The association of insulin resistance with subclinical thyrotoxicosis.

BACKGROUND: Although overt thyrotoxicosis is associated with reduced insulin sensitivity (IS), the effects of subclinical thyrotoxicosis (SCTox) (i.e., suppressed serum thyroid-stimulating hormone with free thyroxine and tri-iodothyronine within the reference range) on glucose metabolism are not clear. SCTox may be of endogenous origin or due to ingestion of supraphysiological amounts of thyroid hormone. Our hypotheses were that reduced IS is present in SCTox and that the degree of reduction differs between SCTox of endogenous and exogenous origin. METHODS: The study population consisted of 125 premenopausal, normal-weight women, divided into four groups: exogenous SCTox due to L-T4 treatment for benign goiter or hypothyroidism (SCTox-ExogG) (n = 53), endogenous SCTox (SCTox-Endog) (n = 12), exogenous SCTox due to L-T4 treatment for differentiated thyroid cancer (SCTox-ExogDTC) (n = 20), and finally euthyroid women (C) (n = 40) as a control group. After a mixed meal challenge, glucose and insulin were determined at baseline and 120 minutes later. IS was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) index, quantitative IS check index (QUICKI), and 2 hours IS Avignon's index amended by Aloulou for mixed food. Secretion by pancreatic B-cells was calculated by HOMA-B index. Comparison among groups was done by analysis of variance followed by Tukey test. Linear regression analysis of T3 versus HOMA-IR was calculated. RESULTS: IS was reduced in all types of SCTox when compared with C. All SCTox groups had significantly higher levels of insulin (baseline and postmeal) and HOMA-IR and lower values of QUICKI and Aloulou when compared with controls. SCTox-Endog, however, had higher baseline insulin levels and HOMA-IR and a lower QUICKI index than the rest of the SCTox groups. Although within the normal range, total T4, free T4, and T3 levels were also significantly higher in the SCTox groups than in euthyroids. In SCTox-Endog, T3/T4 ratio was increased above the rest of SCTox groups. A moderate linear relationship between T3 and HOMA-IR was found in the whole population. CONCLUSIONS: IR is associated with SCTox of either endogenous or exogenous origin. However, based on our findings of lower IS compared with the rest of the SCTox groups, the endogenous subclinical form might have an even larger metabolic impact.

Charcoal hemoperfusion in the treatment of levothyroxine intoxication.

BACKGROUND: Levothyroxine (l-thyroxine) intoxication may arise from intentional or accidental ingestion of excessive doses of the hormone and may cause symptoms equivalent to thyroid storm. We report a case of massive accidental l-thyroxine intoxication resulting from an error in the preparation of capsules to treat goiter. SUMMARY: A 61-year-old woman was admitted showing high levels of thyroid hormones, with serum-free l-thyroxine level of 955.90 nmol/L (74.1 ng/mL) (normal values: 11.61-27.09 nmol/L or 0.9-2.1 ng/mL). It was discovered that she had ingested 50 mg instead of 50 microg/day of l-thyroxine during 9 days. Following charcoal hemoperfusion, the levels of total thyroxine, serum-free l-thyroxine, and triiodothyronine declined dramatically, with a reproducible pattern of reduction in hormone levels observed after each of the three sessions. The patient recovered from her stuporous mental state, atrial fibrillation, and acute respiratory failure. CONCLUSION: The use of hemoperfusion with a charcoal filter appears to be a very important therapeutic tool for the treatment of acute and severe forms of thyrotoxicosis due to l-thyroxine intoxication.

Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by 2-iodohexadecanal.

INTRODUCTION: Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iodo-deltalactone (ILdelta) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids inhibit several thyroid parameters. ILdelta has an antigoitrogenic action but no data about the action of 2-IHDA on this parameter has been published. OBJECTIVES: to study the action of 2-IHDA on methimazole (MMI)-induced goiter and analyze if this compound can cause the involution of preformed goiter. RESULTS: Administration of MMI to rats during 10 days increased thyroid weight by 112%. This effect was significantly inhibited by the simultaneous injection of 20mug/day of 2-IHDA (51% vs. MMI) while iodine or non iodinated hexadecanal were without action. Thyroidal proliferating cell nuclear antigen (PCNA) content was increased by MMI while 2-IHDA decreased this value (control: 100%; MMI: 190+/-11; MMI+2-IHDA: 134+/-10). Serum TSH was increased after MMI administration and 2-IHDA did not modify this parameter (control: 1.89+/-0.10; MMI: 8.19+/-0.93ng/ml; MMI+2-IHDA: 7.38+/-0.72). Treatment with MMI increased thyroidal cAMP content (control: 16.1+/-0.82, MMI: 42.4+/-4.6 fmol/mg protein) while injection of 2-IHDA significantly decreased this value (22.3+/-2.0). Goiter prevention by 2-IHDA was also observed at 30 days of treatment reducing total number of cells (51% inhibition) and epithelial height (81% inhibition). Goiter involution was induced after withdrawal of MMI and injection with 2-IHDA, KI or saline. 2-IHDA led to a reduction of 74.5% in thyroid weight after 3 days while spontaneous involution (saline) was only of 32%. KI failed to alter this value. This significant involution was accompanied by a reduction in the number of cells (66%). Administration of the iodolipids did not produce significant changes in several serum parameters such as total T(3) and T(4), cholesterol, transaminases, urea and creatinine. CONCLUSION: 2-Iodohexadecanal, as 6-iodo-deltalactone, prevents goiter growth in rats and opens a potential therapeutic application of iodolipids.

Hypothyroidism and dyshormonogenesis induced by D-penicillamine in children with Wilson's disease and healthy infants born to a mother with Wilson's disease.

Two siblings born to a mother with Wilson's disease, who was taking D-penicillamine, developed transient goitrous hypothyroidism. A prospective evaluation of 5 patients with Wilson's disease taking and not taking D-penicillamine for as long as 9.5 years showed subclinical hypothyroidism. D-penicillamine probably inhibited thyroperoxidase activity in utero in healthy infants and during childhood in patients with Wilson's disease.

Recombinant human thyrotropin in the management of thyroid disorders.

BACKGROUND: Recombinant human thyroid stimulating hormone (rhTSH) is a valuable tool in the management of thyroid diseases. It is useful for radioiodine ablation in patients with differentiated thyroid carcinoma (DTC), for their follow-up, and for treatment of selected patients with metastatic or recurrent DTC. More recently, it has been suggested that rhTSH is useful for treatment of multinodular goiter and amiodarone-induced thyrotoxicosis, as well as for diagnosis of congenital hypothyroidism. OBJECTIVE: To provide an outline of literature regarding the uses of rhTSH in thyroid diseases. METHODS: We performed a literature search for relevant articles in the PubMed database. CONCLUSION: rhTSH has important roles in management of thyroid diseases, and some are still controversial. For patients with DTC, it avoids the need for thyroid hormone withdrawal, without being detrimental to short-term outcomes. Further studies are warranted to assess its effects on long-term outcomes.

[Triiodothyroacetic acid in euthyroid goiter. New data on its mechanisms of action. Comparison with L-thyroxin]. / Intérêt de l'acide triiodothyroacétique pour le traitement du goître euthyroïdien. Nouvelles données sur son mode d'action. Comparaison avec la L-thyroxine.

Euthyroid goiter is usually treated with THS-inhibiting doses of L-thyroxin (L-T4), which can have troublesome adverse effects. It has been suggested that triiodothyroacetic acid (Triac), a TSH suppressor, might have fewer peripheral effects and better tolerability than T4. We therefore compared the risk-benefit ratios of the two drugs. Thirty-six women with euthyroid goiter (no thyroid cancer) were randomized to receive either Triac (19.6 ug/kg) (n=19) or L-T4 (1.7 ug/kg) (n=17) for 11 months. Goiter volume, lumar and femoral bone mineral density, and serum osteocalcin, deoxypyridinoline, TSH, free T4, and total cholesterol, high-density cholesterol (HDL), low-density cholesterol (LDL), and triglycerides were determined before and after treatment. Student's test and X2 analysis were used. TSH values (microunits/ml) in the Triac and T4 groups were respectively 1.91 +/- 0.6 (basal) and 0.18 +/- 01 (after) and 2.1 +/- 2.5 (basal) and 0.18 +/- 0.3 (after). Thyroid volume fell by 37.9 +/- 35.4% in the Triac group and by 14.5 +/- 39.5% in the L-T4 group (p=0.069). Goiter volume fell by at least 50% in 42% of patients treated with Triac and in 17.7% of patients treated with L-T4 (p=0.15). Triac was associated with fewer adverse events. Changes in bone mineral density, serum deoxypyridinoline, serum osteocalcin and the lipid profile did not differ between the treatment arms. However, the Apo B level fell more strongly on Triac than on T4. These results show that Triac is more effective than L-T4 on goiter size, while having similar peripheral effects.

Tratamiento del bocio tóxico difuso / Treatment of toxic diffuse goiter

El objetivo del tratamiento en el bocio tóxico difuso (BTD) es lograr la disminución en la producción de hormonas tiroideas y consecuentemente una mejoría clínica rápida(AU)

Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid.

Euthyroid goiter is usually treated with TSH-inhibitory doses of levo-T(4) (L-T(4)). Because triiodothyroacetic acid (TRIAC) decreases TSH levels, the following study was perfomed: 36 euthyroid goitrous female patients (no cancer or chronic thyroiditis) were randomized to TRIAC (19.6 micro g/kg) (n = 19) or L-T4 (1.7 microg/kg) (n = 17) treatment during 11 months. Goiter volume; lumbar and femoral bone mineral density; serum osteocalcin; deoxypyridinoline; TSH; free T(4); total, high-density lipoprotein, and low-density lipoprotein cholesterol; and triglycerides were measured before and after the study period. Student's t test and chi(2) analysis were performed. TSH values (microunits per milliliter) in the TRIAC and L-T(4) groups were: 1.91 +/- 0.6 (basal) and 0.180 +/- 0.1 (after) and 2.1 +/- 2.5 (basal) and 0.180 +/- 0.3 (after), respectively. Thyroid volume decreased 37.9 +/- 35.4% in the TRIAC patients and 14.5 +/- 39.5% in the L-T(4) group (P = 0.069). Forty-two percent of the goiters with TRIAC reduced more than 50% their initial volume vs. 17.7% with L-T(4) (P = 0.15). With TRIAC, patients experienced fewer side effects. No differences in the changes of bone mineral density, serum deoxypyridinoline, osteocalcin, or the lipid profile were observed between both groups. The present results show that TRIAC is more effective than L-T(4) in the reduction of goiter size, with comparable effects on peripheral parameters.

Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters.

OBJECTIVE: The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). METHODS: Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Bocio difuso eutiroideo: respuesta al tratamiento con hormonas tiroideas durante 15 años / Euthyroid diffuse goitre. Response to the treatment with thyroid hormones during 15 years

Se realizó un estudio descriptivo y retrospectivo de 107 pacientes con bocio difuso eutiroideo para evaluar los resultados del tratamiento con hormonas tiroideas. Según disminuyó o no el tamaño del bocio se definieron las categorías de respuesta: satisfactoria y no satisfactoria. Se realizaron cortes evaluativos al año, a los 5, 10 y 15 años. Como variables predictoras de la respuesta empleamos: edad, peso inicial de la glándula, antecedentes familiares de tiroidopatías, tiempo de evolución del bocio y dosis de hormonas empleadas. Se aplicaron las pruebas de chi cuadrado y de regresión logística. Se recogieron además las reacciones adversas referidas y la posible asociación con la dosis. Durante el período evaluado, el bocio disminuyó aproximadamente 8 g de 39,74 a 31,35 g como promedio y sólo fue significativo en el primer año de tratamiento (p < 0,001). El riesgo relativo para desarrollar una respuesta no satisfactoria: al año fue, 3 veces mayor cuando el tiempo de evolución referido del bocio era mayor de 1 año y 64 porciento menor cuando se empleó dosis supresiva; a los 5 años, 5 veces mayor cuando el tiempo de evolución era mayor de 1 año; a los 10 años fue 4 y 3 veces mayor cuando el tiempo de evolución fue mayor de 1 año y la edad, superior a los 30, respectivamente; a los 15 años ninguna variable predijo la respuesta. El nerviosismo, la disminución de peso y la sudación fueron los síntomas más frecuentes y se relacionaron con el empleo de dosis supresivas en los primeros 5 años (p < 0,01). Se concluyó que el tiempo máximo para evaluar la respuesta osciló entre 1 y 2 años y que los bocios de poco tiempo de evolución y de causa autoinmune, constituyeron signos de buen pronóstico

The effect of oral administration of iodine to patients with goiter and hypothyroidism due to defective synthesis of thyroglobulin.

The effects of administration of iodine (1 mg/day orally, 64 days) were studied in three siblings with congenital goiter and hypothyroidism due to defective thyroglobulin (Tg) synthesis. The patients presented very large goiters, elevated RAI uptake, negative perchlorate discharge test, low serum T4, and elevated TSH concentrations. Immunoassayable Tg was low and failed to increase after stimulation with exogenous bovine TSH. Analysis of individual thyroid extracts by gel filtration failed to reveal a Tg component; the immunoassayable Tg antigens in these goitrous tissues were 0.12 and 0.21 mg/g tissue, respectively (normal 70-90 mg/g tissue). The histological pattern of their thyroids was compatible with defective Tg synthesis. The administration of iodine caused a rise in the mean serum T4, T3, and free T4 concentrations in all three siblings, but did not alter the serum Tg concentration. TSH concentrations rose in the terminal period of observation in the three subjects and this was considered to be due to a possible effect produced by the iodine load in the thyroperoxidase system (Wolff-Chaikoff effect). One patient showed an increase in goiter size during the period of observation. These results suggest that iodine administration enhanced the ability of the dyshormonogenetic gland to synthesize iodothyronines.

Studies on the goiter inhibiting action of iodolactones.

The thyroid gland synthesizes 6-delta-iodolactone, a compound shown to inhibit goiter growth in vivo and cell proliferation in culture. The present studies were performed to characterize this effect further with the aim of exploring the possible therapeutic action of iodolactones. Prevention assay: rats were treated simultaneously with a goitrogen, methylmercaptoimidazole, and either 6-delta-iodo-lactone or 14-iodo-omega-lactone, a synthetic derivative, given either i.p. or p. o. Both compounds caused a significant decrease in thyroid weight irrespective of the route of administration, but oral administration was less effective. A dose-response relationship was observed, the minimal effective dose (i.p.) being 3 micrograms/day. Involution assay: goiter was first induced with methylmercaptoimidazole and then the iodolactones were injected. Both compounds caused a significant involution, which was dose-related. Acute (10 days) administration of the iodolactones did not produce significant changes in several serum parameters (total T3 and T4, cholesterol, total protein, urea and acetylcholinesterase). These results give further support to the potential therapeutic application of iodolactones.

Effect of thyroid hormone treatment on thyromegaly in children and adolescents with Hashimoto disease.

The effect of thyroid hormone treatment on thyromegaly was evaluated in 69 patients < or = 18 years of age with goitrous Hashimoto disease. Changes in goiter size were related to pretreatment thyroid function (serum thyroxine and thyrotropin concentrations). We found that only hypothyroid patients had a clear diminution of their thyromegaly when given thyroid hormone.

Further studies on the antigoitrogenic action of iodoarachidonates.

Previous studies have shown that iodoarachidonates (IAs) prevent goiter production in rats. In the present studies we show that both IL-d and IL-w (IAs bearing the iodine atom at the positions 6 and 14, respectively), cause a significant involution of preformed goiter. This effect was evident when IAs were administered either orally or via i.p., although the first one required larger doses to obtain the same degree of inhibition. No changes were observed in serum protein, urea, cholesterol, cholinesterase, T3 or T4. In vitro studies with FRTL-5 cells showed that both IAs inhibit iodide and alpha-AIB uptake, as well as ATPase activity.

[Shortened preoperative preparation in diffuse hyperthyroid goiter: experience in 34 patients]. / Preparación preoperatoria abreviada en los bocios difusos hipertiroídeos. Experiencia en 34 pacientes.

Conventional preparation of goitrous hyperthyroid patients using lugol and propranolol may take 2 weeks. This period may be shortened using sodium iopodate and dexamethasone. We used 500 mg of sodium iopodate and 1 mg dexamethasone for 4 days in 34 hyperthyroid patients. Surgical indication derived from failure to medical treatment (68%), large goiter (27%) or adverse reaction to PTU (6%). Clinical euthyroidism was achieved after 4 days in all patients. T3 levels decreased from 482 +/- 26.2 to 137.6 +/- 3.7 ng/dl and T4 from 20.6 +/- 1.04 to 15.2 +/- 0.5 micrograms/dl (p < 0.005). Surgery was uneventful in 33 patients, one subject developed supraventricular tachycardia responsive to verapamil. Electron microscopy of the removed thyroid tissue revealed marked decrease of superficial villi and large phagosomes. Thus, sodium iopodate and dexamethasone are effective and safe for preoperative preparation of hyperthyroid patients.

Natural course of iodine-induced thyrotoxicosis (Jodbasedow) in endemic goiter area: a 5 year follow-up.

In the Balsas region of North Brazil (85% prevalence of goiter), 1876 goitrous subjects (1663 with goiter grade I and II and 103 with grade III multinodular goiter) were treated with 1 ml of iodized oil im (l-oil). From the population with grade III goiter we were able to follow-up for 5 yr 13 euthyroid goitrous patients (group 1) and 8 goitrous individuals (group 2) who developed iodine-induced thyrotoxicosis (IIT, 0.42% of the total population or 7.76% of the multinodular goiter subjects). The two groups were matched for age and goiter size, and had no significant differences in the baseline levels of thyroid hormone concentration, T3/T4 ratio or mean serum TSH. However, group 2 had a higher concentration of serum Tg, and 48 h after challenge with 10 U of bovine TSH (bTSH) had a significantly higher absolute release of T3 and Tg than group 1. In 4 patients IIT was transitory and resolved by 12 months. Four other subjects, however, maintained a mild clinical form of IIT that only normalized at 50 months. Only one patient needed treatment with methylmercaptoimidazol. There was no evidence of autoantibodies (TSH-receptor inhibiting antibody, anti-Tg or anti-microsomal antibodies) against thyroid antigens in group 2 patients. All subjects, including those with thyrotoxicosis, showed a remarkable shrinkage of the goiter by 60 months which was reflected by a significantly lower absolute response of T3 and Tg after bTSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Efeito da administraçäo de iodo em pacientes com bócio difuso atóxico / Effect of iodine administration in patients with diffuse nontoxic goiter

O objetivo do estudo foi avaliar o efeito da administraçäo de iodo a pacientes portadores de bócio difuso atóxico, com teste de perclorato negativo. A resposta de TSH ao TRH e às concentraçöes séricas de T3 total e T4 livre foram estudadas em 8 pacientes da regiäo de Campinas antes e durante a administraçäo de iodeto de potásio (KI) 450 a 600mg/dia por 8 semanas. Näo foram observados aumento de volume do bócio ou quadro compatível com hipotiroidismo ou tirotoxicose neste período. Os auto-anticorpos da tiróide mantiveram-se negativos antes e durante a ingestäo de KI. Apenas um paciente apresentou elevaçäo de T3 após a ingestäo de KI. Os níveis de TSH mantiveram-se inalterados. Os valores de FT4 tornaram-se significativamente (p < 0,01) mais elevados e 5 pacientes apresentaram diminuiçäo sensível do incremento de TSH ao TRH. Os valores de FT4 correlacionaram-se de maneira inversa (p < 0,05) ao incremento do TSH. Os dados sugerem existir risco de induçäo de tirotoxicose em portadores de bócio, mesmo difuso, pela administraçäo de iodo, principalmente nos pacientes procedentes de regiöes endêmicas