[Hypothyreodism. From the latent functional disorder up to coma]. / Hypothyreose. Von der latenten Funktionsstörung zum Koma.

An autoimmune thyroiditis represents the main reason of hypothyroidism, defined as a lack of thyroid hormone. This autoimmune process results in destruction of functioning thyroid follicles. While subclinical or latent hypothyroidism is defined on the basis of laboratory values (an elevation of TSH with normal peripheral hormone levels), the typical signs and symptoms are associated with hypothyroidism. In about 80% of cases antibodies against thyroid peroxidase can be measured, but only in about 40-50% of cases antibodies against thyroglobulin are detectable. If hypothyrodism has been diagnosed, substitution with levothyroxine should be initiated, with the therapeutic goal to decrease TSH level to the lower normal range. In cases of subclinical hypothyroidism, levothyroxine medication should be started in patients with a high TSH value, positive antibodies and/or the typical ultrasound of autoimmune thyroiditis. However, substitution with levothyroxine in any case of elevated TSH values should be avoided.

[Differential indications for thyroid gland operation]. / Differentialinkikation zur Schilddrüsenoperation.

Although the case for thyroid surgery is based on morphologic and physiologic criteria, it is mainly based on individual therapeutic goals. The goals are influenced by various biographic, medical and personal facts and by many environmental conditions. Thus, there is no rationale for cataloguing indications. With the euthyroid goitre the indication for surgery is usually given by the size of the thyroid gland, especially since it has become clear in various studies that with drug therapy the achievable size reduction is rather small. With Graves' disease the pros and cons of the three main methods, surgery, medical treatment or radioiodine, have to be considered in each case. Surgery is mainly indicated when the goal is a rapid and reliable normalization of the hormonal status. Thyroid autonomy is a clear-cut case for radioiodine. Only isolated autonomous nodules can equally well be treated by surgery. In addition, a case for surgery is given when besides the autonomy a large goitre is present. A special indication is iodine-induced thyrotoxicosis that cannot be normalized by medical treatment. All kinds of thyroid carcinoma, with very few exceptions, usually have to be operated on as the first choice.

Risk of iodine-induced thyrotoxicosis after coronary angiography: an investigation in 788 unselected subjects.

In this study, the risk of iodine-induced thyrotoxicosis in unselected patients from an iodine-deficient area was investigated. The patients were consecutively enrolled. Thyroid hormone values and urinary iodine excretion were determined before, as well as 1, 4 and 12 weeks after iodine contamination by coronary angiography. Two of 788 unselected patients developed hyperthyroidism within 12 weeks. The two patients did not belong to a risk group for iodine-induced thyrotoxicosis (i.e. old people, patients with goiter or possible thyroid autonomy, low TSH). Both patients had normal TSH levels at baseline and ultrasound of the thyroid was without evidence of nodules. The study shows that in euthyroid unselected patients from an iodine-deficient area short-term iodine contamination by contrast media rarely leads to hyperthyroidism. On account of these facts, prophylactic therapy, e.g. by perchlorate or thiamazole, is not generally recommended, because the risk of side-effects is perhaps even greater than the risk of iodine-induced thyrotoxicosis.

Hip fractures and the thyroid: a case-control study.

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 levo-thyroxine 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.

[A rare differential diagnosis of waddling gait--osteomalacia caused by vitamin D deficiency]. / Seltene Differentialdiagnose des Watschelgangs-Osteomalazie durch Vitamin-D-Mangel.

The so-called "waddling gait" caused by paresis or mechanical insufficiency of the hip muscles is an ambiguous clinical guiding symptom. This pelvifemorally accentuated muscular weakness coinciding with pain in the range of the locomotor system should make one consider the diagnosis of osteomalacia due to deficiency of vitamin D, especially in Asian patients. In the present case, the course of investigation is described in detail, as well as the effective therapy. The diagnosis of this clinical picture ought to be familiar to any neurologist, since its more frequent appearance must be expected as an increasing number of Asians seek asylum in the years ahead. Social integration of the affected persons may be made easier by treatment on the lines described here.

[Dietary iodine deficiency. Its consequences in the aged]. / Alimentärer Jodmangel. Seine Folgen für Personen im höheren Lebensalter.

Persisting dietary iodine deficiency in the Federal Republic of Germany is reflected in endemic goiter, in particular in the elderly. Among 581 over-60-year-olds, 48.8% revealed enlargement of the thyroid gland on sonography. Thyroid nodules were present in 101 cases, and a cystic lesion in another 43. Goiter is appreciably less responsive to levothyroxine in the elderly than in younger patients. The indication for initiating such medication should therefore be established on an individual basis. A specific problem of iodine deficiency goiter in the elderly is the increasing development with age of autonomously functioning nodules in the thyroid. Iodine contamination can induce thyrotoxicosis, which is often difficult to treat; in the individual case, thyroidectomy must be performed.

Treatment of iodine deficiency goiter with iodine, levothyroxine or a combination of both.

During recent years several studies have been published comparing different ways of pharmacological treatment of a goiter due to iodine deficiency. These studies usually were performed with 300 to 500 micrograms of iodine, 100 to 150 micrograms levothyroxine, or a combination of in most cases 100 micrograms levothyroxine and 100 micrograms iodine. The largest data have been accumulated in 166 patients with in most cases diffuse goiter. Group A (n = 61) received 150 micrograms levothyroxine per day, group B (n = 50) 400 micrograms iodine per day and group C (n = 55) a combination of 75 micrograms levothyroxine and 200 micrograms iodine per day. During the eight months of therapy, in all three groups a significant and comparable mean decrease in goiter size was documented (-32.1% in group A, -37.3% in group B and -38.7% in group C [n.s. between the three groups]). Striking differences between the three groups are evident in the changes of basal and thyrotropin releasing hormone (TRH) stimulated thyrotropin (TSH). In group A, after eight months a sharp and significant decrease of TSH occurred (from 1.2 mU/l to 0.4 mU/l; mean; p < 0.05), while in group B TSH showed only a minor decrease (from 1.3 mU/l to 0.9 mU/l) and remained significantly higher compared to both, group A and C (p < 0.01). Similar changes were documented when the TSH after TRH administration was calculated. It is concluded, that all three therapeutic approaches are effective for goiter reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of thyroid dysfunction in elderly subjects from the general population in an iodine deficiency area.

The prevalence of thyroid disorders was investigated in 466 (403 female, 63 male) subjects over the age of 60 years (79.2 +/- 7.5 years; mean +/- SD) from the general population in an area of iodine deficiency. In addition to thyroid hormone assays, thyroid antibodies and urinary iodine excretion were determined. In cases with thyroid dysfunction, ultrasound investigations were performed. Twenty-two of the 466 subjects (4.7%) showed hyper- or hypothyroidism; 7 subjects were hyperthyroid (1.5%), 5 had primary hypothyroidism (1.1%), and 10 showed "subclinical" hypothyroidism (2.2%). The latter constellation is defined as an elevation of thyrotropin (TSH) with normal values for thyroxine and triiodothyronine. Most subjects with hyperthyroidism had a goiter by palpation (6/7); thyroid volume by ultrasound (median) was 26.2 mL with an inhomogeneous echo pattern in 6 of the 7 subjects. In 4 cases, a rise in urinary iodine excretion was documented; none had TSH-receptor antibodies. Most subjects with overt or subclinical hypothyroidism had a homogeneous or low-echogenic pattern by ultrasound; thyroid volume (median) was 12.9 mL and 12.7 mL, respectively. By palpation, 8 of the 15 subjects had no goiter. In general, these persons had no rise in urinary iodine excretion (11/13), but most showed an elevation of antibodies against the microsomal antigen and/or thyroglobulin (11/15).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of surgical stress on the in vitro metabolism of thyroxine by rat liver, kidney, and brain.

In man, acute stress, like extensive surgery, leads to a rapid and prolonged decrease in serum T3 concentrations. The present study was carried out to investigate the mechanisms that underly the abrupt decrease in T3-neogenesis that occurs in response to acute surgical stress. Male Sprague-Dawley rats, surgically thyroidectomized, and treated with 1.2 micrograms T4/100 g BW/day, underwent wide vertical and horizontal incisions extending into the abdominal cavity while receiving light ether anesthesia. Different dietary manipulations were performed to investigate the superimposed influence of reduced carbohydrate and caloric intake on T3-neogenesis. The metabolism of 125I T4 labeled in its outer (phenolic) ring was investigated in liver, kidney, and brain homogenates of animals killed 48 h after surgery. In liver, values for the proportion of T4 degraded and the percent generation of T3 and iodide were unaffected by laparotomy. The percent T3 generation in experiments with 25 nM T4 concentration was 3.7 +/- 1.24% (mean +/- SD) in fed control animals given free access to 5% glucose, 3.4 +/- 0.67% in unoperated controls given a restricted amount of chow and 5% glucose, and 3.8 +/- 0.67% in operated animals given free access to chow and 5% glucose. As expected, T3 neogenesis in livers from unoperated animals was significantly reduced in rats fasted for 48 h and this reduction was similar in laparotomized rats fasted for 48 h after surgery. As in the liver, no effect of laparotomy on T4 metabolism in kidney and brain homogenates was observed. Finally, serum total T4 and T3 concentrations were not affected by surgery. It is concluded that acute surgical stress in thyroidectomized T4 replaced rats does not influence T4 metabolism in liver, kidney, and brain homogenates or affect the serum T4 and T3 concentrations. Since thyroid secretion of T4 (and T3) was eliminated and careful attention was paid to caloric intake in this rat model, previously reported abnormalities in serum thyroid hormone concentrations and T3-neogenesis in various states of nonthyroidal illness in man and rat, including surgery, are probably contributed to by thyroid secretion of T4 (and T3) and caloric deprivation, especially carbohydrate.

Thyroid volume and goitre prevalence in the elderly as determined by ultrasound and their relationships to laboratory indices.

In 569 unselected elderly subjects over 60 years from the general population of an iodine-deficient area, a palpation and an ultrasound investigation of the thyroid were performed. Additionally, thyroid hormone values were determined in 466 of the 569 subjects (81.9%) and urinary iodine excretion in 491 subjects (86.3%). By palpation, no thyroid enlargement was noticed in 302 subjects (54.2%), goitre Ia in 98 (17.6%), goitre Ib in 94 (16.9%), goitre II in 53 (9.5%), and goitre III in 10 (1.8%). The thyroid volumes (medians) by ultrasound were 18.6 ml in the entire group, in women (N = 489) 19.2 ml, and in men (N = 80) 16.6 ml. One hundred and one subjects had a thyroid nodule (17.6%), 43 persons cystic lesions (7.6%). If, according to the literature, a goitre is defined as a thyroid enlargement of more than 18 ml in women and more than 25 ml in males, a goitre prevalence of 54.2% in females and of 22.5% in males was obtained. The goitre prevalence in the entire group was calculated as 49.7%. Thyroid hormone measurements showed in subjects with goitre a significant lower TSH value (p less than 0.001) and a higher thyroglobulin value (p less than 0.001). In summary, the study shows a high prevalence of goitre in elderly subjects, a high prevalence of nodules in these thyroids, a negative correlation of goitre volume with TSH, and a positive correlation of goitre volume with the thyroglobulin concentration.

Evaluation of a new enzyme immunoassay system for free thyroxine (Enzymun-Test FT4).

Free thyroxine (FT4) represents the metabolically active fraction of the circulating thyroid hormone thyroxine (T4). In this paper the results of the evaluation of a newly developed FT4 assay are reported. This assay system is based on an enzyme-labelled one-step immunoassay. The within-run imprecision, checked using serum pools and several commercial reference materials, showed a coefficient of variation (CV) of between 0.8 and 9.8%, depending on the reference material used. The between-run imprecision showed a CV of between 1.0 and 13.2%. Accuracy experiments yielded values between 80 and 116%. When the new FT4 was compared with the calculation of an index for free thyroxine (FT4I; derived from either the ratio of T4/thyroxine binding coefficient of from T4/thyroxine binding globulin) in a number of samples in the hypo-, eu- and hyperthyroid range, a good correlation was obtained. The same was true when the new FT4 assay was compared with a widely used two-step radioimmunoassay (y = -0.146 + 0.943 x). In euthyroid subjects the measured FT4 concentration was 10.3-25.8 pmol/l. No effect was evident when the influence of EDTA and citrate was investigated, whereas addition of heparin led to an increase in FT4 concentration of about 12 to 15%. Investigation of the possible influence of a large number of drugs showed that probenezid, carbamazepine and furosemide led to an increase in the measured FT4 concentration. Dialysis increased the FT4 concentration, as measured in patients before and after haemodialysis. No effect of alteration in protein concentration and/or protein distribution of FT4 concentration could be detected. In pregnancy, FT4 values were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of endemic goitre due to iodine deficiency with iodine, levothyroxine or both: results of a multicentre trial.

Preliminary clinical studies and recent in vitro investigations suggest that iodine administration may be an effective alternative in the treatment of the diffuse euthyroid goitre of iodine deficiency. Therefore a 12-month multicentre study was initiated in which 166 patients were randomly assigned to take either 150 micrograms levothyroxine day-1 (group A, n = 61), 400 micrograms iodine day-1 (group B, n = 50), or a combination of 75 micrograms levothyroxine and 200 micrograms iodine day-1 (group C, n = 55) for 8 months with follow-up examinations at 4 and 8 months as well as 4 months after cessation of treatment. Initially, thyroid volume, as determined by ultrasound, was not significantly different in the three groups. In all three groups, during treatment a significant and comparable mean decrease in goitre size was documented (-32.1% in group A, -37.3% in group B, -38.7% in group C). After cessation of treatment in group A mean thyroid volume again increased to near the baseline value (-12.0% compared to the initial investigation), while the therapeutic effect was sustained in group B (-32.5%). In group C, only a slight rebound effect was observed (-26.3% vs baseline volume). Total thyroxine (T4) increased sharply and significantly in group A from 7.8 +/- 1.9 to 10.9 +/- 2.8 micrograms dl-1 after 8 months (P less than 0.001), but only slightly, although significantly in group B (from 7.8 +/- 1.5 micrograms dl-1 to 8.9 +/- 1.6 micrograms dl-1; P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)