: Thyroid volume on ultrasound and urinary iodine excretion in relation to creatinine excretion were determined in 252 children (130 boys, 122 girls; mean age 8.7 [2-16] years) from the central Ruhr area of Germany. The data were compared with those published for children of other regions of Germany and Sweden. Mean thyroid volume in the 2-year olds was 2.0 +/- 0.5 ml, in 4-year olds 2.9 +/- 1.1 ml, in 6-year olds 4.2 +/- 1.9 ml, in 9-year olds 5.2 +/- 1.3 ml and in 13-year olds 8.7 +/- 2.4 ml. Mean iodine excretion for the whole group was 101.0 +/- 41.5 micrograms iodine/g creatinine, in the 13-year olds it was 69 +/- 27 micrograms/g. These values are clearly below those of Swedish children on an adequate iodine intake. The thyroid volume measurements agree reasonably well with those published for children in the region of Germany and are clearly above those of the Swedish children. In 69% of cases the thyroid volume was more than 3 S.D. above the mean for Swedish children. The reported data support the demand for a higher iodine intake of the German population.

From 1980 to 1989, 226 patients (199 females, 27 males, median age 41 [18-76] years) underwent surgery because of clinical hyperthyroidism. 152 patients had autoimmune thyrotoxicosis, and 74 functional autonomy. Histological examination of resected thyroid tissue revealed carcinoma in 6 cases (2.6%): 3 (2%) in autoimmune hyperthyroidism, and 3 (4%) in functional autonomy. Five tumours fulfilled the criteria for occult papillary thyroid carcinoma (highly differentiated, less than 1.5 cm diameter). One woman had both a multilocular papillary carcinoma and a medullary carcinoma without proven metastases. In none of the cases was a malignant tumour suspected preoperatively from sonography or scintigraphy studies. In the patients with occult carcinomas, extended bilateral subtotal resection was regarded as curative. In the patient with papillary and medullary carcinoma, remaining thyroid therapy was given. One patient with Basedow's (Graves') disease and a papillary carcinoma of diameter 1.3 cm received radioiodine at her own request. She and the four remaining patients received suppression therapy (150-200 micrograms L-thyroxine daily), with frequent follow-up. During follow-up for a mean period of 24 months (range 6-51 months) there were no metastases or tumour recurrences.

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.

Since in the literature basophilia is frequently related to myxedema, we evaluated basophilic leukocytes in patients with hypothyroidism, applying routine techniques used in clinical laboratories. The study included normal persons, untreated patients with hypothyroidism, and euthyroid subjects with hyperlipidemia. The number of circulating basophils was determined by differential counts of Pappenheim stained blood smears. No difference in relative and total basophil counts was detected in patients with hypothyroidism as compared to healthy controls (1.0% and 58.1 basophils/μl vs. 0.8% and 50.8 basophils/μl, respectively). The percentage of basophils in myxedema associated with hypercholesterolemia amounted to 1.0%, their absolute number to 57.6/μl; in hypothyroid patients presenting normal serum cholesterol levels, the relative and absolute numbers of basophilic leukocytes was not statistically different (0.83% and 61.1 basophils/μl, respectively). We conclude that in patients with hypothyroidism the number of basophils is not statistically different from the values of basophils in healthy controls. Furthermore, the number of peripheral blood basophils in hypothyroidism is not related to the serum cholesterol level.

The postoperative period after cardiac surgery with cardiopulmonary bypass (CPB) is associated with a low T3 syndrome, i.e. low T3 and fT3 concentrations in the presence of normal T4 and TSH concentrations. So far, results from studies evaluating thyroid function during and after CPB are rather conflicting. We therefore evaluated prospectively thyroid function in 28 patients before, during and up to 3 days after coronary artery bypass surgery. We could demonstrate the most significant changes in thyroid hormone concentrations on day 1 after CPB (low T3 and fT3 concentrations, elevated rT3 concentrations in the presence of a significant fall of TSH). T3 fell from 1.93 to 0.6 nmol/l and fT3 from 5.5 to 1.42 pmol/l. Those patients with low cardiac output syndrome after surgery had significantly lower T3 concentrations than patients without this complication. Moreover, those patients, who already had significant lower T3 values prior to CPB, also demonstrated low T3 concentrations on day 1 after CPB. Cortisol usually has a suppressive effect on TSH secretion. However, the effect of cortisol on TSH in patients undergoing CPB seems to be not that important: those patients with high endogenous cortisol concentrations on day 1 after CPB had similar TSH values to those patients with only slightly elevated cortisol concentrations. Also, the application of high doses of catecholamines seems to have only minor effects on TSH secretion, because those patients requiring high doses of dopamine over a prolonged time period had essentially the same TSH values after CPB. Patients who had been exposed preoperatively to high doses of iodine did not demonstrate significantly different thyroid hormone concentrations. In conclusion: We could demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those patients with low T3 concentrations prior to surgery demonstrate postoperatively a more severe degree of nonthyroidal illness (NTI). Catecholamines and cortisol seem to have only minor effects on the TSH secretion after CPB. The influence of a previous iodine contamination is negligible.

Among 334 neck explorations for primary hyperparathyroidism (pHPT) between 1979 and 1993 120 (33,9 %)thyroid operations were performed simultaneously. Histologic examination revealed 40 thyroid adenomas, 43 nodular goiters, 8 thyroiditis and 9 differentiated carcinomas. In 20 cases the indication was doubtful retrospectively, as evaluated by postoperative histology. Of the 9 carcinomas there were 4 small papillary, 3 papillary pT(2) No Mo and 2 follicular pT(2) No Mo.Perioperative morbidity of the simultaneous operations was not significantly increased compared to the parathyroid exploration alone. We conclude, that pre- and intraoperative thyroid examination should be performed in pHPT and decision for a simultaneous operation should be made generously.

Among 334 neck explorations for primary hyperparathyroidism (pHPT) between 1979 and 1993 120 (33.9%) thyroid operations were performed simultaneously. Histologic examination revealed 40 thyroid adenomas, 43 nodular goiters, 8 thyroiditis and 9 differentiated carcinomas. In 20 cases the indication was doubtful retrospectively, as evaluated by postoperative histology. Of the 9 carcinomas there were 4 small papillary, 3 papillary pT2 No Mo and 2 follicular pT2 No Mo. Perioperative morbidity of the simultaneous operations was not significantly increased compared to the parathyroid exploration alone. We conclude, that pre- and intraoperative thyroid examination should be performed in pHPT and decision for a simultaneous operation should be made generously.

Objective. To investigate the prevalence of thyroid illness - especially hyperthyroidism - and exposure to thyroid hormones in patients with hip fracture.Design. A case-control study.Setting. Two surgical/orthopaedic hospital units and 22 facilities for the aged in a moderately iodine-deficient region of Germany.Subjects. A total of 116 postmenopausal females with hip fracture and 402 postmenopausal female controls.Main outcome measures. Hip fracture; thyroid disease confirmed by measurement of serum thyrotropin, total and free thyroxine and triiodothyronine; history of thyroid disease and thyroid medication obtained by a questionnaire.Results. Of the hip fracture patients 4.3% had overt untreated hyperthyroidism, and 6.9% gave a history of past hyperthyroidism (total, 11.2%), The corresponding figures for the controls were 2.0 and 2.7%, respectively (total, 4.7%). 7.8% of the cases had been exposed to levo-thyroxine for 3-29 years, compared to 11.2% of the controls. The odds ratio for hyperthyroidism (present and past) was 2.5 (1.2-5.3, 95% confidence interval), and the odds ratio for levothyroxine exposure was 0.67 (0.32-1.41) in the hip fracture patients.Conclusions. Hyperthyroidism is found 2.5-fold more often in hip fracture patients than in controls. Hence, hyperthyroidism appears to be a significant risk factor for hip fracture and should be investigated by clinical and, when necessary, laboratory means in hip fracture patients. In contrast, no increased risk for hip fracture could be detected after exposure to levothyroxine.

There is no agreement as to whether or not drug treatment after surgery for nodular goiter is effective in preventing recurrence of goiter. Data about recurrences in areas of marginally low iodine intake (like Germany) vary widely. Therefore, we performed a retrospective study in 104 patients who had been treated surgically because of benign uninodular or multinodular goiter. The mean follow-up period was 6.4 years (minimal 1 year) with at least three examinations. Thyroid ultrasound with volumetric analysis was recorded in each patient. Thirty-two patients did not receive any prophylaxis, 50 patients were treated with L-thyroxine, 17 patients with a combination of L-thyroxine and iodine and 5 patients with iodine alone. Recurrence of goiter was documented in 28.0% of the untreated patients and in 8.9% of the patients on prophylaxis (P < 0.05). The mean increase of thyroid volume was 7.3 ml versus 3.1 ml in patients without versus with prophylactic drug treatment (not significant). No significant correlation was found between the increase of thyroid volume and age of the patients, follow-up time, or intial thyroid volume, respectively. These data clearly demonstrate the effectiveness of prophylactic drug therapy to prevent recurrence of goiter after thyroid surgery in an iodine-deficient area.

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 μg/l (normal <0.2) and within 2 days 3 × 200 μg octreotide daily suppressed plasma glucagon to 2.2–2.5 μg/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal <0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very highdosesof octreotide (4 × 600 μg/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.

The frequency, predisposing factors and course of agranulocytosis (granulocytes <250/µl) secondary to antithyroid drugs were studied in a cohort of 1256 continously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0–0.44%). This prevalence appers to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thiyonamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug-induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3±19.7 vs 34.3±29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23–55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5–31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose. Physicians should be aware of this potentially serious complication particularly during this period. A reduction of traditionally prescribed thionamide doses seems quite possible and might lead to considerable reduction of adverse reactions. In severe cases, a trial of recombinant human granulocyte/macrophage colony stimulating factor should be considered.

Article Ein wissensbasiertes System zur Befundung von Schilddrüsenhormonwerten: Studie in fünf Kliniklaboratorien zur Bewertung und Optimierung des Systems Pro.M.D.-SD) was published on January 1, 1994 in the journal Journal of Laboratory Medicine (volume 18, issue 12).

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 mu g/l (normal <0.2) and within 2 days 3x200 mu g octreotide daily suppressed plasma glucagon to 2.2-2.5 mu g/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal <0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A. and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4x600 mu g/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.