PLASMA STEROID CONCENTRATIONS IN PATIENTS WITH HYPOPITUITARISM AND KALLMAN''S SYNDROME: EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY

To determine the adrenal contribution to plasma concentrations of steroids potentially derived from both the adrenal and the testes, plasma levels of pregnenolone (Δ⁵P), progesterone (P), dehydroepiandrosterone and its sulphate (DHA and DHAS) and androstenedione (Δ⁴A) were measured in four men with isolated gonadotrophin deficiency and anosmia (Kallman's syndrome). A comparison of these levels with those seen in ten patients with both adrenal and testicular failure (hypopituitarism) and in sixteen normal age-matched men was made. As expected, the basal plasma levels of most steroids were low in patients with hypopituitarism. An exception was the normal Δ⁵P levels in most patients. In the patients with Kallman's syndrome both DHA and Δ⁵P were elevated whereas Δ⁴A and P were low. When expressed as ratios, Δ⁵P/P was increased in both groups. DHA/Δ⁴A was increased in Kallman's syndrome but not in hypopituitarism. Following ACTH infusion, no significant changes in these ratios were observed. To determine whether testosterone deficiency was in part responsible for the abnormal Δ⁵/Δ⁴ ratios, three patients with hypopituitarism and two with Kallman's syndrome were treated for 3 months with intramuscular testosterone. A decrease in the DHA/Δ⁴A ratio was seen in all patients and a decrease in Δ⁵P/P in all but one patient. In most cases these changes were produced by a fall in the Δ⁵ steroids as well as an increase in Δ⁴ steroids. These findings suggest that a defect in the metabolism of Δ⁵ steroids exists in patients with hypopituitarism and Kallman's syndrome. In hypopituitarism the defect involves the metabolism of Δ⁵P to both DHA and P. In Kallman's syndrome only the metabolism of Δ⁵P to P is defective. Testosterone therapy alone or in combination with other appropriate hormonal replacement increases the metabolism of Δ⁵ to Δ⁴ steroids.