title: Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years.
abstract: BACKGROUND
  Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up.
  
  
  METHODS
  A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (low Free thyroxine [FT4] and increased thyroid-stimulating hormone [TSH] levels >5 μIU/ml); subclinical hypothyroidism (normal FT4, TSH between 5 μIU/ml and 10 μIU/ml) and central (secondary) hypothyroidism (low FT4 and normal or decreased TSH).
  
  
  RESULTS
  A total of 48 patients (22 males and 26 females) completed a 12 year-period of follow-up. During this period, hypothyroidism was diagnosed in 17/48 (35%) of patients. There was no significant difference in the prevalence in males 7/22 (32%) versus females 10/26 (38%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). The prevalence of overt hypothyroidism had risen from 0% at the age of 7 years to 35% at the age of 18 years. None of the patients had high anti-thyroperoxidase antibody titers. Out of 17 patients, 13 patients with hypothyroidism had normal or low TSH level (not appropriately elevated) indicative of defective hypothalamic pituitary response to low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). The general trend of FT4 level showed progressive decrease over the 12 years, whereas, TSH levels did not show a corresponding increase. These data suggested defective hypothalamic pituitary thyroid axis involving both TSH and FT4 sretion in patients with thalassemia major over time. There was a significant negative correlation between serum ferritin and FT4 (r = -0.39, P = 0.007), but no correlation was found between ferritin and TSH.
  
  
  CONCLUSIONS
  Worsening of thyroid function was observed in 35% of the studied thalassemic patients by the age of 18 years. The lack of proper increase of TSH in response to the low circulating levels of FT4 in 13/17 (76%) of these patients indicates a relatively high incidence of defective pituitary thyrotrophic function in these patients.
authors.affiliation: Department of Pediatrics, Hamad Medical Center, Doha - Qatar.
authors.forename: Ashraf T
authors.initials: AT
authors.lastname: Soliman
authors.affiliation: Department of Pediatrics, Hamad Medical Center, Doha - Qatar.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Al Yafei
authors.affiliation: Department of Pediatrics, Hamad Medical Center, Doha - Qatar.
authors.forename: Lolwa
authors.initials: L
authors.lastname: Al-Naimi
authors.affiliation: Department of Pediatrics, Hamad Medical Center, Doha - Qatar.
authors.forename: Noora
authors.initials: N
authors.lastname: Almarri
authors.affiliation: Department of Pediatrics, Hamad Medical Center, Doha - Qatar.
authors.forename: Aml
authors.initials: A
authors.lastname: Sabt
authors.affiliation: Department of Hematology, Hamad Medical Center, Doha - Qatar.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Yassin
authors.affiliation: Department of Pediatric and Adolescent Out patient Clinic, Quisisana Hospital, 44121 Ferrara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Sanctis
keywords: Ferritin; free thyroxine; growth; hypothyroidism; prevalence; thalassemia; thyroid stimulating hormone