Young man with three children presents with low libido, fatigue, ‘brain fog’
A 27-year-old Orthodox Jewish man presented for evaluation of hypogonadism. He is married with three children, but he was accompanied to the office visit by his mother. The man had been noticing decreased libido together with erectile dysfunction, fatigue and impaired cognition, or “brain fog,” since the birth of his second child 36 months ago.
His primary care physician had started him on clomiphene 50 mg every other day. However, the patient reported that he did not feel any different and stopped the medication. His mother also voiced many concerns about her son’s health, appearance and demeanor, including thinning hair, insufficient food intake, lack of consideration for her concerns and his own health, and overall stubbornness, which the patient smilingly shrugged off. With his mother outside the room, he stated that he was immersed in religious studies at a school throughout the day, which left little time for other activities.
History and physical
The young man had entered puberty at the same time as his peers, has not been noticing any changes in body hair or weight, and reports no steroid use. He wishes to maintain fertility.
He reports adherence to prescribed medical regimen, but incomplete adherence to prescribed physical activity and dietary regimens.
The patient describes his diet as “healthy” overall and reports that he does not exercise.
He is not taking any medications or nutritional supplements, does not smoke, drinks one glass of wine per week and takes no recreational drugs.
Review of systems is remarkable for fatigue and a sense of “feeling stressed.”
On physical exam, I was presented with a thin, bespectacled patient with kyphosis. Blood pressure was 99/61 mg Hg, pulse 55 beats per minute, respiratory rate 16 breaths per minute, height 5’ 7” and weight 49 kg (107 lb). No gynecomastia was observed. Phallus was normal in shape and size with normal male-pattern pubic hair distribution; testicular size was also normal at approximately 18 mL bilaterally. It was an otherwise unremarkable exam.
Workup from the patient’s prior physician showed a low total testosterone of 49 ng/dL (reference range, 253-910 ng/dL), free testosterone 0.5 ng/dL, luteinizing hormone (LH) 2.6 mIU/mL and follicle-stimulating hormone (FSH) 4.8 mIU/mL in one instance, and total testosterone 91 ng/dL with a high sex hormone-binding globulin level of 71 nmol/L on a different occasion, both laboratory tests performed in the morning. Hemoglobin, ferritin, prolactin, cortisol, insulin-like growth factor I, thyroid-stimulating hormone, free thyroxine, chemistry, vitamin B12 and folic acid were all normal.
On clomiphene, the patient’s total testosterone was 810 ng/dL with a free testosterone of 7.1 ng/dL, both within the range of normal. An MRI had shown a 2-mm to 3-mm adenoma in the right superior part of the posterior lobe of the pituitary gland.
At the time of our visit, the patient has been off clomiphene for more than 2 months.
What is the next best step in the management of this patient? <ol_alpha-list>
The positive predictive value of an adult male presenting to my practice with his mother is 1.0 for a diagnosis of hypogonadism. But that determination had already been made — with remarkably low testosterone levels, close to the castration range. Hence, answer D, while containing an element of “truthiness,” is not applicable. Inappropriately normal LH and FSH levels, along with the biochemical success of clomiphene treatment, indicate secondary hypogonadism. Treatment with testosterone supplementation in a man who wishes to maintain fertility would, therefore, be counterproductive (A).
An adenoma in the posterior part of the pituitary, particularly if nonsecretory and small, should not affect the patient’s gonadotroph axis and, therefore, does not warrant surgery (B).
Of the many concerns the patient’s mother voiced, one was indeed verifiable: Her boy was too thin! At 5’ 7” and 107 lb, he had a BMI of 17 kg/m2. I advised him in no uncertain terms that he needed to gain weight, ideally 20 lb, and that this also involved educating his wife, who prepared all his food. I also advised him to set reminders to remember to eat when immersed in his studies. A weight-related decrease in sex hormone production is more is more commonly observed in women with secondary amenorrhea due to anorexia or severe negative caloric imbalance, but it can occur in men as well.
The patient underwent laboratory tests 5 weeks later and several pounds heavier, and his morning testosterone level was in the normal range, at 502 ng/dL.
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- Ronald Tamler, MD, PhD, MBA, is clinical director of the Mount Sinai Diabetes Center in New York. He also is an Endocrine Today Editorial Board member. He reports no relevant financial disclosures.