Elsevier

The Lancet

Volume 379, Issue 9821, 24–30 March 2012, Pages 1142-1154
The Lancet

Seminar
Subclinical thyroid disease

https://doi.org/10.1016/S0140-6736(11)60276-6Get rights and content

Summary

Subclinical thyroid diseases—subclinical hyperthyroidism and subclinical hypothyroidism—are common clinical entities that encompass mild degrees of thyroid dysfunction. The clinical significance of mild thyroid overactivity and underactivity is uncertain, which has led to controversy over the appropriateness of diagnostic testing and possible treatment. In this Seminar, we discuss the definition, epidemiology, differential diagnoses, risks of progression to overt thyroid disease, potential effects on various health outcomes, and management of subclinical hyperthyroidism and subclinical hypothyroidism. Treatment recommendations are based on the degree to which thyroid-stimulating hormone concentrations have deviated from normal and underlying comorbidities. Large-scale randomised trials are urgently needed to inform how to best care for individuals with subclinical thyroid disease.

Introduction

The term subclinical denotes the presence of a disease without obvious symptoms, which means that evolution of the disease might be at an early stage.1 Subclinical has been applied to many medical situations (eg, subclinical cardiovascular disease and subclinical Lyme disease), but subclinical thyroid disease is perhaps the most familiar. Subclinical thyroid disease is defined biochemically: subclinical hyperthyroidism occurs when serum thyroid-stimulating hormone (TSH) concentrations are low or undetectable but free thyroxine (T4) and tri-iodothyronine (T3) concentrations are normal, and subclinical hypothyroidism occurs when serum TSH concentrations are raised and serum thyroid hormone concentrations are normal. By contrast, overt thyroid dysfunction describes more severe thyroid derangements, in which serum concentrations of free T4 or T3 are outside of their reference ranges.

Diagnosis of subclinical thyroid disease is based on the exquisite sensitivity of the hypothalamic-pituitary-thyroid axis. Serum TSH secretion changes logarithmically with arithmetic changes in serum concentrations of free T4. Therefore, alterations in serum free T4 that are within the normal range will cause increases or decreases in serum TSH that are likely to be outside its reference range (figure 1). An important corollary to this concept is that each individual seems to have a specific set point for the hypothalamic-pituitary-thyroid axis,2 which is, to a large extent, genetically determined.3, 4

In this Seminar, we present the epidemiology, causes, diagnosis, and management of each disorder, including specific therapies, when indicated. We also discuss issues of controversy, especially in screening and treatment, and we review clinical practice guidelines.

Section snippets

Disease forms

Subclinical hyperthyroidism is a form of hyperthyroidism, such that as TSH progressively decreases indicating worsening thyroid overactivity, the probability of clinically significant consequences increases. Subclinical hyperthyroidism can be divided into two categories: exogenous disease caused intentionally or unintentionally by thyroid hormone therapy, and endogenous disease caused by conditions responsible for most forms of overt hyperthyroidism (panel 1). Exogenous subclinical

Disease forms

Most experts agree that subclinical hypothyroidism represents early, mild thyroid failure. Dependent on the size of the increase in serum TSH, subclinical hypothyroidism can be mild (serum TSH concentrations of 4·5–9 mU/L) or severe (TSH ≥10 mU/L).78 At least 75% of patients with subclinical disease have mild thyroid dysfunction (TSH ≤10 mU/L).5 The definition and the clinical significance of subclinical hypothyroidism are confounded by controversies over the correct upper limit of the

Conclusions

Subclinical thyroid disease is a common clinical problem, and since most patients are asymptomatic, screening is the only way that most patients with the condition will be detected. Yet, experts do not agree about whether screening to diagnose the disease is worthwhile, because there are no large, population-based randomised controlled trials showing that intervention is beneficial to patients. The data are sufficient, however, to recommend treatment of individuals with subclinical

Search strategy and selection criteria

We searched Medline for reports published from January, 2000, to December, 2010, with the search terms “subclinical hyperthyroidism” and “subclinical hypothyroidism”. The search was restricted to reports published in English, but included translated articles. We supplemented the search with records from personal files and references of relevant articles and textbooks. We focused on reports published since 2006, the few clinical trials that have been done, and population-based studies, but

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