There are relatively few side effects; chronic cough is the most worrisome and is
a common reason of discontinuing the use of this group of drugs. Other agents
should be considered for patients at risk for pregnancy (a strict contraindication).
ACE inhibitors can be used in combination with other agents, including diuretics
and calcium channel antagonists. In contrast to beta-blocking agents, these
medications can be used in patients with asthma, depression, and peripheral
vascular disease. For unknown reasons, they are less effective in African
1165Americans unless a diuretic is used concomitantly. Use with diuretics increases
the effectiveness of both drugs, but hypovolemia may result and must be
monitored. Any NSAID, including aspirin, may decrease the antihypertensive
effectiveness. Creatinine levels should be measured at the start of therapy
and 1 week after initiation of any ACE inhibitor. An increase of up to 35% of
the baseline creatinine value is acceptable, and treatment should be continued
unless hyperkalemia develops.
Angiotensin-Receptor Blockers
The angiotensin-receptor blockers such as losartan and valsartan interfere
with the binding of angiotensin II to AT1 receptors. As with ACE inhibitors,
they are effective in lowering blood pressure, without causing the side effect
of coughing. Angiotensin-receptor blockers have favorable effects on the
progression of kidney disease in individuals who have diabetes, and on those
without diabetes and congestive heart failure.
Calcium-Channel Blockers
Calcium-channel blockers represent a major therapeutic breakthrough for
patients with coronary artery disease. They are effective in patients with
hypertension and peripheral vascular disease. The mechanism of action is to
block calcium movement across smooth muscle, therefore promoting vessel wall
relaxation. Calcium channel blockers are useful in treating concurrent
hypertension and ischemic heart disease. In addition, these drugs are particularly
effective in the elderly and African Americans. Side effects noted include
headache, dizziness, constipation, gastroesophageal reflux, and peripheral edema.
The addition of long-acting calcium-channel blockers made these preparations
more amenable for use in hypertension. A relative contraindication for use of
these drugs is the presence of congestive heart failure or conduction disturbances.
Adrenergic Inhibitors
Beta blockers were used extensively for years as antihypertensive agents. The
mechanism of action is decreasing cardiac output and plasma renin activity, with
some increase in total peripheral resistance. As a class, they are an excellent
source of first-line therapy, especially for migraine sufferers. Formulations such
as atenolol are water soluble, beta1 selective, and have fewer side effects than
propranolol. At higher doses, beta2 effects emerge. An advantage of watersoluble agents is a longer half-life. Reduced dosing schedules improve
compliance. Side effects of beta blockers include an increase in triglyceride levels
and a decrease in high-density lipoprotein (HDL) cholesterol and blunting of
1166adrenergic release in response to hypoglycemia. NSAIDs may decrease the
effectiveness of beta blockers. Contraindications to beta blockers are asthma, sick
sinus syndrome, or bradyarrhythmia.
The use of alpha1-adrenergic drugs as single agents decreases total
cholesterol and low-density lipoprotein (LDL) cholesterol while increasing HDL
cholesterol, in contrast to the metabolic effects of beta-blocking agents. They may
contribute to stress urinary incontinence in women because of altered urethral
tone. Their mode of action is to promote vascular relaxation by blocking
postganglionic norepinephrine vasoconstriction in the peripheral vascular smooth
muscle. When alpha1-adrenergic drugs are used in combination with diuretics,
hypotension may be further exacerbated. Therapy should begin with small doses
taken at bedtime followed by incremental increases. Other side effects that may
limit the usefulness of these agents in some patients include tachycardia,
weakness, dizziness, and mild fluid retention.
Direct Vasodilators
Hydralazine is a potent vasodilator used for years in obstetrics for severe
hypertension associated with preeclampsia and eclampsia. The mechanism of
action is direct relaxation of vascular smooth muscle, primarily arterial. Major
side effects include headaches, tachycardia, and fluid (sodium) retention that may
result in paradoxical hypertension. Several drug combinations are used to counter
the side effects and enhance antihypertensive effects of hydralazine. This is not a
typical first line medication.
Central-Acting Agents
Central-acting agents (methyldopa and clonidine) have long been used in
obstetrics. The mechanism of action is to inhibit the sympathetics in the central
nervous system, resulting in peripheral vascular relaxation. Side effects, including
taste disorders, dry mouth, drowsiness, and the need for frequent dosing (except
for the transdermal form of clonidine), limited the popularity of this group of
drugs. Sudden withdrawal of clonidine may precipitate a hypertensive crisis
and induce angina. Compliance is always a major issue, and side-effect profiles
contribute significantly to patient nonadherence. With the introduction of new
classes of drugs with improved efficacy and reduced side effects, the use of
medications in this class is expected to decline.
Monitoring Therapy
Blood pressure readings should be monitored frequently by the patient, or in
the office at 1- to 2-week intervals, when initiating intervention. If the patient
has other diseases (i.e., cardiovascular, renal), therapy should be initiated earlier
1167and directed to the target organ. If lifestyle modification alone is successful, close
monitoring is necessary at 3- to 6-month intervals. When lifestyle modification is
unsuccessful, a blood pressure medication should be started to decrease target
organ disease. When beginning therapy, concurrent medical conditions treatable
with a common agent should be sought. Gender is not an important consideration
in choosing an antihypertensive agent. However, presence of diabetes, renal
disease, or race can impact preferred initial medication. Figure 22-3 shows a
schematic of how to approach initiating pharmacologic interventions.
After antihypertensive medications are initiated, monitoring should be
instituted at approximately monthly intervals to determine blood pressures
and to assess side effects. The serum creatinine and potassium levels should be
monitored one to two times per year. When blood pressure goals are reached,
patients may be seen in the office at 3- to 6-month intervals. Patients capable of
home blood-pressure monitoring should be encouraged to measure the blood
pressure at the same time twice weekly. If intolerable side effects develop, a
different class of medications should be used and the patient’s progress
monitored. Patients whose blood pressure is difficult to control, especially if
requiring two agents, should be considered for referral. Patients with evidence of
target organ disease should be considered for referral to the appropriate specialist
for more intensive diagnostic workup and therapy.
Cholesterol
[3] The dietary influence of cholesterol on atherosclerosis and its relationship
to hypertension and cardiovascular events (myocardial infarction and
stroke) is widely debated in the scientific and lay communities. The
controversy centers on the effect of dietary cholesterol in assessing the risk
and prevention of cardiovascular disease (22). Many assume that all
cholesterol and fat in the diet have negative health consequences. Cholesterol
metabolism is complex, and some of our knowledge is extrapolated from animal
models. The role of cholesterol testing (who, when, and at what age) is hotly
debated among health care professionals, and the test itself is fraught with
multiple variables that affect results.
1168FIGURE 22-4 Metabolic pathways of lipid metabolism. Apo, apoprotein; LP, lipoprotein;
FFA, free fatty acid; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein;
VLDL, very–low-density lipoprotein; HDL, high-density lipoprotein; LCAT, lecithin
cholesterol acyltransferase.
Terms and Definitions
Cholesterol is usually found in an esterized form with various proteins and
glycerides that characterize the stage of metabolism. The important lipid particles
in cholesterol metabolism are noted in the schematic on Figure 22-4.
Metabolism
Cholesterol metabolism is divided into two pathways: (i) the exogenous
pathway derived from dietary sources, and (ii) the endogenous pathway or
the lipid transport pathway. Individuals vary in their ability to metabolize
1169cholesterol. Hyporesponders may be given cholesterol-loaded diets with no effect
on serum cholesterol measurements. Hyperresponders, in contrast, have high
serum cholesterol levels, regardless of dietary intake. Explanations for these
differences are well described in animal models, but not in humans.
Despite the negative connotation of LDL in cardiovascular disease, it is a very
important cellular metabolite and precursor for adrenocortical cells, lymphocytes,
and renal cells. The liver uses LDL for synthesis of bile acids and free cholesterol,
which is secreted into the bile. In the normal human, 70% to 80% of LDL is
removed from the plasma each day and secreted in the bile by utilization of the
LDL receptor pathway.
The final metabolic pathway is the transformation of HDL cholesterol in the
extrahepatic tissue. HDL cholesterol carries the plasma enzyme lecithin
cholesterol acyltransferase (LCAT). LCAT allows HDL cholesterol to
resynthesize lipids to very–low-density lipoprotein (VLDL) cholesterol and
recycle the lipid cascade. HDL cholesterol acts as a “scavenger” and therefore
reverses the deposit of cholesterol into tissues. There is good evidence that HDL
cholesterol is responsible for the reversal of atherosclerotic changes in vessels,
hence the term “good cholesterol” (22).
Hyperlipoproteinemia
When cholesterol is measured, various fractions are reported. Plasma cholesterol
or total cholesterol consists of cholesterol and unesterified cholesterol fractions. If
triglycerides are analyzed in conjunction with cholesterol, then assumptions can
be made concerning which metabolic pathway may be abnormal.
Hyperlipoproteinemias are defined by establishing a “normal population”
and then setting various limits at the 10th and 90th percentiles. Standards
for women set the 80th percentile for cholesterol at 240 mg/dL and the 50th
percentile at 200 mg/dL (Table 22-6). A diet low in animal fat and high in
vegetable and fiber consumption helps control the level of cholesterol. Plasma
elevations of chylomicrons, LDL, VLDL, various remnants of intermediatedensity lipoprotein (IDL), and VLDL are classified by the elevated fraction.
Evaluation
There are multiple causes of variation in cholesterol measurements (23). [3]
Major sources of variation within individuals include diet, obesity, smoking,
ethanol intake, and the effects of exercise. Other clinical conditions that affect
cholesterol measurements include hypothyroidism, diabetes, acute or recent
myocardial infarction, and recent weight changes. Measurements can be altered
by fasting, position of the patient while the sample is drawn, the use and duration
of venous occlusion, various anticoagulants, and the storage and shipping
1170conditions.
Table 22-6 Initial Classification Based on the Total Cholesterol, LDL, HDL, and
Triglyceride Levels
Initial Classification
Total cholesterol
<200 mg/dL Desirable blood cholesterol
200–239 mg/dL Borderline high blood cholesterol
≥240 mg/dL High blood cholesterol
LDL cholesterol
<100 mg/dL Optimal cholesterol
100–129 mg/dL Near or above optimal
130–159 mg/dL Borderline high
160–189 mg/dL High
≥190 mg/dL Very high
HDL cholesterol
<40 mg/dL Low HDL cholesterol
≥60 mg/dL High HDL cholesterol
Triglycerides
<150 mg/dL Normal
150–199 mg/dL Borderline high
200–499 mg/dL High
>500 mg/dL Very high
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Adapted from Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Executive summary of the third report of the National Cholesterol
Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of
1171High Blood Cholesterol in Adults. JAMA 2001;285:2486–2497.
Age and gender contribute to variations in total cholesterol
measurements. [3] Before age 50, women have lower lipid values than
men, after which age the level in women is higher than in men. This
finding may be modified by exogenous oral conjugated estrogens.
Seasonal variation also occurs, with lipid samples in December or
January being found to be approximately 2.5% higher than those measured
in June or July.
The effect of diet and obesity is well established. [3] Weight reduction in
an obese individual affects the triglyceride level, which may decrease as
much as 40%. Total cholesterol and LDL decrease less than 10% with diet;
however, HDL increases approximately 10%. Weight gain negates any
benefit from prior weight loss. Accuracy of lipid measurements depends on
the stability of the patient’s weight.
Alcohol and cigarette smoking are well-known modifiers of cholesterol.
Moderate sustained alcohol intake increases HDL and decreases LDL;
there is a complementary increase in triglycerides. [3] Alcohol has a
protective effect when taken in moderation (defined as approximately
two alcoholic drinks [2 oz of absolute alcohol] per day), but this effect
is negated in higher quantities. Smoking has the opposite effect,
increasing LDL and triglyceride levels and decreasing HDL. HDL3
decreases with cigarette smoking. The critical number of cigarettes smoked
is 15 to 20 per day, regardless of gender, and a variation in the number
smoked will affect results. Caffeine has a mixed effect on lipoprotein
measurements and should be avoided for 12 hours before blood collection.
Exercise is an important variable in the overall risk management of
heart disease. [3] Moderate levels of exercise are as important in the
overall cardiovascular health as control of hypertension and cessation of
cigarette smoking. Strenuous exercise lowers the concentrations of
triglycerides and LDL and increases HDL in the serum. Because of these
acute blood changes, vigorous exercise should be avoided within 12 hours
of drawing the blood for testing.
Patients with hypothyroidism have increased levels of total cholesterol
and LDL.
Testing
Because of the diurnal variation of blood triglycerides, blood samples should
be collected in the morning after a 12-hour fast. One of the most important
aspects of overall standardization of lipoprotein measurements is the laboratory
1172used. It may be worthwhile to consult a clinical pathologist to determine if the
laboratory complies with CDC standards for cholesterol and lipoprotein
measurements.
Management
When hyperlipidemia is confirmed on at least two separate occasions, secondary
causes should be diagnosed or excluded by taking a detailed medical and drug
history, comprehensive physical examination, and appropriate laboratory tests.
Causes of secondary dyslipidemia include diabetes, hypothyroidism, obesity,
obstructive liver disease, chronic renal failure, pregnancy, and use of medications
such as progestins, anabolic steroids, and corticosteroids. Therapeutic lifestyle
changes should be initiated in all patients to reduce their risk of coronary
heart disease:
1. [3] Reduced intakes of saturated fats (<7% of total calories) and
cholesterol (<200 mg per day)
2. Therapeutic options for enhancing LDL lowering, such as plant
stanols/sterols 2 g per day and increased viscous (soluble) fiber 10 to 25 g
per day
3. Weight reduction
4. Increased physical activity
5. Smoking cessation and alcohol only in moderation
The 2013 ACC/AHA Cholesterol Management guidelines changed the
management of cholesterol to prevent the occurrence of cardiovascular disease
including stroke (24). The recommendations primarily involved patient age,
family history of hypercholesterolism, gender, and presence of comorbidities,
along with lipid levels. To assist in judging individual risks, an atherosclerotic
cardiovascular disease (ASCVD) risk calculator has been developed by the AHA
(25). Although many groups challenge the accuracy of the calculations stating
they consistently overestimate risks, it is still a useful tool.
[3] The level I recommendations from the 2013 guidelines regarding initiation of
medication included:
High-intensity statin therapy should be initiated (or continued) in patients
≤75 with clinical ASCVD. If not tolerated, moderate-intensity therapy is
second line.
Individuals with LDL ≥190 mg/dL or triglycerides ≥500 need to be
evaluated for secondary causes of hyperlipidemia.
Adults >21 with LDL >190 mg/dL should be treated with statins (high
1173intensity if tolerated).
Moderate-intensity statin therapy should be initiated (continued) for adults
aged 40 to 75 years with diabetes.
ASCVD calculator should be used to estimate 10-year ASCVD risk for
individuals with LDL 70 to 189 mg/dL without clinical ASCVD to guide
when statins should be initiated.
Adults 40 to 75 years of age with LDL 70 to 189 mg/dL without clinical
ASCVD or diabetes and an estimated 10-year risk of ASCVD ≥7.5%
should be treated with moderate-intensity statins.
[3] Patients with a family history of cardiovascular disease (history of
premature coronary artery problems and strokes) should be tested and
started on conservative programs in their 20s. As noted above, if their LDL
is greater than 190 mg/dL, they should be started on statins. Otherwise an
ASCVD calculation should be done and pharmaceutical therapy started if the 10-
year risk is 7.5% or more. Any woman with coronary heart disease or equivalents
such as diabetes or other forms of atherosclerotic disease (peripheral arterial
disease, abdominal aortic aneurysm, and symptomatic carotid artery disease)
should initiate lifestyle changes if her LDL is 100 mg/dL or more and drug
therapy if her LDL is 190 mg/dL or her 10-year risk calculation is 7.5% or more.
Periodic assessment of cardiovascular risk factors should be done starting at
age 40 in patients without prior identified risks. An annual assessment of weight,
blood pressure, exercise routine, and smoking status is supported by expert
opinion. A true screen requires lipid profile. Recommendations are to do this
every 5 years unless there is a significant change in the patient’s risk profile,
which may merit more frequent screens. The data for routine screening in patients
less than age 40 is unclear with no study clearly demonstrating a benefit. For
these reasons, USPSTF states it can make no recommendation for or against such
screening (26).
Prior to the 2013 ACC/AHA guidelines and confirmed by the U.S. Preventive
Service Task Force recommendation, bile acid–binding resins cholestyramine and
colestipol were the mainstay of therapy (26). The significant side effects of
nicotinic acid and fibric acid derivatives and poor patient compliance caused by
those side effects relegated them to second or third line treatment.
[3] Statins (HMG-CoA [3]-hydroxy-3methyl-glutaryl-coenzyme A reductase
inhibitors) have become the mainstay of treatment and prevention. These include
atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. These
medicines inhibit HMG-CoA reductase, the enzyme that catalyzes the ratelimiting step in cholesterol synthesis. Multiple clinical trials showed that
pravastatin, simvastatin, and lovastatin have a beneficial effect in
1174cardiovascular disease. Statins are better tolerated than other lipid-lowering
drugs, but reported side effects have concerned patients. These include severe
myalgias, muscle weakness with increases in creatine phosphokinase, and, rarely,
rhabdomyolysis, leading to renal failure. Detailed studies have shown that most of
these are mild and resolve with cessation of the medication (24,26,27). The severe
side effects of rhabdomyolysis and renal failure are extremely rare. This results in
a very favorable benefit to risk ratio for the statins when used in a moderate-risk
population (27). As the 10-year risk decreases, the benefit to risk ratio also
decreases. For this reason, the USPSTF recommends that patients with less than a
10% risk of an ASCVD event in the next 10 years not start statins without a
physician/patient discussion of risks and benefits of statins.
DIABETES MELLITUS
DM is a chronic disorder of altered carbohydrate, protein, and fat metabolism
resulting from a deficiency in the secretion or function of insulin. The disease is
defined by the presence of either fasting hyperglycemia or elevated plasma
glucose levels based on an oral glucose tolerance testing (OGTT). The major
complications of DM are primarily vascular, renal, and metabolic. [4] The
prevalence of DM is higher in women (especially with a history of gestational
diabetes) and certain ethnic groups, although a background rate in the general
population is 6.29%, which has increased threefold in 15 years (28).
[4] Risk factors for DM are:
1. Age greater than 45 years
2. Adiposity or obesity
3. A family history of diabetes
4. Race/ethnicity
5. Hypertension (blood pressure 140/90 mm Hg or greater)
6. HDL cholesterol less than or equal to 35 mg/dL and/or a triglyceride level
greater than or equal to 250 mg/dL
7. History of gestational diabetes or delivery of a baby weighing more than 9
lb
Major complications of DM include blindness, renal disease, gangrene of an
extremity, heart disease, and stroke. Diabetes is one of the four major risk factors
for cardiovascular disease.
Classification
In 2016, an expert committee was convened by the American Diabetes
1175Association to review the proposed standards for medical care in diabetes. Their
findings were reported in 2017 in Diabetes Care. The goal of the revision was to
clarify guidelines for nomenclature and testing that might reduce diagnostic
confusion and improve patient well-being (Table 22-7). The terms insulindependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus
(NIDDM) were replaced by the terms type 1 and type 2 DM based on insulin
levels and function but not on the patient’s age.
Type 1 Diabetes Mellitus
With type 1 diabetes, the major metabolic disturbance is the absence of
insulin from the destruction of beta cells in the pancreas. Insulin is necessary
for glucose metabolism and cellular respiration. When insulin is absent, ketosis
results. The cause of type 1 diabetes is unknown; data suggest an autoimmune
association from either a viral infection or toxic components in the environment.
Studies in the past decade showed a correlation between many autoimmune
diseases and the human leukocyte antigens (HLA).
Table 22-7 Classification of Diabetes Mellitus
1. Type 1 diabetes
Characterized by pancreatic destruction leading to insulin deficiency typically due to
autoimmune beta cell destruction
2. Type 2 diabetes
A combination of insulin resistance and some degree of inadequate insulin secretion
3. Gestational diabetes mellitus
Is diabetes diagnosed in the second or third trimester of pregnancy without preexisting diabetes
4. Specific types of diabetes due to other causes
A. Endocrinopathies (Cushing, acromegaly, pheochromocytoma,
hyperaldosteronism)
B. Drug- or chemical-induced (esp. organ transplant medications or glucocorticoids)
C. Diseases of the exocrine pancreas (pancreatitis, neoplasia, cystic fibrosis)
D. Infections
E. Genetic defects of beta-cell function and insulin action
Adapted from Cefalu W, ed. Standards of medical care in diabetes—2017. Diabetes Care
2017;40(supplement 1).
Insulin-sensitive tissues (muscle, liver, and fat) fail to metabolize glucose
efficiently in the absence of insulin. In uncontrolled type 1 diabetes, an excess
1176of counter-regulatory hormones (cortisol, catecholamines, and glucagon)
contributes to further metabolic dysfunction. In the absence of adequate amounts
of insulin, increasing breakdown products of muscle (amino acid proteolysis), fat
(fatty acid lipolysis), and glycogen (glucose glycogenolysis) are recognized.
There is an increase in glucose production from noncarbohydrate precursors as a
result of gluconeogenesis and ketogenesis in the liver. Without prompt treatment,
severe metabolic decompensation (i.e., diabetic ketoacidosis) will occur and may
lead to death.
Given the significant complexity and risks involved in the management of type
I DM, it is not advised that a generalist be primarily responsible for the
management of insulin and the associated comorbidities. These patients should be
followed by a provider who specializes in diabetes management.
Type 2 Diabetes Mellitus
[4] Type 2 DM is a heterogeneous form of diabetes that commonly occurs in
older age groups (>40 years) and more frequently has a familial tendency
than type 1 diabetes. This form of DM accounts for approximately 90% to 95%
of those with diabetes. The presence of risk factors strongly influences the
development of type 2 diabetes in susceptible populations.
[4] Risk factors for type 2 diabetes include ethnicity, obesity, family history
of DM, sedentary lifestyle, impaired glucose tolerance (IGT), upper-body
adiposity, and a history of gestational diabetes and hyperinsulinemia.
In contrast to the absence of insulin that occurs with type 1 diabetes, in
type 2 diabetes the altered metabolism of insulin results in insulin resistance.
[4] This condition is characterized by impaired glucose uptake in target tissues. A
compensatory increase in insulin secretion results, causing higher-than-normal
circulating insulin levels (29). Obesity is present in 85% of affected patients. The
cause of type 2 diabetes is unknown, but defects in the secretion and action of
insulin are suspected.
Diagnosis
Three methods are available to diagnose DM in nonpregnant women:
1. A single fasting blood glucose greater than or equal to 126 mg/dL on two
separate occasions
2. An A1c ≥6.5% or random blood glucose equal to or above 200 mg/dL in
an individual with classic signs and symptoms of diabetes (polydipsia,
polyuria, polyphagia, and weight loss)
A 2-hour OGTT greater than or equal to 200 mg/dL after a 75-g load of
1177glucose. [4] The term IGT has been replaced with the term prediabetic state
and is not considered diabetes diagnosis. However, it is important to identify
these individuals for more frequent screening and intervention. Diagnostic
criterion for prediabetes is fasting glucose greater than or equal to 100
mg/dL but less than 126 mg/dL, or A1c between 5.7% and 6.4%, or a 2-hour
value on a 75-g OGTT between 140 and 199 mg/dL (29).
It should be noted that fasting blood glucose, 2-hour OGTT, and A1c
screenings perform similarly but interestingly often pick up different patients with
positive screens. The 2-hour OGTT will result in the largest number of patients
receiving a diagnosis of diabetes. A1c is often the easiest initial screen but the
results can be impacted by race/ethnicity and anemia/hemoglobulinopathies.
[4] Patients who should be considered for diabetes testing can be
determined by the use of a diabetes risk calculator or using a listing of risk
factors. The calculators can be found at the American Diabetes Association
website and are available for downloads (30). Historical risk factors include:
All individuals 45 years of age or older (repeat at a minimum of 3-year
intervals)
Persons with classic signs and symptoms of diabetes (i.e., polyuria,
polydipsia, polyphagia, and weight loss)
Ethnic groups at high risk (Pacific Islanders, Native Americans,
African Americans, Hispanic Americans, and Asian Americans)
Obesity or overweight (body mass index >25 kg/m2) (or 23 kg/m2 if
Asian American)
History of a first-degree relative with diabetes
Women with gestational diabetes or who have delivered a baby
weighing more than 9 lb
Individuals with hypertension (blood pressure >140/90 mm Hg), or on
treatment for HBP or have a history of CVD
An HDL cholesterol level less than or equal to 35 mg/dL or triglyceride
level greater than or equal to 250 mg/dL
Presence of IGT/prediabetes on previous testing
Women with PCOS or other conditions associated with insulin
resistance.
Table 22-8 Generalist Physician Guidelines in the Therapy of Type II Diabetes
Mellitus
• Establish diagnosis and classify the type of diabetes mellitus (DM) (if type I, refer to
specialist in diabetes).
1178• Initiate diabetes education classes to learn blood glucose monitoring and diabetes
medications; to learn signs, symptoms, and complications; and to learn how to
manage sick days (may be available through local hospital or insurance plan).
• Place patient on ADA diet with appropriate caloric, sodium, and lipid restrictions
with aid of nutritionist or diabetologist to help with education and support.
• Establish baseline cardiac and renal risk factors, check feet and toenails at least once
a year, and refer to a foot specialist.
• Use finger-stick blood glucose for daily diabetic control.
• Follow chronic glycemic control by HgA1c every 2 to 3 mo in the office.
• Initial general health evaluation should consist of a complete history and physical
examination and the following laboratory tests: CBC with differential, chemistry
profile, lipid profile, urinalysis, thyroid function tests, urine for microalbuminuria,
and ECG (baseline at age 40 or older, repeat yearly).
• Development of vascular, ocular, neurologic, or renal compromise should prompt
immediate referral.
• Oral hypoglycemic agents may be considered if fasting blood glucose does not
decline or increases despite lifestyle changes. While on oral hypoglycemic agents,
check the HgA1C every 3 mo and at least two times a year if stable.
• If the fasting serum glucose is >200 mg/dL consistently or the HgA1C is more than
10%, consider starting insulin and referring the patient to an internist.
• Administer the flu vaccine every fall and the pneumococcal vaccine every 6 yrs.
ADA, American Diabetic Association; HgA1c, hemoglobin A1C; CBC, complete blood
count; ECG, electrocardiogram.
Adapted from Cefalu W, ed. Standards of medical care in diabetes—2017. Diabetes Care
2017;40(supplement 1).
Assessment of Glycemic Control
The only acceptable method for assessment of glycemic control is
determination of blood glucose by direct enzyme analysis. Glucometers with
memory storage made home glucose monitoring more reliable. Physician
treatment guidelines are in Table 22-8.
1179Treatment
Despite clear treatment recommendations, most diabetic patients have not reached
goals regarding A1c, LDL, and BP levels. Many continue to smoke and/or not
exercise. The reasons for the lack of success are complex, as is the care for most
patients with a chronic disease, especially those with a large behavioral
component. If a patient is not reaching goals through lifestyle adjustments and
oral medications, referral to a clinic system set up to deal with the multiple facets
of care should be made (29).
[4] Patients with prediabetes should be encouraged to implement the lifestyle
changes. This group has up to a 25% risk of developing true diabetes within 5
years. If their A1c continues to worsen despite lifestyle intervention, initiation of
metformin prior to actual diagnosis of diabetes can be considered.
The purpose of diabetes treatment is to prevent renal, cardiac, and neurologic
comorbidities, among others. The purpose of prediabetes treatment is to prevent
or at least delay the development of true diabetes. The sooner and more effective
the intervention, the better.
Type 2 diabetes is treated by a combination of lifestyle adjustments and
medications.
Lifestyle
[4] Diet is the most important component of DM management (both overt
diabetes and prediabetics) and usually the hardest way to achieve control. Three
major strategies are used: weight loss, low-fat diet (Ä30% of calories from
fat), and physical exercise. Obese patients should reduce their weight to the ideal
body weight. Metabolic advantages of weight reduction are improved lipid profile
and improved glucose control secondary to increased insulin sensitivity and
decreased insulin resistance. The greater the weight loss, the greater the
improvement in lipid disorders. In the setting of severe obesity (BMI ≥40 or BMI
≥35 with comorbidities), recommendations include consideration of metabolic
surgery (formally called bariatric surgery) (29). [4] Physical exercise promotes
weight loss and improves insulin sensitivity and dyslipidemia in those people who
are in high-risk groups for cardiovascular and microvascular diseases. Treatment
with a statin is recommended in the setting of diabetes to decrease LDL.
Oral Hypoglycemic Agents
Oral hypoglycemic agents are recommended for many type 2 diabetic
patients. The first oral hypoglycemic agents introduced were sulfonylureas (i.e.,
glyburide). The mode of action of sulfonylureas is based on two different
mechanisms: (i) enhanced insulin secretion from the pancreas, and (ii) an
extrapancreatic effect that is poorly understood. Other classes of drugs that have
1180different effects in patients with type 2 diabetes—such as biguanides (metformin),
thiazolidinediones, alpha-glucosidase inhibitors, and insulin secretagogues—were
introduced. Endogenous insulin secretion (as measured by C-peptide) is necessary
for oral hypoglycemic agents to work. If the fasting blood glucose on an adequate
diabetic diet is greater than 250 mg/dL, there is little effect. Frequent evaluation
to monitor control (every 3 to 4 months) is important. If glucose levels cannot be
controlled with oral hypoglycemic agents (i.e., metformin, a biguanide) or other
medicines (i.e., sulfonylureas), insulin therapy should be initiated and referral
should be considered because of the increased rate of complications.
THYROID DISEASES
[5] Thyroid disorders are more common in women and some families,
although the exact rate of inheritance is unknown in geriatric populations,
the incidence may be as high as 5% (31). Thyroid hormones act in target tissues
by binding to nuclear receptors, which induce change in gene expression.
Extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3) takes place in
the target tissue. T3 binds the nuclear receptor with higher affinity than T4, which
makes T3 more biologically active. Pituitary TSH and hypothalamic thyrotropinreleasing hormone (TRH) regulate hormone production and thyroid growth by
normal feedback physiology. Thyroid-stimulating immunoglobulins (TSI), once
known as a long-acting thyroid stimulator (LATS), bind to the TSH receptor,
which results in the hyperthyroid Graves disease.
More than 99% of circulating T4 and T3 concentrations are bound by
plasma proteins, predominately to thyroxine-binding globulin (TBG), with
the remaining 1% being free. Free levels of thyroid hormones remain constant
despite physiologic or pharmacologic alterations. Regardless of total serum
protein levels, active thyroid hormone levels remain stable. In healthy women,
transitions from puberty to menopause do not alter free thyroid hormone
concentrations. Excess endogenous or exogenous sources of estrogen increase
TBG plasma concentration by decreasing hepatic clearance. Androgens
(especially testosterone) and corticosteroids have the opposite effect by increasing
hepatic TBG clearance.
Thyroid function tests may be misleading in women receiving exogenous
sources of estrogen because of these altered binding characteristics.
Postmenopausal hormonal therapy and pregnancy alter laboratory findings and
complicate interpretation of thyroid function studies. Most laboratories
compensate by reporting a free T4 and T3 level that mathematically corrects for
such physiologic alterations rather than the traditional total T4, and T3 resin
1181uptake (32). Another confounder is that hCG can mimic TSH during the first
trimester of a pregnancy thereby resulting in a falsely low TSH result raising
concerns for hyperthyroidism. If questions arise, a clinical pathologist should be
consulted.
Hypothyroidism
[5] Overt hypothyroidism occurs in 2% of women, and at least an additional
5% develop a laboratory diagnosis of subclinical hypothyroidism.
Hypothyroidism is another disease that disproportionally impacts women five- to
eightfold more commonly than men. The principal cause of hypothyroidism in
countries without iodine deficiencies is autoimmune thyroiditis (Hashimoto
thyroiditis). A familial predisposition is observed in many cases, but the specific
genetic or environmental trigger is unknown. The incidence of autoimmune
thyroiditis increases with age, affecting up to 15% of women older than 65 years
who commonly have only subtle signs or symptoms. [5] Many have “subclinical
hypothyroidism,” which is defined as an elevated serum TSH concentration
with a normal serum free T4 level. It is uncertain whether treatment will
improve the quality of life in otherwise healthy patients who have subclinical
hypothyroidism (31,33). In a setting of autoimmune thyroiditis, one has both
cellular and antibody-mediated destruction of the thyroid, which can result in
either a goiter or atrophic thyroid. Autoimmune thyroiditis may be associated
with other endocrine (e.g., type 1 diabetes, primary ovarian failure, adrenal
insufficiency, and hypoparathyroidism) and nonendocrine (e.g., vitiligo and
pernicious anemia) disorders (33). When any autoimmune disease is diagnosed,
there should be a high degree of suspicion for concurrent thyroid disorders. With
postpartum thyroiditis, there will be a hyperthyroid phase followed by a
hypothyroid phase that can last for months. Iatrogenic causes of hypothyroidism
occur after surgical removal or radioactive iodine therapy for hyperthyroidism
(Graves) or thyroid cancer. Radiation was used to treat acne and other
dermatologic disorders 45 years ago. These patients, now in their 60s or older,
have an increased risk of thyroid cancer and require close monitoring. Although
worldwide iodine deficiency goiter is the most common form of hypothyroidism,
this is uncommon in North America, given the iodine supplementation in salt and
other dietary sources. Hypothyroidism rarely occurs secondary to pituitary or
hypothalamic diseases from TSH or TRH deficiency, but this must be considered
if symptoms occur after neurosurgical procedures.
Clinical Features
Manifestations of hypothyroidism include a broad range of signs and
1182symptoms: fatigue, lethargy, cold intolerance, nightmares, dry skin, hair loss,
constipation, periorbital carotene deposition (causing a yellow discoloration),
carpal tunnel syndrome, weight gain (usually less than 5 to 10 kg),
depression, irritability, hyperlipidemia, and impaired memory. Menstrual
dysfunction is common, either as menorrhagia or amenorrhea. The finding of
hyperlipidemia may be the first indication of hypothyroidism, especially the
presence of high triglycerides. Hypothyroidism may cause precocious or delayed
puberty. Hyperprolactinemia and galactorrhea are unusual manifestations of
hypothyroidism; however, assessment of thyroid function should be considered.
To distinguish primary hypothyroidism from a prolactin-secreting pituitary
adenoma, TSH levels should be assessed in women who have amenorrhea,
galactorrhea, and hyperprolactinemia.
Diagnosis
Recommendations for screening asymptomatic women for thyroid disorders in
women range from every 5 years starting at age 35 in women (American Thyroid
Association), to age 50 (American College of Physicians). Other groups have
recommended periodic screening in older women (American Academy of Family
Physicians and American Association of Clinical Endocrinologists). The USPSTF
stated in their recommendation in 2004 that the evidence is insufficient to
recommend for or against screening (31). In 2014, the USPSTF reviewed the data
regarding routine screening for asymptomatic women without risk factors and
reaffirmed that the evidence is insufficient to recommend for or against screening
(34). [5] For this reason, screening should be reserved for patients at risk (prior
history of thyroiditis or other autoimmune diseases or history of treatment for
hyperthyroidism) or women with symptoms or signs that could represent a
thyroid dysfunction. Suspected hypothyroidism should [5] always be
confirmed with laboratory studies. Primary hypothyroidism is characterized
by the combination of an elevated serum TSH with a low serum free T4 level.
Autoimmune thyroiditis can be confirmed by the presence of serum antithyroid
peroxidase (formerly referred to as antimicrosomal) antibodies. An elevated TSH
with a normal free T4 level implies subclinical hypothyroidism. Central
hypothyroidism, although rare, is distinguished by a low or low-normal serum
free T4 level with either a low or inappropriate normal serum TSH concentration.
Therapy
Synthetic L-thyroxine (T4) is the treatment of choice for hypothyroidism and
is available as generic levothyroxine (35). There is debate about the value of
replacing thyroxine in the subclinical hypothyroidism patient. Such replacement
1183did not result in improved survival, decreased cardiovascular morbidity, or
improve the quality of life (36). The mode of action is by conversion of T4 to T3
in peripheral tissues. Levothyroxine should be taken on an empty stomach.
Absorption may be poor when taken in combination with aluminum hydroxide
(common in antacids), cholestyramine, ferrous sulfate, or fatty meals. The usual
T4 requirement is weight related (approximately 1.6 μg/kg) but decreases for the
elderly. Normal daily dosage is 0.1 to 0.15 mg but should be adjusted to maintain
TSH levels within the normal range. TSH levels should initially be checked in 6
weeks and whenever dosages or brands are changed. When the dose is stabilized,
TSH check once every year or two is adequate unless there is a change in the
patient’s status (i.e., pregnancy).
A low initial T4 dose (0.025 mg per day) should be initiated in the elderly or
patients with known or suspected coronary artery disease. Rapid replacement may
worsen angina and in some cases, induce myocardial infarction.
The use of combined T3 and T4 therapy (desiccated thyroid extracts) is not
recommended for a number of reasons. The conversion of T4 to T3 allows the
normal hormonal regulation to control T3 levels. The use of a combined therapy
overrides that and can result in excessive and nonphysiologic levels of T3
resulting in mild hyperthyroidism. During pregnancy, fetal neurogenesis is
dependent on maternal T4 levels until the estimated gestational age of 16 to 18
weeks (37).
Hyperthyroidism
Hyperthyroidism affects 2% of women during their lifetime, most often
during their childbearing years and impacts women fivefold more commonly
than men. The Graves disease represents the most common disorder; it is
associated with orbital inflammation, causing the classic exophthalmos associated
with the disease and a characteristic dermopathy, pretibial myxedema. It is an
autoimmune disorder caused by TSH reception antibodies that stimulate gland
growth and hormone synthesis. The etiology of the Graves disease in genetically
susceptible women is unknown. Autonomously functioning benign thyroid
neoplasias are less common causes of hyperthyroidism and are associated with
toxic adenomas and toxic multinodular goiter. Transient thyrotoxicosis may be
the result of unregulated glandular release of thyroid hormone in postpartum
(painless, silent, or lymphocytic) thyroiditis and subacute (painful) thyroiditis.
Other rare causes of thyroid overactivity include human chorionic gonadotropin–
secreting choriocarcinoma, TSH-secreting pituitary adenoma, and struma ovarii.
Factitious ingestion or iatrogenic overprescribing should be considered in patients
1184with eating disorders as they use this as a weight control strategy.
Clinical Features
Symptoms of thyrotoxicosis include fatigue, diarrhea, heat intolerance,
palpitations, dyspnea, nervousness, and weight loss. In young patients, there
may be paradoxical weight gain from an increased appetite. Thyrotoxicosis
may cause vomiting in pregnant women, which may be confused with
hyperemesis gravidarum. Tachycardia, lid lag, tremor, proximal muscle
weakness, and warm moist skin are classic physical findings. The most dramatic
physical changes are ophthalmologic and include lid retraction, periorbital edema,
and proptosis. These eye findings occur in less than one-third of women. In
elderly adults, symptoms are often more subtle, with presentations of unexplained
weight loss, atrial fibrillation, or new onset angina pectoris. Menstrual
abnormalities span from regular menses to light flow to anovulatory menses and
associated infertility. Goiter is common in younger women with the Graves
disease, but may be absent in older women. Toxic nodular goiter is associated
with nonhomogeneous glandular enlargement, whereas in subacute thyroiditis the
gland is tender, hard, and enlarged.
Diagnosis
All patients with symptoms of hyperthyroidism should have a complete history
and examination done with focus on the thyroid (nodule, tenderness, or goiter),
cardiac (hypertension tachycardia), pulmonary (tachypnea), neurologic
(peripheral weakness), the eye signs, and presence of peripheral edema or
pretibial myxedema (38).
Most thyrotoxic patients have elevated total and free T4 and T3
concentrations. In thyrotoxicosis, serum TSH concentrations are virtually
undetectable, even with very sensitive assays (sensitivity measured to 0.1 units).
Radioiodine uptake scans are useful in the differential diagnosis of established
hyperthyroidism. Scans with homogeneous uptake of radioactive iodine are
suggestive of the Graves disease, whereas heterogeneous tracer uptake is
suggestive of a diagnosis of toxic nodular goiter. Thyroiditis and medicationinduced thyrotoxicosis have diminished glandular radioisotope concentration.
There is only a modest correlation between the severity of symptoms and the level
of thyroid hormones (38).
Therapy
Therapy can be pharmaceutical, thyroid ablation, thyroidectomy, or a
combination of the three depending on many variables that include the patient’s
age, childbearing plans, and response to other therapies (38).
1185Antithyroid medications, either methimazole (10 to 30 mg per day) or
propylthiouracil (PTU; 50 to 300 mg every 6 to 8 hours) are used for initial
therapy. Both antithyroid drugs block thyroid hormone biosynthesis and may
have additional immunosuppressive effects on the gland. The primary difference
in oral medications is that PTU partially inhibits extrathyroidal T4-to-T3
conversion, whereas methimazole does not. Methimazole has a longer half-life
and permits single daily dosing, which may encourage compliance. Except during
the first trimester of pregnancy when PTU therapy is preferred, methimazole is
the typical first choice in antithyroid medications. Euthyroidism is typically
restored in 3 to 10 weeks, and treatment with oral antithyroid agents is continued
for 6 to 24 months, unless total ablation with radioiodine or surgical resection is
performed. Surgery is less popular because it is invasive and may result in
inadvertent parathyroid removal, which commits the patient to lifelong calcium
therapy.
Beta-adrenergic blocking agents such as propranolol or atenolol are useful
adjunctive therapy for control of sympathomimetic symptoms such as tachycardia
(38). An additional benefit of beta blockers is the blocking of peripheral
conversion of T4 to T3. If a patient is having symptomatic thyrotoxicosis with
heart rate greater than 90 beats per minute or there is a history of pre-existing
cardiovascular disease the patient should be referred to an endocrinologist or even
an emergency room. In rare cases of thyroid storm, PTU, beta blockers,
glucocorticoids, and high-dose iodine preparations (intravenous sodium iodide)
should be administered immediately, and referral to an intensive care unit is
advisable.
The relapse rate with oral antithyroid medications is 50% over a lifetime.
Lifelong follow-up is important when medical therapy is used solely because of
the high relapse rate. Both medications have infrequent (5%) minor side effects,
which include fever, rash, or arthralgias. Major toxicity (e.g., hepatitis, vasculitis,
and agranulocytosis) occurs in less than 1%. PTU appears to be more responsible
for major toxicities than methimazole. Patients on either medication should be
followed with serial complete blood count (CBC) and liver function tests.
However, agranulocytosis cannot be predicted by periodic complete blood counts;
therefore, patients who have a sore throat or fever should stop taking the
medication and call their physician immediately (38).
Therapy with iodine-131 provides a permanent cure of hyperthyroidism in
90% of patients. The principal drawback to radioactive iodine therapy is the high
rate of postablative hypothyroidism, which occurs in at least 50% of patients
immediately after therapy, with additional cases developing at a rate of 2% to 3%
per year. Based on the assumption that hypothyroidism will develop, these
patients should be given lifetime thyroid replacement therapy.
1186Thyroid Nodules and Cancer
[5] Thyroid nodules are common and are more prevalent in adults aged less
than 30 or over 60 years. This is a group that encompasses much of the
population seen by an ob-gyn. For this reason, an understanding of the screening
and diagnosing is important. The vast majority of nodules when discovered by the
patient or the provider, are asymptomatic and benign; however, malignancy (4%
to 6% of all nodules) and hyperthyroidism must be excluded (39). The common
differential includes multinodular goiter, the Hashimoto thyroiditis, colloid/simple
cyst, follicular adenoma, and malignancy. Ultrasound-guided fine-needle
aspiration (FNA) is recommended in the presence of the following factors: history
of radiation to the head, neck, or upper chest; family history of thyroid cancer;
ultrasound findings suggestive of malignancy; or a nodule larger than 1.5 cm in
diameter (40).
Thyroid function tests should be performed before FNA and, if results are
abnormal, the underlying disease should be treated. A markedly suppressed
TSH level implies the nodule is hyperfunctioning and unlikely to be malignant.
Because most nodules are “cold” on scanning (especially if TSH is normal), it is
more cost effective to proceed with ultrasound rather than radioactive scanning.
An ultrasound can determine additional nodules, size of nodule(s), characteristics
of the nodules (solid/cystic), thyroid size, and presence of enlarged lymph nodes.
Thyroid ultrasound findings of solid hypoechoic nodule or features of
microcalcifications, irregular margins, rim calcifications, or evidence of extension
into the surrounding tissue, raise concerns for malignancy. These should be
sampled by FNA irrespective of other findings. The presence of
lymphadenopathy should prompt FNA sampling.
Needle biopsy provides a diagnosis in 95% of cases; in the 5% of patients in
whom the diagnosis cannot be established, excisional biopsy is necessary. Only
20% of excisional biopsies of an “indeterminate aspiration” are found to be
malignant (40). Lesions that are confirmed malignant on biopsy should be treated
with extirpative surgery, and benign nodules should be palpated every 6 to 12
months for growth but surgical intervention is not indicated. Thyroxine
suppressive therapy for benign nodules is not recommended (41).
Papillary thyroid carcinoma is the most common malignancy, found in
75% of thyroid cancers. The majority of cancers are found incidentally during
routine examinations. Risk factors include a history of radiation exposure during
childhood and family history. Signs include rapid growth of neck mass, new onset
hoarseness, or vocal cord paralysis. In the setting of rapid growth, fixed nodule,
new onset hoarseness, or the presence of lymphadenopathy, it is important to be
sure an FNA is done. Thyroidectomy is the primary treatment with radioactive
iodine and TSH suppression with thyroxine. Patients younger than 50 years of age
1187with a primary tumor of less than 4 cm at presentation, even with associated
cervical lymph node metastasis, are usually cured. In the elderly, anaplastic
tumors have a poor prognosis and progress rapidly despite therapy.
Follicular thyroid cancer is the second most common thyroid cancer,
comprising up to 10% of cases. These tend to occur in an older population with
peak ages of 40 to 60. It has a threefold greater prevalence in women than men.
This form of cancer tends to have vascular invasion, frequently with distant
metastases. The prognosis tends to be less favorable with this form of cancer than
with papillary cancers, although women do have a better prognosis than men.
IRRITABLE BOWEL SYNDROME
Irritable bowel syndrome (IBS) is a common problem, affecting about 10% to
15% of the population, with women being twice as likely to have the diagnosis
(42). Given that its primary symptom is typically crampy chronic abdominal pain,
IBS is often in the differential diagnosis for patients with chronic pelvic pain.
Stress and certain foods will often trigger the pain, and defecation often will
provide some relief from the pain. Other gastrointestinal symptoms include
diarrhea and constipation, gastroesophageal reflux disease, nausea, bloating, and
flatulence. What makes this a more difficult diagnosis is the spectrum of
additional symptoms, including dysmenorrhea, dyspareunia, fibromyalgia
complaints, urinary symptoms of frequency and urgency, and even sexual
dysfunction.
This spectrum of symptoms renders diagnosis difficult and led to a consensus
group that created the Rome criteria in 1992, revised in 2005 (43). The resulting
Rome III criteria are: recurrent abdominal pain or discomfort for at least 3 days
per month for 3 months associated with two or more of the following:
Improvement with defecation
Onset associated with a change in the frequency of the stool
Onset associated with a change in the appearance of the stool—
constipation (IBS-C) or diarrhea (IBS-D)
IBS should be a diagnosis of exclusion with consideration initially given to
other causes for the dominant symptom. If that is diarrhea, considerations of
lactose intolerance, infectious etiology, malabsorption, or celiac disease
should be entertained. Symptoms that result in weight loss, rectal bleeding,
anemia, or that are noctural or progressive suggests something other than
IBS unless proven otherwise.
A basic workup might include complete blood count and chemistries.
1188Evaluation of diarrhea, if that is the dominant symptom, should potentially
include stool cultures if infectious etiology is suspected or 24-hour stool
collection (if osmotic) if secretory diarrhea is suspected. Initiate dietary reviews
for lactose intolerance or gluten sensitivity. Flexible sigmoidoscopy/ colonoscopy
is not done routinely unless needed to rule out inflammatory conditions or
malignancy in families with Lynch syndrome or the patient is 50 or older with
sudden onset of symptoms.
Management
General management of IBS can be extremely difficult. Often, the first step is
to reassure the patient that this is a functional disease and is not related to
cancer or malignancy, assuming those were eliminated by history and
examination (44). Many individuals have some underlying concerns that
diagnostic testing needs to be performed or that something is being missed.
Constant reassurance is an important aspect of management. The patient needs to
be an active participant in her care and understand the chronic nature of the
disease. A symptom diary for several weeks may show a link between various
foods and stressors that may be modifiable. Some individuals are able to link
various stressors in their lives to symptoms while others will not have identifiable
causes. Common triggers include stress, anxiety, medication (antibiotics,
antacids), menstrual cycles, abusive relationships, certain foods (lactose,
sorbitol), and travel. Patients should be counseled about dietary
interventions, including increasing dietary fiber, decreasing total fat intake,
and avoiding foods that trigger symptoms. Stool softeners are recommended
for individuals with (IBS-C) hard stools, and bulk aiding agents may be helpful
for those individuals with constipation. The overuse of laxatives is to be
discouraged. Good bowel habits should be discussed. Patients with poor habits
should set aside a quiet time every day to attempt defecation. Many individuals
get into a habit of ignoring stooling symptoms, leading to further problems with
lower gastrointestinal disease.
Antidiarrheal agents, specifically loperamide or diphenoxylate, are often useful
in patients with mild disease with diarrhea as a component (IBS-D). The goal is to
reduce the number of bowel movements and help to relieve rectal urgency.
Anticholinergics including hyoscyamine and dicyclomine hydrochloride often are
helpful. Antispasmodic agents have anticholinergic agents as the primary
ingredient, and compliance may be a problem because side effects include dry
mouth, visual disturbances, and constipation. These agents can precipitate toxic
megacolon, which may result in severe colitis. Toxic megacolon is a medical and
potential surgical emergency, in some cases requiring colectomy. Even though
these patients may be extremely difficult to treat, judicious use of symptom-
1189based pharmacologic approaches (because none have clear benefit),
reassurance, and patient insight may be helpful. The quality of life for some
individuals with IBS is extremely compromised, requiring intense counseling.
It may be difficult to treat them in a busy primary care practice. Those with a
concurrent psychiatric disease, such as depression, will often benefit from
psychiatric consultation and pharmacologic treatment of the underlying disease in
the overall management (45).
Individuals with chronic, debilitating IBS should be referred to a
gastroenterologist. Any suspicion of organic disease with systemic changes,
including weight loss and bloody diarrhea, should be considered for referral.
GASTROESOPHAGEAL REFLUX DISEASE
The term GERD is a commonly used label for many forms of indigestion and
heartburn. The American College of Gastroenterology defines it as
symptoms or mucosal damage produced by the abnormal reflux of gastric
contents into the esophagus (46). The term “abnormal” is key because some
reflux is physiologic, usually occurring postprandial and typically being
asymptomatic. Given the variation in definition, its prevalence is hard to
determine, but it is clear that GERD is more common in the Western world.
Symptoms of GERD include heartburn (burning sensation in the retrosternal
area) commonly postprandial, regurgitation gastric contents into mouth,
dysphagia from esophageal inflammation, and chest pain that can be confused as
angina. The definitive diagnosis of GERD is difficult, so empiric treatment with
acid suppression is reasonable. Dysphagia that is progressive is concerning for
Barrett metaplasia or adenocarcinoma and merits an endoscopic evaluation
(47). Endoscopy should not be used as the first test to diagnose GERD (48).
Treatment of GERD is multifaceted with lifestyle modification and use of
antacids and over-the-counter H2 receptor antagonists or proton pump
inhibitors (PPI) (49). Lifestyle modifications include smoking cessation,
avoidance of eating late in the evening, avoidance of being supine after
eating, weight loss, avoidance of tight clothing, and restriction of alcohol use.
Dietary modifications are helpful but should not be draconian, which will ensure
noncompliance. Key foods to try to minimize are fatty foods, chocolate,
peppermint, and excessive alcohol. The patient can monitor her own symptoms
for the foods that are most problematic for her.
Medications that reduce acid secretions are best and include H2 blockers
or PPIs. They do not prevent the reflux but decrease the damage done by the acid
when refluxed. Medication needs to be titrated to the severity of the symptoms.
H2 blockers commonly work well for acute pain but in placebo-controlled studies
1190in chronic cases without resolution of heartburn after the common 6-week course,
it was found that patients on PPI do better. Maintenance therapy is recommended
for patients who have rapid recurrence of symptoms (in less than 2 to 3 months)
after they stop their medication. Otherwise patients can be managed with episodic
treatments. The linkage of Helicobacter pylori infections and GERD is poorly
understood but seems to be mediated through increased gastric acid
secretion. Treatment can initially worsen GERD and may not improve it (50).
Benefits and risks should be discussed with the patient prior to testing and
treating for H. pylori. The management of GERD during pregnancy is similar to
the treatment in the nonpregnant patient.
CARPAL TUNNEL SYNDROME
Carpal tunnel syndrome (CTS) is the cluster of symptoms brought on by
compression in the carpal tunnel of the median nerve. These are paresthesia,
pain, and weakness. The symptoms are commonly worse at night and may wake
the patient from sleep. It is thought women may be more likely to present with
complaints of CTS because of their small wrists, repetitive motion injury at work
(typing, holding telephone, and reading), and pregnancy with increased edema.
The pain and paresthesia can be located in the wrist or hand or can be in the
forearm. The weakness may cause a patient to have difficulty opening jars, lifting
a plate, turning a doorknob, or holding a glass.
A detailed history is very diagnostic but the use of a couple of simple tests can
help to confirm it (51). The most common one is the Phalen maneuver, in which
the patient flexes her palms at the wrist as close to 90 degrees as possible. Then
with the dorsal portion of the hands touching and the arms parallel to the floor,
the patient presses the flexed hands against each other for approximately 1
minute. This should reproduce her symptoms along the median nerve. The Tinel
test involves percussion over the top of the carpal tunnel where the median nerve
travels. A positive test is when the percussion reproduces the pain and
paresthesia. Additional testing such as nerve conduction studies should be
reserved for patients who do not respond to conservative management or have
significant muscle weakness.
Treatment involves lifestyle modification to decrease repetitive motion
injuries or prolonged marked flexion at the wrist. A carpal tunnel brace can
be very helpful in maintaining adequate extension at the wrist, thereby
“opening” the tunnel and reducing compression on the medial nerve. Only if
these strategies do not work is a surgical intervention indicated.
MITRAL VALVE PROLAPSE SYNDROME, DYSAUTONOMIA,
1191AND POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME
The terms mitral valve prolapse syndrome (MVPS), dysautonomia, and
postural orthostatic tachycardia syndrome (POTS) all refer to a syndrome in
which the patient has problems with palpitations, hypotension, syncope,
dyspnea, panic/anxiety disorder, numbness, hyperflexible joints, pectus
excavatum, and gastric emptying disorders. Initially patients (typically fivefold
times more likely to be women) who presented with these symptoms were
thought to be somatizing their anxiety disorder. It is now accepted that it is a
syndrome that appears to involve the autonomic nervous system (52). This often
will present first in early adolescence with gradual worsening of the symptoms.
The patients are very slender in build and lose weight to a low body mass index
over a number of months as the syndrome evolves. This weight loss is the
probable cause of the secondary amenorrhea that prompts these women to seek
gynecologic care. The symptoms are not clearly explained by the degree of mitral
valve prolapse, so many feel MVPS is a marker for individuals at risk for this
complex of symptoms. Studies have shown that dysautonomia is an extraarticular
manifestation in the joint hypermobility syndrome (53). Increased sympathetic
activity is the common pathway for most of the proposed mechanisms for POTS
or MVPS. There appears to be a genetic component, with over 10% of patients
reporting the diagnosis in family members with orthostatic intolerance (54). It
needs to be stressed to the patient that the heart is structurally normal.
A tilt table test is often key to the diagnosis. Treatment focuses on the
symptoms and maintaining intravascular volume by encouraging oral intake of
water and salts (55). Physical fitness with aerobic exercises to increase muscle
mass and reduce dependent pooling of blood; avoidance of smoking, caffeine, and
alcohol; and limiting simple carbohydrates will minimize symptoms over time.
Additional medications, including adrenoreceptor agonists, acetylcholinesterase
inhibitor, mineralocorticoid agonist, beta blockers, and selective serotonin
reuptake inhibitors, may be necessary to deal with incompassating symptoms
during the acute phase. Because this is a multifaceted disease, it may be best to
refer the patient during the acute phase to a physician who is experienced with
this syndrome
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