The effect of cyproheptadine and/or bromocriptine on plasma ACTH levels in patients cured of Cushing's disease by bilateral adrenalectomy.

Cyproheptadine and bromocriptine have been reported to be therapeutic in suppressing ACTH levels in Cushing's disease and Nelson's syndrome. However, there have been only scattered reports of their effect in suppressing raised ACTH levels found in patients cured of Cushing's disease by bilateral adrenalectomy. In order to assess whether these agents could prove beneficial in such patients we studied 12 patients previously treated with bilateral adrenalectomy alone for Cushing's disease before and after 3 weeks of cyproheptadine and/or bromocroptine therapy. All had raised plasma ACTH values but no patient had evidence of a pituitary macroadenoma. Plasma ACTH and cortisol were sampled 2-hourly for 24 h. Neither drug regime led to any change in plasma levels of cortisol for 24 h after a 20 mg dose of oral hydrocortisone. Plasma ACTH (mean +/- SEM) showed a small but significant overall reduction (523 +/- 45 vs 392 +/- 34 ng/l; P less than 0.05) while on bromocriptine alone (5 mg given at 0800 and 1800 h, n = 5). When each time point was analysed individually this reduction was significant at only five out of 13 time points. At 0400 h plasma ACTH (mean +/- SEM) was 758.4 +/- 298.1 vs 380.2 +/- 166.6; 0600 h, 795 +/- 288.7 vs 477.8 +/- 191.7; 1200 h, 266.8 +/- 106.2 vs 187.0 +/- 80.3; 1400 h, 470.0 +/- 239.0 vs 302.0 +/- 135.9; 1600 h, 548.6 +/- 262.5 vs 394.2 +/- 178.5 ng/l (P less than 0.05). There was no significant change in plasma ACTH during treatment with the combination of bromocriptine and cyproheptadine.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma ACTH responses to cortisol infusion are similar in patients with primary hypoadrenalism and patients studied some years after bilateral adrenalectomy for Cushing's syndrome.

It has been suggested that the first-phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary-directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first-phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.

Studies of hypothalamic pituitary structure and function in patients previously treated with bilateral adrenalectomy alone for Cushing's disease.

A controversy still exists in regard to hypothalamic pituitary function long-term after cure of hypercortisolism due to Cushing's disease. In an attempt to resolve this controversy, we have studied 15 patients, treated at least 6 years previously, by bilateral adrenalectomy. None of these patients had had pituitary-directed therapy. The maximum increment response of serum TSH in response to TRH was greater than 5 mU/l in 13 of the 15. Serum PRL response to TRH, GH response to insulin-induced hypoglycaemia, gonadotrophin responses to LHRH and nocturnal PRL secretion were normal in all patients studied. When nocturnal GH secretion was corrected for age, body mass index and menopausal status it was definitely abnormal in only two patients. The mean nocturnal GH secretion did not differ from that measured in a control group of Addisonian patients. The series of patients also did not differ significantly from the Addisonian patients in relation to the pattern of changes in plasma ACTH, over 24 h after an 0800 h oral dose of hydrocortisone. There was a significant rise in plasma ACTH between 2200 h and 0600 h in both groups of patients. The plasma ACTH concentrations were significantly higher in post-adrenalectomy patients. Hypothalamic pituitary function is normal in the long-term in the majority of patients treated by bilateral adrenalectomy for Cushing's disease.

Limited joint mobility in insulin-dependent diabetes: relationship to retinopathy, peripheral nerve function and HLA status.

Eighty-eight (43 per cent) of 204 patients with insulin-dependent diabetes had limited joint mobility affecting mainly the small joints of the hands. The presence of limited joint mobility correlated with duration of diabetes and with the presence of retinopathy. Patients with longstanding diabetes were approximately 2.5 times more likely to have proliferative retinopathy if limited joint mobility was present than if it was absent, although the risk for non-proliferative or background retinopathy was not increased. In patients with longstanding diabetes and limited joint mobility nerve conduction velocity and vibration perception threshold were significantly reduced compared with patients having similar duration of diabetes but normal joints. The association between insulin-dependent diabetes and HLA-DR3 and HLA-DR4 was confirmed, but there was no difference, between patients with and without limited joint mobility, in the frequency of the various HLA types. Limitation of joint mobility appears to be another "chronic complication' of diabetes, developing in parallel with retinopathy and deteriorating peripheral nerve function, and possibly of similar aetiology.