Recovery pattern of hypothalamo-pituitary-testicular axis in patients with macroprolactinomas after treatment with cabergoline.

Background & objectives: Hyperprolactinaemia affects testicular functions by influencing hypothalamo-pituitary-testicular (HPT) axis at various levels. Available literature on the level of defect, time course of improvement of gonadal functions and its relation with decline in prolactin levels is scanty. We carried out this study to evaluate the HPT axis in patients with macroprolactinomas, before and six months after cabergoline therapy. Methods: Fifteen men with macroprolactinomas underwent gonadotropin and testosterone response to their respective stimuli before and after six months of cabergoline therapy. Results: Serum prolactin levels decreased after six months of therapy. Pretreatment, mean lutenizing and follicle stimulating hormones (LH and FSH) levels were 2.0 ± 0.4 and 1.4 ± 0.2 IU/l, respectively. However, LH and FSH responses to GnRH were preserved in majority of the patients and LH peaked to 12.1 ± 2.3 IU/l (P<0.01), while FSH to 2.9 ± 0.4 IU/l suggesting the influence of hyperprolactinaemia at the level of hypothalamus with preserved gonadotrope reserve. After cabergoline therapy, there was an increase in basal as well as stimulated LH and FSH levels, though these were not statistically significant when compared to respective pretherapy levels. Basal testosterone (T) levels significantly improved after therapy, but peak T response to hCG was similar at both pre- and post treatment. A significant correlation was observed between peak LH and peak T at baseline (r=0.53, P<0.01) and it further strengthened after therapy (r=0.70, P<0.01). After cabergoline therapy, there was significant improvement in seminal volume, sperm count and motility and sperm count correlated with peak FSH response (r=0.53, P<0.05). Interpretation & conclusions: Hyperprolactinaemia affects testicular functions probably by influencing at the level of hypothalamus resulting in subnormal basal secretion of gonadotropins required for optimal testicular functions.

A pilot study on hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism.

Background & objectives: Parathormone (PTH) and calcium, both have been shown to stimulate adrenal steroidogenesis in animal models and in vitro experiments. This is attributed to structural similarity between 15-25 amino acid region of the parathyroid hormone (PTH) and 1-11 amino acid region of adrenocorticotropin (ACTH). However, there are no in vivo human data regarding the effect of PTHcalcium axis on adrenocortical function. Materials: Ten patients with primary hyperparathyroidism underwent evaluation for cortisol dynamics including 0800 h and 2000 h plasma cortisol on day 1, cortisol response to insulin induced hypoglycaemia (IIH) on day 2, and 1 mg overnight dexamethasone suppression test (ONDST) on day 4. Serum aldosterone was also measured at 0800 h in fasting state on salt ad libitum for three days. These parameters were repeated 3 months after curative parathyroidectomy. Results: Basal plasma cortisol level at 0800 h and 2000 h were within upper normal range and loss of circadian rhythm in cortisol secretion was observed in half and forty per cent of patients had nonsuppressibility with ONDST. The defined peak cortisol response to insulin induced hypoglycaemia (>550 nmol/l) was achieved in all and nearly one third of patients had exaggerated response (>2000 nmol/l). After curative parathyroidectomy, the abnormalities in circadian rhythm and non-suppressibility with ONDST continued to prevail in 40 per cent of patients. The peak cortisol response to IIH showed a decrement but remained higher than normal. No correlation was observed between circulating parathyroid hormone and calcium with cortisol levels. Serum aldosterone was in upper normal range pre - and postoperatively, though it decreased postoperatively, but it could not attain a statistical significance (p = 0.5). Interpretation & conclusion: Abnormalities in hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism do occur, however these are inconsistent and do not recover in majority of patients even after 3 months of curative parathyroidectomy.