J. Cassar

Bromocriptine treatment of acromegaly

Bromocriptine at a dose of 7.5-30 mg/day was given to 12 acromegalics for 6 mo. Mean serum growth hormone (GH) levels during a glucose tolerance test (GTT) were significantly lowered by the drug. In four patients the serum GH response during a GTT was suppressed to normal (i.e. less than or equal to 5 mlU/liter). If bromocriptine had not brought the serum GH response to a GTT to normal at a dose of 20 mg/day, this effect was not achieved by raising the dose to 30 mg/day. Bromocriptine was effective for the duration of treatment. On discontinuing therapy there was an increase in serum GH levels. No obvious clinical changes in the acromegalic features were noted. One patient with impaired glucose tolerance and one with established diabetes had normal glucose tolerance while on bromocriptine and another two patients with impaired glucose tolerance showed no obvious changes while on the drug. Side effects were minor. X-rays of the pituitary fossa before starting and at the end of treatment showed no significant change. We conclude that although bromocriptine is the most promising form of medical treatment for acromegaly to date, it is fully effective only in a minority of patients.

TREATMENT OF CUSHING'S DISEASE IN JUVENILES WITH INTERSTITIAL PITUITARY IRRADIATION

Nine juvenile patients (five boys and four girls aged 10–18) with Cushings disease were treated with pituitary implantation of 198 Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushings disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149–172 cm (59–67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushings disease in juveniles.

Serum T4, T3, and TSH levels in primary hypothyroidism during replacement therapy with thyroxine

Forty-five patients with primary hypothyroidism were studied during the first 4 to 36 months of replacement therapy with thyroxine. All became clinically euthyroid (23 patients while taking 0.1 mg/d, 14 patients while taking 0.15 mg/d, 7 patients while taking 0.2 mg/d, and 1 patient while taking 0.25 mg/d) over a period of three to six months. The patients were then divided for data analysis into two groups. Group I had normal serum T3 levels, normal (or elevated) serum T4 levels, and normal serum TSH levels. Group II had normal serum T3 levels, normal (or elevated) serum T4 levels, but high serum TSH levels. Group II was subdivided further into a group of 13 patients (group IIa) whose dose of thyroxine was deliberately increased until the serum TSH level was normalized; five of these patients became clinically and biochemically hyperthyroid. Group IIb consisted of eight patients with normal serum T3 and T4 levels and high serum TSH levels who were followed up without attempting to normalize their serum TSH levels. None became thyrotoxic, and their serum TSH levels showed little change. These findings suggest that serum TSH levels alone are not adequate to assess the required dose of thyroxine replacement therapy.

Diabetic retinopathy and pregnancy

SummaryDiabetic retinopathy was found to be present in 12 out of a group of 67 diabetic patients supervised by us during 92 pregnancies, and 3 further pregnant diabetics were referred to us because of retinopathy. The mean duration of diabetes was 13 years (range 3–25 years). Nine patients had minimal retinopathy, 2 had background retinopathy, and the remaining 4 proliferative retinopathy. The cases with minimal retinopathy showed no progression during pregnancy. In 1 patient with background retinopathy there was deterioration. Of the 4 patients with proliferative retinopathy 1 showed regression during the pregnancy, 2 showed advance and were treated with photocoagulation (these 2 patients now have normal vision), while the patient with extensive retinitis proliferans, with retinal detachment in both eyes and previous photocoagulation remained unchanged. The prognosis during pregnancy for patients with diabetic retinopathy is reasonable and has been improved by the advent of photocoagulation.

Deoxycorticosterone and aldosterone excretion in Cushing's syndrome

We have used specific radioimmunoassays to measure urinary free deoxycorticosterone (DOC) and total aldosterone excretion in 15 patients with Cushings syndrome. Free DOC excretion was increased in 6 of 8 patients with pituitary-dependent adrenal hyperplasia, in 2 of 3 patients with adrenal adenoma, and in all 4 cases with adrenal carcinoma. The most marked increase was noted in the adrenal carcinoma cases. Aldosterone excretion was high, normal, or low in each of the three types of Cushings syndrome. The free DOC response to metyrapone in Cushings syndrome due to adrenal adenoma was markedly different from that in patients with adrenal hyperplasia (pituitary-dependent) and may serve as a test to ascertain the etiology of the disorder. Correlations of free DOC and aldosterone excretion with free cortisol excretion, and their responses to the administration of metyrapone and dexamethasone were compatible with ACTH dependency in adrenal hyperplasia, autonomous production of steroids in adrenal adenomas and a chaotic steroidogenesis in adrenal carcinoma.

ENTEROGLUCAGON AND GIP AFTER ORAL GLUCOSE IN PATIENTS WITH PROLACTINOMA AND ACROMEGALY

We have performed oral glucose tolerance tests (OGTT) in nine patients with prolactinomas, eight patients with active acromegaly, five patients with acromegaly in remission and nine normal controls, and measured blood glucose, plasma insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide (GIP) and GH during the test. Patients with prolactinomas and with active acromegaly were hyperinsulinaemic and five of the nine patients with prolactinomas had impaired glucose tolerance, with blood glucose levels that were significantly higher than the normal controls. Prolactinoma patients had higher GIP levels than those with active acromegaly and both showed a failure of suppression of pancreatic glucagon. Of particular interest was the finding that enteroglucagon, a putative gut growth factor, was low in active acromegaly when compared with acromegaly in remission, but similar to normal in the rest of the patients.

Insulin secretory response to oral glucose load, diabetic microangiopathy and diabetic control: A study in non-insulin dependent diabetics

To study the importance of the residual insulin secretion for the degree of diabetic control and for the development of microangiopathy 55 patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. A 1 hr oral glucose tolerance test was performed at diagnosis and 5-10 yr later. At diagnosis all patients were free of microangiopathy, at reassessment 24 patients had evidence of microangiopathy, i.e. retinopathy, neuropathy or nephropathy, alone or in combination. The glucose induced increments of insulin levels (delta IRI) at reassessment correlated inversely with the degree of diabetic control, measured by Haemoglobin A1 (r = -0.466, p less than 0.01), and with the mean fasting blood glucose throughout the follow up period (r = -0.491, p less than 0.01). delta IRI at diagnosis was similar in patients with and without microangiopathy, and at reassessment, although lower in the microangiopathy group (11.2 +/- 2.1 vs. 16.4 +/- 2.1 microunits/ml, p less than 0.1). The difference between the 2 groups did not reach statistical significance. When patients were separated into those treated with diet alone and those treated with oral antidiabetic agents, delta IRI at reassessment was significantly lower in patients on oral agents (10.5 +/- 1.9 vs. 17.2 +/- 2.2 microunits ml, p less than 0.01), but the prevalence of microangiopathy was not different between 2 groups (37% and 52%, respectively). These findings show that in patients with NIDDM the residual beta cell function is important for the degree of diabetic control, but a direct relationship between the degree of insulin deficiency and the presence of diabetic microangiopathy is not established.