Avaliação comparativa dos efeitos do tratamento do Hipotireoidismo primário entre pacientes mantidos com níveis de hormônio estimulador da tireóide sérico normal - alto e normal - baixo.

Orientadora: Profª Drª Gisah Amaral de CarvalhoCo-orientador: Prof. Dr. Rosana Bento RadominskiDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Medicina Interna. Defesa : Curitiba, 07/08/2009Bibliografia: fls. 120-130Resumo: Dados recentes da literatura apresentam evidências que sugerem a redução do limite superior de referência de normalidade do hormônio estimulador da tireóide (TSH) sérico. O objetivo do presente estudo foi determinar se a terapia com levotiroxina, durante o tratamento do hipotireoidismo primário em um grupo de pacientes mantidos com níveis de TSH sérico normal-baixo (0,4 – 2,0 mUI/L), estaria associada a melhores resultados clínicos do que em um outro grupo de pacientes mantidos com níveis de TSH sérico normal-alto (2,0 – 4,0 mUI/L). Conduziu-se um estudo prospectivo experimental envolvendo 42 pacientes com hipotireoidismo primário, recém-diagnosticados e sem tratamento prévio. Os pacientes foram pareados em 2 grupos de acordo com o sexo, a idade e o índice de massa corporal (IMC): Grupo 1 (n=20) – TSH alvo normal-baixo (0,4 – 2,0 mUI/L) e Grupo 2 (n=22) – TSH alvo normal-alto (2,0 – 4,0 mUI/L). O tratamento com levotiroxina foi iniciado para a obtenção e manutenção dos níveis de TSH sérico dentro do alvo adequado durante todo o estudo. Os pacientes foram avaliados no diagnóstico (basal), mensalmente até a obtenção de 2 valores consecutivos de TSH sérico dentro do alvo determinado para o grupo e trimestralmente até o término do estudo com 12 meses de seguimento. As variáveis avaliadas foram: função tireoidiana, perfil lipídico, creatino-fosfoquinase (CPK), gasto energético basal, peso, IMC, composição corporal e densidade mineral óssea (DMO). 35 pacientes completaram o estudo, sendo 19 do Grupo 1 e 16 do Grupo 2. Os efeitos do uso da levotiroxina no tratamento do hipotireoidismo foram avaliados no grupo total (n=35). A análise estatística demonstrou uma significativa redução percentual nos níveis de colesterol total (p=0,01), LDL colesterol (p=0,004), triglicerídios (p<0,001) e CPK (p=0,001). Adicionalmente, o tratamento do hipotireoidismo associou-se a uma elevação estatisticamente significativa do gasto energético basal por quilograma de massa magra corporal (p=0,001) e do percentual de gordura corporal (p=0,02). Durante o tratamento do hipotireoidismo, o grupo 1 apresentou uma menor elevação percentual dos níveis de colesterol total do que o grupo 2 (p=0,043). Demonstrou-se também que o grupo 1 apresentou uma maior elevação percentual no gasto energético basal do que o grupo 2 (p=0,02). Não foram apresentadas variações percentuais estatisticamente significativas entre os dois grupos de tratamento em relação às demais variáveis avaliadas. Apesar dos dados da literatura apresentarem evidências que tendem a recomendar a redução do limite superior de normalidade do TSH, os resultados do presente estudo não demonstram evidências clínicas significativas para corroborar com a recomendação de que pacientes com hipotireoidismo primário em tratamento com levotiroxina devam ser mantidos com níveis de TSH sérico normal-baixo.Abstract: Recent specific literature provided data that supports the recommendation to decrease the upper limit of the normal thyroid stimulating hormone (TSH) reference range. The aim of this study was to determine whether treatment with levothyroxine in a group of hypothyroid patients maintained within a low-normal TSH range (0,4 – 2,0 mUI/L) was associated with better clinical outcomes than those observed in a group of hypothyroid patients maintained within a high-normal TSH range (2,0 – 4,0 mUI/L). We conducted a prospective interventional study with 42 subjects newly-diagnosed with primary hypothyroidism, without previous treatment. Patients were paired in two groups by age, sex and body mass index (BMI): Group 1(n=20): low-normal TSH target (0,4 – 2,0 mUI/L) and Group 2 (n=22): high-normal TSH target (2,0 – 4,0 mUI/L). Levothyroxine was initiated to maintain the correct TSH target value during the study period. Patients were evaluated on baseline, monthly until they reached the target TSH and every 3 months until study termination with a 12 month follow-up. Evaluated variables were: thyroid function, serum lipid profile, CPK levels, resting energy expenditure, weight, BMI, body composition and bone mineral density. 35 patients completed the study, 19 in group 1 and 16 in group 2. The effects of levothyroxine treatment of hypothyroidism were analyzed within the whole group (n=35). Statistical analysis demonstrated a significant relative reduction in total cholesterol (p=0,01), LDL cholesterol (p=0,004), triglicerydes (p<0,001) and CPK levels (p=0,001). Also, treatment of hypothyroidism was associated with a significant relative increase in the resting energy expenditure per kilogram of lean body mass (p=0,001) and in the percentage of body fat (p=0,02). During the treatment of hypothyroidism, the group 1 presented a significant lower elevation of total cholesterol levels than the group 2 (p=0,043). Also, the group 1 presented a significant higher relative increase of the resting energy expenditure than the group 2 (p=0,02). The other evaluated variables showed no relative differences between the groups during the study period. Despite recent literature trends towards lowering the upper limit of normal TSH range, the results of the present study provided no clinical evidence to corroborate that patients on levothyroxine treatment for primary hypothyroidism should be maintained in a low-normal TSH range

First reports of computed tomographic colonography for the screening of colorectal polyps in acromegalic patients

*Aim:* To analyze the CTC performance for the screening of colorectal polyps in acromegalic patients. &#xd;&#xa;&#xd;&#xa;*Materials and Methods:* A prospective study of 21 acromegalic patients, 12 male and 9 female, average age 49, who underwent CTC and CC. CTC was performed with a GE Helical Multislice Computed Tomography Apparatus. The colonoscopy was performed, in the same day, without previous knowledge of the CTC diagnostics. The study evaluated the capacity of CTC to detect patients with colorectal polyps and identify each colorectal lesion described by CC. &#xd;&#xa;&#xd;&#xa;*Results:* In two patients (2/21), CC was incomplete. However, in all patients CTC was complete. In Phase I (&#x201c;Per Patient&#x201d;), CTC diagnosed 8 of the 9 patients with colorectal polyps and showed 88% sensitivity, 75% specificity and 81% accuracy. In Phase II (&#x201c;Per Polyp&#x201d;), out of the 21 acromegalic patients included in this study, 12 presented normal findings at CC. A total of 19 polyps were identified in 9 patients. 10 of the 19 polyps were smaller than 10 mm, and 9 were equal to or larger than 10. CTC identified 7 of the 9 polyps &#x2265; 10 mm described by CC and only 6 of the 10 small polyps identified at CC were detected by CTC. The histological analysis of resected lesions revealed 12 tubular adenomas, 6 hyperplastic polyps and 1 colonic tubulo-villous adenoma with an adenocarcinoma focus. &#xd;&#xa;&#xd;&#xa;*Conclusion:* In this study, CTC was performed without complications and a complete and safe colorectal evaluation was possible in all acromegalic patients. Moreover, CTC showed good sensitivity to identify acromegalic patients with colorectal polyps

Efeito dos antidepressivos ISRS sobre os hormônios tireoidianos

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

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 (0.4-2.0mIU/L) have better clinical outcomes than those maintained within a high-normal TSH range (2.0-4.0mIU/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

Outcome of surgical treatment for acromegaly performed by a single neurosurgeon and cumulative meta-analysis

The aim of this retrospective study was to evaluate the results of transsphenoidal surgery in a group of patients with acromegaly who were operated by the same neurosurgeon. Our results were compared to those from a cumulative meta-analysis of 10 series (1,632 patients) published between 1992-2005. We followed 28 patients (17M/11F; 44.1 ± 12.7 yr; 27 with macroadenomas; 86% being invasive) during 21.4 ± 17.6 months after treatment. Patients were classified according to disease activity as follows: 1) controlled (CD): basal or mean GH 2.5 ng/ml or nadir GH > 1 ng/ml and elevated IGF-1; 3) inadequately controlled (ICD): normal GH and elevated IGF-1 or elevated GH and normal IGF-1. After surgery, GH levels decreased from 61.7 ± 101.1 ng/ml to 7.2 ± 13.7 ng/ml (p< 0.001) and mean IGF-1 from 673.1 ± 257.7 ng/ml to 471.2 ± 285 ng/ml (p= 0.01). Biochemical remission rate was 57% [10 (35.5%) patients with CD and 6 (21.5%) with ICD], similar to the mean remission rate observed in the meta-analysis of surgical outcome of macroadenomas. Seven of 28 patients were submitted to surgical re-intervention (4 had been previously operated elsewhere and 3 by our neurosurgeon), with CD observed in 5 (71.5%) on follow-up. Cavernous sinuses invasion was more prevalent in UCD and ICD, whereas infundibular stalk deviation occurred only in patients with UCD. Remission rate was significantly higher in series where all surgical procedures were performed by the same surgeon (66% vs. 49%; p< 0.05). Thus, the surgeon's experience significantly improves the surgical outcome in acromegaly, especially in patients harboring large and invasive tumors, and re-intervention performed by an experienced surgeon should be considered in the algorithms for clinical management of this disease