Endocrine Abstracts (2002) 3 P190

Functional neurosecretory GnRH deficiency in a man with adult onset hypogonadotrophic hypogonadism: an unrecognised entity?

LGF Silveira1, M Thomas2 & PMG Bouloux1

1Department of Medicine, Royal Free and University College Medical School, London, UK; 2Department of Clinical Biochemistry, Royal Free Hospital, London, UK.

Hypothalamic GnRH neuronal dysfunction is a frequent cause of hypogonadotrophic hypogonadism (HH) in women with secondary amenohrroea. However, the entity is poorly characterized in men, possibly due to lack of a sensitive equivalent clinical marker of the condition.

A 40-year-old man presented with a 7-year history of progressive lack of energy, loss of libido, decreased sexual function, and loss of morning erections. Puberty had occurred normally and he had normal sense of smell, dietary habits, body mass index (24.5) and body proportions, with no history of excessive exercise, drug or alcohol abuse, or depression. Serum testosterone (T) levels measured at different occasions were low normal, with normal LH, FSH and SHBG levels, ruling out obvious hypogonadism. Sperm count (49 x 10[super>6[/super>/ml) and all other pituitary hormones were normal, as well as a hypothalamo-pituitary MRI. Endogenous LH, FSH and T pulsatility evaluated at 20 minutes intervals over a 12h period, showed low LH and FSH pulse amplitude and frequency, with correspondingly low T levels (7.7 to 10.7 nmol/l) with absent circadian rhythmicity.

Amplitude/frequency dysfunction of the GnRH pulse generator was hypothesised, secondary to a low threshold for sexual steroids negative feedback. Tamoxifen 20mg/day was initiated and, 3 weeks later, LH/FSH and testosterone pulsatility reassessed using the previous protocol. A clear increase in LH and FSH levels was discernible associated with increased testosterone pulsatility, though the levels remained around the lower limit (4.7 to 13.5nmol/l). The patient described some improvement in symptomatology. Replacement treatment was then started with transdermal testosterone patches and, subsequently, subcutaneous testosterone implants 800mg every 6 months, with complete improvement of the symptoms.

The patient described here clearly displays a mild, though symptomatic and testosterone responsive form of adult onset HH, which would have remained undiagnosed without pulsatility studies. In the absence of any apparent cause, abnormal gonadotrophin pulsatility pattern suggested a primary hypothalamic GnRH neurosecretory dysfunction, possibly due to altered set point for negative androgen feedback.

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