title: Syndromes of hormone resistance in the hypothalamic-pituitary-thyroid axis.
abstract: Forty years have elapsed since the first description of a syndrome of resistance in the hypothalamic-pituitary-thyroid axis, i.e., resistance to thyroid hormone action. In the last two decades many other types of resistance have been discovered, including resistance to the action of thyrotropin-releasing hormone (TRH), of thyroid-stimulating hormone (TSH), and of thyroid hormones (THs); the latter can be due not only to thyroid hormone receptor defects but also to alteration in genes encoding TH-specific transporters or components involved in metabolic pathways of THs. Moreover, alteration in genes encoding for second messengers may cause forms of resistance other than those due to receptor mutations, the most important one being that of an inactivating mutation in the G-protein alpha-subunit leading to TSH resistance in the setting of pseudohypoparathyroidism type 1a. Recognition of these rare thyroid disorders is of great importance not only for informed genetic counselling but also for avoiding diagnostic mistakes that may lead to incorrect and potentially dangerous treatments.
authors.affiliation: Department of Medical Sciences, Endocrine and Metabolic Unit, Fondazione Ospedale Maggiore IRCCS, Padiglione Granelli, Via Francesco Sforza 35, 20122-Milano, Italy. paolo.beckpeccoz@unimi.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Davide
authors.initials: D
authors.lastname: Calebiro
authors.forename: Marco
authors.initials: M
authors.lastname: Bonomi
authors.forename: Deborah
authors.initials: D
authors.lastname: Mannavola
authors.forename: Irene
authors.initials: I
authors.lastname: Campi
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007037:Hypothyroidism / Q000235:genetics; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000235:genetics; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics; D027981:Symporters; D013961:Thyroid Gland / Q000502:physiology*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis / Q000503:physiopathology; D013972:Thyrotropin / Q000502:physiology
chemical_list: D027501:Monocarboxylic Acid Transporters; D016601:RNA-Binding Proteins; D011989:Receptors, Thyrotropin; D018025:Receptors, Thyrotropin-Releasing Hormone; C121530:SECISBP2 protein, human; C090735:SLC16A2 protein, human; D027981:Symporters; D037042:Thyroid Hormone Receptors beta; D013972:Thyrotropin