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The effectiveness of combined cytostatic treatment with doxorubicin and bleomycin was analysed in 21 patients with metastasising thyroid carcinoma which had progressed despite both surgical and radiotherapy. Tumour histology (anaplastic carcinoma in 50%), age and general condition of all patients pointed to a poor prognosis. Significant success (full or partial remission) occurred in eight patients. It is possible that these results can be improved if chemotherapy is started earlier and other cytostatic drugs are used in case of failure of treatment.

Initial symptoms of thyroid cancer were collected and analysed for 1116 patients with thyroid cancer in an iodine-deficient region, retrospectively for the period 1960-80 (604 patients), prospectively for 1981-87 (512). Using the WHO classification, 56.1% of patients had papillary, 32.7% follicular, 4.8% C-cell, 3.7% anaplastic and 2.7% various other malignant tumours. In 40% of all patients the initial sign had been a solitary intrathyroid nodule. Cervical lymph node swelling as initial sign had been significantly more frequent in men (21.1%) than in women (10.3%; P less than 0.003). In patients aged under 40 years the cervical lymph node signs were three times as common as among those over 50 years. Distant metastases as initial sign of papillary carcinoma were seen only in those over 60 years. Tumour stages T3 and T4 were seen significantly more frequently in over 60-year-old (42.2%) than under 40-year-old (25.1%; P less than 0.001), independent of histological type. Composition and initial signs of this patient cohort in an iodine-deficient region differed only slightly from those in an iodine-rich region.

We determined HBA1 (microcolumn method) and glycosylated albumin (fructosamine) in 23 healthy subjects, 35 patients with renal insufficiency without diabetes and 14 patients with diabetes mellitus and renal insufficiency. All patients with renal insufficiency required dialysis. All diabetics were of type I and had been compensated on insulin. The HBA1 in the nondiabetic patients with renal insufficiency (9.4 +/- 1.4%) was significantly raised compared to that in the control group with healthy metabolism (7.3 +/- 0.6%). Irrespective of the quality of compensation, the diabetic patients had HBA1 values of more than 11% of average. On the other hand, the concentrations of glycosylated albumin in healthy nondiabetic patients and in diabetic patients with renal insufficiency did not differ (1.3 +/- 0.5 as compared to 1.1 +/- 0.4 mmol/l) and were all in the normal range. Well-adjusted diabetics with renal insufficiency had a fructosamine concentration of 1.9 +/- 0.7 mmol/l (theoretical value for a good compensation 2.0 to 2.8). We conclude that determination of HBA1 in pronounced renal insufficiency does not provide reliable values because carbamylated hemoglobin is also registered and determination of fructosamine (which only indicates the metabolic situation in the last three weeks, however) is to be preferred in this situation.

Doxorubicin chemotherapy was performed in 52 patients with thyroid malignancies. Data from 47 patients could be evaluated. 16 remissions and partial remissions were seen, 15 cases had a progressive course, and in 16 patients there was no change of tumour size during the period of treatment. Results of treatment were worse in locally invasive tumour growth and reduced general state of health as well as in anaplastic carcinomas. Results were best in follicular and C-cell carcinomas. The mean survival time of patients responding to treatment was longer than in non-responders. The main indication for treatment is alleviation of tumour symptoms (bone pain, threatening fractures, pressure due to tumour); further indications are anaplastic carcinomas because of their bad prognosis and C-cell carcinomas because of their comparatively satisfactory response.

Side effects of antithyroid treatment were retrospectively analysed in 1256 patients with hyperthyroidism. Overall rate of side effects was 14.3%. Skin reactions were the most frequent ones (5.6%), followed by arthropathies (1.6%). The incidence of agranulocytosis was 0.14%. Median duration of all side effects was 1.5 months. In half the cases the side effects were controllable so that treatment was continued, although at a changed dosage. The rate of cross-reaction between carbimazole and thiamazole, on the one hand, and propylthiouracil, on the other, was 13.8% and 15.2%, respectively. The side effects became apparent after a mean of one month's treatment, almost always (in 97.1%) within the first year of treatment. There was a significant dose dependence for an initial thiamazole dose of over 20 mg (relative side effect risk of 2.3), and for an initial dose of over 30 mg for carbimazole (relative side effect risk of 1.6). Although most side effects were not dangerous, in normal instances the lowest possible dosage should be administered to control hyperthyroid metabolism. Long-term treatment with low doses seem to be without problems.

Marked insulin sensitivity, accompanied by unusual hypoglycaemic symptoms, was observed in three patients with juvenile diabetes mellitus. All three had anterior hypopituitarism, developing post-partum in two, a craniopharyngioma being the cause in the third. These are thus three examples of the Houssay phenomenon of which only 37 cases have previously been described.

In a prospective study 39 patients with diffuse euthyroid goitre were treated for one year with 100 micrograms levothyroxine (n = 19) or 500 micrograms iodide (n = 20). Efficacy of treatment was assessed by sonographic thyroid volumetry . In both forms of treatment maximum volume decrease was already seen within the first six months. After treatment for one year the mean decrease of thyroid volumes was 27.5% in the thyroxine group and 22% in the iodide group. This difference was statistically not significant. There was no difference in the extent of goitre size reduction within the thyroxine group among patients with complete TSH suppression and with still positive TRH test. Significant increases of T4 and of fT4 values within the normal range were observed already after one month with thyroxine treatment and only after 3 months with iodide treatment. There were no changes of the T3 values. In one female patient iodine-induced hyperthyroidism occurred. However, there were no further side effects in both treatment groups. This randomised study documents for the first time that both 500 micrograms of iodide and 100 micrograms of levothyroxine have a comparable efficacy for reduction of goitres.

Echography of the thyroid was performed on 542 persons with thyroid glands normal to palpation. Thyroid volume in men ranged between 9 and 38 ml, in females between 6 and 25 ml; median 16.7 ml and 13.5 ml, respectively. This sex difference is significant. There was only a weakly positive correlation between thyroid size, on one hand, and age or surface area, on the other. In future, thyroid echography should be used as reliable and yet simple method in any epidemiological study of the incidence of goitre.

In hypercalcaemic crisis sonographic identification of an enlarged parathyroid permits the indication for parathyroidectomy. This is particularly important as determination of the parathormone concentration to find out the cause of hypercalcaemia takes too long and thus delays diagnosis and therapy. In two patients with symptoms of crisis successful parathyroidectomy was performed solely on the basis of a raised serum calcium concentration and a sonographically proven enlarged parathyroid.

ACTH concentration was measured in simultaneously drawn blood samples from the left and right inferior petrosal sinuses before and after administration of corticotropin-releasing hormone (CRH). Such samples were successfully obtained in 20 of 21 patients with ACTH-dependent Cushing's syndrome on whom it was attempted. In 11 of the 20 patients there was no concentration difference between petrosal sinus and peripheral blood. But 13 of 19 patients had a unilateral central to peripheral concentration gradient greater than 1.4 after CRH administration. In the other six patients no ipsi- to contralateral gradient was demonstrable. Two of these patients had a proven ectopic ACTH-producing tumor; no adenoma was found at operation in three; on patient is awaiting operation. In 10 of 13 patients with unilateral gradient a microadenoma was found on the same side at operation. One patient had a hemi-hypophysectomy on the side of the higher gradient: hypocortisolemia developed in her postoperatively. Two other patients are awaiting operation. The results indicate that simultaneous bilateral catheterization of the inferior petrosal sinus with CRH stimulation is a highly informative examination with few side-effects and will contribute to better diagnosis and treatment of Cushing's syndrome.