Subclinical hypothyroidism: deciding when to treat

While screening patients for thyroid disease, physicians often find increased thyrotropin-stimulating hormone (TSH) levels in patients whose free thyroxine (T4) levels are not below normal. This state, termed "subclinical hypothyroidism," is most commonly an early stage of hypothyroidism. Although the condition may resolve or remain unchanged, within a few years in some patients, overt hypothyroidism develops, with low free T4 levels as well as a raised TSH level. The likelihood that this will happen increases with greater TSH elevations and detectable antithyroid antibodies. Because patients with subclinical hypothyroidism sometimes have subtle hypothyroid symptoms and may have mild abnormalities of serum lipoproteins and cardiac function, patients with definite and persistent TSH elevation should be considered for thyroid treatment. Levothyroxine, in a dosage that maintains serum TSH levels within the normal range, is the preferred therapy in these patients.     

Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians

PURPOSE: To review information on the benefits of screening with a sensitive thyroid-stimulating hormone (TSH) test for thyroid dysfunction in asymptomatic patients seeking primary care for other reasons. This paper focuses on whether screening should be aimed at detection of subclinical thyroid dysfunction and whether persons with mildly abnormal TSH levels can benefit. DATA SOURCES: A MEDLINE search for studies of screening for thyroid dysfunction and of treatment for complications of subclinical thyroid dysfunction. STUDY SELECTION: Studies of screening with thyroid function tests in the general adult population or in patients seen in the general office setting were selected (n=33). All controlled studies of treatment in patients with subclinical hypothyroidism or subclinical hyperthyroidism were also included (n=23). DATA EXTRACTION: The prevalence of overt and subclinical thyroid dysfunction, the evidence for the efficacy of treatment, and the incidence of complications in defined age and sex groups were extracted from each study. DATA SYNTHESIS: Screening can detect symptomatic but unsuspected overt thyroid dysfunction. The yield is highest for women older than 50 years of age: In this group, 1 in 71 women screened could benefit from relief of symptoms. Evidence of the efficacy of treatment for subclinical thyroid dysfunction is inconclusive. CONCLUSIONS: Even though treatment for subclinical thyroid dysfunction is controversial, office-based screening to detect overt thyroid dysfunction may be indicated in women older than 50 years of age. Large randomized trials are needed to determine the likelihood that treatment will improve quality of life in otherwise healthy patients who have mildly elevated TSH levels.     

Medical treatment of multinodular goiter

Thyroid nodules are among the most common clinical problems in endocrinology. Among several factors responsible for the development of goiter, circulating TSH plays a major role because of its direct growth-promoting effects on the thyroid cells; moreover TSH may enhance the effects of other local growth factors which act in a paracrine mode in the thyroid gland. In addition, autoimmune thyroiditis can clinically appear as thyroid nodules frequently with the functional aspect of a subclinical hypothyroidism. For these reasons a therapeutical approach based on the thyroxine suppression of TSH secretion has become largely used by 1970s and is correctly employed in 75% of the patients with thyroid nodules whose biopsies result benign.     

Molecular analysis of p21 and p27 genes in human pituitary adenomas

OBJECTIVES: To determine the prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town and to assess the usefulness of an abnormal thyroid-stimulating hormone (TSH) concentration as a screening test in this group. DESIGN: Cross-sectional survey. SETTING: Four old-age homes in Cape Town. SUBJECTS: Old-age home residents aged 60 years and over. OUTCOME MEASURES: Serum concentrations of TSH, free thyroxine and free tri-iodothyronine. RESULTS: Serum TSH estimations were performed on 658 participants, and were abnormal in 103 (15.6%)-41 (6.2%) being elevated (> 5.0 microU/ml) and 62 (9.4%) being low (> 0.4 microU/ml). There were 3 newly diagnosed cases of hyperthyroidism and 7 of hypothyroidism. Subclinical disease was diagnosed in 40 subjects. The overall prevalence of thyroid dysfunction in this population was 11.2%. In 22 (3.4%) this had previously been recognised, while in 50 (7.8%) the dysfunction was newly diagnosed by the current survey. The positive predictive value of a TSH concentration > 20 microU/ml in predicting hypothyroidism is 67%, while it will predict 100% of cases of subclinical hypothyroidism. A TSH concentration < 0.1 microU/ml will predict 23% of cases of hyperthyroidism, but 81% of cases of subclinical disease. CONCLUSIONS: The prevalence of thyroid dysfunction in institutionalised elderly people in Cape Town is similar to that reported for elderly people in other centres. Thyroid dysfunction had not previously been recognised in approximately two-thirds of the subjects in this study. The serum TSH concentration is a reliable screening test for thyroid dysfunction in the elderly, but is less useful if used to identify biochemical thyroid disease. An elevated TSH concentration is a better predictor of thyroid dysfunction in the elderly than a depressed TSH concentration.     

Subclinical prenatal iodine deficiency negatively affects infant development in Northern China

Although mild-to-moderate levels of iodine deficiency (ID) have been associated with poor cognitive outcomes in children, little is known about subclinical prenatal ID and infant development. In this study, the association between elevated cord blood thyroid stimulating hormone (TSH, thyrotropin) and infant development was examined in Northern China. Three groups of infants with elevated cord blood TSH were compared with infants with normal TSH levels on an information processing task at 7 mo, and in cognitive and motor developmental assessments at 13 mo. Infants with elevated TSH had poorer information processing skills and lower scores on the cognitive development index. There were no differences in motor abilities. Relationships between socioenvironmental factors and iodine status were assessed. Infants from more rural settings and those whose mothers had completed fewer years of schooling and had lower paying occupations had higher cord blood TSH levels. A regression analysis indicated that maternal education was predictive of cognitive performance among infants with elevated TSH but not control infants. The findings suggest that subclinical prenatal ID has negative effects on infant development and that, in some instances, maternal education may ameliorate these effects.     

Modern diagnostic methods for thyroid gland diseases]

The paper overviews the role of diagnostic procedures in evaluating patient with thyroid gland disease. It focuses on the diagnostics of functional disturbances and on the modern approach to the nodular goitre. The role of supersensitive, immunoenzymatic assay of TSH (sTSH) in the diagnostics of functional disturbances in underlined, particularly in subclinical course of thyroid gland diseases, or in diagnostically difficult cases. The complimentary role of tests' triangle-ultrasound, scintigraphy and fine needle biopsy in the evaluation of focal changes of the thyroid (nodular goitre) is discussed and the diagnostic algorithm of patient's qualification to surgery is proposed.     

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.     

First results of radioiodine therapy of multifocal and disseminated thyroid gland autonomy and use of a TcTUs-adapted dose concept

AIM: The presented study examines prospectively the efficiency of a dose concept for radioiodine therapy (RIT) adapted to the pretherapeutic 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) in patients with multifocal (MFA) and disseminated (DISA) autonomy. This concept considers the total thyroid as target volume and uses target doses from 150 Gy to 300 Gy according to the TcTUs, which is as a measure for the "autonomous volume" of the thyroid. METHODS: The data of 75 patients (54 female, 21 male; age 71 +/- 9 years) with MFA of DISA were evaluated. RIT was performed on patients presenting with normal values for free triiodothyronine and thyroxine and endogenous suppression of the basal thyrotropin (TSH). The following target dose were used for a TcTUs of 1.5-2.5% 150 Gy, for 2.51-3.5% 200 Gy, for 3.51-4.5% 250 Gy, and for > 4.5% 300 Gy. The radiation dose to be administered was calculated using a modified Marinelli formula. The therapy was considered as successful. When the basal TSH was above 0.5 mU/l and autonomous areas had disappeared in thyroid scintigraphy or the TcTU was below 1.5%, respectively. The average follow-up period was 8 +/- 4 months. RESULTS: The success rates average to 92%. Only in one case a subsequent subclinical hypothyroidism and in a further case an immunogenic hyperthyroidism occurred. CONCLUSION: The presented data indicate that even patients with a marked autonomy (TcTUs > 3.5%) can thus expected to be cured by of a one time therapy with success rate of over 90% using the presented dose concept. The rate of early hypothyroidism can altogether be estimated as very low.     

One-year outcome analysis of functional endoscopic sinus surgery for chronic sinusitis

We studied, by means of TSH nocturnal secretion and TRH test, 42 children (4.2-19.9 years) with hypothalamic pituitary disorders and 24 healthy euthyroid children (5.7-15.4 years) as control group. Patients were divided according to their serum values of FT4 in group 1 (n = 27) with FT4 >/=10.3 pmol/l and group 2 (n = 15) with FT4 <10.3 pmol/l. TSH was measured by immunoradiometric assay. TSH nadir, TSH peak and TSH surge were calculated. Both groups differed significantly from control group in TSH surge values: group 1 (p < 0. 05), group 2 (p < 0.01). TRH test was abnormal in 11/27 patients of group 1 and 10/15 patients of group 2. In group 1, 7 patients had normal tests, 2 had abnormalities in both tests, 9 had only TSH nocturnal surge altered and 9 showed only TRH alterations. All patients of group 2 presented thyroid axis abnormalities. In conclusion, in patients with hypothalamic pituitary disorders with low FT4, no further investigation is required to demonstrate thyroid axis alterations, however in patients with normal FT4, nocturnal TSH secretion and TRH test may be required to evidence thyroid abnormalities.     

The difficulties of treating infection in adults with cystic fibrosis

OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN: Prospective study. PATIENTS: A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS: Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 1.5 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION: (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy; (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.     

Autoimmune hypothyroidism and hyperthyroidism in patients with Turner's syndrome

A high prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS) but the extent of this association is controversial for the prevalence of thyroid autoantibody and the clinical impact of thyroid dysfunction. In this study we searched for thyroid disease and thyroid autoantibodies in patients with TS. Seventy-five unselected TS patients (age range 3-30 years) were studied. Sera were tested for thyroid hormones, thyrotropin (TSH), thyroglobulin (TG-ab) and thyroperoxidase (TPO-ab) antibodies. The TSH-receptor antibodies with thyroid-stimulating (TS-ab) or TSH-blocking activity (TSHB-ab) were measured in the IgG fraction using a bioassay. Ten out of 75 (13.3%) TS patients had AITD: eight had autoimmune thyroiditis (AT) (six with subclinical and two with overt hypothyroidism and one with euthyroidism) and one had Graves' disease. The prevalence of AITD increased significantly (p < 0.05) from the first (15%) to the third (30%) decade of life. The prevalence of TPO-ab and/or TG-ab (20%) was higher (p < 0.05) in TS than in age-matched female controls and increased from the first (15%) to the third (30%) decade of life. Clinical AITD was diagnosed in 46% of TS patients with TPO-ab and/or TG-ab. Thyroid-stimulating antibody was detected in the hyperthyroid patient, and TSHB-ab was found in one of eight patients with hypothyroid AT. It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.     

Training for Iowa physicians

"Autonomous" thyroid nodule is a localized nodular lesion of the thyroid gland characterized by growth, iodine uptake and function, all independent from TSH control. These nodules represent a heterogeneous anatomic and clinical entity. The clinical diagnosis is based upon a negative suppression of nodule iodine uptake and scan imaging by T3 administration. The nodule function is determined by high serum thyroid hormone levels and/or low TSH (measured by ultrasensitive assay). Etiology and pathogenesis of these nodules is not yet completely clarified. Both genetic and environmental factors determine nodule growth and function: thyroid cells, in fact, are genetically heterogeneous and may have intrinsic (congenital) characteristics that may promote the growth of cellular clones having mitotic and functional activity that is partially independent of TSH. In these particular cell clones, environmental factors like iodine deficiency or other goitrogens may favour the growth of autonomous nodules and also, by activating their function, may induce toxicity. The autonomous thyroid nodules need to be treated only when they become toxic: in this case both surgical excision or radioiodine may be used.     

Thyroid hormones and cytogenetic outcomes in backpack sprayers using ethylenebis(dithiocarbamate) (EBDC) fungicides in Mexico

Ethylenebis(dithiocarbamate) (EBDC) fungicides are used heavily in the United States. EBDCs (e.g., mancozeb, maneb) are metabolized to ethylene thiourea (ETU). The EPA classifies ETU as a carcinogen, based on thyroid and other cancers in rodents, and has restricted the use of EBDCs, while requiring workers to use protective equipment. There are no data on the potential carcinogenicity of EBDCs in humans, and there is only one study on human genotoxicity. ETU is known to cause decreases of thyroxine (T4) and increases in thyroid-stimulating hormone (TSH) in rodents. We have studied cytogenetic outcomes and serum thyroid hormone levels among 49 heavily exposed workers without protective equipment spraying EBDC on tomatoes in Mexico. We also studied 14 lightly exposed landowners and 31 nonexposed controls. Urinary ETU was used to compare exposure between groups. We found an increase in TSH (p = 0.05) among applicators compared to controls, but no decrease in thyroid hormone (T4). We found increases in sister chromatid exchange (p = 0.03) and in chromosome translocations (chromosome aberrations that persist through cell division) for applicators compared to controls (p = 0.05). However, the subset of reciprocal translocations showed a lesser increase (p = 0.24). Our data suggest that EBDCs affect the thyroid gland and the lymphocyte genome among heavily exposed workers. However, our data are limited to subclinical outcomes, are of borderline statistical significance, and should be interpreted with caution.     

Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease

We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroid-stimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3',5'-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 mug of the IgG of one patient with Graves' disease or 8 muU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a maximal dose of TSH. The effect of HTACS on AC was slower in onset and longer in duration than an equipotent dose of TSH. HTACS was detectable in IgGs of 9 of 15 untreated hyperthyroid Graves' disease patients; its concentration, however, did not correlate significantly with tests of thyroid function, nor with long-acting thyroid stimulator (LATS) activity. In another 11 treated patients with Graves' disease, selected for the presence of LATS, HTACS and LATS were significantly correlated. We observed no inhibition of LATS activity in a Graves' IgG chosen for such testing because of its high titer of HTACS and no detectable LATS. However, an inhibitor of HTACS was detected in 2 of 4 IgGs; one of these two IgGs also inhibited AC stimulation by TSH. Conclusions: 1) Some Graves' disease IgGs contain a human thyroid AC stimulator (HTACS), probably different from LATS. 2) HTACS may act via a common pathway with TSH; it differs from TSH, however, in having a slower onset and a greater effect during more prolonged incubation with plasma membranes. 3) There is also an inhibitor of HTACS activity in some Graves' disease IgGs.     

Neonatal transient hypothyroidism: aetiological study. Italian Collaborative Study on Transient Hypothyroidism

AIMS: To define the aetiology of neonatal transient hypothyroidism (NTH) and recommend preventive measures. METHODS: Maternal and perinatal clinical data on the use of antiseptics, drugs, and contrast agents containing iodine were collected from 40 subjects. Thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), thyroglobulin (TG), TSH receptor antibodies, thyroid peroxidase antibodies and urinary iodine were measured in random neonatal samples. In the mothers with known or suspected thyroid disorders, TSH, FT4, TSH receptor antibodies and thyroid peroxidase antibodies were also measured. RESULTS: The NTH aetiology was identified in 85% of cases. More than 50% of the babies with transient hypothyroidism had been exposed to iodine; maternal transfer of antibodies had occurred in a third of them. CONCLUSIONS: It is suggested that the practice of using iodine containing disinfectants should be withdrawn, and chlorhexidine substituted instead; that pregnant women should be advised of the adverse effects of using iodine products; and that thyroid function should be monitored whenever iodine is used.     

TSH receptor antibodies in the recurrent goiter after surgical treatment of Graves-Basedow disease

The serious complication after surgical treatment is goitre renewai. Very important is therefore the correct diagnosis based also on laboratory investigation, enabling early detection of dysthyreosis. The aim of work was assessment of immunological states of thyroid gland of patients with goitre recurrence treated surgically because of Graves-Basedow, based on investigation of TSH receptor antibodies. The time from the surgery to the examination ranged from two to eleven years. The laboratory investigation contained determination of thyroxin, free thyroxin triiodothyronin, thyreotropin and antibodies directed against TSH receptor(TRAb). It has been found that average concentration of TRAb and frequency was significantly higher in recurrent goitre then in group without goitre renewal. The results of investigation indicates usefulness of determination of thyroid antibodies in diagnosis of recurrent goitre after surgical treatment of Graves-Basedow disease.     

Thyroid hormones in depressive disorders: a reappraisal of clinical utility

Centuries of clinical observation suggest a connection between thyroid function and behavior. Advances in neuroendocrinology of the hypothalamic-pituitary-thyroid (HPT) axis provide many techniques for examining the role of thyroid function in psychiatric disorders. HPT hypofunctioning may be especially relevant to the pathophysiology of major mood disorders, although the diagnostic specificity and prognostic value of its assessment remain tentative. Evidence that synthesis and actions of thyroid hormones in the brain may not parallel those in the periphery further complicates such assessments. Nevertheless, measures of HPT function show some promise of contributing to the clinical evaluation and treatment of depression. Research findings include an association of subclinical hypothyroidism with unsatisfactory responses to antidepressant treatment, evidence that triiodothyronine and thyroid-stimulating hormone may speed recovery in acute depression, and limited and inconsistent support for the effectiveness of exogenous thyroid hormones to augment antidepressants. Additional systematic and controlled studies comparing various types and doses of thyroid hormones are needed to establish their efficacy and safety. Of special interest would be studies that use contemporary diagnostic methods, assess thyroid function, and employ the newer, safer antidepressants.     

Fetal thyroid function

Cordocentesis has permitted the study of fetal thyroid function. In normal pregnancy, fetal blood thyroid-stimulating hormone (TSH), thyroid hormones and thyroid-binding globulin increase with advancing gestation demonstrating functional maturation of the pituitary, thyroid and liver, respectively. The administration of thyroid-releasing hormone to the mother produces a rapid increase in fetal TSH from at least 25 weeks gestation. In hypoxemic growth-retarded fetuses, the concentrations of TSH are higher, and the concentrations of total and free thyroxine are lower than in appropriately grown fetuses. In anemic fetuses from red cell-isoimmunized pregnancies, serum TSH and thyroid hormone concentrations are increased. In some chromosomally abnormal fetuses, particularly those with trisomy 21, TSH is increased.     

Health learning materials support in South Africa compared with other developing countries

An investigation was carried out in to thyroid hormones (TSH, T3, T4) and lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride) in 136 adolescents (94 femals, average age 13 years). An iodine deficiency (grade II-II) with respect to the daily urine excretion per 1,73 m2 BSA was found in 75%. With few exceptions the serum levels of TSH and T4 were in the normal range. In 36% of the patients we noticed compensatory elevated T3 levels. Correlations between thyroid hormones TSH, T4, renal iodine excretion and the volume of thyroid glands were not detectable, only T3 showed a dignificant positive correlation to the thyroid gland volume. The average values of lipids in patients were found to be higher than in normals. We consider the changed lipids as a sign of a disturbed efficacy of thyroid hormones. The regional insufficient iodine supply causes goiters and to a high degree the observed hyperchole-sterolemia, too. Our results underline the necessity of a common iodine salt prophylaxis as well as the treatment of "harmless" goiters in puberty.     

Insulin receptor substrate-2 amino acid polymorphisms are not associated with random type 2 diabetes among Caucasians

OBJECTIVE: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. METHODS: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. RESULTS: The prevalence of anti-TPO was higher in celiac patients (29.7%) than in healthy controls (9.6%) (p < 0.001) and thyroid echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO-positive celiac patients were hypothyroid (two overt, three subclinical). A higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was found in celiac patients displaying the DQB1*0502 genotype, when compared with the remaining patients (8/29 = 27.6%). CONCLUSIONS: An elevated prevalence of clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian celiac patients, especially in those displaying the DQB1*0502 genotype; this finding could be related to a particular genetic background of the Sardinian population.