Diseases of the thyroid are very common and in Germany one out of three adults has a goiter or thyroid nodules. Thyroid dysfunction, including its subclinical forms is found in up to 6% (hyperthyroidism) and up to 10% (hypothyroidism) of the population, respectively. The aim of a structured approach to patients is to obtain a diagnosis by evaluating morphological findings, thyroid dysfunction, signs suggestive of autoimmune disease or inflammation and accompanying disorders (notably, thyroid-associated orbitopathy). Euthyroid goiter and benign thyroid nodules may benefit from supplementation with iodine and thyroxine. Differentiated thyroid carcinoma is treated by thyroidectomy and subsequent radioiodine ablation. Antithyroid drugs are the primary treatment for Graves' disease. Many cases of autoimmune thyroid diseases require thyroxine treatment.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Die Funktion der Nebenschilddrüsen wird durch die Änderung der Calcium-, Magnesiumund Phosphatspiegel reguliert (8, 11, 13). In den letzten 2 Jahren wurde häufiger über Versuche berichtet, eine Nebenschilddrüsenüberfunktion medikamentös auch mit Cimetidin zu beeinflussen. Zu diesem Thema entwickelte sich eine lebhafte, zum Teil kontroverse Korrespondenz, die sich überwiegend in Leserbriefen und Veröffentlichungen in den Zeitschriften »The Lancet* und »New England Journal of Medicineniederschlug. Wegen der widersprüchlichen Berichte aus verschiedenen Arbeitsgruppen erscheint es angebracht, den jetzigen Stand der Ergebnisse zusammenzufassen, um kritisch die Frage zu prüfen, ob mit dem Histamin2-Antagonisten Cimetidin eine medikamentöse Behandlung des Hyperparathyreoidismus möglich ist.

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.

BACKGROUND:Iodine deficiency (even moderate) plays a major role in pregnancy associated goiter development, which is only party reversible after pregnancy. The prevalence of post partum thyroiditis is reported to be slightly lower in areas of iodine deficiency. Thus iodine supplementation may be effective in decreasing pregnancy associated increase in thyroid volume, but enhances the risk of increasing the prevalence of thyroid dysfunction in the post partum period. Therefore, we evaluated the effect of iodine supplementation (with two different doses: 50 microg and 250 microg) on the prevalence of post partum thyroiditis and the decrease in thyroid volume up to 8 months post partum in an area of mild iodine deficiency.PATIENTS AND METHODS:Thyroid volume of 56 women was evaluated 5 days and 3 months after delivery (study I). In an intervention study (Study II) 70 women were randomized to receive 50 or 250 microg of potassium iodide for a period of 8 months post partum beginning five days after delivery. Thyroid volume, the echogenecity of the thyroid gland, thyroid hormone parameters (T4, T3, fT4, TSH) and thyroid antibodies (TPO and Tg-Ab) were measured 5 days, 3 and 8 months after delivery.RESULTS:A total number of 11 women developed postpartum thyroid dysfunction: 4 women developed manifest thyroid dysfunction (3 hyperthyroidism and 1 hypothyroidism) 3 months post partum. The remaining seven had subclinical hypo- or hyperthyroidism. All changes were clinically mild and transient as evidenced by normalization of thyroid hormone parameters on reexamination at 8 months. Among the eleven, 6 women in the 50 microg iodine group and 5 women of the 250 microg iodine group developed thyroid dysfunction, suggesting that the iodine dose did not affect post partum thyroiditis. The administration of only 50 microg iodine was associated with a significant fall of thyroid size already 3 months after delivery (25.4 +/- 1.5 ml (mean +/- sem) to 18.2 +/- 1.25 p <0.001). The application of 250 microg iodine was equally effective. 8 months post partum a slight but further decrease could be demonstrated. On the other hand, in study I no significant reduction in thyroid volume was observed in women receiving no supplementary iodine (thyroid volume at delivery 29 +/- 2.2 ml; at 3 months 27.5 +/- 3.0 ml.CONCLUSION:The administration of supplementary iodine (up to 250 microg) to an unselected population, residing in an area of mild iodine deficiency, in the post partum period is save as indicated by a prevalence of 5.7% manifest thyroid dysfunction. These changes are clinically mild and transient. Even the amount of 50 microg of iodine supplementation seems to by very efficient in reducing pregnancy associated increments in thyroid volume.

OBJECTIVE The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease.DESIGN Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37 and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome.PATIENTS Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required.MEASUREMENTS At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins.RESULTS The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echo-structure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group).CONCLUSIONS The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.

UNLABELLED:Many studies have been carried out evaluating thyroid hormone parameters in patients suffering from various illnessess. However data on thyroid function after a recreation period are missing. Therefore we evaluated thyroid hormone parameters in 178 patients (mostly suffering from chronic obstructive lung disease) undergoing a four week recreation period in a health spa on the island Borkum at the North Sea. We observed a subtle, but significant increase in basal TSH concentrations from 1.20 mU/l (median) to 1.50 mU/l; (p<0. 001) and a fall in T4 values from 97.5 +/- 17.7 nmol/l (mean +/- SD) to 90.3 +/- 17.0 (p<0.001) and T3 from 2.21 +/- 0.33 nmol/l to 2.09 +/- 0.33 (p<0.001). However no increase in iodine intake occurred during the four weeks: median iodine excretion 61 microg iodine/g creatinine at the beginning vs 65 microg iodine/g creatinine at the end.IN CONCLUSION:a recreation period at the North Sea is associated with subtle but significant changes in thyroid hormone parameters. However no increase in iodine intake occurs during the four week observation period.

SummaryOBJECTIVE A variety of regimens continue to be used In the treatment of Graves' disease with antithyrold drugs. We have lnvestigated the factors which determine the initial response to methimazole (time until euthyroidism Is achieved) In Graves' disease.PATIENTS Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months.MEASUREMENTS Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary Iodide excretion were measured centrally. Twenty‐minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, Index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase.RESULTS Within 3 weeks, 40.2% of patients responded to 10mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroldism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), Index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed In patients with large goitres, iodine excretion of ≧ 100μg/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10‐mg group, 46% of patients were euthyrold within 3 weeks when urinary Iodide was <50μg/g of creatinine, and only 27% when iodide was above 100μg/g. By stepwise logistic regression, the main factors for the response to methimazole were dally dose, pretreatment T3 levels, and goitre size. CONCLUSION Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole In Graves' disease, at least In areas comprising low, subnormal and normal iodine supply.

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.

We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5–30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23000±13 600 mU/1 (range 1500–141000 mU/1; 20 mU/l=1 μg/1) by 37 ± 11 % after 1 week, by 49±9% after 4 weeks, and by 65±11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20–25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.

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.

Objectives. To review factors associated with development of osteoporosis in patients with rheumatic diseases, as well as the preventive and therapeutic measures.Design. A MEDLINE literature search.Results. 1 Pathogenesis. Rheumatoid arthritis in itself causes reduction of bone mass; this process can be aggravated by glucocorticoid treatment. With glucocorticoid treatment, bone mineral density decrease is most pronounced during the first months of treatment. There is no agreement on the effects of daily dose, cumulative dose, and duration of glucocorticoid treatment on the rate of bone loss. However, with treatment by low doses (< 10 mg of prednisone equivalent per day), bone loss appears to be minimal or even undetectable compared to controls. Alternate day treatment, or treatment with steroid 'pulses' have not been shown to protect from bone loss. 2 Prevention and treatment. Prophylactic and therapeutic measures for glucocorticoid-induced osteoporosis include calcium supplementation, vitamin D in physiological doses and oestrogen in perimenopausal female patients. Efficacy has not always been shown in this particular indication but is extrapolated from other forms of osteoporosis. Limited data exist on treatment with anabolic steroids, calcitonin (with an additional analgesic effect) and biphosphonates and reduction of fracture rates has not yet been investigated. At present, there is insufficient evidence to show that altered steroid molecules can dissociate adverse effects on bone from clinically desirable effects.Conclusion. In view of the paucity of study data, prophylaxis and therapy of glucocorticoid-induced osteoporosis should receive more attention in future clinical studies.

SummaryOBJECTIVE We investigated the effect of intramuscular injections of long‐acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS Thirty patients with PRL‐secreting pituitary macroadenomas were treated with repeated 4‐weekly intramuscular injections of 50 or 100 mg of a long‐acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n= 7), oral bromocriptine (7), and pituitary Irradiation (2). MEASUREMENTS A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection therafter. RESULTS In all patients PRL was suppressed from a mean ± SEM pretreatment level of 32 620 ± 8680 to 4480 ± 1140 mU/l on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/l) with the first to fourth injection, in three additional patients PRL levels normalized after 8–15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean SEM) decreased to 66 ± 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side‐effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0 6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site.CONCLUSION We conclude that long‐acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long‐term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.

Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression).

We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50–100 mg depot-bromocriptine at 4-week intervals for 3–24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 ±12.3 μg/l (mean ± SEM) to 19.4 ± 4.7 μg/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.