Although glucocorticoid replacement is conventionally administered twice daily, the pharmacokinetics of hydrocortisone would predict very low levels of plasma cortisol by mid-afternoon. This study compared plasma cortisol day profiles in 7 hypoadrenal patients while on twice daily and thrice daily hydrocortisone replacement. The twice daily regimen was associated with very low levels of cortisol at 16.00 and 18.00 h. This was eliminated by administering the same total dose in a thrice daily regimen. Furthermore, estimates of 'well-being' by visual analogue scale correlated significantly with simultaneous plasma cortisol levels and 5 of the patients expressed a preference for the thrice daily regimen. The findings suggest that thrice daily glucocorticoid replacement therapy should be adopted routinely.

Although selective transsphenoidal surgery is an effective treatment for pituitary-dependent Cushing's syndrome the definition of cure as distinct from improvement is unclear. Complete tumor removal should be associated with very low serum cortisol levels because of long-term suppression of normal corticotrophs but the optimum timing of this investigation after surgery has not been established. Eleven consecutive patients with surgical and histological confirmation of a corticotroph adenoma removed at transsphenoidal surgery for proven Cushing's disease were studied with 0900 h serum cortisol levels at 5-14 days and 6-12 weeks postoperatively. Patients were maintained on hydrocortisone 10 mg three times daily (final dose at 1800 h) pending recovery of the hypothalamic-pituitary axis which was assessed by periodic short tetracosactrin tests and continued remission of the condition was confirmed by low dose dexamethasone suppression testing. All patients achieved clinical resolution of their disease but four subsequently developed biochemical evidence of recurrence with incomplete suppression on low dose dexamethasone testing at 2-48 months after surgery. These patients had 0900 h serum cortisol levels of 124, 95, 186, and 265 nmol/L at 5-14 days and 334, 52, 130, and 240 nmol/L at 6-12 weeks postoperatively. The remaining seven patients, who are in remission after 8-83 (median 24) months of follow-up, demonstrated 0900 h serum cortisol levels of 30-75 (median 31) nmol/L at 5-14 days but lower levels at 6-12 weeks (< 20 nmol/L in three patients and 22, 30, 30, and 33 nmol/L in the remainder). In this series, serum cortisol measurements at 6-12 weeks after transsphenoidal surgery for Cushing's disease are lower than levels obtained within 2 weeks of surgery and appear to give better discrimination of continuing remission; levels less than 35 nmol/L suggest a favorable long-term outcome.

Using a specific immunoradiometric assay method the in vitro alpha interferon response to polyinosinic:polycytidylic acid (poly-I:C) and the gamma interferon response to concanavalin A were measured in peripheral blood mononuclear cells from 11 healthy matched pairs of Type 1 diabetic patients and normal subjects. The alpha-interferon response to poly-I:C was significantly higher in the diabetic group (median 3.7 (range less than 1-25.7) u ml-1) than in the normal group (1.1 (less than 1-15.4) u ml-1, p less than 0.01). The mean gamma-interferon response to concanavalin A was 64.3 +/- 46.9 (+/- SD) u ml-1 in the diabetic patients and 49.4 +/- 18.5 u ml-1 in the normal group (NS). The higher alpha-interferon response to poly-I:C in the diabetic patients was not related to blood glucose concentration, HbA1, age of onset of diabetes, duration of diabetes, or islet cell antibody positivity, and may therefore indicate intrinsic hyper-responsiveness of circulating mononuclear cells in Type 1 diabetes.

SummaryThe possible relationship between antecedent diabetic control, as determined by serial glycosylated haemoglobin (HbA1) measurements, and diabetic retinopathy was examined in 40 insulin-dependent and 41 non-insulin-dependent diabetics selected consecutively from our clinic population. Multiple logistic regression analysis demonstrated a significant association between mean HbAj and prevalence of retinopathy in both groups of patients. This association was independent of duration of diabetes which was also significantly associated with retinopathy prevalence. Hypertension and smoking were not obvious risk factors in this group of patients; an apparent association of hypertension and diabetes was entirely accounted for by a positive relationship between the presence of hypertension and duration of diabetes.