A 36-year-old man comes to the office with a 6-month history of fatigue, mild headache, and decreased libido. His past medical history is notable for type 2 diabetes and bipolar disorder. His medications include metformin and risperidone. The patient smokes a pack of cigarettes a day and drinks 2 or 3 cans of beer daily. Blood pressure is 126/73 mm Hg and pulse is 86/min. His BMI is 31 kg/m2. Physical examination shows decreased testicular volume but is otherwise normal. Laboratory results are as follows:
LH 0.5 mIU/mL Testosterone, total 100 ng/dL (normal: 240-950 ng/dL) TSH 0.05 μU/mL Thyroxine (T4), free 0.45 ng/dL (normal: 0.9-1.7 ng/dL) Prolactin 35 ng/mL
Which of the following is the most likely diagnosis?
Common causes of hypogonadism in men | |
Primary (testicular) |
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Secondary (pituitary/hypothalamic) |
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Combined (primary & secondary) |
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This patient has hypopituitarism featuring central hypogonadism (low LH and testosterone) and central hypothyroidism (low TSH and thyroxine) along with mildly elevated prolactin. This is strongly suggestive of a nonfunctioning pituitary adenoma, which usually arises from the gonadotropin-secreting cells (gonadotrophs) in the pituitary gland. Normal gonadotrophs secrete LH and FSH (which are dimeric hormones consisting of a common α-subunit and a different β-subunit), but the dysfunctional cells in most gonadotroph adenomas secrete primarily the common α-subunit.
The clinical symptoms of α-subunit overproduction are usually minimal ("nonfunctioning" adenoma), and the diagnosis is not usually apparent until the adenoma is large enough to cause features of mass effect on local tissues (eg, headache, visual field defects, disruption of the surrounding pituitary function). Production of most pituitary hormones (eg, TSH, LH) will be decreased due to compression of the neighboring normal pituitary cells. By contrast, prolactin levels are often mildly to moderately elevated due to anatomic disruption of the dopaminergic neural pathways that normally suppress prolactin secretion. (A more significant elevation of prolactin [eg, >200 ng/mL] would suggest a prolactin-secreting adenoma (prolactinoma) rather than a nonfunctioning adenoma.)
(Choice A) Excessive alcohol intake can cause hypogonadism by suppressing LH release by the pituitary or by directly inhibiting testosterone production in the testes. However, pituitary TSH production is usually unaffected by alcohol, and this patient's moderate intake is unlikely to have significant endocrine effects.
(Choice B) Klinefelter syndrome (47,XXY) is a chromosomal disorder associated with hypogonadism, small testes, and decreased virilization. The hypothalamic-pituitary axis is usually intact, however, and LH is increased. This patient's late onset of symptoms makes a chromosomal abnormality unlikely.
(Choice C) Chronic autoimmune thyroiditis (Hashimoto thyroiditis) is characterized by immune-mediated destruction of thyroid follicles and is the most common cause of hypothyroidism in the general population. Patients will have low free T4 and elevated TSH.
(Choice D) Many commonly used antipsychotic medications (eg, risperidone) can cause hyperprolactinemia due to blockade of the normal dopamine-dependent regulation of prolactin secretion. However, TSH is usually unaffected.
Educational objective:
Hypopituitarism with a mild to moderate increase in prolactin suggests a nonfunctioning (gonadotroph) adenoma. Patients may develop symptomatic hypogonadism or hypothyroidism but are frequently asymptomatic until the adenoma becomes very large and causes a mass effect on surrounding tissues.