A 52-year-old man comes to the office due to decreased libido and inability to achieve and maintain erections for the past several months. He has also had fatigue, anorexia, and a 5-kg (11-lb) weight loss over the same duration. The patient is married and has one child. He drinks alcohol but does not use tobacco or illicit drugs. Blood pressure is 110/70 mm Hg and pulse is 82/min. Physical examination shows bilateral gynecomastia and firm and small testes. Laboratory testing shows normal TSH with decreased levels of total triiodothyronine (T3) and thyroxine (T4). Which of the following is the most likely diagnosis?
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This patient's erectile dysfunction and testicular atrophy are most likely due to hypogonadism, which is a common complication of chronic liver disease with cirrhosis. Cirrhosis (especially due to alcoholic liver disease or hemochromatosis) can cause hypogonadism due to primary gonadal injury or hypothalamic-pituitary dysfunction. Cirrhosis is also associated with elevated circulating levels of estradiol due to increased conversion from androgens. Findings due to excess estrogen include telangiectasias, palmar erythema, testicular atrophy, and gynecomastia (usually bilateral but can be unilateral).
In addition, the liver produces serum binding proteins for thyroid hormones (eg, thyroxine-binding globulin, transthyretin, albumin, lipoproteins). Cirrhosis leads to decreased synthesis of these proteins, which lowers the total triiodothyronine (T3) and thyroxine (T4) in circulation; however, free T3 and T4 levels are unchanged, and TSH will be normal, reflecting a euthyroid status.
(Choice A) Adrenal insufficiency (AI) can cause fatigue, weakness, anorexia, and weight loss. In women with AI, features of hypogonadism (eg, loss of libido, decreased pubic hair) can be seen due to decreased adrenal androgen production; however, men with AI do not develop these findings as androgens are primarily produced in the testes. In addition, AI would not explain this patient's gynecomastia, testicular atrophy, or thyroid hormone laboratory abnormalities.
(Choice C) Exogenous thyroid hormone intake can cause weight loss, fatigue, and anxiety. However, TSH would be suppressed.
(Choice D) Hashimoto thyroiditis (chronic autoimmune thyroiditis) is due to lymphocytic infiltration of the thyroid causing hypothyroidism. Laboratory studies show elevated TSH, decreased T4, and antithyroid peroxidase antibodies.
(Choice E) Arterial insufficiency is a common cause of erectile dysfunction. However, this would not cause gynecomastia or testicular atrophy, and most patients would have other signs of arterial disease.
(Choice F) Androgen insensitivity is caused by mutations in the androgen receptor and would cause primary infertility (eg, primary amenorrhea in a genetically male but phenotypically female individual [complete androgen insensitivity syndrome]). It is unlikely in this patient with recent-onset sexual dysfunction.
Educational objective:
Cirrhosis can cause hypogonadism due to primary gonadal injury or hypothalamic-pituitary dysfunction. Cirrhosis is also associated with elevated circulating levels of estradiol due to increased conversion from androgens.