A correlative study between cortisol and ACTH in Cushing's disease following bilateral adrenalectomy and in Nelson's syndrome.

Correlation analysis was used to investigate the interrelation between plasma ACTH and serum cortisol concentrations determined at 8:00, 12:00, 16:00 and 22:00 h in 48 patients bilaterally adrenalectomized for Cushing's disease, including 23 patients with a pituitary adenoma (Nelson's syndrome). In the patients without evidence of a pituitary adenoma a significant inverse correlation was found at 8:00, 16:00, 22:00 h and additionally when all the pairs of estimations were analyzed. In a full-blown Nelson's syndrome an inverse correlation was not proved (p = 0.05). During remission in Nelson's syndrome an inverse correlation between cortisol and ACTH concentrations was stated at 8:00 h and after the evaluation of all the pairs of estimations. The results of our studies have shown that exogenous cortisol exerts a partial inhibitory action on ACTH secretion in patients bilaterally adrenalectomized for Cushing's disease. In active Nelson's syndrome this influence is questionable, it comes however into prominence during remission.     

Transient thyrotoxicosis after unilateral adrenalectomy in two patients with Cushing's syndrome

We found transient hyperthyroidism in the course of hydrocortisone withdrawal in two patients who had undergone unilateral adrenalectomy to resect cortisol-hypersecreting adenoma. A 38-yr-old woman showed clinical thyrotoxicosis 3 months after the operation. Serum T4, T3 and TBG levels were 11.9 micrograms/dl, 310 ng/dl and 16.5 micrograms/ml, respectively. She was given methimazole (MMI) 15 mg/day for 4 weeks. After the cessation of MMI treatment, she eventually recovered to the euthyroid state. The other patient, a 34-yr-old man showed very mild clinical symptoms of hyperthyroidism 2 months after the operation. Serum T4, T3 and TBG levels were 10.4 micrograms/dl, 240 ng/dl and 14.5 micrograms/ml, respectively. In this case, no antithyroid drug was given. Two to three months after the onset of hyperthyroidism, he returned to the euthyroid state spontaneously. We carefully eliminated the possibility of factitious thyrotoxicosis in both cases. They had neither neck pain nor fever. Both had low radioactive iodine uptake by the thyroid. Therefore, we diagnosed them as painless thyroiditis induced after the resection of hypersecreting adrenal adenoma.     

Sexually dependent changes in rat somatotropic cells following bilateral adrenalectomy.

In order to elucidate the existence of gender-related variations in both growth hormone (GH) release and the activity of somatotropic cells following bilateral adrenalectomy, a morphometric analysis was performed on GH-immunoreactive cells from adult male and female rats after bilateral adrenalectomy, correlating the findings with the serum levels of the hormone. The results obtained were compared to those found in untreated animals. Bilateral adrenalectomy was seen to induce a decrease in serum GH levels (p less than 0.01) in male rats; this was accompanied by a significant decrease in cellular area (p less than 0.01), cytoplasmic area (p less than 0.05) and nuclear area (p less than 0.01) and by a decrease in the cytoplasmic immunoreaction intensity of GH cells. By contrast, the above-mentioned changes did not appear in the female rats. These results suggest that the action of glucocorticoids on the synthesis and release of GH depends on the sex of the animal.     

Studies on pituitary-gonadal function in patients with Cushing's syndrome

Basal levels of sex steroids, and the responses of LH and FSH to LH-RH were studied in twenty-five female patients with Cushing's syndrome (17 Cushing's disease and 8 adrenocortical adenoma). Only two patients had a regular menstrual cycle. Amenorrhea or oligomenorrhea had been of long duration in the other cases except for three postmenopausal patients. In patients with Cushing's disease, basal estradiol was low or below normal in 86%. Progesterone was normal in 83%, but testosterone was high in half of the cases. The response of LH to LH-RH in patients with Cushing's disease was normal in 35%, low in 35% and high in 29% of the cases. FSH response to LH-RH was normal in 23.5%, low in 23.5% and high in 53%. In patients with adrenocortical adenoma, basal of estradiol was low or below normal, but progesterone and testosterone were normal in all cases. The response of LH and FSH to LH-RH in all patients with adrenocortical adenoma was higher than normal. In three postmenopausal women, a higher response of LH and FSH to LH-RH was seen in two cases and suppressed in one case. These data suggest that the main site of suppression of the gonadal axis in patients with adrenocortical adenoma is the gonad rather than the pituitary gland or hypothalamus, though the mechanism of hypogonadism in patients with Cushing's disease is heterogeneous.     

Allan-Herndon syndrome. I. Clinical studies.

A large family with X-linked mental retardation, originally reported in 1944 by Allan, Herndon, and Dudley, has been reinvestigated. Twenty-nine males have been affected in seven generations. Clinical features include severe mental retardation, dysarthria, ataxia, athetoid movements, muscle hypoplasia, and spastic paraplegia with hyperreflexia, clonus, and Babinski reflexes. The facies appear elongated with normal head circumference, bitemporal narrowing, and large, simple ears. Contractures develop at both small and large joint. Statural growth is normal and macroorchidism does not occur. Longevity is not impaired. High-resolution chromosomes, serum creatine kinase, and amino acids are normal. This condition, termed the Allan-Herndon syndrome, appears distinct from other X-linked disorders having mental retardation, muscle hypoplasia, and spastic paraplegia.