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14.3
Hirsutism
Razan Taha and Reshma Gandhi
I. BACKGROUND. The presence of abundant terminal hair in women in a male pattern is known
as hirsutism. The degree of hirsutism is based upon the level of androgen in the body. It is
important to differentiate hirsutism from hypertrichosis, which can be defined as the presence
of nonterminal hair in a generalized pattern and unrelated to the effect of androgens (1, 2).
Hirsutism can signal a pathologic disorder and also have a negative impact on a patient’s self-
esteem, so recognizing the etiology and assessing this condition are important.
II. PATHOPHYSIOLOGY
A. Etiology.
Hirsutism can be caused by either excessive androgen production or excessive
sensitivity of hair follicles to normal levels of androgen (2).
The majority of cases of hirsutism are caused by functional hyperandrogenism, which
includes conditions such as polycystic ovarian syndrome (PCOS), idiopathic hyperan-
drogenism, idiopathic hirsutism, and congenital adrenal hyperplasia (3).
Less commonly, other adrenal pathology, ovarian issues, medications, and pituitary and
gestational hyperandrogenism are the cause of hirsutism (3). Adrenal causes include con-
genital adrenal hyperplasia, Cushing’s syndrome, and adrenal virilizing tumors. Ovarian
causes include hilus cell tumors, granulosa cell tumors, and Sertoli-Leydig cell tumors.
Drugs that induce hirsutism include high-dose glucocorticoids, anabolic steroids, valproic
acid, phenytoin, danazol, and minocycline. Pituitary causes include hyperprolactinemia and
Cushing’s disease (4).
Table 14.3.1 lists the causes of hirsutism.
B. Epidemiology. The prevalence of hirsutism in the United States is estimated to involve
about 7% of women (1). Between 70 and 80% of the cases of hirsutism are caused by
PCOS (1).
III. EVALUATION
A. History.
The first step in evaluating hirsutism includes a detailed history. Details of the his-
tory should include the onset and progression of hair growth, sites of hair growth, pubertal,
menstrual, and reproductive history, a family history of hirsutism, and any potentially viril-
izing alterations in voice, abdomen, breasts, weight, and acne (1). History should also include
the use of anabolic steroids and the psychosocial effects of hirsutism on the patient (4).
B. Physical examination. The evaluation should include height, weight, and body mass
index. The severity of hirsutism can be assessed using the Ferriman-Gallwey scale. This scor-
ing system assesses nine areas of the body (upper lip, chin, chest, abdomen, superior pubic
triangle, upper arms, thighs, upper back, and buttocks) using a score of 1–4. Hirsutism is
diagnosed as mild with a score of 8–15 and moderate to severe if the score is more than 15.
A score less than 8 is considered normal (1).
To assess signs of virilization, a clinician should look for clitoromegaly, acne, male
pattern hair loss, deepened voice, breast atrophy, and increase in muscle mass. A detailed
skin exam may reveal acne, acanthosis nigricans, seborrhea, and androgenic alopecia (1,4).
A thorough abdominal and pelvic bimanual exam should always be performed to exclude
ovarian and adrenal tumors (1). A breast exam can help detect galactorrhea (1). Signs of con-
ditions like Cushing’s syndrome, acromegaly, thyroid dysfunction, and hyperprolactinemia
can sometimes be detected by detailed physical examination.
C. Testing. If the patient’s history and physical examination are unremarkable, serum levels
of total testosterone and dehydroepiandrosterone sulfate can be obtained to exclude an
androgen-producing tumor. Elevated levels of androgens over twice the normal values
should prompt an evaluation for an ovarian or adrenal tumor. High-resolution pelvic
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Taylor’s DifferenTial Diagnosis Manual
TABLE 14.3.1 Diagnostic Features and Clinical Manifestations
Common causes
of hirusutism Percentage Clinical manifestations Laboratory tests
Polycystic
ovarian
syndrome
“PCOS”
72–82% Menstrual irregularity
or amenorrhea
Insulin resistance
Infertility
Sonographic evidence
of ovarian cysts
Truncal obesity
Variations in
androgen lev-
els (normal or
elevated)
Idiopathic
hyperandrogen-
emia
6–15% Normal menstrual period
No evidence of cysts
on ultrasonography
Etiology not explained by
other causes
High levels of
androgen
Idiopathic
hirsutism
4–7% No menstrual
abnormalities
No evidence of cysts
on ultrasonography
Etiology not explained by
other causes
Normal androgen
levels
Adrenal
hyperplasia
2–4% Two forms:
1) Classic: early onset, char-
acterized by ambiguous
genitalia in newborns
2) Non classic: late onset,
menstrual irregularities,
infertility
Hispanics and Ashkenazi
Jews are at higher risk
Positive history of congeni-
tal adrenal hyperplasia
(CAH) in the family
Confirm by
high levels of
17-hydroxypro-
gesterone before
and after cortico-
trophin stimula-
tion test
Androgen
secreting tumors
0.2% Abdominal or pelvic mass
on physical exam
Virilization
Dramatic onset of hirsutism
Worsening of hirsutism in
spite of treatment
Elevated early
morning total
testosterone more
than 200 ng/dL
Iatrogenic
hirsutism
Relatively rare Medications like
systemic and topical
corticosteroids,
clonazepam, isotretinoin,
paxil, etc.
(Continued)
Chapter 14 • Endocrine and Metabolic Problems
319
TABLE 14.3.1 Diagnostic Features and Clinical Manifestations
Common causes
of hirusutism Percentage Clinical manifestations Laboratory tests
Acromegaly Rare incidence
with isolated
hirsutism
Coarse facial features,
enlargement of hands
and feet
Cushing syndrome Rare incidence
with isolated
hirsutism
Moon faces, central obesity,
hypertension
High 24-h urine
free cortisol level
Hyperprolactinemia Rare incidence
with isolated
hirsutism
Menstrual irregularities,
infertility
High prolactin levels
Thyroid dysfunction Rare incidence
with isolated
hirsutism
Hypothyroidism or
hyperthyroidism
Abnormal thyroid
function tests
Above table has been modified from AAFP (1)
ultrasonography with a transvaginal probe can identify ovarian follicles and cysts as small as
3–5 mm in diameter. Basal body temperature charts and serum progesterone levels in the
luteal phase (20–24 days) of the menstrual cycle can be used to document the normal ovar-
ian function of women who are thought to have idiopathic hirsutism. A clinical suspicion
of hypothyroidism, hyperprolactinemia, or Cushing’s disease requires confirmatory testing.
Referral and further diagnostic testing may be warranted for patients with early-onset,
severe, or rapidly progressive hirsutism.
IV. DIAGNOSIS
A. Differential diagnosis.
PCOS and idiopathic hyperandrogenemia cause the major-
ity of cases of hirsutism (1). See Table 14.3.1 for diagnostic features and clinical
manifestations.
REFERENCES
1. Bode D, Seehusen DA, Baird D. Hirsutism in women. Am Acad Family Pract 2012;3:374–377.
2.
Sathyapalan T, Atkin SL. Investigating hirsutism. BMJ 2009;338:912.
3. Escobar-Morreale HF. Diagnosis and management of hirsutism. Ann N Y Acad Sci 2010;4:166–174.
4.
Somani N, Harrison S, Bergfeld WF. The clinical evaluation of hirsutism. Dermatol Therapy 2008;7:376–391.
14.4
Hypothyroidism
Riad Z. Abdelkarim
I. BACKGROUND. Hypothyroidism is a common clinical syndrome resulting from thyroid hor-
mone deficiency.
II. PATHOPHYSIOLOGY. Thyrotropin-releasing hormone (TRH), secreted by the hypothala-
mus, stimulates the anterior pituitary to produce thyroid-stimulating hormone (TSH), which
(Continued)
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Taylor’s DifferenTial Diagnosis Manual
mediates the production of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland.
T4 is converted into T3 (the active form of thyroid hormone) in the peripheral tissues.
Hypothyroidism can be classified into primary, secondary, or tertiary conditions. Primary
hypothyroidism—the most common type—results when inadequate amounts of thyroid
hormone are produced by the thyroid gland due to a localized gland disorder. Thus, primary
hypothyroidism is the result of thyroid gland failure (1). In a primary hypothyroid state, the
decreased production of T4 results in increased pituitary secretion of TSH, which in turn
stimulates thyroid gland hypertrophy and hyperplasia. Secondary hypothyroidism occurs when
inadequate amounts of thyroid-stimulating hormone (TSH, or thyrotropin) are secreted from
the pituitary gland, leading to diminished thyroid hormone release from the thyroid gland.
Tertiary hypothyroidism results when the hypothalamus secretes insufficient amounts of TRH,
leading to inadequate pituitary secretion of TSH, which in turn results in reduced thyroid
gland production of thyroid hormone. Subclinical hypothyroidism, diagnosed on the basis of
laboratory test results, is defined as a normal serum T4 level in the presence of an elevated
serum TSH concentration.
Thyroid hormones stimulate diverse metabolic activities in most tissues and have profound
effects on many major physiologic processes, such as development, growth, and metabolism.
Thus, regardless of the cause, deficiency of thyroid hormone has numerous systemic effects.
III. EPIDEMIOLOGY. Overt primary hypothyroidism is prevalent in 0.3% of the US popula-
tion, while subclinical hypothyroidism has a prevalence of 4.3%. The combined prevalence
of overt and subclinical hypothyroidism is 5.1% in Caucasians, 4.2% in Hispanics, and
1.7% in blacks (1). The prevalence is higher in women than in men, and it increases with
age. In women aged 18–24 years, the prevalence is 4%, while prevalence in women older
than 74 years is 21%, according to one US study of over 25,000 people (2). Additionally,
hypothyroidism is more common in women with small body size at birth and during child-
hood (3).
IV. ETIOLOGY. The most common cause of primary hypothyroidism is autoimmune thyroiditis,
or Hashimoto disease, which results from the gradual destruction of the thyroid by T cells. Up
to 95% of individuals with Hashimoto disease will have circulating antibodies to thyroid tis-
sue. Another common cause is subacute granulomatous thyroiditis, in which viral syndromes
or other inflammatory conditions can be associated with a transient hyperthyroid state followed
by transient hypothyroidism (de Quervain thyroiditis). The patient with subacute thyroiditis
may have fever and a painful thyroid gland. Various drugs have been associated with primary
hypothyroidism, including amiodarone, interferon alpha, lithium, and stavudine. Iatrogenic
hypothyroidism from either radioactive iodine or surgery can also occur. Radioactive iodine
used for the treatment of Graves’ disease usually causes permanent hypothyroidism within
1 year. Radiation of the external neck for neoplastic disease may also result in hypothyroidism.
While still common in the developing world, goitrous hypothyroidism from iodine deficiency
is rare in the United States and other developed countries since the introduction of iodized salt.
Secondary or tertiary hypothyroidism is caused by pituitary or hypothalamic disease, respec-
tively. The most common cause of secondary hypothyroidism is a pituitary adenoma. Other
causes include tumors impinging on the hypothalamus; pituitary surgery; cranial radiation
therapy; postpartum hemorrhage (Sheehan’s syndrome); head trauma; granulomatous diseases;
metastatic disease (breast, lung, colon, and prostate); infectious diseases (tuberculosis and oth-
ers); and genetic disorders (4). Multiple endocrine end-organ failure caused by the autoimmune
destruction of endocrine glands (Schmidt’s syndrome) is a rare cause of primary hypothyroid-
ism that mimics secondary disease.
V. EVALUATION
A. History.
Hypothyroidism can be asymptomatic, but often manifests as diminished physi-
cal and mental activity. Symptoms generally correspond directly to the duration and severity
of disease, and the probability of thyroid disease is directly related to the number of typical
symptoms manifested by the patient. Signs and symptoms include weakness, lethargy or
fatigue, constipation, hair loss, muscle or joint pain, depression or slowed mentation, and
menstrual disturbances. Neonates may present with prolonged jaundice, macroglossia,
Chapter 14 • Endocrine and Metabolic Problems
321
enlarged fontanelles, growth failure, failure to attain developmental milestones, or altered
school performance.
Symptoms more specific to Hashimoto’s thyroiditis include painless enlargement of
the thyroid; a feeling of fullness in the throat; low-grade fever; neck pain and/or sore
throat; and exhaustion. Symptoms suggestive of secondary or tertiary hypothyroidism
include loss of axillary or pubic hair; headaches; visual field defects; amenorrhea, galac-
torrhea, or postural hypotension. Clinicians should determine whether patients they are
evaluating for possible hypothyroidism fall into any of the following higher risk groups:
women 4–8 weeks postpartum; women older than 50 years of age; patients with immuno-
logically mediated diseases (including type 1 diabetes mellitus, pernicious anemia, vitiligo,
Addison’s disease, and rheumatoid arthritis); and persons with a family history of thyroid
disease.
B. Physical examination. Physical examination findings can be quite subtle. Thus, clini-
cians must conduct a careful and detailed physical examination if hypothyroidism is sus-
pected. A systematic head-to-toe examination is helpful, because all major organ systems are
affected by thyroid hormone deficiency.
1. Observation. A welcoming handshake may reveal cold, dry skin, and further observa-
tions might uncover altered affect; a hoarse voice while relating the history; facial or
eyelid edema; hair loss (scalp and eyebrows); and apparent physical or mental slowing.
2. General examination. Specific findings may include
• Vital sign abnormalities
o Hypothermia
o Elevated diastolic blood pressure
o Decreased systolic blood pressure
o Bradycardia
o Orthostatic hypotension (in secondary or tertiary hypothyroidism)
o Increased weight
• Head, ears, eyes, nose, throat, and neck
o Coarse, brittle hair; loss of scalp hair
o Dull facial expression/affect
o Coarse facial features
o Periorbital puffiness
o Macroglossia
o Hoarseness
o Goiter (diffuse or nodular)
• Cardiac
o Cardiac rub or distant heart sounds (due to pericardial effusion)
• Breasts
o Galactorrhea (in secondary or tertiary hypothyroidism)
• Abdomen
o Abdominal distension or ileus
o Ascites (uncommon)
• Extremities/skin
o Dry skin
o Jaundice
o Pallor
o Loss of axillary and/or pubic hair
o Nonpitting edema (myxedema); pitting edema of lower extremities
• Neurologic
o Slowed speech and movements
o Hyporeflexia, prolonged relaxation phase of deep tendon reflexes
o Carpal tunnel syndrome
o Visual field defects (in secondary or tertiary hypothyroidism)
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Taylor’s DifferenTial Diagnosis Manual
3. Thyroid examination. The thyroid gland itself should always be examined if hypothy-
roidism is suspected. The location, size, consistency, mobility, and tenderness of any
nodules should be noted.
C. Testing
1. Laboratory Studies. The widely available third-generation TSH assays serve as the
most useful and sensitive screening test for primary hypothyroidism (5). If a screening
TSH is found to be above the reference range, a free T4 level can be checked. Primary
hypothyroidism is characterized by an elevated TSH level with decreased free T4 levels.
An elevated TSH level in the presence of normal free T4 levels is indicative of subclinical
hypothyroidism. As TSH levels increase in early disease, T3 levels are maintained by an
increased conversion of T4 to T3. Thus, early hypothyroidism may be characterized by
elevated TSH, normal or low T4, and normal T3.
Although the TSH is characteristically elevated in primary hypothyroidism, pitfalls
can occur. Starvation, corticosteroid administration, and use of dopamine can lower
TSH, even in patients with hypothyroidism. In some hospitalized patients with severe
nonthyroidal illness, low peripheral thyroid hormone levels may suggest hypothyroidism,
although the TSH may be normal or decreased in this setting. In such patients, with the
so-called euthyroid sick syndrome, the primary abnormality is the decreased peripheral
conversion of T4 to T3, as well as an increased reverse T3 level (which can be measured).
Additionally, during recovery from acute illness, some patients may exhibit transient
elevations in TSH levels. Thus, thyroid function should not be tested in critically ill
individuals unless there is a high index of suspicion for thyroid disease (5).
2. Imaging Studies. Ultrasound scans of the neck and thyroid are useful to detect nodules,
but such studies are not indicated for routine evaluation of hypothyroidism. Radioactive
iodine uptake and thyroid scanning are not generally helpful in evaluating hypothyroid-
ism, because these tests require some level of endogenous functioning (6).
D. Genetics. Molecular defects have been identified in only a few causes of human hypothy-
roidism (7). Hypothyroidism remains primarily an acquired disease associated with aging.
IV. DIAGNOSIS
A. Differential diagnosis.
Because the symptoms of hypothyroidism are nonspecific, its
differential diagnosis is large and includes such variable entities as depression, sleep apnea,
fibromyalgia, chronic infections, autoimmune disorders, anemia, menopause, cardiovascular
disease, occult malignancies, adverse reactions to medication, and other endocrine disorders
such as Addison disease, panhypopituitarism, and diabetes.
B. Making the diagnosis. Most patients have only mild or moderate disease at the time of
diagnosis. Subclinical hypothyroidism occurs when the TSH is mildly elevated and there are
no associated signs or symptoms. Primary hypothyroidism can be diagnosed by the typical
findings on history and physical examination, coupled with an elevated TSH and a low free
T4. Secondary hypothyroidism should be suspected when both the TSH and the free T4 are
low. Myxedema coma is a life-threatening complication of long-standing hypothyroidism.
These patients may present with stupor, areflexia, respiratory depression, hypercapnia, and
profound hypothermia. Prompt diagnosis, hospitalization, and rapid treatment are required
to prevent death.
REFERENCES
1. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in the
United States population (1988 to 1994): National Health and Nutrition Examination Survey
(HHANES III). J Clin Endocrinol Metab 2002;87:489–499.
2. Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study. Arch
Intern Med 2000;160:526–534.
3. Kajantie E, Phillips DI, Osmond C, Barker DJ, Forsen T, Eriksson JG. Spontaneous hypothyroid-
ism in adult women is predicted by small body size at birth and during childhood. J Clin Endocrinol
Metab Dec 2006;9(12):4953–4956.
Chapter 14 • Endocrine and Metabolic Problems
323
4. Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central
hypothyroidism. Nat Clin Pract Endocrinol Metab Dec 2008;4(12):683–94.
5. U.S. Preventive Services Task Force. Recommendation statement: screening for thyroid disease (January
2004). Available at: http://www.uspreventiveservicestaskforce.org/uspstf/uspsthyr.htm, accessed on
July 29, 2012.
6. Moreno JC, de Vijlder JJ, Vulsma T, et al. Genetic basis of hypothyroidism: recent advances, gaps and
strategies for future research. Trends Endocrinol Metab 2003;14(7):318–326.
7. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists
medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and
hypothyroidism. Endocr Pract Nov–Dec 2002;8(6);457–469.
14.5
Polydipsia
Mohammed Zalabani
I. BACKGROUND. Polydipsia is a symptom in which the patient displays excessive thirst. The
word derives from the Greek word polys, meaning “much, many” and dipsa, “thirst” and is
attributed to medical or psychogenic causes.
II. PATHOPHYSIOLOGY
A. Epidemiology.
Polydipsia is a common symptom among patients with diabetes mellitus
(DM) and is prominent in patients with diabetes insipidus (DI). Polydipsia has a prevalence
of 3–39% among chronic psychiatric inpatients (1).
B. Etiology. Polyuria is the most common symptom associated with polydipsia. There are
several causes of polydipsia associated with polyuria:
1. Poorly resorbed solutes—Glucose, mannitol, or sorbitol can cause an osmotic diuresis.
DM should be suspected in any patient with polydipsia and polyuria of recent onset.
2. Primary Polydipsia—Psychiatric patients infrequently suffer from polydipsia, because of
dry mouth from medications with anticholinergic properties and/or delusions. Another
term that has been used for primary polydipsia is psychogenic water drinking (2).
3. Diabetes Insipidus (DI)—This may be due to either a central (neurogenic DI) or
a renal (nephrogenic DI) cause. Central DI is associated with deficient secretion of
antidiuretic hormone (ADH). This condition can be idiopathic, genetic, or secondary to
intracranial pathology such as a brain tumor, head trauma, toxic brain injury, metastatic
cancer, and granulomatous disease (tuberculosis, sarcoidosis) or from a complication
of a neurosurgic procedure. Vasopressinase-induced DI occurs in the last trimester of
pregnancy and is often associated with preeclampsia. Nephrogenic DI is characterized
by normal ADH secretion but varying degrees of renal resistance to its water-retaining
effect. Nephrogenic DI presenting in childhood is almost always due to inherited defects,
e.g., mutations in the AVPR2 gene and mutations in the aquaporin-2 (water channel)
gene. It can also be secondary to medications (lithium, methoxyflurane, demeclocycline)
or secondary to systemic disease (hypokalemia, hypercalcemia) (3).
III. EVALUATION
A. History.
In eliciting the history, the clinician should take note of the onset of symptoms.
Symptoms presenting at an early age may indicate a hereditary nature of the disease, while
symptoms occurring after neurosurgery or a history of cancer may suggest the cause of the
symptoms. Presence of neurologic symptoms (problems with visual fields, headaches) must
be assessed and a detailed history of cancer, particularly metastatic brain cancer, or encepha-
litis must be obtained. The patient’s psychiatric history may also be relevant (4).
324
Taylor’s DifferenTial Diagnosis Manual
B. Physical examination. A good general physical examination, including vital signs, is
helpful in making the diagnosis, but the emphasis is on the neurologic examination (i.e.,
visual fields, cranial nerve deficits, oculomotor palsies, and reflexes). Signs of recent weight
loss or the presence of peripheral neuropathy suggests the diagnosis of DM.
C. Testing
1. Laboratory tests—A urinalysis needs to be performed to check for glucosuria or low
specific gravity associated with DI. A chemistry panel is helpful in checking for
elevated serum glucose levels or elevated creatinine seen with renal disease and neph-
rogenic DI. A calcium level could be useful if hypercalcemia is suspected. Serum and
urine osmolality are useful in differentiating between DI and primary polydipsia. DI
presents with increased serum osmolality and a low urine osmolality (specific gravity
<1.005), while primary polydipsia presents with low or normal serum osmolality
and an appropriately low urine osmolality. Normal serum values are between 285
and 295 mOsm/L.
2. Imaging—Magnetic resonance imaging (MRI) of the head may be indicated to exclude
pituitary or hypothalamic tumors. In DI associated with pituitary disease, MRI is quite
specific, because the normal bright spot of a functioning pituitary gland is absent (5).
3. Water deprivation test—This test may be useful in the diagnosis of DI and to dif-
ferentiate between neurogenic and nephrogenic DI by determining the effects of water
deprivation (mild dehydration) on ADH secretion by measuring serum, urine osmolar-
ity, urine specific gravity, and serum sodium in a controlled environment. This test
needs to be carefully supervised by someone able to treat severe hypertonic dehydration,
if necessary. Patients with mild polydipsia are placed on a fluid restriction starting at
midnight prior to testing, but in those with severe polydipsia, fluids are restricted only
during the day. Baseline body weight, plasma osmolarity, serum sodium, and urine
osmolarity are determined. Urine osmolarity and weight are assessed on an hourly
basis. Adequate dehydration is noted by a decrease in body weight by 5% and serum
osmolarity greater than 275 mOsm/L. A normal response would show normal plasma
osmolarity and sodium concentration with decreased urine output and increasing
urine osmolarity to greater than 800 mOsm/L (i.e., two to four times greater than the
plasma). In contrast, healthy patients with DI cannot concentrate their urine in response
to dehydration. Patients with central DI respond to desmopressin (a synthetic analog of
vasopressin) administered intranasally, whereas patients with nephrogenic DI do not.
Patients may not fall into a definite category sometimes (e.g., partial central DI). The
direct form of testing where ADH levels are measured after infusing hypertonic saline is
rarely performed (6).
D. Genetics. An inherited autosomally dominant form of neurogenic DI is caused by muta-
tions in the AVP neurophysin II gene (AVP-NPII gene), and hereditary nephrogenic DI can
be caused by V2 receptor problems (X-linked mode of inheritance or a defect in the ADH-
sensitive aquaporin-2 water channels) (5).
IV. DIAGNOSIS
A. Differential diagnosis.
Often, important clues about the cause of polydipsia can be
obtained with a directed clinical history with particular attention to the onset of symptoms,
the presence of nocturia, and the medication history. The value of the physical examina-
tion is limited unless there are signs of defects due to a pituitary tumor (e.g., progressive
headaches, visual field defects) or endocrinologic symptoms (e.g., amenorrhea, galactorrhea,
acromegaly, Cushing’s syndrome). The diagnosis is often made with routine laboratory tests.
Sometimes, a water deprivation test needs to be performed to make the diagnosis, but this
test should be performed in a hospital setting with the patient monitored closely for signs
of dehydration.
B. Clinical manifestations. Thirst associated with polyuria is the chief complaint in patients
with DM, DI, and psychogenic polydipsia. Nocturia occurs more frequently with DM and
DI than with psychogenic polydipsia. Patients with psychogenic polydipsia may have delu-
sions leading to increased fluid intake of up to 20 L/d (1).
Chapter 14 • Endocrine and Metabolic Problems
325
REFERENCES
1. Greendyke RM, Bernhardt AJ, Tasbas HE, et al. Polydipsia in chronic psychiatric patients: therapeutic
trials of clonidine and enalapril. Neuropsychopharmacology 1998;18:272–281.
2. Schrier RW, Body water homeostasis: clinical disorders of urinary dilution and concentration J Am Soc
Nephrol Jul 2006;17(7):1820–1832.
3. Miller, M., Dalakos, T., Moses, A., Fellerman, H., & Streeten, D. (1970). Recognition of partial
defects in antidiuretic hormone secreation. Annals of Internal Medicine, 73(5), 721–729.
4. Olapade-Olaopa EO, Morley RN, Ahiaku EK, et al. Iatrogenic polydipsia: a rare cause of water intoxi-
cation in urology. Br J Urol 1997;79:488.
5. Robertson GL. Disorders of the neurohypophysis. In: Kasper DL, Fauci AS, Longo DL, eds. Harrison’s
principles of internal medicine, 16th ed. New York, NY: McGraw-Hill, 1998:2098–2103.
6. Adam P. Evaluation and management of diabetes insipidus. Am Fam Physician 1997;55:2146–2153.
14.6
Thyroid Enlargement/
Goiter
Toby D. Free
I. BACKGROUND. Goiter, an enlarged thyroid gland, is the most common thyroid abnormality.
The mean weight of the thyroid gland in iodine-sufficient populations is 10 g, with the upper limit
of the normal being 20 g (1). Goiter is termed endemic if it occurs in more than 10% of the popu-
lation. Endemic goiter most commonly results from dietary iodine deficiency and is extremely rare
in the United States. Goiter is termed sporadic if it arises in nonendemic areas and from various
causes (2). Simple goiter describes a diffusely enlarged thyroid gland and multinodular goiter is an
enlarged gland with multiple areas of nodularity. Finally, functional status of a goiter is considered
nontoxic if the patient is in a euthymic state, but is toxic in a patient who is hyperthyroid.
II. PATHOPHYSIOLOGY
A. Etiology.
Any process that impedes thyroid hormone synthesis or release can cause goiter.
By far the most important risk factor for the development of goiter is iodine deficiency.
Some situations exacerbate iodine deficiency. For example, cigarette smoking has been
linked to the development of goiter in iodine-deficient areas and is believed to interfere
with iodine uptake of the thyroid gland. Also, pregnancy-induced goiter is related to the
exacerbation of existing iodine deficiency and proliferative effect of estrogen on the thyroid
gland. (However, the use of oral contraceptives has been found to be associated with reduced
incidence of goiter) (3). Goitrogens, substances that interfere with thyroid hormone produc-
tion and action, can cause sporadic goiter. This category includes certain drugs (thioamide
derivatives, lithium, iodides, amiodarone, and others) and foods (rutabagas, cabbage, tur-
nips, soybeans, kelp, and others) (2).
B. Epidemiology. The prevalence of goiter in the United States is estimated to be 4–7% but
varies widely, depending on the regional iodine intake. One autopsy study of thyroid glands
that were thought to contain no pathology demonstrated a 38% incidence of multinodular
goiter, showing the prevalence of substantial, subclinical disease (1). Goiter prevalence does
increase with age and is 5–10 times more common in women than in men (2).
III. EVALUATION
A. History.
Although simple goiters are usually euthyroid, typical symptoms of hypothyroid-
ism or thyrotoxicosis should be sought. Asking about pain and the quality of pain is helpful.
Generalized thyroid pain suggests subacute thyroiditis, whereas sudden localized pain and
swelling are consistent with hemorrhage into a nodule (4). A family history of goiter and a
personal history of residing in an endemic area or ingesting goitrogens may be significant.
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B. Physical examination. Full extension of the neck enhances the visibility of the gland.
Inspection from the side with measurement of any prominence of the normally smooth and
straight contour between the cricoid cartilage and the suprasternal notch is useful. Inspect
the neck below the thyroid cartilage from the front, using cross-lighting to accentuate
shadows and masses. Palpitation is performed using the technique with which the examiner
is most experienced and skilled. The thyroid is palpated by using the fingers or thumbs
while standing in front of or behind the patient. If felt between the cricoid cartilage and
the suprasternal notch, the thyroid isthmus can be used to help locate the gland. Palpation
of the lobes can be improved by relaxation of the sternocleidomastoid; for example, the left
lobe can be defined better by having the patient slightly flex and rotate the neck to the left.
Other useful maneuvers include measuring the circumference of the neck or the dimensions
of each lobe. The location, size, consistency, mobility, and tenderness of any nodules should
be noted. Having the patient swallow during both inspection and palpation causes the
thyroid to move and aids in developing a three-dimensional impression of the gland’s shape
and size. This maneuver can also make a low-placed gland accessible. The patient should be
placed in the supine position to determine the inferior extent of the gland (1, 5). Pemberton’s
sign can be induced by having the patient raise both arms above the head for 1 minute. The
patient develops facial and neck plethora if venous outflow is obstructed by the thyroid
gland. Physical signs consistent with hypothyroidism or thyrotoxicosis may be present.
C. Testing
1. Laboratory tests. The highly sensitive thyroid-stimulating hormone (TSH) assay is the
single best test to evaluate the thyroid status. An elevated TSH is highly suggestive of
hypothyroidism. If TSH is suppressed, an elevated free thyroxine index (FTI) or free
thyroxine (fT
4
) measured directly confirms thyrotoxicosis. In a patient with a suppressed
TSH and a normal FTI or fT
4
, serum triiodothyronine (T
3
) should be measured to assess
for possible T
3
thyrotoxicosis. Antithyroid antibodies can help predict those patients at
a higher risk for developing thyroiditis, hypothyroidism, or Graves’ disease.
2. Imaging. Nuclear scans are not warranted in the routine evaluation of simple or mul-
tinodular goiter. Ultrasonography should be used in cases of multinodular goiter to
rule out a dominant nodule and may be helpful in patients with equivocal findings on
palpation (6). Symptoms suggestive of substernal mechanical pressure require evaluation,
usually by computed tomography or magnetic resonance imaging (4).
3. Other tests. Fine needle biopsy should be performed in cases of a solitary or dominant
nodule found by palpation or ultrasound. Pulmonary function tests are warranted if
there is a question of inspiratory impairment. Barium swallow is indicated to evaluate
goiter-associated dysphagia (4).
D. Genetics. Currently, no genetic markers are used in evaluating goiter. Family and twin
studies have demonstrated that genetic factors play a role in the development of goiter, but
at present, the results cannot be extrapolated to the general population (5).
IV. DIAGNOSIS
A. Differential diagnosis.
A cystic hygroma or a thyroglossal duct cyst, which may transil-
luminate, and lymphadenopathy can be confused with goiter. Primary thyroid cancers,
lymphomas, or metastatic cancers may present as a firm mass in the neck. Patients with
thyroiditis (Hashimoto’s, subacute, or silent) can present with an enlarged thyroid gland.
An asymptomatic patient with a simple or multinodular goiter associated with a normal
metabolic state does not necessarily require further diagnostic studies or treatment. Periodic
assessment, at least annually, to evaluate growth, function, and symptoms is warranted. In
two studies, it was shown that 10% of patients with nodular goiter developed thyrotoxicosis
during a 7- to 10-year follow-up period (2).
B. Clinical manifestations. In simple goiter, patients are asymptomatic or, if the gland is
sufficiently enlarged, present with symptoms caused by mechanical pressure. Substernal goi-
ters are frequently responsible for tracheal pressure symptoms, including dyspnea and inspi-
ratory stridor. They can also obstruct the large cervical veins at the thoracic inlet, causing
suffusion of the face, giddiness, and syncope (Pemberton’s sign). Esophageal compression
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