title: Diagnosis and management of congenital hypothyroidism associated with pseudohypoparathyroidism.
abstract: Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide-binding protein α-subunit) mutation (PHP1A) or epimutation (PHP1B). To determine the presence of hypothyroidism at birth we conducted a retrospective study in our cohort of patients presenting with either PHP1A (n = 116) or PHP1B (n = 99). We also investigated patients presenting at birth with congenital hypothyroidism (CH) and a eutopic thyroid gland for phosphocalcium abnormalities suggesting PTH resistance and PHP. Our study reveals CH as the earliest diagnostic clue for PHP1A, but not for PHP1B. We estimated the frequency of CH at birth to be between 8 and 34% in patients presenting with PHP1A. The elevation of phosphatemia and PTH concentration precedes hypocalcemia in PHP1A. Conversely, the frequency of PHP1A in patients presenting CH is dramatically low. This may be due to the low prevalence of PHP1A which remains unknown.
  
  
  CONCLUSIONS
  Subclinical and overt hypothyroidism can occur in PHP1A patients at birth many years before PTH resistance becomes clinically apparent. Although such cases appear to be rare, some pediatric patients with unexplained CH are likely to benefit from measuring calcium, phosphorus, and PTH for extended periods of time.
authors.affiliation: Service de Génétique, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, CHU de Caen, Caen, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Picard
authors.forename: Anne
authors.initials: A
authors.lastname: Decrequy
authors.forename: David
authors.initials: D
authors.lastname: Guenet
authors.forename: Anne Claire
authors.initials: AC
authors.lastname: Bursztejn
authors.forename: Daniel
authors.initials: D
authors.lastname: Toledano
authors.forename: Nicolas
authors.initials: N
authors.lastname: Richard
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Kottler
mesh_terms: D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D003409:Congenital Hypothyroidism / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011547:Pseudohypoparathyroidism / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D014430:Twins, Monozygotic
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs