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Association of the HLA A2-B46-DR9 haplotype with autoimmune thyroid dysfunction after bone marrow transplantation in Chinese patients.

Autoimmune thyroid disease (AITD) may occur in patients after bone marrow transplantation (BMT). At a median follow-up of 4 years, among 194 allografts and 28 autografts, four patients (three allografts, one autograft) developed AITD. All carried the human leucocyte antigen (HLA) A2-B46-DR9 haplotype, strongly associated with AITD in the Chinese population. No significant thyroid disorder was detected in 190 patients without this haplotype. The frequency of AITD in BMT patients with the HLA A2-B46-DR9 haplotype was 12.5%, with a relative risk of 7.8 times that of non-carriers (P < 0.001). The risk of AITD should be recognized in recipients with high-risk HLA haplotypes, and regular screening might be warranted.

Adult↗

Thyroid hormones and thyroid antibodies in infertile males.

OBJECTIVE: To investigate the incidence of thyroid dysfunction, thyroid antibodies, and the correlation with semen and hormonal parameters in infertile men. DESIGN: Prospective study. SETTING: University-based andrology laboratory. PATIENT(S): Three hundred five infertile men with idiopathic infertility. INTERVENTION(S): Medical history, clinical examination, semen analysis, measurement of free thyroxin (fT4), free triiodothyronine (fT3), basal thyroid-stimulating hormone (bTSH), LH, FSH, T, free testosterone (fT), PRL, E2, sex hormone-binding globulin (SHBG), DHEAS, and the thyroid antibodies thyreoglobulin antibody (TGA), thyroid peroxidase antibody (TPO-Ab), and thyroid receptor antibody (TRAK). MAIN OUTCOME MEASURE(S): Incidence of thyroid dysfunction and thyroid antibodies, as well as the correlation with hormones and the results of semen analyses. RESULT(S): No manifest thyroid dysfunction was observed. Latent thyroid dysfunction and latent hypothyroidism were diagnosed in 11.5% and 3% of infertile men, respectively. No correlation between thyroid dysfunction and semen parameters was detected. bTSH correlated significantly with PRL (P<.001). Thyroid antibodies were elevated in 7.5%. Elevated TPO-Ab were significantly correlated with pathozoospermia (P=.036) and asthenozoospermia (P=.049). CONCLUSION(S): Latent thyroid dysfunction had no impact on semen parameters. In patients with elevated TPO-Ab levels, pathozoospermia or asthenozoospermia should be considered.

Adult↗

Prevalence and characteristics of postpartum thyroid dysfunction in Tehran.

OBJECTIVE: To determine the prevalence of postpartum thyroiditis (PPT), one of the autoimmune disorders of the thyroid which usually occurs in women in the first year after parturition. PPT presents with periods of transient thyrotoxicosis and hypothyroidism, in many cases resulting in permanent hypothyroidism. DESIGN: The study involved 1040 mothers who had contacted five health centers in Tehran for vaccination of their children. METHODS: Signs and symptoms of hypothyroidism and thyrotoxicosis, and the presence of goiter (using the World Health Organization classification), were sought. Serum T3, T4, TSH, anti-TPO and anti-Tg antibodies were measured at 3, 4.5, 6 and 9 months after parturition. In those with hypothyroidism or thyrotoxicosis and a matched group of normal women, thyroid sonography was performed. RESULTS: The prevalence of thyroiditis was 11.4%. Hypothyroidism and thyrotoxicosis occurred in 68 and 42 mothers respectively. Nine had thyrotoxicosis followed by hypothyroidism. There was one case of Graves' disease. Out of 68 hypothyroid patients, 33 women underwent treatment with levothyroxine (because of the severity of symptoms) for 12 months. Six women showed increased TSH at 6 weeks after discontinuation of thyroxine. Stage II goiter (World Health Organization classification) were observed in 21.8% of patients and in 6.7% of pospartum euthyroid women (P<0.001). Positive anti-TPO was found in 61.5% of patients and in 19% of the control group; positive anti-Tg was found in 58% of patients and in 6% of the control group (P<0.001). Sonographic changes were observed in 96% of the patients and in 7% of the control group (P<0.001). There was no significant correlation between the occurrence of thyroiditis and parity, the age of the mother, a previous history of thyroid disease in the patient or family, breast-feeding, or the gender of the child. CONCLUSION: The results of this study show a high prevalence of PPT in Tehranian women. This may be due to the length and frequency of follow-up and/or the transition from low to adequate iodine intake. The major difference with respect to other studies is the low frequency of the biphasic form of PPT.

Adult↗

Serum leptin and lipids in patients with thyroid dysfunction.

This work was undertaken to examine the relationship between thyroid hormone and serum leptin concentration. This study included 368 Japanese female subjects (27 were affected with pretreatment hyperthyroidism, 68 with hyperthyroidism during treatment, 19 with pretreatment hypothyroidism, 57 with hypothyroidism during treatment and 197 euthyroid control subjects) and 60 control male subjects. In the control group, serum leptin levels in males were lower than those recorded in females (mean +/- SD; 4.6 +/- 4.1 vs 9.5 +/- 6.4 ng/ml, p < 0.001). The leptin values correlated well with body mass index (BMI) and body fat mass (BFM) in both control male and female subjects (p < 0.001 for each). The serum leptin levels in pretreatment female patients with hyperthyroidism were significantly lower than those in the pretreatment patients with primary hypothyroidism and control female subjects (6.4 +/- 3.0 vs 9.7 +/- 6.3, 9.5 +/- 6.4 ng/ml; p < 0.05, 0.02, respectively), but after adjusting for BMI and BFM, the difference was mainly due to the significantly different BMI and BFM. Furthermore, serum leptin did not change significantly during the treatment in hyper and hypothyroidism. There was no correlation between serum leptin and thyroid hormones or lipids levels in female patients with thyroid disorders. Adiposity and gender were the major determinants of leptin concentration, but thyroid hormones did not appear to play any relevant role in leptin synthesis and secretion in human.

Adolescent↗

Thyroid dysfunction in patients on regular hemodialysis: evaluation of the stable intrathyroidal iodine pool, incidence of goiter and free thyroid hormone concentration.

Thyroid function tests and stable intrathyroidal iodine were evaluated in 17 patients on regular hemodialysis treatment (RHD). Triiodothyronine levels in the hypothyroid range, thyroxine levels in the low normal range, but normal levels of thyroid-stimulating hormone, free thyroxine and free triiodothyronine were found. Normal values of stable intrathyroidal iodine and a normal incidence of goiter for our region were also found. It is concluded that in patients on RHD: (1) free thyroid hormone levels are normal and probably represent the most meaningful way of evaluating thyroid function; (2) in our RHD population goiter is no more prevalent than in normal persons; (3) the iodine storage function of the thyroid is not always altered.

Adult↗

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Amiodarone-induced thyroid dysfunction associated with cumulative dose.

PURPOSE: To obtain risk estimates of thyroid disorder in patients starting amiodarone. METHODS: We followed a cohort of 5522 patients with a first prescription for an anti-arrhythmic drug and no previous use of thyroid drugs. Within this cohort we conducted a nested case-control analysis. Cases were defined as all patients who started a thyreomimetic or thyreostatic drug no sooner than 3 months after the start of an anti-arrhythmic drug. Controls were patients with a comparable follow-up period not receiving any thyroid drugs during the observation period. RESULTS: We identified 123 cases who had started thyreostatic drugs and 96 cases who had started a thyreomimetic drug. In users of amiodarone we found an adjusted odds ratio of 6.3 (3.9-10.2) for hyperthyroidism and 6.6 (3.9-11.1) for hypothyroid disease compared to users of other antiarrhythmics. Patients who were exposed to a cumulative dose exceeding 144 g of amiodarone had an adjusted odds ratio of 12.9 (6.1-27.3) for the development of hyperthyroid disease. The dose response for development of hypothyroidism was less pronounced. CONCLUSIONS: We observed an increased risk for thyroid disorder at the high end of that reported in the literature. The risk of thyroid disorder increased with exposure to higher cumulative doses. Clinicians should keep in mind the possibility of development of thyroid disorders in patients on treatment with amiodarone even after several years of use.

Age Factors↗

Correlation between severity of thyroid dysfunction and renal function.

OBJECTIVE: Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively. DESIGN AND PATIENTS: In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism. RESULTS: Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log(10)(fT4 post-treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r(2) = 0.81, P < 0.0001) and estimated GFR (0.69, P < 0.0001). CONCLUSION: The kidney is an important target of thyroid hormone action.

Antithyroid Agents↗

Thyroid dysfunction and rheumatic diseases.

Musculoskeletal symptoms developing during the treatment of thyroid disease were studied in 150 patients; 17 developed a symptom complex of early morning stiffness together with shoulder girdle pain and weakness; similar symptoms were seen in only 3 of 100 controls. A prospective study of 16 patients with recent onset rheumatoid arthritis followed during the first 6 months of penicillamine therapy showed no changes in thyroid function tests. It is suggested that changing or abnormal thyroid status may precipitate or exacerbate musculoskeletal disease. Finally, in a retrospective study of 26 patients with both thyroid disease and rheumatoid arthritis, 4 patients had a simultaneous onset of both myxoedema and rheumatoid arthritis, the activity of which was greatly improved by correction of the hypothyroid state.

Adolescent↗

Thyroid dysfunction in megalin deficient mice.

Megalin mediates transcytosis of thyroglobulin (Tg), the thyroid hormone precursor, resulting in its passage into the bloodstream. The process involves especially hormone-poor Tg, which may favour hormone secretion by preventing competition with hormone-rich Tg for proteolytic degradation. To gain more insight into the role of megalin, here we studied thyroid function and histology in megalin deficient mice compared with WT mice. As expected from the knowledge that megalin mediates Tg transcytosis, serum Tg levels were significantly reduced in homozygous (megalin-/-) mice, which, more importantly, were found to be hypothyroid, as demonstrated by significantly reduced serum free thyroxine and significantly increased serum thyroid stimulating hormone (TSH) levels. In heterozygous (megalin+/-) mice, in which megalin expression was normal, thyroid function was unaffected. Although the serological phenotype in megalin-/- mice was not associated with histological alterations or goiter, our results support a major role of megalin in thyroid hormone secretion.

Animals↗

Thyroid dysfunction in patients with amyloid goitre.

OBJECTIVES: Widespread amyloid deposition in the thyroid gland causes diffuse, clinically apparent enlargement of the thyroid (amyloid goitre: AG). The aim of this study was to clarify the abnormalities of thyroid function in patients with AG. DESIGN: Thirty patients with secondary amyloidosis were retrospectively analysed. Their thyroid status was evaluated using the results of routine thyroid function tests and measurement of thyroid autoantibodies. Thyroid needle biopsy was carried out to identify amyloid deposition in the thyroid gland. RESULTS: Thyroid enlargement was observed in 19 (63%) of 30 patients with amyloidosis. Eleven of these 19 patients had a thyroid biopsy and/or autopsy and amyloid deposition was histologically revealed in 10 (defined as AG) of these 11 patients. Nine of 10 patients (90%) with AG had abnormalities of thyroid function, including five patients with hypothyroidism, one with hyperthyroidism, one with transient hypothyroidism, and two with low T3 syndrome. Five had thyroid autoantibodies. The patient with hyperthyroidism had positive thyroid stimulating antibody (TSAb) and high 131I thyroidal uptake, suggesting the coexistence of Graves' disease. Another patient suffered from thyroidal pain and showed transient hypothyroidism, high level of serum thyroglobulin and low thyroidal uptake of 123I, the clinical course being compatible with subacute thyroiditis. CONCLUSIONS: The incidence of thyroid abnormalities accompanied by AG, although asymptomatic, is unexpectedly high. Thyroid function should therefore be regularly assessed during follow-up of patients with systemic amyloidosis.

Adult↗

Thyroid disease in middle-aged and elderly Swedish women: thyroid-related hormones, thyroid dysfunction and goitre in relation to age and smoking.

The prevalence of thyroid disease and the concentration of thyroid hormones and thyrotropin were studied in a random population sample of 1154 women, aged 50-72 years, with special reference to the effect of age and smoking. The prevalence of spontaneous hypothyroidism was 3.3% (previously unknown overt and mild disease 1.3%) and the prevalence of hyperthyroidism was 2.5% (previously unknown disease 0.2%). Clinically suspected hyper- or hypothyroidism (very weak to strong) was recorded in 288 women, but was only verified in three cases. The prevalence of visible and palpable thyroid enlargement was 2.1% and 13-14%, respectively. Total thyroxine concentrations increased and free tri-iodothyronine levels decreased significantly with age (P less than 0.001). The serum thyrotropin concentrations were lower in smoking women than in non-smokers in the 50- and 58-year age groups (P less than 0.05). There was no increase in the prevalence of thyroid disease or goitre in the women who were smokers at the time of the study.

Age Factors↗