An update on subclinical hypothyroidism and subclinical hyperthyroidism

Abstract

Subclinical thyroid dysfunction is characterized by normal levels of peripheral thyroid hormone, paired with a TSH level that is either lower than (subclinical hyperthyroidism) or higher than (subclinical hypothyroidism) the normal laboratory reference range. Slight shifts in peripheral hormone levels result in significant serum TSH changes. The exact upper limit of normal TSH and the management of subclinical hypothyroidism are still controversial. For those with TSH between high upper limit of normal and 10 mIU/L, the authors suggest selective use of thyroxine therapy. The authors agree with the general consensus in favor of therapy for those with serum TSH levels above 10 mIU/L. This recommendation is compatible with guidelines of American Thyroid Association and American Association of Clinical Endocrinologists. For subclinical hyperthyroidism persistent serum TSH <0.1 mIU/L should be treated particularly if the etiology is nodular toxic goiter. For serum TSH between 0.1 mIU/L and lower limit of normal, serum TSH co-morbidities such as cardiac risk factors and osteoporosis may favor therapy.

Keywords::

• antithyroid antibodies
• autoimmune thyroid disease
• cardiac risk factors
• hyperthyroidism
• hypothyroidism
• screening with TSH
• subclinical hyperthyroidism
• subclinical hypothyroidism
• suppressed TSH
• thyroxine therapy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Subclinical hypothyroidism involves approximately 10% of women and 8% of men over age 50.

• Seventy-five percent of patients with subclinical hypothyroidism have serum thyroid-stimulating hormone (TSH) between 4.5 and 10 mIU/L.

• Persistent serum TSH above 10 mIU/L requires thyroxine therapy. However, it is acceptable for some patients to opt for observation.

• Individuals older than age 70 may have higher upper limit of normal for serum TSH and age-adjusted values should be considered.

• Many patients with mildly elevated serum TSH may normalize in follow-up.

• Observational studies and meta-analyses suggest subclinical hypothyroidism as a cardiovascular risk factor in individuals younger than age 65 and suggest the possibility of benefit from therapy. However, before a definite conclusion randomized controlled studies are need.

• The authors recommend individualized and selective rather than uniform therapy of subclinical hypothyroid patients with TSH <10 mIU/L.

• All women of childbearing age with subclinical hypothyroidism should receive thyroxine therapy.

• In differential diagnosis of subclinical hyperthyroidism and low TSH, euthyroid sick syndrome and other causes of low serum TSH should be excluded.

• Subclinical hyperthyroidism causes bone loss in postmenopausal women who are not on hormone or bisphosphonate therapy.

• Subclinical hyperthyroidism increases the risk of atrial fibrillation by a factor of 3 in individuals older than age 60, and may increase the risk of heart failure and risk of cardiac and overall mortality.

• Nodular goiter with subclinical hyperthyroidism is unlikely to resolve and requires intervention.

Notes

TSH: Thyroid-stimulating hormone.

TSH: Thyroid-stimulating hormone.

TSH: Thyroid-stimulating hormone.

^†Down syndrome patients are at high risk of progression to overt hypothyroidism.

TSH: Thyroid-stimulating hormone.