title: Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.
abstract: OBJECTIVE
  Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms.
  
  
  METHODS
  The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations.
  
  
  RESULTS
  Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy.
  
  
  CONCLUSIONS
  The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.
authors.affiliation: Department of Paediatrics, Endocrine Research Unit, Karolinska University Hospital Huddinge, Stockholm, Sweden. aziz.elgadi@klinvet.ki.se
authors.forename: Aziz
authors.initials: A
authors.lastname: Elgadi
authors.forename: C-G
authors.initials: CG
authors.lastname: Arvidsson
authors.forename: Annika
authors.initials: A
authors.lastname: Janson
authors.forename: Claude
authors.initials: C
authors.lastname: Marcus
authors.forename: Sabine
authors.initials: S
authors.lastname: Costagliola
authors.forename: Svante
authors.initials: S
authors.lastname: Norgren
mesh_terms: D002648:Child; D003937:Diagnosis, Differential; D005799:Genes, Dominant; D018095:Germ-Line Mutation; D006801:Humans; D006980:Hyperthyroidism / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008713:Methimazole / Q000627:therapeutic use; D009468:Neuromuscular Diseases / Q000175:diagnosis*; D011989:Receptors, Thyrotropin / Q000235:genetics*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013960:Thyroid Function Tests
chemical_list: D011989:Receptors, Thyrotropin; D008713:Methimazole