title: The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.
abstract: BACKGROUND
  Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism.
  
  
  OBJECTIVE
  To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy.
  
  
  METHODS
  A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 μIU/ml.
  
  
  RESULTS
  Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 μg/kg, P<0.005). Patients of group CH treated with l-T4 had significantly higher serum TSH levels than patients of group AH (P=0.05) as well as higher FT4 concentrations.
  
  
  CONCLUSIONS
  To correct hypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis.
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Bagattini
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Caterina Di
authors.initials: CD
authors.lastname: Cosmo
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Montanelli
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Piaggi
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Ciampi
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Giuseppina De
authors.initials: GD
authors.lastname: Marco
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Endocrinology SectionDepartment of Clinical and Experimental Medicine, University Hospital of Pisa, University of Pisa, Via Paradisa 2, Cisanello, Pisa 56124, Italy mtonacchera@hotmail.com.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
mesh_terms: D000293:Adolescent; D000328:Adult; D003409:Congenital Hypothyroidism / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D050033:Thyroid Dysgenesis / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D018382:Thyroid Hormone Resistance Syndrome / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D013963:Thyroid Hormones / Q000097:blood; D013965:Thyroidectomy; D013974:Thyroxine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D013963:Thyroid Hormones; D013974:Thyroxine