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The sticky side of hypogonadism
This patient was initially introduced in the last issue of Endocrine Today, and we are following him again for his next challenge.
A 45-year-old man who had presented for adrenal insufficiency and panhypopituitarism last visit is returning for follow-up.
He had been diagnosed with adrenal insufficiency three years ago after loss of consciousness and admission to the hospital for hyponatremia. The patient started noticing erectile dysfunction, as well as testicular shrinkage, hot flashes and loss of body hair about 10 months ago, and was started on testosterone gel 5 g daily (androgel 1%, Solvay) by a colleague one month before his first visit to me, without significant effect on his fatigue. He now returned to discuss his lab results and treatment options.
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Review of symptoms: The patient describes decreased libido, erectile dysfunction and fatigue. He shaves twice a week and denies gynecomastia. His weight has been stable since an initial weight loss of 50 lb at the time of diagnosis with adrenal insufficiency.
Other medical history: ulcerative colitis (quiescent), peptic ulcer disease, scabies, sinusitis and removal of anal fissure. Medications include mesalamine, prednisone and testosterone gel. The patient has no known drug allergies, is married and is not trying for children. He denies use of tobacco, alcohol or recreational drugs.
Physical exam is unremarkable, unless indicated otherwise: blood pressure 118/80 mm Hg, pulse 62, height 6’, weight 184 lb. Breast, no gynecomastia; phallus normal in shape and size; decreased urigenital hair distribution in female pattern distribution; testicles small at about 5 mL bilaterally.
Total testosterone (morning draw) before testosterone supplementation was <2 ng/dL, and total testosterone (afternoon lab draw) on daily transdermal testosterone supplementation was 1,236 ng/dL.
What is the next best step to help this patient with secondary hypogonadism and very high testosterone level on a standard dose of supplementation?
A. Halve the dose of testosterone gel to 2.5 g daily.
B. Explain to the patient that he has androgen insensitivity syndrome (high testosterone levels, no symptoms consistent with hyperandrogenism).
C. Start anastrozole 1 mg daily.
D. Repeat the lab draw in the morning to account for the diurnal variation in androgen secretion.
E. Ask the patient to demonstrate how he administers the testosterone gel.
Case Discussion:
Answer: E
This is a man with secondary hypogonadism and a high testosterone level drawn one month after initiation of treatment with transdermal testosterone. The patient certainly does not have androgen insensitivity syndrome, because he is exhibiting normal primary and secondary sexual characteristics and had normal pubertal development (B). Anastrozole has been successfully used to decrease aromatization of testosterone to estradiol in hyperestrogenic hypogonadotropic hypogonadism, but it will not significantly raise a testosterone level of 2 ng/dL (C). Physiologic diurnal variation should no longer play a role in this man whose sole source of testosterone is external (D). Ordinarily, high testosterone levels in a patient on testosterone supplementation should lead to downtitration of the medication (A). However, it occurred to me that this patient may never have been properly instructed how to use the gel; administration is not as straight-forward as one might think. Indeed, the patient not only used the gel on the shoulders and abdominal area as directed, but also on his arms, including the antecubital fossa. Testosterone gel can leave a film that may falsely elevate testosterone levels when applied over the site of phlebotomy. I instructed him to avoid application to the arms and other body areas such as the groin area and repeated the lab draw from a vein on the back of his hand. His testosterone level came back within the therapeutic range: 462 ng/dL.
Ronald Tamler, MD, PhD, MBA, is Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine, N.Y.