The incidence of recurrence and hypothyroidism following treatment with antithyroid drugs, surgery or radioiodine in all patients with thyrotoxicosis in Malmö during the period 1970-1974.

The incidence of recurrence and of hypothyroidism was determined in all new patients treated for thyrotoxicosis during the period 1970-1974 in an unselected, well-defined urban population. A total of 309 patients were followed up for a median time period of 108 (1-192) months. There was a cumulative incidence of 51% recurrence in patients who were treated with antithyroid drugs for Graves' thyrotoxicosis, whereas after surgery or radioiodine treatment there were few recurrences, but 32% and 78% cumulative incidences of hypothyroidism. There were no recurrences after surgery or radioiodine treatment in patients with toxic multinodular goitre or solitary toxic adenoma, but 29% and 40% cumulative incidences of hypothyroidism following radioiodine treatment. Late hypothyroidism occurred after surgery for Graves' thyrotoxicosis, and in all groups treated with radioiodine. Thus it is advisable that all patients with Graves' thyrotoxicosis, regardless of treatment, and all patients with toxic multinodular goitre or solitary toxic adenoma treated with radioiodine, should be followed up for many years, and probably for life.

Use of anabolic-androgenic steroids among body builders--frequency and attitudes.

A total of 138 male body builders who regularly attended a gym participated anonymously in a study of the use of anabolic-androgenic steroids in relation to side-effects, blood pressure, body mass index (BMI; kg m-2), training frequency, social background, occupation, knowledge and attitudes to steroid use. Fifty-three of the 138 body builders had used anabolic-androgenic steroids for a median duration of 2 years. Steroid use was linked to a higher BMI and more frequent training. Seventy-five per cent (n = 18) of those attending body building for competition, and 24% (n = 11) of those attending to improve their sense of well-being, used anabolic-androgenic steroids. Of all body builders, 94% considered anabolic-androgenic steroids to be dangerous. Of the users, 81% experienced side-effects, but 74% still intended to continue steroid medication.

Effect of therapy on the serum thyroglobulin concentration in patients with toxic diffuse goiter, toxic nodular goiter and toxic adenoma.

Serum thyroglobulin (S-Tg) was measured in 104 patients with thyrotoxicosis, 59 of whom had toxic diffuse goiter (Graves' disease), in 30 with toxic nodular goiter and in 15 with toxic adenoma. Before treatment, most patients had increased S-Tg concentrations, regardless of what type of thyrotoxicosis they had. After therapy the course of the S-Tg varied, two major patterns being observed: the S-Tg concentration increased in some patients but decreased in others, although no relationship could be found between these patterns and the outcome of therapy, the presence or absence of thyroglobulin antibodies (Tg-ab) or changes in the Tg-ab titer. However, the median pretreatment concentrations of S-Tg were significantly higher in patients with toxic nodular goiter and toxic adenoma than in those with toxic diffuse goiter (p less than 0.001 and p less than 0.05, respectively), but did not differ significantly between patients with toxic nodular goiter and toxic adenoma. The lowest posttreatment S-Tg concentrations were found after surgery, irrespective of type of thyrotoxicosis. The median pretreatment and posttreatment S-Tg concentrations in patients with toxic diffuse goiter who relapsed, did not differ from those patients in remission. This was also true of patients with toxic nodular goiter. In both groups, however, there was a tendency towards higher pretreatment S-Tg values in patients who subsequently relapsed. Serial determinations of S-Tg, on the other hand, are of limited value in predicting the risk of recurrence, independent of which type of thyrotoxicosis is involved.

Buffer effect, secretion rate, pH and electrolytes of stimulated whole saliva in relation to the renin-aldosterone system.

The aim of this investigation was to study the relationship between the activity of the renin-aldosterone system and the buffer effect, secretion rate and electrolyte concentration of stimulated saliva in healthy subjects. Based on the results of previous salivary tests, 10 subjects with "low" (group A) and 10 subjects with "high" (group B) buffer effect and secretion rate of stimulated whole saliva were studied. Samples of stimulated whole saliva, blood and urine were collected on three occasions with one week intervals. For saliva, buffer effect, secretion rate, pH, Na+ and K+ concentrations, and Na+/K+ ratio were determined as were plasma renin activity (PRA), plasma concentration of aldosterone, and concentration of Na+ and K+ in serum, and Na+, K+ and creatinine in urine. The daily sodium and potassium intake was also calculated but did not differ between the groups. With the exception of K+ concentration, which was significantly higher, all salivary values of group A were significantly lower. In group A there was a relationship between PRA and plasma concentration of aldosterone, on the one hand, and buffer effect, secretion rate, and salivary K+ concentration, on the other. This relationship could not be demonstrated in group B. A possible explanation is that the higher secretion rate of the latter group obscured the effect of the renin-aldosterone system.

Hypercalcaemia induced by increased thyroxine substitution in a patient treated with dihydrotachysterol.

The metabolism of vitamin D is essential in the control of bone and mineral metabolism. Hyperthyroidism as well as hypothyroidism effect the metabolism of bone tissue and vitamin D. We present a dihydrotachysterol-calcium treated patient with post-operative hypothyroidism, who developed hypercalcaemia, when the thyroxine dosage was increased.

Effect of danazol on thyroid function in postmenopausal women.

During treatment with danazol the serum concentration of thyroxin-binding globulin (TBG) decreases. This effect is probably a direct effect on TBG production at the cellular level. In order to exclude an indirect effect on TBG production via the well known suppressing effect of danazol on serum estrogen concentrations, the following study was performed. Twelve healthy female volunteers, who were at least 3 years past the menopause and with serum-estradiol levels below 100 pmol/l, were treated with danazol in dosages of 400, 600 or 800 mg daily. The concentrations of TBG, TSH, total thyroxin (T4), total triiodothyronine (T3) and free dialysable fractions of T4 and T3 were determined, before, and after 2 and 4 weeks of medications. The serum concentrations of TBG, total T4 and T3 decreased. The TSH concentration and the free dialysable fraction of T4 were essentially unaltered after 2 weeks but the TSH had decreased slightly and free T4 increased slightly after 4 weeks. The free dialysable fraction of T3 decreased transiently at 2 weeks. All the observations proved to be independent of the three dosages of danazol applied in this study. In conclusion, danazol treatment influences available tests of thyroid function by reducing the concentration of TBG. This is most probably a direct effect of the drug, and it is clearly independent of the effect on estrogen production. Clinically there is no evidence of a decreased effect of thyroid hormones on the target organs.

Effects of penbutolol and metoprolol on blood pressure, plasma catecholamines and renin activity in hypertensive patients.

The effects of penbutolol 20-30 mg twice daily and of metoprolol 50-150 mg three times daily were studied in five and nine patients, respectively, with moderate hypertension. Both drugs significantly reduced blood pressure and pulse rate under basal conditions and in connection with exercise. Plasma catecholamine levels were not altered in supine or upright position, neither during penbutolol nor during metoprolol treatment. Following work there was an enhanced response in both plasma noradrenaline and adrenaline during penbutolol but only in plasma noradrenaline during metoprolol treatment. Both drugs effectively reduced basal plasma renin activity but only penbutolol abolished the renin response to work. Penbutolol significantly reduced urinary aldosterone excretion whereas metoprolol caused no significant changes. Neither penbutolol nor metoprolol affected maximal working capacity.

Unsuccessful DTIC treatment of a patient with glucagonoma syndrome.

Various chemotherapeutic modalities have been tried in the treatment of patients with malignant glucagonomas. Promising results have been reported after drug treatment with dimethyltriazenoimidazole carboxamide (DTIC). We present a patient with a metastasizing pancreatic glucagonoma, in whom treatment with neither DTIC nor with the combination of streptozotocin and 5-fluorouracil resulted in any noticeable improvement.

Pre- and postoperative studies in 72 hypertensive patients with renal artery stenosis, with special reference to renin activity and aldosterone.

Seventy-two patients, aged 6-69 years, were operated on because of presumed renovascular hypertension and subjected to follow-up studies for 4-60 months (mean 28). Unilateral renal artery stenosis was present in 47 patients. Surgery was followed by normalization of blood pressure (BP) in 28 and improvement in 7, whereas 12 showed no response. Sixteen were below the age of 40 and only one failed to respond to surgery. Peripheral venous plasma renin activity (PRA) was increased in 32 and urinary aldosterone elevated in 22 of 35 patients responding favourably to surgery. Renal vein PRA was higher from the kidney with the stenotic renal artery as compared to the contralateral side in all patients responding to surgery. Preoperative peripheral PRA difference was also found in 7 of 12 patients not responding to surgery. Preoperative peripheral PRA was increased in 26 of the patients becoming normotensive after surgery. In 20 of these patients normalization of BP was associated with a fall in peripheral PR. Twenty-five patients had bilateral renal artery stenosis. Four of them had severe hypertension, renal insufficiency and generalized atherosclerosis. They died in immediate connection with operation. Unilateral operation, performed in 11 of the remaining 21 patients, was followed by normalization of BP in 3 and no response in 8. Bilateral reconstructive surgery, performed in 10 patients, resulted in normotension in 2 and improvement in 7. Our studies indicate that determination of peripheral PRA and/or urinary aldosterone can serve as a useful prognostic indicator after surgery in hypertensive patients with renal artery stenosis.

Kinins in relation to kallikrein activity, kininogen, electrolytes, aldosterone and catecholamines in urine from normal individuals.

The object of the present study was to test the hypothesis that urinary kinin excretion is an indicator of intrarenal kinin formation and to investigate urinary excretion of kinins in relation to natriuresis, kaliuresis, diuresis and urinary aldosterone and catecholamines in normal individuals on a free salt and water intake. In freshly voided urine collected from 24 normal individuals kinin concentration was directly related to kallikrein activity. Kininogen concentration was very low and neither related to kallikrein activity nor to kinin concentration. The excretion rates of kinins and kininogen were unrelated to the time interval between micturitions. In 24 hour urine collections from 50 normal individuals the excretion of kinins was positively correlated to natriuresis, kaliuresis and diuresis and also to dopamine but not to aldosterone, noradrenaline and adrenaline. Kinin excretion was inversely related to age and was lower in women than in men. On the basis of these results it is concluded that urinary kinin excretion reflects intrarenal kinin formation in normal ambulatory individuals and that urinary kinins are formed mainly in the interstitial and vascular space of the kidney. Furthermore, kinins and dopamine seem to play a physiological role in the renal handling of electrolytes and water.

Streptozotocin treatment of a pancreatic tumour producing VIP and gastrin associated with Verner-Morrison syndrome.

A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.

Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome.

A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% "proglucagon". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the "proglucagon", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the "proglucagon". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria.

Effect of danazol on thyroid function in women.

A longitudinal study of thyroid function during danazol treatment was performed in 18 women. Serum concentrations of thyroid stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3), free T4-and free T3 index as well as thyroid hormone binding globulin (TBG) were measured before and during 6 months therapy. Thyroxine binding globulin showed a marked decrease to one third of the pretreatment level. All the hormones showed significant alterations within the normal ranges for this group. T3 and T4 decreased slightly and the free T4 and free T3 index showed an increase. TSH decreased from 2.4 +/- 0.6 to 1.7 +/- 0.3 mIU/l. The observed hormonal changes were most likely induced by the decreased TBG concentrations and were probably without pathological significance. However these changes must be kept in mind when thyroid function tests from patients with danazol are evaluated.

Unilateral renal artery stenosis and hypertension. II. Angiographic findings correlated with blood pressure response after surgery.

The findings at preoperative nephroangiography of 42 hypertensive patients with unilateral renal artery stenosis or occlusion were correlated with the blood pressure response following surgery and also with the preoperative renal vein renin activity ratio. A stenosis reducing luminal area by at least 90 per cent (or occlusion) and the presence of collateral circulation are considered to be highly suggestive of renovascular hypertension.

Bilateral renal artery stenosis/occlusion and renovascular hypertension. Correlation of angiographic findings with blood pressure response after surgery.

In a previous study of unilateral renal artery stenosis the angiograms of patients with a favourable blood pressure response after surgery were found to be characterized by a reduction of renal arterial lumen greater than or equal to 90% and/or renal collateral circulation. Ancillary features were post-stenotic dilatation and a reduction of kidney length greater than or equal to 1 cm (Andersson; Andersson, Bergentz, Dymling, Ericsson, Hansson & Hökfelt). This report deals with 32 patients with bilateral renal artery stenosis who were followed 6--54 months after operation. The preoperative angiograms were analysed retrospectively without knowledge of the blood pressure response. In patients with bilateral fibromuscular dysplasia a good correlation was found between the above-mentioned criteria and a favourable blood pressure respone. In patients with bilateral arteriosclerotic stenosis no correlation was found. It was concluded that renal angiography constitutes a valuable predictive test in bilateral non-arteriosclerotic stenosis. In the presence of bilateral arteriosclerotic stenosis the selection of patients for surgery should be based on other parameters such as kidney function, age and general vascular status of the patient.

Biochemical variables related to calcium metabolism in epileptics.

Five biochemical variables, S-Ca, U-Ca, S-P, U-P and S-ALP, all involved in calcium metabolism, have been investigated in 86 epileptics on long-term medication. We found hypocalciuria in half of the epileptics and increased S-ALP in one third. In contrast to earlier reports there was no hypocalcemia, whereas hypercalcemia was found in 7 epileptics. We have previously reported a high frequency of fractures in these epileptics. An increased fracture rate was found in the 13 epileptics with both hypocalciuria and increased S-ALP, indicating osteomalacia.