Central Hypothyroidism: Pathogenic, Diagnostic, and Therapeutic Challenges

CONTEXT: Central hypothyroidism (CH) is a particular hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. This condition raises several challenges for clinicians; therefore, a review of the most relevant findings on CH epidemiology, pathogenesis, and clinical management has been performed. METHODOLOGY: The relevant papers were selected by a PubMed search using appropriate key words. MAIN FINDINGS: CH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus, but most frequently affecting both of them. CH is about 1000-fold rarer than primary hypothyroidism. Except for the neonatal CH due to biallelic TSHβ mutations, the thyroid hormone defect is rarely as profound as can be observed in some primary forms. In contrast with primary hypothyroidism, CH is most frequently characterized by low/normal TSH levels, and adequate thyroid hormone replacement is associated with the suppression of residual TSH secretion. Thus, CH often represents a clinical challenge because physicians cannot rely on the systematic use of the "reflex TSH strategy." The clinical management of CH is further complicated by the frequent combination with other pituitary deficiencies and their substitution.