Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study

ABSTRACT Objective To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Large thyroid cyst in a patient with congenital hypothyroidism / Grande cisto tiroidiano em paciente com hipotireoidismo congênito

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

Os defeitos de biossíntese do hormônio tiroidiano são causas raras de hipotireoidismo congênito. Embora as apresentações iniciais sejam geralmente bócio difuso e hipotireoidismo, nódulos tiroidianos ou câncer de tiroide podem se desenvolver subsequentemente. Descrevemos aqui um caso de hipotireoidismo causado por disormonogênese e no qual um dos nódulos sólidos degenerou em um grande cisto. Um homem de 22 anos de idade foi encaminhado para nossa clínica para avaliação do aumento de um nódulo tiroidiano. O hipotireoidismo foi diagnosticado na infância. Entretanto, em razão da baixa conformidade ao tratamento, os valores de TSH estavam elevados na maior parte do tempo. Quando o paciente tinha 15 anos de idade, um primeiro nódulo sólido e frio foi detectado. A aspiração por agulha fina mostrou um nódulo folicular benigno. Sete anos depois encontramos múltiplos nódulos na tiroide e um grande cisto predominante que correspondia ao nódulo sólido anteriormente detectado. Foram aspirados 21cc de fluido cor de palha. A citologia mostrou um nódulo cístico benigno. O paciente foi submetido à tiroidectomia e o exame histopatológico confirmou um cisto tiroidiano benigno. Embora não seja comumente relatada, a disormonogênese da tiroide pode progredir para a degeneração cística. Ao serem considerados o risco de malignidade e a eventual formação de cistos, recomendamos uma avaliação mais frequente da formação de nódulos nesses pacientes. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

A case of thyroid hormone resistance: a rare mutation / Caso de resistência aos hormônios tireóideos: mutação rara

Reduced sensitivity to thyroid hormones (RSTH) is a rare disease that affects about 3,000 individuals, belonging to about 1,000 families. It results from reduced intracellular action of thyroid hormones (TH) genetically determined and manifests as persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH). We describe a 67-years old, Caucasian woman, with past history of subtotal thyroidectomy due to diffuse goiter, who presents with a recurrence of goiter. Although she is clinically euthyroid, laboratory evaluation shows persistent hyperthyroxinemia with non-suppressed TSH. Response to thyrotropin releasing hormone (TRH) test was normal and TSH concentrations were not suppressed during oral administration of suprafisiologic doses of levothyroxine (L-T4). Peripheral blood DNA was extracted from the patient and a mutation was found localized in cluster one, at codon 346 of the ligand binding domain of the THRB gene. The patient’s son underwent thyroid function testing (TFT) and genetic study, both negative, suggesting a sporadic mutation. RSTH should be considered in all hyperthyroxinemic patients who are clinically euthyroid. Mutations interfering with three major steps required for TH action on target tissues have been, so far, identified (TR-β, TR-α, MCT8, SPB2). Each mutation is associated with a distinctive syndrome. Goal of management is to maintain a normal serum TSH level and a eumetabolic state and offer appropriate genetic counselling and prenatal diagnosis. Inappropriate treatment of eumetabolic patients results in hypothyroidism and need for TH replacement.

A sensibilidade reduzida aos hormônios tiroidianos (RSTH) é uma doença rara que afeta cerca de 3.000 indivíduos em 1.000 famílias. Ela resulta de uma ação intracelular reduzida de hormônios tiroidianos (TH), é geneticamente determinada e se manifesta como hipertiroxinemia persistente com hormônio tireoestimulante (TSH) não suprimido. Descrevemos o caso de uma mulher caucasiana de 67 anos de idade com histórico de tiroidectomia subtotal por bócio difuso e que apresentou recorrência do bócio. Embora ela fosse clinicamente eutiroide, a avaliação laboratorial mostrou hipertiroxinemia persistente com TSH não suprimido. A resposta ao hormônio liberador da tireotrofina (TRH) foi normal e as concentrações de TSH não foram suprimidas durante a administração oral de doses suprafisiológicas de levotiroxina (L-T4). Foi extraído DNA de sangue periférico da paciente e encontrada uma mutação no cluster um do códon 346 do domínio de ligação do ligante do gene THRB. O filho da paciente foi submetido a um teste de função da tiroide e a um estudo genético, ambos negativos, o que sugeriu uma mutação esporádica. O RSTH deve ser considerado em todos os pacientes hipertiroxinêmicos que sejam clinicamente eutiroides. Foram identificadas, até hoje, mutações que interferem com os três passos principais necessários para a ação do TH sobre os tecidos-alvo (TR-b, TR-α, MCT8, SPB2). Cada mutação está associada com uma síndrome distinta. O objetivo do manejo é manter o nível sérico normal de TSH e um estado eumetabólico, além de se oferecer aconselhamento genético adequado e diagnóstico pré-natal. O tratamento inadequado de pacientes eumetabólicos leva ao hipotireoidismo e requer reposição de TH.

Effects of combined interferon alpha and ribavirin therapy on thyroid functions in patients with chronic hepatitis C attending hepatitis centre Ghulam Mohammad Medical College Hospital Sukkur

To determine the frequency of thyroid dysfunction in patients of chronic hepatitis C during treatment with interferon alpha-2b and ribavirin therapy. A cohort study. Hepatitis Centre Ghulam Mohammad Mahar Medical College Hospital, Sukkur, from February 2009 to January 2010. One hundred and sixty seven non-cirrhotic chronic hepatitis C patients were grouped into treatment group [n=107] and control group [n=60] awaiting treatment. Baseline serum [s.] Alanine Transferase [ALT] and S. Aspartate Transferase [AST] were measured by IFCC method. Serum Thyroid Stimulating Hormone [S. TSH], serum free thyroxine [S. Free T4] and serum total triiodothyronine [S.T3] level were determined by chemiluminescence. Study group patients underwent 24 weeks IFN and ribavirin therapy and were followed-up for thyroid dysfunction at weeks 0, 12 and 24. Control group patients underwent the same tests at weeks 0, 12 and 24. Statistical analysis was done on SPSS 15. Out of 107 patients of treatment group, 20 patients [18.69%] developed thyroid dysfunction. Females were at higher risk with Relative Risk [RR] of 11.25 and Attributable Risk [AR] of 91%. Hypothyroidism was more common than hyperthyroidism. Interferon-alpha and ribavirin therapy induces thyroid dysfunction in chronic hepatitis C patients. Hypothyroidism was more common. Females are at a higher risk of developing thyroid dysfunction

Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study / Tratamento de hipotiroidismo primário com doses semanais de levotiroxina: um estudo randomizado, unicego, crossover

OBJECTIVE: Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative. SUBJECTS AND METHODS: This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4. After six weeks, they switched regimens. Thyroid parameters were measured at baseline, and after 42 and 84 days. Echocardiogram and hyperthyroidism symptoms were evaluated before and four hours after LT4 intake. RESULTS: In the weekly dose treatment, fT4 levels were higher after taking LT4, and lower seven days after the last dose; by the 6th week there was a small decrease in T3 levels. TSH remained unchanged and there were no hyperthyroidism symptoms or echocardiographic manifestations. CONCLUSION: Weekly dose leads to transient increases in fT4, without hyperthyroidism or cardiac symptoms. That approach seems to be a safe alternative for the treatment of hypothyroidism.

OBJETIVO: Aderência ao tratamento do hipotiroidismo é comprometido pelo uso diário de levotiroxina, e doses semanais poderiam ser uma alternativa. SUJEITOS E MÉTODOS: Este é um estudo randomizado, crossover. Quatorze mulheres foram selecionadas para receber LT4 diariamente ou semanalmente. Após seis semanas, houve inversão do regime de tratamento. Avaliações tireoideanas foram realizadas antes, após 42 e 84 dias. Avaliação de sintomas de hipertireoidismo e ecocardiograma foi realizada antes e após quatro horas de LT4. RESULTADOS: Com dose semanal, os níveis de fT4 foram mais elevados logo após a dose de LT4, e menores após sete dias; após seis semanas, houve diminuição de T3. TSH permaneceu inalterado e não houve manifestações ecocardiográficas ou de hipertireodismo. CONCLUSÃO: Dose semanal de LT4 leva à elevação de fT4, sem manifestações de hipertireoidismo, e parece ser uma alternativa segura para o tratamento do hipotireoidismo.

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. In conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

O iodo é essencial para a síntese de hormônios tireóideos e tanto a deficiência crônica deste halogeno como o excesso nutricional de iodo levam a hiperplasia e hipertrofia dos elementos foliculares (por excesso de TSH). Esse fenômeno pode se associar a maior risco de câncer de tireóide, especialmente no sexo feminino. Estudos experimentais documentam indução de câncer de tireóide após prolongado excesso circulante de TSH, o qual induz aumento da proliferação celular medida por fator de crescimento epidermal (EGF), decréscimo de síntese de fator de transformação do crescimento (TGFbeta 1) e aumento da angiogenese. Estudos epidemiológicos entre nutrição de iodo e câncer de tireóide são conflitantes. É, todavia, aceito que a correção de prévia deficiência de iodo com aporte nutricional adequado deste halogeno leva à maior prevalência de carcinoma papilífero (e decréscimo de carcinoma folicular). Em alguns países, o excesso de iodo foi apontado como causa aparente de maior prevalência de câncer de tireóide. Em conclusão: não existe uma relação causa-efeito entre iodo nutricional e prevalência de câncer de tireóide, e outros fatores intervenientes ambientais devem ser considerados.

Biphasic modulation of insulin receptor substrate-1 during goitrogenesis

Insulin receptor substrate-1 (IRS-1) is the main intracellular substrate for both insulin and insulin-like growth factor I (IGF-I) receptors and is critical for cell mitogenesis. Thyrotropin is able to induce thyroid cell proliferation through the cyclic AMP intracellular cascade; however, the presence of either insulin or IGF-I is required for the mitogenic effect of thyroid-stimulating hormone (TSH) to occur. The aim of the present study was to determine whether thyroid IRS-1 content is modulated by TSH in vivo. Strikingly, hypothyroid goitrous rats, which have chronically high serum TSH levels (control, C = 2.31 ± 0.28; methimazole (MMI) 21d = 51.02 ± 6.02 ng/mL, N = 12 rats), when treated with 0.03 percent MMI in drinking water for 21 days, showed significantly reduced thyroid IRS-1 mRNA content. Since goiter was already established in these animals by MMI for 21 days, we also evaluated IRS-1 expression during goitrogenesis. Animals treated with MMI for different periods of time showed a progressive increase in thyroid weight (C = 22.18 ± 1.21; MMI 5d = 32.83 ± 1.48; MMI 7d = 31.1 ± 3.25; MMI 10d = 33.8 ± 1.25; MMI 14d = 45.5 ± 2.56; MMI 18d = 53.0 ± 3.01; MMI 21d = 61.9 ± 3.92 mg, N = 9-15 animals per group) and serum TSH levels (C = 1.57 ± 0.2; MMI 5d = 9.95 ± 0.74; MMI 7d = 10.38 ± 0.84; MMI 10d = 17.72 ± 1.47; MMI 14d = 25.65 ± 1.23; MMI 18d = 35.38 ± 3.69; MMI 21d = 31.3 ± 2.7 ng/mL, N = 9-15 animals per group). Thyroid IRS-1 mRNA expression increased progressively during goitrogenesis, being significantly higher by the 14th day of MMI treatment, and then started to decline, reaching the lowest values by the 21st day, when a significant reduction was detected. In the liver of these animals, however, a significant decrease of IRS-1 mRNA was detected after 14 days of MMI treatment, a mechanism probably involved in the insulin resistance that occurs in hypothyroidism. The increase in IRS-1 expression during goitrogenesis may represent...

Effect of conjugated equine estrogens and tamoxifen administration on thyroid gland histomorphology of the rat

OBJETIVO: Avaliar a ação dos estrogênios conjugados eqüinos e do tamoxifeno na histomorfologia da tireóide de ratas. MÉTODO: Estrogênios conjugados eqüinos são ministrados clinicamente como terapia estrogênica e contêm formulação complexa com muitos tipos de estrogênios que diminuem os sintomas da pós-menopausa. Trinta ratas adultas ooforectomizadas foram divididas aleatoriamente em três grupos: GI – veículo (propilenoglicol); GII - ECE 200 µg/Kg por dia; e GIII – TAM 1 mg/Kg por dia. Acrescentou-se ainda um grupo de 10 animais com os ovários intactos e tratados com veículo (GIV). Todos os animais foram tratados por gavagem durante 50 dias consecutivos, ao final foram coletadas amostras do sangue e a tireóide removida e processada para análise morfológica e imunohistoquímico para avaliar o PCNA. RESULTADOS: A maior altura das células foliculares foi observada nos animais tratados com ECE (14,90 ± 0,20 µm), TAM (14,90 ± 0,10 µm) e no grupo com ovários intactos (15,10 ± 0,50 µm), comparando-se aos controles ovariectomizados (GI) (9,90 ± 0,20 µm) (p<0,001). A maior área folicular foi detectada nos grupos tratados com ECE (2.225 ± 51 µm2) e com TAM (2.127 ± 67 µm2), comparado ao veículo (5.016 ± 53 µm2) em animais ooforectomizados. Os níveis de T4 e T3 nos grupos tratados com ECE, com TAM e no grupo com ovários intactos foram maiores do que no grupo tratado com veículo (p<0,001). O índice do PCNA no grupo tratado com veículo foi menor do que em todos os outros grupos. CONCLUSÃO: Nossos dados sugerem que a administração de ECE e TAM resulta em atividade proliferativa na tireóide.

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0.25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro

Interaction between substance P and gastrin-releasing peptide on thyrotropin secretion by rat pituitary in vitro

The effect of substance P (SP) on thyrotropin (TSH) secretion is controversial. In this study we evaluated the effect of SP on TSH secretion by hemipituitaries of 3-month-old Wistar rats in vitro and its interaction with gastrin-releasing peptide (GRP) at equimolar concentrations (1 µM and 10 µM). TSH release was measured under basal conditions and 30 min after incubation in the absence or presence of SP, GRP or both peptides. Pituitary TSH content was also measured in the pituitary homogenate after incubation. SP at both concentrations caused a significant (P<0.05) increase in TSH secretion compared with all other groups, which was approximately 60 percent (1 µM) and 85 percent (10 µM) higher than that of the control group (23.3 + or - 3.0 ng/ml). GRP at the lower concentration did not produce a statistically significant change in TSH secretion, whereas at the concentration of 10 µM it produced a 50 percent reduction in TSH. GRP co-incubated with substance P completely blocked the stimulatory effect of SP at both concentrations. Pituitary TSH content decreased in the SP-treated group compared to controls (0.75 + or - 0.03 µg/hemipituitary) at the same proportion as the increase in TSH secretion, and this effect was also blocked when GRP and SP were co-incubated. In conclusion, in an in vitro system, SP increased TSH secretion acting directly at the pituitary level and this effect was blocked by GRP, suggesting that GRP is more potent than SP on TSH secretion, and that this inhibitory effect could be the predominant effect in vivo

Alteraciones en la regulación de tirotrofina en el hipotiroidismo congénito / Thyrotropin regulation impairments in congenital hypothyroidism

La TSH constituye uno de los marcadores más importantes para el diagnóstico y control del tratamiento de pacientes con hipotiroidismo congénito (HC). Por otra parte, es conocido desde hace muchos años que algunos niños con HC presentan desde el nacimiento una alteración del umbral de sensibilidad de su unidad hipotálamo-hipofisaria, con niveles elevados de TSH a pesar de una sustitución apropiada. Sin embargo, no existen referencias sobre alteraciones de estas características desarrolladas tardíamente en la evolución del HC. En los últimos 20 años se evaluaron 8 pacientes (7 y 1 ) que presentaban esta situación clínica con diagnóstico etiológico de disenzimia (alteración de la organificación) en 4 casos, disgenesia en 4. La edad cronológica (EC) al diagnóstico e inicio del tratamiento fue de (x y rango): 3,25 (1-8) meses y los valores pretratamiento (mediana y rango) fueron: T4 (µg/dl) = 1,28 (0,2-2,8); TSH = 50 (27-250) mUI/l. La dosis media de T4 utilizada a partir del primer año de vida fue 3,95 (3,03-6,30) µg/kg/día. Bajo tratamiento sustitutivo los pacientes mantuvieron niveles normales para su EC de T3, T4 y TSH durante 7,1 (3,2-10,4) años, a partir del cual presentaron elevación de la TSH a pesar que sus hormonas tiroideas se encontraban en el rango normal: T3 (ng/dl) = 136 (105-180), T4 = 11,1 (8,4-12,0), T4l (ng/dl) = 1,9 (1,4-2,0), TSH basal = 23,5 (14-45,5), TSH post TRH = 55 (40-90). El seguimiento de los pacientes a partir de detectarse la secreción inapropiada de TSH fue de 6,3 (2,8-9,6) años, no constatándose normalización durante dicho período en ninguno de ellos. En todos los casos se incrementó la opoterapia alcanzando valores suprafisiológicos de T4: 13,38 (12,5-15,1) y T4l: 2,16 (2,1-2,3), con manifestaciones de sobredosificación en algunos, obteniéndose la normalización de la TSH basal y post TRH sólo en 2 de ellos. El diagnóstico por imágenes de la región selar no mostró alteraciones en ninguno. En 6 casos se asoció TRIAC al tratamiento con T4 en una dosis de 350 µg (8,1-14,6 µg/kg) con lo que se obtuvo normalización de los niveles de TSH en todos ellos; no constatándose ningún efecto indeseable. Se concluye: * Parecería existir un subgrupo de pacientes con HC quienes desarrollan tardíamente una alteración en la regulación de TSH. * Esto podría reflejar una alteración adquirida en el mecanismo de regulación de la TSH, posiblemente vinculada a una relativa insensibilidad a la T4...

Assessment of levothyroxine suppressive therapy in patients with solitary thyroid nodules: a double-blind, placebo-controlled, clinical trial

The aim of the study was to evaluate the effect of TSH-suppressive therapy with levothyroxine (LT4) on the volume of clinically solitary thyroid nodules, assessing possible correlations between response to therapy and clinical and laboratory parameters. Forty-eight euthyroid patients with a single palpable thyroid nodule (non-autonomous on thyroid scanning, solid or predominantly solid on ultrasonography (US), and benign by fine-needle aspiration biopsy), were followed for 1 year at 3-month intervals. The study group was randomly divided to receive LT4 (200 or 250mcg/day) or placebo, in tablets that were externally identifical. Nodule size was determined by palpation and by US every 6-month. Measurements of T3, T4, TSH, thyroglobulin and anti-thyroid antibodies were performed at baseline and repeated after 3, 6 and 12 months of therapy, whereas thyrotropin-releasing hormone (TRH) test was carried out at 6 months. The number of nodules that decreased in volume on US was not significantly different between the two groups. The mean nodule volume decreased significantly at 6 months in the LT4-treated group, but did not remain significant at 12 months. In the placebo group, the mean nodule volume showed a progressive and significant increase during the study. No correlation was found between clinical and US measurements of the nodules. In the treatment group, nodule size changes were correlated to the scintigraphic characteristics of the nodules. We conclude that LT4 is not effective in reducing the size of most solitary thyroid nodules after 12 months of treatment, although some may shrink or stop to grow after LT4. Further studies are necessary to identify clinical or biochemical variables that could potentially identify the sub-group of responsive nodules.

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (P

Effect of equine hypothalamic extract on hormone secretion by the adenohypophysis of rats

The effect of Equine Hypothalamic Extract (EHE) on pituitary weight and secretion of TSH, FSH-LH and ACTH was studied in the rat. The pituitary respponse to EHE was assessed by measuring (131) I uptake by the thyroid and by weight changes of the pituituray glands, thyroids, adrenals, ovaries and uteri. (131) I uptake of the thyroid and weights of the pituitary, thyroid, adrenal and uterus increased in the treated rats, whereas ovarian weights were similar to control groups. These findings indicate that the EHE containes hypophysiotropic peptides which can stimulate the secretion of pituitary hormones in the rat.

Amiodarona: uma agressäo à funçäo tiroidiana / Amiodarone: a agression to the thyroid function

A presente revisao foi realizada com a finalidade de verificar os efeitos da amiodarona sobre a funcao tiroidiana , visto que a droga e um derivado benzofurano de estrutura similar a iodo-tironina e tambem possui atomos de iodo em sua composicao molecular. O estudo foi baseado na analise retrospectiva dos ultimos 10 anos, quanto as propriedades da aminodarona em relacao ao tempo de administracao e quanto aos possiveis efeitos sobre os hormonios tiroidianos TSH e proteinas ligadoras de tiroxina, bem como o desencadeamento do fenomeno autoimune corroborando numa das provaveis patogeneses do desenvilvimento de hipo ou hipertiroidismo. Foram tambem relatados estudos da cinetica dos hormonimos tiroidianos e acoes farmacologicas da aminodarona em outros orgaos. Um numero significativo de pacientes desenvolveu alteracoes da glandula tireoide durante a terapia com amiodarona e tal fato pode ser explicado pelo excesso de iodo contido na droga, o qual pode acarretar tanto hipotiroidismo como hipertiroidismo, existindo controversias quanto a incidencia de ambos. A aminodarona e um antiarritmico de classe III, usado no tratamento e prevencao das arritmias cardiacas, sendo de suma importancia que sua administracao seja criteriosa, uma vez conhecidas as anormalidades induzidas pela droga, principalmente na glandula tireoide. Se possivel proscrever o seu uso em individuos com antecedente pessoal ou familiar, com patologias da tireoide