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Thyroid hormone replacement for subclinical hypothyroidism

  • Review
  • Intervention

Authors

  • Heloisa Cerqueira Cesar Esteves Villar,

    Corresponding author
    1. Faculdade Estadual de Medicina de Marília, Departamento de Medicina Interna, Marília, São Paulo, Brazil
    • Heloisa Cerqueira Cesar Esteves Villar, Departamento de Medicina Interna, Faculdade Estadual de Medicina de Marília, Av. Cascata 123, Marília, São Paulo, 17515-300, Brazil. hvillar@famema.br.

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  • Humberto Saconato,

    1. Federal University of Rio Grande do norte, Department of Medicine, São Paulo, Vila Clementino, Brazil
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  • Orsine Valente,

    1. Universidade Federal de São Paulo / Escola Paulista de Medicina, Department of Internal Medicine, São Paulo, Brazil
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  • Álvaro N Atallah

    1. Universidade Federal de São Paulo / Escola Paulista de Medicina, Brazilian Cochrane Centre, São Paulo, SP, Brazil
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Abstract

Background

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormones values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general population, and up to 15% to 18% in women who are over 60 years of age. There is considerable controversy regarding the morbidity, the clinical significance of subclinical hypothyroidism and if these patients should be treated.

Objectives

To assess the effects of thyroid hormone replacement for subclinical hypothyroidism.

Search methods

We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. Ongoing trials databases, reference lists and abstracts of congresses were scrutinized as well.

Selection criteria

All studies had to be randomised controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. We contacted study authors for missing or additional information.

Main results

Twelve trials of six to 14 months duration involving 350 people were included. Eleven trials investigated levothyroxine replacement with placebo, one study compared levothyroxine replacement with no treatment. We did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids, there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time as well as diastolic dysfunction. Only four studies reported adverse events with no statistically significant differences between groups.

Authors' conclusions

In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.

Plain language summary

Thyroid hormone replacement for subclinical hypothyroidism

Subclinical hypothyroidism is a condition where some laboratory findings point at a thyroid gland not working properly. Patients with subclinical hypothyroidism may have vague, non-specific symptoms of actual hypothyroidism (for example dry skin, cold skin or feeling colder, constipation, slower thinking, poor memory) but these thyroid-related symptoms are not specific, that is why the diagnosis is based on test results. The fundamental question regarding people with subclinical hypothyroidism is whether they should be treated with thyroid hormones. To answer this question twelve studies of six to 14 months duration involving 350 people were analysed. Thyroid hormone therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity (for example less heart attacks or strokes). Data on health-related quality of life and symptoms did not demonstrate significant differences between placebo and thyroid hormone therapy. Some evidence indicated that thyroid hormone had some effects on blood lipids and technical measurements of heart function. Adverse effects were inadequately addressed in most of the included studies and have to be urgently investigated in future studies, especially in older patients.

Ringkasan bahasa mudah

Penggantian hormon tiroid untuk hipotiroidisma subklinikal

Hipotiroidisma subklinikal adalah satu keadaan di mana beberapa keputusan makmal yang menunjukkan kelenjar tiroid tidak berfungsi dengan baik. Pesakit dengan hipotiroidisma subklinikal mungkin mempunyai tanda-tanda yang tidak jelas dan spesifik seperti dalam hipotiroidisma sebenar (contohnya kering kulit, kulit yang sejuk atau rasa kesejukan, sembelit, lambat berfikir, ingatan lemah) tetapi mengalami gejala-gejala berkaitan tiroid yang tidak spesifik, yang oleh sebab itulah diagnosisnya berdasarkan keputusan ujian makmal. Persoalan asas mengenai penghidap hipotiroidisma subklinikal adalah sama ada mereka harus dirawat dengan hormon tiroid atau tidak. Untuk menjawab persoalan ini, dua belas kajian yang dijalankan dalam tempoh enam hingga 14 bulan yang melibatkan 350 orang telah dianalisa. Terapi hormon tiroid untuk hipotiroidisma subklinikal tidak meningkatkan jangkahayat atau menurunkan morbiditi berkaitan kardiovaskular (contohnya mengurangkan serangan jantung atau angin ahmar). Data kualiti hidup yang berkaitan kesihatan dan gejala-gejala yang dihadapi tidak pula menunjukkan perbezaan yang signifikan antara plasebo dan terapi hormon tiroid. Beberapa bukti menunjukkan bahawa hormon tiroid mempunyai kesan ke atas kandungan lipid darah dan pengukuran teknikal fungsi jantung. Kesan sampingan tidak diberi perhatian secukupnya dalam kebanyakan kajian dan perlu diselidik segera dalam kajian akan datang, terutamanya dalam kalangan pesakit yang lebih tua.

Catatan terjemahan

Diterjemahkan oleh Irfan Mohamad (Universiti Sains Malaysia). Disunting oleh Norhayati Mohd Noor (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi irfankb@usm.my Untuk sebarang pertanyaan berkaitan suntingan ini, sila hubungi hayatikk@usm.my

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