Review: Molecular thyroidology

Novel disorders involving aberrations of the hypothalamic-pituitary-thyroid gland-thyroid hormone axis have been described in the last 5 to 10 years. The following topics are addressed: molecular mutations causing central hyp othyroidism (isolated autosomal recessive TRH deficiency; autosomal recessi ve TRH-receptor inactivating mutations; TSH beta-subunit bio-inactivating m utations; Pit-1 mutations; Prop1 mutations; high molecular weight bio-inact ive TSH); defects in response to TSH (mutations in the TSH receptor: TSH re ceptor gain-of-function mutations; TSH receptor loss-of-function mutations) ; defects in thyroid gland formation: transcription factor mutations (TTF-2 and Pax8); defects in peripheral thyroid hormone metabolism (defective int rapituitary conversion of T4 to T3; hemangioma consumption of thyroid hormo ne); and defects in tissue response to thyroid hormone (generalized thyroid hormone resistance, selective pituitary thyroid hormone resistance). While molecular diagnosis of such conditions is rarely indicated for clinical ma nagement, knowledge of the molecular mechanisms of these diseases can great ly enhance the clinical laboratory scientist's ability to advise clinicians about appropriate thyroid testing and to interpret the complex and sometim es confusing results of thyroid function tests.