Cushing's disease: clinical and laboratory response to bromocriptine therapy.

Four patients with Cushing's disease were treated with bromocriptine, administered three times daily, in doses ranging from 7.5 to 15 mg/day, during an average period of 80 days. Daily urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroids (17-KS) excretion was measured during dynamic tests and at two-week intervals. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were also assayed before and after therapy. A marked clinical and laboratory improvement was noted in two patients, in another some clinical and laboratory improvement was obtained only after bromocriptine dosage was increased to 15 mg/day. There was no effect in the fourth patient. Thus, at least for a short period of time, bromocriptine may be useful therapy for some patients with Cushing's disease.

Propranolol and hyperthyroidism: sequential changes in serum iodothyronine (T4, T3, rT3) concentrations during therapy until clinical remission.

The sequential clinical and laboratory (serum T4, T3 and rT3 concentrations) effects of propranolol were studied in 21 hyperthyroid patients. The amount of propranolol required to achieve clinical compensation ranged from 240 to 400 mg/day. For two patients, 480 mg/day, the maximal dose used, did not produce clinical compensation. The only significant changes in serum iodothyronines was detected in the 9 patients compensated with 240 mg/day. T3 decreased from 362 to 299 ng/dl (P less than 0.05) and the rT3/T3 molar ratio increased from 3.4 to 6.5 (P less than 0.025). The increases of rT3 from 113 to 168 ng/dl and of the rT3/T4 molar ratio from 6.7 to 10.8 were not statistically significant (P = 0.052). A slight decrease of serum T3 and increase of serum rT3 occurred during the first or second week in the other patients but the changes were not sustained over the whole period of treatment. These results show that the effects of propranolol on hyperthyroidism were independent of its transitory effects on the peripheral metabolism of thyroid hormones, thus providing further support for the current view that the clinical improvement of hyperthyroid patients on propranolol therapy is probably due to beta-adrenergic receptor blockade. A small percentage of thyrotoxic patients may not show clinical improvement even when propranolol doses of more than 400 mg/day are used.

Propranolol and hyperthyroidism: serum free fatty acids and glucose-induced insulin release in nondiabetic thyrotoxic patients during treatment to clinical compensation.

Glucose-induced insulin secretion was studied in 10 hyperthyroid patients, without personal or familial diabetic background, treated with increasing weekly doses of propranolol until clinical compensation was obtained. Intravenous glucose tolerance tests (25g) with concomitant determination of serum glucose, insulin and FFA were done before treatment, at 240 mg/day of propranolol and after clinical compensation. Patients were divided into two groups according to laboratory data and propranolol dosage needed for clinical compensation (group A: 240 mg/day; group B: 320-400 mg/day). Fasting serum insulin, glucose disappearance rate, and estimates of total insulin secretion after intravenous glucose did not change significantly during propranolol therapy and were within the normal range. Fasting FFA of untreated patients were significantly higher than control values (p less than 0.001), but a significant decrease was already seen at 240 mg/day of propranolol, even before clinical compensation. There was a marked difference in the insulin secretion pattern of thyrotoxic patients as compared to controls. Serum insulin and insulin:glucose ratios increased promptly, and at 5 min after glucose reached significantly higher levels than in normal subjects, before treatment as well as after clinical compensation with the propranolol therapy. Both the increased levels of FFA and of T3 could be involved in this pattern of the insulin response of nondiabetic thyrotoxic patients, since the secretion of insulin during the first 10 min after intravenous glucose was directly correlated to fasting serum FFA before propranolol, and serum T3 was directly correlated with total insulin response after clinical compensation. Furthermore the comparison of the results obtained in group A and group B patients raises the possibility that an increased beta-cell responsiveness to beta-adrenergic stimuli might also be involved in this pattern of insulin secretion.