Overt and subclinical hypothyroidism: who to treat and how

Hypothyroidism denotes deficient production of thyroid hormone by the thyroid gland and can be primary (abnormality in thyroid gland itself) or secondary/central (as a result of hypothalamic or pituitary disease). The term 'subclinical hypothyroidism' is used to define that grade of primary hypothyroidism in which there is an elevated thyroid-stimulating hormone (TSH) concentration in the presence of normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations. Subclinical hypothyroidism may progress to overt hypothyroidism in approximately 2-5% cases annually. All patients with overt hypothyroidism and subclinical hypothyroidism with TSH >10 mIU/L should be treated. There is consensus on the need to treat subclinical hypothyroidism of any magnitude in pregnant women and women who are contemplating pregnancy, to decrease the risk of pregnancy complications and impaired cognitive development of the offspring. However, controversy remains regarding treatment of non-pregnant adult patients with subclinical hypothyroidism and serum TSH values ≤10 mIU/L. In this subgroup, treatment should be considered in symptomatic patients, patients with infertility, and patients with goitre or positive anti-thyroid peroxidase (TPO) antibodies. Limited evidence suggests that treatment of subclinical hypothyroidism in patients with serum TSH of up to 10 mIU/L should probably be avoided in those aged >85 years. Other pituitary hormones should be evaluated in patients with central hypothyroidism, especially assessment of the hypothalamic-pituitary-adrenal axis, since hypocortisolism, if present, needs to be rectified prior to initiating thyroid hormone replacement. Levothyroxine (LT4) monotherapy remains the current standard for management of primary, as well as central, hypothyroidism. Treatment can be started with the full calculated dose for most young patients. However, treatment should be initiated at a low dose in elderly patients, patients with coronary artery disease and patients with long-standing severe hypothyroidism. In primary hypothyroidism, treatment is monitored with serum TSH, with a target of 0.5-2.0 mIU/L. In patients with central hypothyroidism, treatment is tailored according to free or total T4 levels, which should be maintained in the upper half of the normal range for age. In patients with persistently elevated TSH despite an apparently adequate replacement dose of LT4, poor compliance, malabsorption and the presence of drug interactions should be checked. Over-replacement is common in clinical practice and is associated with increased risk of atrial fibrillation and osteoporosis, and hence should be avoided.