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A 36‑year‑old man is referred for evaluation of a 3-month history of tender gynecomastia and a high total testosterone concentration. He tells you he has been following the “hCG diet” for the last 2 months, which combines oral hCG and a very low-calorie diet (500 calories/day). He has lost 10 lb (4.5 kg), but has been feeling tired. He reports no heat intolerance, diaphoresis, or tachycardia. His medical history is remarkable for hepatitis C and premature male-pattern baldness. His medications include finasteride, 1 mg daily, which he started 1 year ago to treat alopecia.
On physical examination, his height is 73 in (185.4 cm), BMI is 22 kg/m2, and pulse rate is 72 beats/min. His thyroid gland is normal. He has tender bilateral gynecomastia measuring about 3 cm bilaterally. His phallus is normal, and testes are 15 mL bilaterally.
Laboratory test results:
- Total testosterone = 900 ng/dL (31.2 nmol/L) (reference range, 300-900 ng/dL [10.4-31.2 nmol/L])
- Free testosterone (calculated) = 28.0 ng/dL (0.97 nmol/L) (reference range, 9.0-30.0 ng/dL [0.31-1.04 nmol/L])
- Estradiol = 90 pg/mL (330.4 pmol/L) (reference range, 10-40 pg/mL [36.7-146.8 pmol/L])
- FSH = 0.5 mIU/mL (0.5 IU/L) (reference range, 1.0-13.0 mIU/mL [1.0-13.0 IU/L])
- LH = 0.5 mIU/mL (0.5 IU/L) (reference range, 1.0-9.0 mIU/mL [1.0-9.0 IU/L])
Which of the following most likely explains his hormone profile?
- Elevated sex hormone–binding globulin due to hepatitis C
- Primary hypothyroidism
- Oral hCG
- Decreased 5α-reduction due to finasteride
- Testosterone abuse
This patient has tender gynecomastia. Breast tenderness suggests benign breast growth of recent onset (<6 months). He also has a high-normal to high total testosterone concentration, and his high normal calculated free testosterone concentration confirms that this is not strictly due to high sex hormone–binding globulin concentrations, which can be seen in hepatitis and would decrease the free testosterone concentration. He also has high estradiol and low gonadotropin concentrations. This combination can be due to exogenous testosterone use or abuse (Answer E), endogenous or exogenous testosterone precursors (e.g., dehydroepiandrosterone from an adrenal tumor), endogenous or exogenous hCG (e.g., hCG from a germ-cell tumor), or exogenous LH.
Although chronic hepatitis (Answer A) is commonly associated with elevated sex hormone–binding globulin concentrations, the calculated free testosterone concentration remains normal unless the patient has underlying hypogonadism. Sex hormone–binding globulin concentrations may be very high and result in a high or high-normal total testosterone level in patients with chronic hepatitis or hepatopathy. Primary hypothyroidism (Answer B) does not cause elevated testosterone and estradiol concentrations. Because hCG (Answer C) is a protein, oral hCG is digested in the gut and is not bioavailable when taken orally. Finasteride (Answer D) modestly raises serum testosterone concentrations by blocking the conversion of testosterone to dihydrotestosterone, but finasteride and dutasteride, the other available 5α-reductase inhibitor, do not suppress gonadotropin (LH, FSH) concentrations.
Identify the clinical and biochemical features of exogenous testosterone abuse.
Amory JK, Wang C, Swerdloff RS, et al. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men [published correction appears in J Clin Endocrinol Metab. 2007;92(11):4379]. J Clin Endocrinol Metab. 2007;92(5):1659-1665.
Anawalt BD. Gynecomastia. In: Jameson JL, De Groot LJ, eds. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia, PA: Saunders Elsevier; 2015.
Bhasin S, Cunningham GR, Hayes FJ, et al; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.