A study of beta-cell function after glucagon stimulation in thalassaemia major treated by high transfusion programme.

An increased incidence of diabetes mellitus and glucose intolerance has been reported in thalassaemia major treated with a high transfusion programme (HTP). To investigate beta-cell function, serum immunoreactive insulin (IRI), C-peptide (CP) and glucose were measured fasting and at 3, 6 and 10 min after i.v. administration of 1 mg glucagon in 20 thalassaemia patients treated by many transfusions and in nine healthy control subjects. Fasting C-peptide concentrations (mean +/- SEM) were higher in the thalassaemic group (2.15 +/- 0.17 ng/ml) than in the controls (1.41 +/- 0.13 ng/ml). After stimulation with glucagon, C-peptide concentrations were consistently higher (P less than 0.01) by approximately 50% in the thalassaemic than in the control group (5.29 +/- 0.31 vs 3.36 +/- 0.21 ng/ml, at 3 min; 5.22 +/- 0.30 vs 3.53 +/- 0.21 ng/ml at 6 min and 4.69 +/- 0.27 vs 3.30 +/- 0.17 ng/ml after 10 min). Plasma IRI concentrations increased in both groups after glucagon stimulation but were not significantly different. The glucose values were approximately 15% higher at each sampling time in the thalassaemic group than those of the normal subjects. It is concluded that disturbances in carbohydrate metabolism in thalassaemia major treated with HTP are the consequence of hepatic cirrhosis which accompanies secondary haemosiderosis, and possibly iron deposition in the beta-cells of the pancreas.

Pituitary and thyroid insufficiency in thalassaemic haemosiderosis.

Thyroid and pituitary function tests using hypothalamic releasing factors were performed in seven patients with thalassaemia and secondary haemosiderosis and in a control group of seven healthy subjects. The TSH level in the thalassaemic patients (18.07 +/- 1.10 microU/ml) was higher than in the controls (1.01 +/- 0.14 microU/ml, P less than 0.001). After TRH administration the TSH values increased less than in controls. Serum thyroxine and FT41 values were lower in the group of patients with thalassaemia (76.7 +/- 7.8 nmol/l and 19.3 +/- 2.2) compared to the controls (116.1 +/- 6.9 nmol/l, P less than 0.005 and 38.6 +/- 3.6, P less than 0.001). The basal prolactin values did not differ significantly between the two groups, but after TRH administration the increment was significantly lower in thalassaemics than in controls (P less than 0.005). The basal LH values were lower in the thalassaemic patients (1.37 +/- 0.24 ng/ml) than in the controls (3.23 +/- 0.50 ng/ml) and did not increase significantly after LHRH administration. The FSH values were also lower in the thalassaemic group (0.46 +/- 0.15 ng/ml) compared to the controls (2.06 +/- 0.08 ng/ml, P less than 0.001), and increased only slightly after LHRH administration. We conclude that in thalassaemia pituitary deficiency exists, mostly of gonadotrophs, but possibly also for the thyrotrophs and the lactotrophs. Latent primary hypothyroidism has also been found in the thalassaemic group. The functional abnormalities found in both endocrine glands are best explained as a consequence of coexisting haemosiderosis.

An epidemiologic survey of thyroid enlargement among schoolchildren in a non-endemic area.

In 534 unselected schoolchildren aged 6-14 yr from the greater Athens area the size of the thyroid gland was assessed by palpation, and information was obtained on sex, age, height, weight, skinfold thickness, socioeconomic class, eye colour and urinary iodine excretion. The results were analysed by discriminant analysis. Altogether 14% of these children had a thyroid enlargement (7% had a definite goitre and another 7% a smaller enlargement). The set of variables studied were significantly discriminatory (Wilk's lambda 0.926, p approximately equal to 0.004). Most of the discrimination was accounted for by height (positive association, b coefficient 0.0114, SE 0.0029, t = 3.95) and weight (negative association, b coefficient 0.0107, SE 0.0030, t = 3.61). No other parameter, including iodine excretion, showed a significant difference between goitrous and nongoitrous. It is concluded that the only genuine difference is that goitrous are heavier for a given height or shorter for a given weight, i.e. more obese. The reason for which obesity protects from sporadic nontoxic goitre is not entirely clear, but probably both nutritional and genetic factors are involved.

Some epidemiologic studies of HBSAg in Greece.

In an epidemiologic study in 17 villages from different areas of Greece, 2898 persons were examined in order to find possible relations between HBSAg prevalence, altitude and endemic goitre morbidity. A lower prevalence with a significant difference was found in areas with a high altitude as compared with those with a low one, in endemic goitre than non-endemic areas, and in low altitude endemic than in low altitude non-endemic areas. Goitrous subjects had a lower HBSAg prevalence than non-goitrous subjects, but the difference was of borderline significance. The results can probably be explained by the presence of an environmental factor associated with altitude acting together with a host factor predisposing to endemic goitre and favouring the immunity to HBV infection.

The toxic effect of small iodine supplements in patients with autonomous thyroid nodules.

In sixteen cases of toxic adenoma of the thyroid (autonomous hot nodule with complete suppression of the surrounding normal parenchyma) potassium iodide was given in doses of 100 microgram/day for one week, 200 microgram/day for another and 400 microgram/day for a third week. There was a progressive increase in the serum T4 level. Serum T3 also increased, although this was significant only after the first week. Serum TSH was undetectable throughout the entire period of the study. This metabolic pattern is different from the response seen in cases of nontoxic endemic goitre, where small iodine supplements induce an increase in serum T4 but a decrease in serum T3. Furthermore, the present results may explain the phenomenon of iodine-induced or iodine-precipitated hyperthyroidism (Jod-Basedow) when patients with autonomous thyroid are presented with a high iodine intake. In contrast to the results obtained with small iodide doses, two other cases treated with large pharmacological doses of iodide showed a decrease in both serum T4 and serum T3. It is concluded that the physician should be aware of the possibility of precipitating or aggravating thyrotoxicosis in patients with an autonomous hot nodule by increasing their intake of iodine.

Comparison of various treatment schedules for accelerating the elimination of radioiodine from the thyroid and the human body.

In 68 euthyroid patients undergoing 131I thyroid function tests the thyroidal, urinary and plasma protein-bound radioactivity has been serially measured for 14 days. The patients were subdivided in controls and 9 groups treated with potassium iodide, carbimazole, potassium perchlorate and TSH, singly or in combination. The aim was to devise a treatment scheme for accelerating the release of iodine from the thyroid and the elimination from the body in cases of accidental radioiodine poisoning if the patient is seen after the radioiodine has already been taken up by the gland. All treatment schedules were effective, but TSH injections gave the best results, especially if combined with carbimazole and potassium perchlorate. This combination is the treatment of choice under these circumstances.