cortodoxone and Hypoglycemia

In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histology-proven NFMA were studied and hyperPRL was defined as serum prolactin (PRL) > 200 mIU/l in men and > 600 mIU/l in women. The pituitary-adrenal axis was evaluated by measurement of urinary free cortisol (N = 38), peak cortisol to insulin-induced hypoglycaemia (IIH, N = 36) and to human corticotrophin-releasing hormone (hCRF, N = 40) and by urinary tetrahydrol 11-deoxycortisol (H4S, N = 39), plasma androstenedione increment (N = 39) and serum 11-deoxycortisol (N = 1) after metyrapone. Central hypothyroidism, gonadotrophin deficiency and growth hormone (GH) reserve were also assessed. Twenty patients had hyperPRL (serum PRL 331 (223-1120) mIU/l (median, range) in men and 932 (660-3927) mIU/l in women): urinary free cortisol excretion (p < 0.03) and peak serum cortisol in response to IIH (p < 0.02) were lower in hyperPRL than in normoPRL patients; peak serum cortisol after hCRF was not different between groups but occurred later in hyperPRL patients (at 60vs 30 min, p < 0.03); urinary H4S excretion and androstenedione response after metyrapone were lower in hyperPRL than in normoPRL patients (p < 0.05 for both): 60% of hyperPRL patients and 15% of normoPRL patients had an abnormal H4S response (p < 0.025): central hypothyroidism (overt + subclinical) was present in 74% of hyperPRL and in 60% of normoPRL patients (NS); 78% of hyperPRL and 55% of normoPRL patients had gonadotrophin deficiency (NS): growth hormone (GH) deficiency was present in 83% of hyperPRL and in 89% of normoPRL patients (NS); 73.3% of 75 evaluable pituitary hormone axes were abnormal in hyperPRL patients compared to 53.8% of 78 hormone axes in normoPRL patients (by metyrapone test to examine adrenal function, p < 0.025); and no significant differences in tumour grade and stage distribution were found between hyperPRL and normoPRL patients. It is concluded that hyper-prolactinaemia in NFMA is associated with a higher prevalence of pituitary-adrenal dysfunction, which is likely to be explained at least in part by functional hypothalamic-pituitary interruption.

Topics: Adenoma; Adult; Aged; Corticotropin-Releasing Hormone; Cortodoxone; Female; Humans; Hydrocortisone; Hyperprolactinemia; Hypoglycemia; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System

The ACTH stimulation test examines adrenal responsiveness but may not examine the entire hypothalamic-pituitary-adrenal (HPA) axis and requires parenteral administration. The cortisol response to hypoglycaemia provides an index of activity of the entire HPA axis but is demanding for patients and medical staff. The aim of the present study was to examine the performance of the overnight single-dose metyrapone test as it provides a simple alternative test for HPA axis function.. Audit of the overnight metyrapone test performed in one centre between 1979 and 1991.. Three hundred and ninety-eight patients underwent 576 tests. Comparisons between the responses to metyrapone and the ACTH stimulation test and of the responses to metyrapone and insulin induced hypoglycaemia test were possible in 87 and 17 patients respectively.. Following the midnight administration of metyrapone tablets, 30 mg/kg orally, blood samples were obtained between 0800 and 0930 h for radioimmunoassay of both 11-deoxycortisol and cortisol.. Five hundred and seventy-six metyrapone tests were performed on 398 patients with no serious side-effects encountered. Adrenal insufficiency was diagnosed in 105 patients. Of these, 18 had a primary adrenal disorder and 87 had a disorder of the hypothalamic-pituitary unit. One hundred per cent concordance between the metyrapone, the ACTH and the hypoglycaemia test was seen in patients with primary adrenal insufficiency. In 19 patients with secondary adrenal insufficiency, who underwent both the metyrapone and the ACTH tests, discord between these two tests was observed in 10 patients (53%). Nine of these patients demonstrated a normal response to ACTH and a subnormal response to metyrapone. In only one patient was an abnormal cortisol response to ACTH associated with a normal response to metyrapone. In contrast, in 17 patients discord between the metyrapone and the hypoglycaemia test was seen in only 1 patient who demonstrated a normal response to the metyrapone test and a subnormal response to hypoglycaemia.. Since the metyrapone test gives similar information about hypothalamic-pituitary axis function as does the hypoglycaemia test, we recommend the use of the overnight metyrapone test as a safe, simple and reliable index of the hypothalamic-pituitary axis integrity. The ACTH stimulation test should not be used for patients suspected of having secondary adrenal insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cortodoxone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Medical Audit; Metyrapone; Pituitary-Adrenal System

Russell-Silver syndrome (RSS) is a sporadic form of prenatal onset dwarfism with typical facial features, variable asymmetry, and linear growth 3 to 4 SDs below the mean. Endocrinologic studies are usually normal; however, six cases of RSS with growth hormone deficiency have been reported, three of which had additional pituitary abnormalities. We describe another case, a 7-year-old girl with RSS and deficiencies of growth hormone, corticotropin, and thyroid-stimulating hormone. Replacement therapy including growth hormone resulted in an improved growth velocity, though twice the usual dose of growth hormone was required and short stature persisted. Since growth hormone secretion is usually normal in RSS, the existence of individuals with RSS phenotype and hypopituitarism including growth hormone deficiency suggests etiologic heterogeneity. We recommend that those individuals with RSS phenotype and a continuous significant decline in height velocity be investigated for pituitary abnormalities. Unusually high replacement doses of growth hormone may be required to overcome deficiency.

Topics: Adolescent; Body Height; Child; Child, Preschool; Cortodoxone; Dwarfism; Female; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypopituitarism; Infant; Male; Syndrome

Simultaneous measurements of both beta-melanocyte stimulating hormone (beta-MSH) and adrenocorticotropic hormone (ACTH) in extracted plasma were performed by specific radioimmunoassays. During insulin-induced hypoglycemia, there was a marked increase of plasma ACTH levels and a slight but significant increase of plasma beta-MSH levels. Lysine-vasopressin on the other hand, caused a significant rise of plasma ACTH levels without corresponding response of plasma beta-MSH. Following glucagon administration, neither hormone rose significantly. However, metyrapone infusion caused a significant increase of both ACTH and beta-MSH levels, and frequent blood sampling revealed that both hormones were secreted episodically, and that peaks generally coincided with each other. These data suggest that the secretion of these two hormones can occur together in most instances, and that the same mechanism is involved in the secretion of both hormones under the negative feedback control.

Topics: Adrenocorticotropic Hormone; Adult; Cortodoxone; Feedback; Glucagon; Humans; Hypoglycemia; Insulin; Lypressin; Male; Melanocyte-Stimulating Hormones; Metyrapone; Pituitary Gland

Topics: Adrenal Cortex; Adrenal Cortex Neoplasms; Cortodoxone; Humans; Hydrocortisone; Hypoglycemia; Pancreatic Diseases