Search

We describe an unusual cause of severe hypoglycaemia, secondary to hypopituitarism as a result of antepartum pituitary failure, in a pregnant patient with type 1 diabetes mellitus (T1DM). Antepartum pituitary failure is a very rare condition, which has been reported only in a very small number of pregnant patients with diabetes and presents with an acute onset headache and a sub-arachnoid haemorrhage-like picture. It is a potentially fatal condition to the mother and the child if not recognised and treated. Our case report highlights the importance of thinking about hypopituitarism, as a cause of recurrent hypoglycaemia in pregnant patients with T1DM as missing the diagnosis could be fatal to the mother and child.

Answers on 666. In August 1993, a 42 year old woman presented for definitive treatment of hyperthyroidism secondary to Graves’ disease. In 1970 she had undergone subtotal thyroidectomy for the first episode of hyperthyroidism but after a recurrence in 1977, she had been …

Seven normal male volunteers were given a 2 h intravenous infusion of insulin (2 mu kg-1 min-1). During the first hour, in which nomoglycaemia was maintained by glucose infusion, no detectable increase in growth hormone (GH) secretion occurred. When controlled symptomatic hypoglycaemia was produced during the second hour of the insulin infusion a brisk rise in plasma GH concentration was observed in all the subjects studied. Since it was possible that the falls in the concentration of plasma free fatty acids (FFA) occurring during infusion of insulin also acted as a stimulus to GH release the study was repeated in four subjects but normoglycaemia was maintained throughout the entire 2 h period of insulin infusion. In these experiments there was no rise in plasma GH concentration although a similar fall in plasma FFA was produced. These results clearly indicate that hypoglycaemia per se was the important stimulus to GH secretion and not hyperinsulinaemia or a lowering of plasma FFA. Furthermore there appeared to be a threshold hypoglycaemic stimulus to GH secretion. In no subject was a rise in plasma GH seen without a fall in plasma glucose greater than 1.4 mmol/l. Prolonged mild hypoglycaemia did not stimulate GH secretion.

Hypoglycaemic and growth hormone responses were studied at different steady-state plasma insulin concentrations during a graded infusion of monocomponent human insulin. The control group consisted of ten volunteer subjects. The other groups studied included women taking oral contraceptives and patients with obesity, thyrotoxicosis, myxoedema, acromegaly, diabetes mellitus (moderate and severe) and liver disease. The hypoglycaemic response was measured in two ways: (i) the percentage reduction in plasma glucose below basal, and (ii) the rate of fall of plasma glucose (Kg-%/min). Insulin sensitivity was greatest in the normal subjects and in the other groups decreased in the order thyrotoxicosis greater than oral contraceptive greater than obesity greater than myxoedema greater than acromegaly greater than liver disease. Insulin sensitivity was difficult to assess in the diabetic patients because basal plasma glucose concentrations were elevated. At any given insulin concentration, the diabetics metabolized approximately the same amount of glucose as the normal subjects but the fact that this rate of glucose turnover occurred at higher plasma glucose concentrations probably indicated insulin resistance. Within each group Kg at each dose level of insulin correlated with the steady state plasma insulin concentration during the same infusion period. Diminishing sensitivity to insulin was reflected in an increasing fasting plasma insulin and insulin/glucose ratio except in patients with diabetes. GH responses to insulin infusion in normal subjects reflected the pattern of fall of plasma glucose. In the diabetic patients GH secretion appeared to be related to the infusion of insulin and occurred before plasma glucose had fallen to hypoglycaemic levels. GH secretory patterns were within normal limits in women taking oral contraceptives and in seven of eleven patients with liver disease but were impaired in three of seven patients with thyrotoxicosis and four of five patients with myxoedema. Four obese patients had a markedly delayed but eventually normal GH response.

Twenty diabetic patients, whose hyperglycaemia had been shown to fail to respond to at least one month's dietary treatment, completed a crossover study in order to: 1) compare the effectiveness of two sulphonylureas, chlorpropamide and glibenclamide, and 2) study the effects of sulphonylureas on insulin secretion and on biochemical indices of glucose intolerance. Fasting blood glucose fell on active treatment from 10.7±0.6 (mean ± SEM) to 6.6+0.7 mmol/l and rose again to 10.6±0.7 after 4 months placebo. A second period of 4 months sulphonylurea therapy resulted in a comparable fall in blood glucose (to 6.9±0.7 mmol/l) and a similar relapse was seen after the second placebo period (to 10.5±0.9 mmol/l). Glucose tolerance and associated insulin secretion improved markedly on active treatment, with ketone bodies, non-esterified fatty acids, and glycerol falling to within the reference range. Sulphonylurea therapy was associated with a small but significant increase in the fasting insulin level. These effects were nearly all reversed 4 months after withdrawal of the sulphonylureas. No marked changes were found in growth hormone, lactate, pyruvate, lactate/pyruvate ratio or fasting cholesterol, triglycerides and lipoproteins. On a weight basis, glibenclamide was 26 times more potent than chlorpropamide and, in the doses used in this study, their biochemical effects were indistinguishable. The effects of these two sulphonylureas seem most likely to be mediated by a direct stimulation of insulin secretion by the B-cell.

SUMMARY The plasma clearance of calcitonin (TC) was studied by following the disappearance of radioactivity after intravenous injection of labelled TC, and the disappearance of bio-assayable activity after intravenous injection of unlabelled hormone. The turnover was shown to be rapid: two exponential components were involved with half times of 4–5 and 35–40 min. respectively. Similar values were obtained in experiments in which TC was infused to obtain raised, steady concentrations after which the disappearance of biologically active material was followed for up to 100 min. The normal concentration of TC in porcine peripheral plasma was calculated to be about 9 μu./ml.

SUMMARY Hypocalcaemia was produced by i.v. infusion of EDTA into pigs from which the thyroid venous effluent could be quantitatively collected. Calcitonin in the effluent was measured by radioimmunoassay. Reduction of plasma calcium concentration rapidly suppressed the secretion of calcitonin. In contrast, as plasma calcium was raised slowly from hypocalcaemic levels by infusion of CaCl2, calcitonin secretion quickly returned and increased rapidly. The secretion rate observed when the plasma calcium concentration had been raised from hypocalcaemia to the initial normocalcaemic level was 3½–10 times greater than that observed during the normocalcaemia which pertained at the start of each experiment. A previous period of hypocalcaemia also produced an exaggerated response to a subsequent hypercalcaemic stimulus. It is suggested that the preconditioned response of calcitonin secretion increases the efficiency of the role of calcitonin in calcium homeostasis.

Thirty-five freshly presenting, diabetic patients received 5 hour, 100 g oral glucose tolerance tests when first seen and after a period of carbohydrate and energy restriction. After treatment, the significant improvement in glucose tolerance was accompanied by increased insulin secretion and lower concentrations of blood ketone bodies, lactate, glycerol, FFA, triglycerides, cholesterol and pre-beta lipoprotein. There were no significant changes in serum growth hormone or blood pyruvate concentrations. Improvement in glucose tolerance was greater in patients who were obese (greater than 115% of desirable body weight for height) on presentation and was related to the improvement in insulin secretion and the diminished lipolysis. An hypothesis to explain the changes in insulin secretion is prosposed. Eleven out of the 35 patients showed sufficient improvement in glucose tolerance to require no treatment other than diet.

Thirty-eight patients in diabetic coma from four different centres were treated with a continuous low-dose intravenous infusion of insulin at an average dose of 7·2 IU/hr. All patients recovered rapidly except for one profoundly shocked patient who died. The mean fall in plasma glucose was 58% four hours after the start of insulin. Blood ketone bodies and plasma free fatty acids showed a similar response. There was no significant difference in plasma glucose response according to severity of acidosis or previous treatment with insulin. Hypokalaemia was uncommon. In the treatment of diabetic coma this technique has proved simple, safe, and effective.

During 15 labours in diabetic women blood glucose concentrations were controlled with simultaneous infusion of insulin and glucose. The mean insulin infusion rate was between 1 and 2 U/h. No infant showed evidence of neonatal hypoglycaemia. The procedure is simple to use and may be carried out in any labour ward.