title: Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers.
abstract: Subclinical hypothyroidism (SH) is a condition characterized by a mild persistent thyroid failure. The main cause is represented by autoimmune thyroiditis, but mutations in genes encoding proteins involved in TSH pathway are thought to be responsible for SH, particularly in cases arising in familial settings. Patients with the syndrome of TSH unresponsiveness may have compensated or overt hypothyroidism with a wide spectrum of clinical and morphological alterations depending on the degree of impairment of TSH-receptor (TSH-R) function. We describe the case of two brothers with non autoimmune SH carrying the same heterozygous mutation in the extracellular domain of TSH-R and presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, a normal thyroid ultrasound and did never require l- thyroxine (L-T4) replacement treatment. The second one had a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life.These two cases support the recent association of TSH-R mutations inheritance as an autosomal dominant pattern with variable expressivity and suggest that the decision to start replacement therapy in patients with persistent SH due to TSH resistance should be individualized.
authors: Department of Pediatrics, University of Naples Federico II, Naples, Italy.
authors: Manuela
authors: M
authors: Cerbone
authors: Patrizia
authors: P
authors: Agretti
authors: Giuseppina
authors: G
authors: De Marco
authors: Nicola
authors: N
authors: Improda
authors: Claudio
authors: C
authors: Pignata
authors: Francesca
authors: F
authors: Santamaria
authors: Massimo
authors: M
authors: Tonacchera
authors: Mariacarolina
authors: M
authors: Salerno
mesh_terms: D015415:Biomarkers / Q000097:blood; D002648:Child; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D011989:Receptors, Thyrotropin / Q000235:genetics*; D035781:Siblings; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011989:Receptors, Thyrotropin; D013974:Thyroxine