Two ends of the spectrum

Recently I saw two middle-aged men back to back as new patients. One was referred for evaluation of a low testosterone level at ~60 ng/dL, and the other for a high level at >1,400 ng/dL (reference interval 2141-827).

The first patient was quite unwell having “coded” twice in four days about four weeks before I saw him. His cardiac status was stable, but his higher functioning was impaired, and his wife provided most of the history. He had not complained of any symptoms related to his hypogonadism, but the testosterone level was ordered by one of his physicians because the patient was feeling weak. The only other endocrine testing that was done was a thyroid-stimulating hormone level that was “normal." There was no history relating to hypogonadism other than this generalized weakness. A few months earlier, he and his wife had gone on a cruise to celebrate an anniversary, and there was no issue with libido or sexual function. Nor was there any problem prior to the two acute events. Physical examination, including blood pressure, visual fields and gonadal examination, was normal, as was muscle tone and power. There was no loss of body hair, and there was no apparent decrease in beard growth. Other than the low testosterone, the lab values, including electrolytes, renal function and complete blood count, were normal.

His evaluation is still in process, but what are the possibilities? He certainly could have sustained ischemic damage to the hypothalamus or pituitary. Major infarct as is seen in pituitary apoplexy most often includes more than just loss of gonadotropins, and checking growth hormone, adrenocorticotropic hormone, TSH and gonadotropins is essential. There does seem to be a “pecking order” with respect to more gradual loss of pituitary function — first to go is GH followed in order by gonadotropins, TSH and lastly ACTH, but all must be evaluated. A prolactin-secreting tumor must also be ruled out in all cases of hypogonadism but the onset of symptoms is usually more gradual than in this case. Another avenue to explore is one I am not sure how to categorize, but severe emotional distress can impair gonadal function as is seen in prisoner-of-war camps, and in a nonviolent world, conditions such as anorexia.

The second patient is even more worrying. He is a healthy man in his mid-50s who presented for evaluation of erectile dysfunction worsening over a period of months. Checking the testosterone was appropriate, but it's worth remembering that the loss of libido that characterizes hypogonadism often puts erectile dysfunction into the background. In this case the very elevated testosterone was a surprise finding, confirmed on repeat. Missing from the evaluation was any gonadal examination and any measurement of gonadotropins. (When it comes to gonadal examination, all too often the documentation “WNL” really means “we never looked!")

He was fit person but not overly active. His favorite pastime was golf, which I have never recognized as vigorous physical activity. (In the interests of full disclosure, I should quickly say that my golfing skills are nonexistent — I have been known to miss the net at the practice tee more often that not.) He did not admit to using any performance-enhancing preparations, and given his current occupation, I am very confident he is telling the truth about this. His self-reported health status was 9+ on a scale of 1-10.

On examination he was a well-appearing man weighing 210 lb, and his height was 68.5 in. Visual fields were normal, the thyroid was not palpable, there was no gynecomastia, and muscle strength and tone were normal.

The left testis was small with a volume of 12 cc, and the volume on the right was 20 cc. This finding increases the suspicion of exogenous testosterone use, but there are gonadotropin-secreting tumors that must be excluded, and this is my major concern, particularly since locating such a tumor is not always easy.

The main message from these two patients is not so much what diagnosis I will eventually find. What I want to stress is the importance of the physical examination — there is no excuse for not examining the testes — and the understanding that the initial laboratory investigation should include the pituitary-end organ axis.