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
SeminarSubclinical 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
References (145)
- et al.
Iodine intake as a determinant of thyroid disorders in populations
Best Pract Res Clin Endocrinol Metab
(2010) - et al.
The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis
Am J Med
(1994) - et al.
An analysis of the natural course of subclinical hyperthyroidism
Am J Med Sci
(2009) - et al.
Thyroid hormones and cardiac arrhythmias
Vascul Pharmacol
(2010) - et al.
Endogenous subclinical hyperthyroidism: Metabolic and cardiac parameters
Eur J Intern Med
(2007) - et al.
Subclinical hyperthyroidism as a risk factor for atrial fibrillation
Am Heart J
(2001) - et al.
Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: a meta-analysis
Int J Cardiol
(2008) - et al.
Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism
Maturitas
(2004) - et al.
A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism
Am J Med
(2002) Stedman's Medical Dictionary
(2006)
Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease
J Clin Endocrinol Metab
Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins
J Clin Endocrinol Metab
Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity
J Clin Endocrinol Metab
The Colorado thyroid disease prevalence study
Arch Intern Med
High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over
J Clin Endocrinol Metab
The clinical significance of subclinical thyroid dysfunction
Endocr Rev
Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy
J Clin Endocrinol Metab
Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)
J Clin Endocrinol Metab
The Thyroid Epidemiology, Audit, and Research Study (TEARS): the natural history of endogenous subclinical hyperthyroidism
J Clin Endocrinol Metab
Thyroid status, cardiovascular risk, and mortality in older adults
JAMA
Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark
J Clin Endocrinol Metab
Complex alteration of thyroid function in healthy centenarians
J Clin Endocrinol Metab
Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III)
J Clin Endocrinol Metab
Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom
Clin Endocrinol (Oxf)
Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians
Arch Intern Med
The natural history of subclinical hyperthyroidism in patients below the age of 65 years
Clin Endocrinol (Oxf)
Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0·1 and 0·4 mIU/l: a prospective study
Clin Endocrinol (Oxf)
Subclinical thyrotoxicosis in an outpatient population-predictors of outcome
Clin Endocrinol (Oxf)
Incidence of hyperthyroidism in Stockholm, Sweden, 2003–2005
Eur J Endocrinol
Hyperthyroidism in patients older than 55 years: an analysis of the etiology and management
Gerontology
Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy
J Endocrinol Invest
Thyroid disease and the heart
Circulation
Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients
J Clin Endocrinol Metab
The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism on clinical and heart abnormalities
J Clin Endocrinol Metab
Thyroid function and left ventricular structure and function in the Framingham Heart Study
Thyroid
Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up
Clin Endocrinol (Oxf)
Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism
Eur J Endocrinol
Normal systolic time intervals in subclinical hyperthyroidism
J Endocrinol Invest
Low serum thyrotropin is associated with high plasma fibrinogen
J Clin Endocrinol Metab
Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity
Clin Endocrinol (Oxf)
Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review
Clin Appl Thromb Hemost
Thyroid function and carotid wall thickness
J Clin Endocrinol Metab
The association of thyroid function with carotid artery plaque burden and strokes in a population-based sample from a previously iodine-deficient area
Eur J Endocrinol
Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the Carotid Atherosclerosis Progression Study (CAPS)
Eur Heart J
Association between serum free thyroxine concentration and atrial fibrillation
Arch Intern Med
Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons
N Engl J Med
Thyroid status, disability and cognitive function, and survival in old age
JAMA
Association between increased mortality and mild thyroid dysfunction in cardiac patients
Arch Intern Med
Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study
Eur J Endocrinol
Subclinical thyroid dysfunction as a risk factor for cardiovascular disease
Arch Intern Med
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