Gisah Amaral de Carvalho

Low-normal or high-normal thyrotropin target levels during treatment of hypothyroidism: a prospective, comparative study.

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

A relação entre a função tireoidiana e a depressão: uma revisão

OBJECTIVE The role of the thyroid gland in primary depressive disorder is unclear. Although there is evidence that patients with subtle underlying defects in thyroid function may be more prone to developing depressive disease, the specific abnormality in thyroid function associated with depressive disorders remains poorly understood. In this review, we outline the major findings concerning depression and thyroid function, with particular attention on the relationship between thyroid function and cerebral monoamines. METHODS Literature searches were performed by Medline, with secondary-source follow-up. RESULTS The documented hypothalamus-pituitary-thyroid (HPT) axis abnormalities in some depressed patients are: elevated T4 concentrations, abnormal TSH responses to TRH; presence of antithyroid antibodies and elevated CSF - TRH concentrations. The relation of these abnormalities of HPT function, the main monoamines and the diagnostic subtypes of patients with depression is complex and does not directly support a linear relationship. CONCLUSIONS After many years of research, the precise relationship between the HPT axis and depressive disorders remains obscure, and the mechanism underlying the thyroid abnormalities in depressive patients remains indeterminate. Thus, considerable further investigation will be necessary to understand the role of the HPT axis in the pathogenesis and treatment of depressive disorders.

Clinical and Molecular Analysis of Thyroid Hypoplasia: A Population-Based Approach in Southern Brazil

BACKGROUND Congenital hypothyroidism (CH) is mainly due to developmental abnormalities leading to thyroid dysgenesis (TD). TD encompasses very distinct morphologic subtypes of disease. This study examined and compared the phenotype in TD variants and searched for genetic alterations in sporadic thyroid hypoplasia (TH), the most misdiagnosed form of CH. This was a longitudinal study over a 14-year period (1990-2004). METHODS A continuous series of 353 children with TD was identified using thyroid function tests [thyroxine (T4) and TSH], scintigraphy, and ultrasound as diagnostic tools. Individual phenotypes were analyzed in 253 children with TD. Mutations in the most likely candidate genes were studied in 35 cases of TH. RESULTS The overall birth prevalence of permanent CH was 1:4795. Ectopy represented 37% of all cases of permanent primary CH, dyshormonogenesis 28%, agenesis 24%, hypoplasia 10%, and hemiagenesis 1%. The lowest screening T4 level and the highest TSH level were in the agenetic group, followed by TH. The TH group had an improvement in the thyroid function showing less-severe phenotype with aging. In the molecular analysis, one patient was identified with a mutation in the PAX8 gene (155G>C; R52P); four patients had a heterozygous G>C substitution in position -569; two patients showed a (234C>A; P52T) or (2181C>G; D727E) polymorphic variants of the TSH-R gene; and one patient presented a novel heterozygous nonsynonymous substitution, 293G>A; S98N, in the NKX2.5 gene. CONCLUSIONS The prevalence of CH was within the previously reported range of 1:3000-4000. Ectopy was the most common etiology. Clinical analysis revealed distinct hormonal patterns in TH subgroup when compared with other variants of TD, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes.

Nódulos de tireóide e câncer diferenciado de tireóide: consenso brasileiro

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5‐10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. (Arq Bras Endocrinol Metab 2007;51/5:867-893)Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 +/- 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 +/- 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 +/- 9.7 to 49.6 +/- 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 +/- 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 +/- 0.48 ng/dL for free-T4, 204.61 +/- 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 +/- 14.3% after 6 months (P < 0.001) and by 46.0 +/- 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre.

Context:  High doses of 131I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid‐stimulating hormone (rhTSH) is an adjuvant to enhance 131I uptake, allowing a decrease in radiation activity and enhancing 131I efficacy.

Effects of selective serotonin reuptake inhibitors on thyroid function in depressed patients with primary hypothyroidism or normal thyroid function.

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 (T(4)), free thyroxine, triiodothyronine (T(3)), 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 T(3) after 15 and 30 days of treatment (p = 0.034 and p = 0.011) and a significant reduction of T(4) throughout 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 T(3) levels reduction among patients with normal thyroid function randomized for sertraline and among patients with hypothyroidism randomized for fluoxetine. T(3) levels 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.

Adequacy and Diagnostic Accuracy of Aspiration vs. Capillary Fine Needle Thyroid Biopsies

Thyroid nodules can be biopsied by fine needle aspiration (FNA) or fine needle capillary (FNC) biopsies. However, there is controversy on whether one technique is superior to another. In a randomized cytopathologist-blinded cross-sectional study, 260 patients (238 females, age 43.2 ± 12.6) with nodular (82.7%) and diffuse goiter (17.3%) underwent 520 FNAs and 520 FNCs (not guided by ultrasound). Smears were scored for sample adequacy, and diagnosed as malignant, benign, suspicious, or nondiagnostic. Diagnostic accuracy was calculated based on the histological findings of 58 patients submitted to surgery. Intra-technique diagnostic accuracy and sample adequacy was seen in all samples. FNA and FNC provided similar cytological diagnosis, respectively (benign: 75.8% vs. 74.2%, p = 0.600; malignant: 3.8% vs. 3.8%, p = 0.871; suspicious: 10.4% vs. 10.8%, p = 0.913; and nondiagnostic: 10.0% vs. 11.2%, p = 0.598). Adequacy scores were similar by FNA (7.94 ± 2.84) and FNC (7.96 ± 2.81, p = 0.909). The same proportion of adequate or superior samples was seen in both techniques (91.6%). Sensitivity was equal to 85.7% for FNA and 100% for FNC. Similarly, specificity was 100% for both techniques. FNA and FNC provide the similar sample adequacy and diagnostic accuracy. The choice of technique should be based on the operator’s personal preferences and experience.

Serum Thyrotropin Levels Following Levothyroxine Administration at Breakfast

BACKGROUND Hypothyroidism is treated with oral levothyroxine. Some patients fail to attain adequate control because of poor compliance. Delaying breakfast to take levothyroxine on an empty stomach can decrease adherence to hypothyroidism treatment. The objective of this study was to evaluate whether administering levothyroxine with breakfast can maintain thyrotropin (TSH) levels in the therapeutic range, without major clinical changes. METHODS A prospective, randomized, open-label, crossover study was conducted to compare usual levothyroxine administration while in a fasting state with administration during breakfast. From September 2008 to April 2009, 45 patients with primary hypothyroidism who received levothyroxine were recruited. The patients completed 180 days of the protocol and were randomized to 90 days of each levothyroxine administration regimen (while fasting or with breakfast). Clinical and biochemical analyses were performed at baseline and on days 45, 90, 135, and 180. The primary outcome was TSH level. RESULTS Forty-two patients completed the protocol. The TSH level was higher for levothyroxine administration with breakfast than while fasting (2.89 vs. 1.9 mIU/L, p=0.028). Uncontrolled hypothyroidism (TSH ≥3.5 mIU/L) occurred regardless of the type of levothyroxine administration (p=0.26). No risk factors were identified for TSH elevation. CONCLUSIONS Levothyroxine administration with breakfast could be an alternative regimen for patients who have adherence difficulties due to the need for delaying intake, and is more likely to cause variability in the TSH level, meaning the patient should be followed more closely. For patients in whom a specific serum TSH goal is important, taking levothyroxine while fasting is recommended.

How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study.

Background: Studies from every continent have shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range. However, to date, there are no consistent data about Brazil. Objectives: To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil. Methods: Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro — UFRJ, Unicamp, Universidade Federal do Paraná — UFPR and Universidade Federal do Ceará-UFC) answered a questionnaire that inquired about clinical and biochemical conditions, social-economic status, life quality and clinicians’ orientations as well as their understanding about the information given. Serum TSH was checked close to the interview. Results: 2292 consecutive patients met the inclusion criteria. Mean age 51.2 yr and TSH values between 0.4 and 4.0 mUI/l were considered to be within the reference range. Among all patients taking thyroid medication, 42.7% had an abnormal serum TSH (28.3% were undertreated and 14.4% were overtreated). Approximately all patients (99%) took LT4 in the morning but less than 30 min before breakfast (85.4%). Regarding the clinicians’ orientations: 97.5% of the patients were instructed to take the medication daily, and 92.6% to take 30 min before breakfast (92.6%). However, only 52.1% were told not to take LT4 along with other medication. Conclusions: Our study found that a significant number of patients taking thyroid hormones were not in the therapeutic range. Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.