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ABSTRACT Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

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.

O objetivo deste artigo é realizar uma atualização sobre a ação de antidepressivos, com destaque aos inibidores seletivos de recaptação de serotonina (ISRS) na função tireoidiana de pacientes com depressão. Sete ensaios clínicos investigaram o efeito dos ISRS sobre a função tireoidiana. Apesar das diferenças metodológicas, o principal achado foi a tendência à diminuição dos níveis plasmáticos de tiroxina, não necessariamente relacionada com a resposta clínica, e sem efeito sobre a tireotropina na maioria das pesquisas. Os estudos sugerem que os ISRS promovem efeitos na função tireoidiana em alguns pacientes com depressão, especificamente diminuição nos níveis plasmáticos de tiroxina. Porém, observou-se que a relação entre o uso de antidepressivos ISRS e a função tireoidiana não está suficientemente esclarecida. Mesmo nos casos de alteração nos níveis plasmáticos dos hormônios tireoidianos em resposta a ação dos ISRS, esta pode ser uma ação não específica sobre a função tireoidiana.This article aims at updating antidepressant action, especially using selective serotonin reuptake inhibitors, on thyroid function in depressed patients. Seven clinical trials investigated the status of thyroid hormones after treatment with SSRIs. Despite methodological differences, the main finding indicated a tendency towards decreased serum thyroxine levels, The majority of studies could not find a positive relationship between lower serum thyroxine level and a favorable treatment response. Also, an effect on thyrotropin could not be found. Those study results suggest SSRIs promote effects on thyroid function in some depressed patients, specifically decreased serum thyroxine levels. However, the relation between SSRIs antidepressant use and thyroid function is not clear. Even when there was a change in serum thyroid hormone levels due to SSRI therapy, this could be a non-specific effect on thyroid function.

OBJETIVO: O papel da função tireoidiana nas doenças depressivas é pouco claro. Embora existam algumas evidências de que discretas alterações tireoidianas predisponham a casos de depressão, as anormalidades específicas envolvendo a tireóide e os quadros depressivos permanecem pouco conhecidas. Serão destacados nesta revisão os principais achados envolvendo os quadros depressivos e a função tireoidiana, com especial atenção na participação das monoaminas cerebrais nesta relação. MÉTODO: Foram realizados levantamento no sistema Medline e na literatura. RESULTADOS: Existem evidências de atividade alterada do eixo hipotálamo-hipófise-tireóide (HHT) em alguns casos de depressão, que incluem: aumento dos níveis de T4, resposta alterada do TSH pós-estímulo com TRH, presença de anticorpos antitireoidianos e concentração elevada de TRH no LCR. A relação entre estas anormalidades, as principais monoaminas cerebrais e os subtipos de quadros depressivos é complexa e ainda não permite o estabelecimento de hipóteses diretas de compreensão. CONCLUSÕES: Após anos de pesquisas, permanece pouco esclarecida a importância da relação entre o eixo HHT e as depressões, assim como os mecanismos subjacentes às alterações tireoidianas encontradas nos pacientes deprimidos. Portanto, mais pesquisas serão necessárias para uma melhor compreensão do papel do eixo HHT na patogênese e no tratamento dos quadros depressivos.

Background:Recent literature advocates the decrease of the upper limit of the normal thyrotropin (TSH) reference range. The objective of this study was to determine whether treated hypothyroid patients maintained within a low-normal TSH range (0.4–2.0 mIU/L) have better clinical outcomes than those maintained within a high-normal TSH range (2.0–4.0 mIU/L).Methods:The study was performed in a thyroid outpatient clinic of a tertiary hospital. This was a prospective, interventional study. Forty-two participants with newly diagnosed overt primary hypothyroidism were paired in two groups: group 1 (n= 20), low-normal target TSH; group 2 (n= 22), high-normal target TSH. Levothyroxine was initiated, and dose was adjusted to achieve and sustain the target TSH value during the study period. After the target TSH was reached, participants were evaluated every 3 months for thyroid function, serum lipid profile, resting energy expenditure (REE), body composition, and bone mineral density, for 12 months.Results:Nineteen patients in group 1 and 16 in group 2 completed the study. In the whole-group analysis, total cholesterol (p= 0.01), low-density lipoprotein cholesterol (p= 0.004), and triglycerides (p< 0.001) decreased after treatment, whereas REE per kilogram of lean body mass (p= 0.001) and total fat body mass (p= 0.02) increased. Group 1 patients had a significantly higher relative increase in REE (+7.1% ± 11.3% vs. +3.6% ± 15.1%, p= 0.02). There was no difference between the groups in the other variables.Conclusions:Despite recent trends toward lowering the upper limit of normal TSH range, the results of this 12-month study provided no substantial clinical evidence to corroborate that treatment of primary hypothyroidism should aim at maintaining TSH levels in a low-normal range. [ABSTRACT FROM AUTHOR]

Background:Several studies with ambiguous results have examined the effects of selective serotonin reuptake inhibitors (SSRIs) on thyroid function. This study aimed to establish the effects of fluoxetine and sertraline treatments on thyroid function and thyroid autoimmunity in patients with major depression and primary hypothyroidism and in patients with major depression and normal thyroid function.Methods:This was a prospective, controlled, intervention study involving 67 subjects: 28 patients with major depression and hypothyroidism on adequate levothyroxine therapy randomized for treatment with fluoxetine (n= 13) or sertraline (n= 15); 29 patients with major depression and normal thyroid function treated with fluoxetine (n= 15) or sertraline (n= 14) and 10 control patients with hypothyroidism on adequate levothyroxine therapy without depression. Main outcome measures included thyrotropin, thyroxine (T4), free thyroxine, triiodothyronine (T3), anti–thyroid peroxidase antibodies, and Hamilton depression (HAM-D) rating scale.Results:Patients with normal thyroid function who were treated with fluoxetine demonstrated a significant reduction of T3after 15 and 30 days of treatment (p= 0.034 and p= 0.011) and a significant reduction of T4throughout the intervention period (p= 0.04 after 15 days; p= 0.015 after 30 days; and p= 0.029 after 90 days). However, all thyroid parameters remained within the euthyroid range. No changes were observed among hypothyroid patients on levothyroxine replacement therapy who were treated with either SSRI. The degree of improvement in depression symptoms (HAM-D rating scale) after 90 days of SSRI treatment was correlated with T3levels reduction among patients with normal thyroid function randomized for sertraline and among patients with hypothyroidism randomized for fluoxetine. T3levels remained within the euthyroid range during the study period.Conclusions:Neither fluoxetine nor sertraline was associated with clinically significant changes in thyroid function or thyroid autoimmunity in either primary hypothyroid or normal thyroid function patients with depression. However, results suggest that patients with normal thyroid function who were treated with fluoxetine are more susceptible to minor changes within the serotoninergic system than patients with hypothyroidism on the same SSRI therapy. To the best of our knowledge, this is the first study to demonstrate the safety of administering SSRIs in hypothyroid patients. [ABSTRACT FROM AUTHOR]