Pituitary-testicular reserve in men with low serum testosterone and normal serum luteinizing hormone

Men with low serum testosterone levels who do not have elevated serum LH levels are generally thought to have hypothalamic-pituitary dysfunction. To evaluate this concept, seven men with a combination of low serum testosterone and normal serum LH underwent standard tests of hypothalamic-pituitary-testicular reserve. Pituitary reserve, tested with LHRH, showed exaggerated responses in two subjects, low-normal responses in one subject, and normal responses in the remaining four. Testing of hypothalamic-pituitary reserve with clomiphene showed normal gonadotropin responses in six subjects and blunted response in one (the same subject with the low LHRH response). Direct stimulation with hCG showed normal percentage increases in testosterone but low absolute levels, comparable to responses in patients with Klinefelter's syndrome. However, 17-OH-progresterone responses to hCG were lower in these subjects than in either controls or subjects with Klinefelter's syndrome. During follow-up, one subject developed frank primary testicular failure. It was concluded that men with low serum testosterone but normal serum LH are a heterogeneous group, and this pattern occasionally reflects early primary testicular failure rather than hypothalamic-pituitary dysfunction. Standard tests of pituitary-testicular reserve are generally not useful in defining abnormal hormonal output, although measurement of the 17-OH-progesterone response to hCG may improve their diagnostic utility.