The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

[Prospective study of determining the value of D-dimer in diagnosing pulmonary embolism]. / Prospektive Untersuchung zur Erfassung der Wertigkeit von D-Dimer in der Pulmonalembolie-(PE)-Diagnostik.

Pulmonary embolism (PE) is still misdiagnosed in a high proportion of cases. 107 patients admitted for suspected pulmonary embolism were studied prospectively to shed light on the value of ELISA-D-dimer and Latex-D-dimer. Pulmonary embolism was ruled out by negative perfusion scans in 66 patients (61.7%) and by angiography in 24 patients. 58% of the scans suggesting a high probability of PE were confirmed by angiography, but only 18% of the scans suggesting a low or intermediate probability of PE. Sensitivity and specificity were 88% and 79%, respectively for the D-dimer ELISA, versus 94% and 90% for the Latex agglutination test. The Latex test increased the positive predictive value of lung scanning suggesting low to intermediate probability of PE (group B) from 18% to 75% and that of lung scanning suggesting high probability of PE (group C) from 58% to 93%. The positive predictive value was improved by ELISA-D-dimer in both groups to 75%. In order to augment the diagnostic efficacy in clinical practice the determination of Latex-D-dimer simultaneously with lung scanning is recommended.

[Diagnosis of psoriatic osteoarthropathy: comparison of clinical, radiologic and scintigraphic findings]. / Zur Diagnose der Osteoarthropathia psoriatica: Gegenüberstellung von klinischen, radiologischen und szintigraphischen Befunden.

Among the group of seronegative spondarthritides psoriatic osteoarthropathy can be differentiated from rheumatoid arthritis as a separate disease with generalized osseous proliferation. 33 cases were evaluated and clinical data, X-ray films and nuclear bone scans were compared. Pathological alterations in the bone structure can be found by bone scintigraphy already at very early, even subclinical stages of the disease, thus allowing early diagnosis. In a high percentage of our cases pathological alterations could be demonstrated by scintigraphy long before they were revealed on X-ray films. Scintigraphic methods may help to evaluate the activity of the disease. Furthermore, in many of our cases, localization and concentration of the tracer in the skeleton were so typical, that they may be considered pathognomonic for psoriatic osteoarthropathy. Thus bone scanning appears to be a useful tool for the diagnostic evaluation and follow up in cases of psoriatic arthropathy, in particular if the low exposure to radiation is taken into account.

Familial thyroxine-binding globulin deficiency in association with non-toxic goitre.

A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 microgram/ml; normal range 12.5--26.0 microgram/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.

The pharmacokinetics of digoxin in patients with manifest hyperthyroidism and after normalization of thyroid function.

The pharmakokinetic data (elimination half-life, apparent distribution volume, total and renal clearance and cumulative urine excretion) were determined after intravenous administration of 1 mg digoxin in 9 female patients with an average age of 52 +/- 15 years with manifest hyperthyroidism. The study protocol was repeated after normalization of thyroid function by means of conventional thyrostatic therapy. Digoxin was determined by radioimmunoassay.

Hypergonadotrophic male pseudohermaphroditism due to complete 17-alpha-hyroxylase deficiency.

This is a case report of a 43 years old phaenotypic female (karyotype 46 XY) with congenital adrenal hyperplasia and male pseudohermaphroditism presenting with severe hypertension and hypokalaemic alkalosis. Evaluation of the steroid biosynthesis of the adrenals as well as of the intraabdominal testes demonstrated a severe degree of 17-alpha-hydroxylase deficiency in this patient. This defect was associated by a complete lack of deoxycortisol and cortisol as well as of testicular testosterone synthesis, and by an overproduction of DOC and corticosterone. Sruvival of the patient in spite of severe cortisol deficiency was due to the glucocorticoid activity of corticosterone. This compound and DOC account also -- due to their mineralocorticoid properties -- for the hypertensive state of this male pseudohermaphrodite.

ACTH and cortisol responses to glucagon stimulation.

The effect of the intramuscular injection of various doses of glucagon in 15 healthy subjects was studied. Significant elevations of plasma ACTH, and cortisol were found to occur 3 h after the administration of 4 mg of crystalline glucagon. Mean levels in 7 subjects were for ACTH 44 +/- 30 (SD) pg/ml, and for cortisol 14 +/- 6 (SD) mug/100 ml at the beginning of the test, and rose to 109 +/- 48 (SD) pg/ml and to 23 +/- 5 (SD) mug/100 ml respectively following glucagon. The peak response of ACTH and cortisol was preceded by a significant rise of plasma insulin, by a fall of the blood glucose, which was initially increased by the administration of glucagon, and by the symptoms of nausea and sweating. This study demonstrates that the intramuscluar administration of glucagon (4 mg) provids a potent stimulus to ACTH and cortisol secretion in healthy subjects.

Effect of iodine upon the TRH induced release of TSH in euthyroid, hypothyroid and hyperthyroid individuals.

The effects of prolonged administration of iodide upon the serum concentrations of thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) and their response to thyrotropin releasing hormone (TRH, 400 mug i.v.) have been studied in euthyroid (n = 9) subjects, and in hypothyroid (n = 4) patients. Administration of iodide (25 mg daily for two weeks) increased in healthy subjects the basal concentrations of TSH and the release of TSH in response to TRH (p less than 0.05-0.01). Serum concentrations of T4 and T3 were reduced (T4, 6.5 +/- 0.2 mug/100 ml to 5.9 +/- 0.3 mug/100 ml; T3, 159 +/- 8.3 ng/100 ml to 145 +/- 7.3 ng/100 ml) in parallel. Responses of T4 but not of T3 to TRH were also reduced after iodide. Two out of four hypothyroid patients also showed an increased response of TSH to TRH. Changes in serum T4 and T3 were due to their low basal concentration not measureable in this group. No response of TSH, T4 or T3 to TRH was observed in hyperthyroid patients either before or after iodide treatment (708 mg daily for one week), in spite of a fall in serum T4 (25%) and T3 (50%) upon iodide administration. These observations demonstrate that small changes in serum T4 and T3 are easily monitored by the thyrotrophs in the normal or in the hypothyroid range. Conversely a reduced sensitivity of the anterior pituitary upon the administration of TRH is found in hyperthyroid patients, since even large reductions in serum T4 and T3 do not facilitate an increased response of TSH to TRH in this group.

[The effect of iodide on the TRH-induced release of HTSH, T4 and T3 in euthyroid subjects (author's transl)]. / Der Einfluss von Jod auf die TRH-induzierte Ausschüttung von TSH, Trijodthyronin und Thyroxin euthyreoter Personen

Prolonged administration of 25 mg iodide per day to euthyroid subjects caused an increased release of HTSH in response to the i.v. administration of TRH. This effect was significant (p less than 0.01) intraindividually in eight out of nine subjects. The maximum serum HTSH level was observed twenty minutes after the administration of TRH. It reached 8.0 +/- 1.7 muU/ml during the control period and increased to 11.6 +/- 1.6 muU/ml after two weeks of 25 mg iodide per day. Basal serum concentrations of HTSH remained unchanged (p less than 0.05) and were 1.2 +/- 0.3 muU/ml before, and 1.7 +/- 0.3 muU/ml after iodide ingestion. Basal serum T4 concentrations and T4 release were diminished after prolonged administration of iodide in the nine subjects on the basis of an intraindividual comparison. Serum triiodothyronine showed a similar behavior as far as basal conditions were concerned, but no difference was observed for the peak levels of T3, which were obtained 2 to 3 h after injection of 400 mug TRH. The obtained data show that the prolonged ingestion of iodide induces a relatively hypothyroid state with an increased release of HTSH in response to the injection of TRH. This effect is paralleled by a decreased secretion of thyroxine and, to some extent, of triiodthyronine. The Wolff-Chaikoff effect, which is induced by the administration of excess iodide, appears to be the cause of the observed increase in TSH secretion upon TRH administration in iodide-treated subjects.

[The clinical significance of the radioimmunological determination of plasma ACTH (author's transl)]. / Die klinische Bedeutung der radioimmunologischen Bestimmung von ACTH

The clinical significance of the direct determination of plasma ACTH was investigated in healthy persons and in patients with primary or secondary adrenocortical insufficiency, with Cushing's syndrome or with acromegaly. The sensitivity of the radioimmunological method facilitated the detection of diurnal changes in plasma ACTH in healthy subjects and of variations in plasma ACTH after the administration of dexamethasone and glucagon. The determination of plasma ACTH appears to be a useful procedure of diagnostic value in patients suffering from primary adrenal insufficiency accompanied by high concentrations of plasma ACTH. However, in patients suffering from Cushing's syndrome or secondary adrenocortical insufficiency it is still essential to carry out the dexamethasone suppression test or the metopiron test, respectively.

[Hypoglycaemic coma in Boeck's sarcoidosis (author's transl)]. / Hypoglykämisches Koma bei Boeckscher Sarkoidose

The diversity of clinical manifestations of Boeck's sarcoidosis may also include endocrine disorders. One year after diagnosis of sarcoidosis in a 29 year-old female patient, endocrinological complications became manifest with amenorrhoea. The course of the disease was additionally complicated by hypoglycaemic episodes. Thorough clinical investigation of the patient revealed sarcoid involvement of the skin, lungs, liver and lymph nodes and an extensive retroperitoneal surgically-verified lymph tumour. After tolbutamide and in reaction to an intravenous glucose tolerance test the blood glucose was found to be very low, whilst the immunoreactive insulin was normal. Further investigation of the endocrine functions of the patient revealed normal functioning of the thyroid gland, subnormal values for the follicle stimulating hormone and extremely low serum ACTH and serum cortisol values, without any diurnal changes in these parameters. The clinical symptoms of the patient and the biochemical findings were regarded as manifestations of secondary adrenal failure due to sarcoid involvement of the hypothalamus and pituitary. Hence, treatment with corticosteroids was started. Hypoglycaemia has not since been observed in this patient and the other clinical features of (secondary) adrenal failure have disappeared slowly.