Lack of glucagon response to hypoglycemia in diabetic autonomic neuropathy.

Glucagon response to insulin hypoglycemia was tested in diabetics with autonomic neuropathy (N=9), diabetics without neuropathy (N=8), and normals (N=9). With similar levels of hypoglycemia, growth hormone and plasma cortisol increased in all groups. The glucagon response in normals (121+/-19 vs. 308+/-30 pg./ml., mean+/-S.E.M. of baseline vs. hypoglycemia peak) was significantly less in nonneuropathic diabetics than in normals (128+/-13 vs. 209+/-30) and absent in neuropathic diabetes (128+/-23 vs. 115+/-20). Arginine stimulation produced a glucagon response in the neuropathic diabetics (106+/-16 vs. 523+/-103). The data indicate that the capacity to release glucagon during hypoglycemia is lost in diabetic neuropathy while glucagon responsiveness to arginine is retained. Neuropathy in diabetes may contribute to metabolic instability.

Cortisol secretion by an incidentally discovered nonfunctional adrenal adenoma.

We describe a middle-aged man with late-onset multiple sclerosis and an incidentally discovered asymptomatic adrenal mass. He had no symptoms or signs of hypercortisolism. A 24-h profile revealed fluctuating serum cortisol values (between 15.1 and 4.7 micrograms/dl) and inappropriately low plasma ACTH values. Urinary cortisol excretion was 89 and 106 micrograms/day on two occasions. After a 4-h ACTH infusion, serum cortisol rose from 6.3 to 108 micrograms/dl. The serum dehydroepiandrosterone level, 33 ng/dl before ACTH stimulation, did not change. During dexamethasone administration, the lowest daily urinary cortisol excretion was 37 micrograms/day, and 17-ketosteroid excretion was 8 mg/day. The response to metyrapone showed a rise of serum 11-deoxycortisol to 25.6 micrograms/dl and of ACTH to 169.5 pg/ml. After removal of the tumor, most likely an adenoma, the circadian pattern of cortisol and ACTH was normal. During a 4-h ACTH infusion, the serum cortisol level rose from 10 to 27 micrograms/dl, and dehydroepiandrosterone rose from 62 to 90 ng/dl. During dexamethasone administration, daily urinary cortisol excretion decreased to 12 micrograms/day, and 17-ketosteroid excretion dropped to 3.9 mg/day. These data show that while the tumor appeared clinically to be nonfunctional, it was producing cortisol and possibly androgens autonomously, albeit at levels too low to cause complete suppression of the pituitary-adrenal axis.

Anti-estrogens and plasma proteins. II. Contraceptive drugs and gestagens.

PIP: The effects of Ovral (.5 mg norgestrel and .05 mg ethinyl estradiol (EE), and Norlestrin (1 mg norethindrone acetate and .05 mg EE) in women; dydrogesterone alone and with EE in men; and norgestrel, chlormadinone, EE, cyproterone and 17-alpha-methyltestosterone in green monkeys, on plasma proteins and hormones were studied, in an attempt to reverse estrogenic changes. Both contraceptives, given for 2 cycles to 25 women, increased corticosteroid-binding globulin, cortisol, thyroxin, and plasminogen, and Norlestrin increased fibrinogen. 30 or 40 mg dydrogesterone with .01 mg EE did not block the changes induced by estrogen alone in 5 men. Plasma protein and hormone levels in monkeys, tabulated after 2.5 mcg EE, 2 mg norgestrel alone and with 2.5 mcg EE showed that the estrogen effects of EE on corticosteroid-binding globulin and haptoglobin could be reversed by norgestrel. Similarly, 12.5 mg chlormadinone blocked the action of EE on thyroxine. The experiment with cyproterone acetate and methyltestosterone did not yield significant results.^ieng

Vitamin B-12 (cobalamin) deficiency: a heretofore undescribed control mechanism for plasma corticosteroid-binding globulin concentration in man.

Six of eight patients with Addisonian pernicious anemia were found to have diminished corticosteroid-binding globulin (CBG) concentrations, which returned within 2 weeks to normal after the im administration of cobalamin. T4-binding globulin was found to be completely normal before and after cobalamin replacement. Other estrogen-responsive proteins, i.e. ceruloplasmin, alpha 1-trypsin inhibitor, haptoglobin, transferrin, and alpha 2-macroglobulin, also did not follow CBG concentration in a parallel fashion. The immunoglobulins similarly did not follow a course parallel to that of CBG. The CBG concentration in two untreated patients had a normal increase in response to estrogen administration, similar to that described in CBG deficiency from other causes. No clue was found regarding the mechanism by which B12 influences the putative hepatic control of CBG concentration. It is speculated that at least two control points may be necessary for a normal CBG concentration. Patients with a genetic deficiency of CBG may also have to have cobalamin deficiency in order for them to reach a concentration approaching zero.

Surgical management of Cushing's syndrome.

Twenty-seven operations for Cushing's syndrome were reviewed. Included were five cases of adenoma and 22 of adrenal cortical hyperplasia. Preoperative laboratory data, particularly the metyrapone test, were highly accurate in distinguishing adenoma from hyperplasia. Bilateral flank incisions are preferable to the transabdominal approach, with fewer complications, less postoperative ileus, and shorter hospital stays. The inability to inspect both glands simultaneously is of little consequence because biochemical testing data are sufficiently accurate to obviate the need for gross evaluation. The use of perioperative prophylaxis seems to be of importance for preventing thromboembolism in these hypercoagulable patients. The preoperative use of adrenal cortical blocking agents has not proved to yield significant advantages.

Steroid use in the elderly. Guidelines for avoiding adverse effects.

The effects of aging on adrenal function should be considered when prescribing steroid for the elderly. For glucocorticoids, the changes of decreased production and decreased clearance are relatively balanced, resulting in levels that are still within the normal range. Responses of the hypothalamic-pituitary-adrenal axis to stress are not altered. However, androgens appear to be affected by an "adrenopause," the mechanism(s) and the clinical relevance of which remain to be elucidated. The risk/benefit factors in steroid use are always of utmost concern. The physician may consider lowering the steroid dose in elderly patients of asthenic build because of the diminution of muscle mass and plasma volume that occurs with aging. Despite the physiologic changes that accompany aging, steroid used carefully and appropriately can be both safe and effective in the elderly.