title: Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?
abstract: OBJECTIVE
  In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T(4)) therapy.
  
  
  METHODS
  We have examined the interrelationships between free triiodothyronine (FT(3)), free T(4) (FT(4)) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of l-T(4) and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis.
  
  
  RESULTS
  Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT(3) and FT(4) between untreated patients and l-T(4) groups. Total deiodinase activity (G(D)) was positively correlated with TSH in untreated subjects. However, G(D) was significantly altered and the correlation was lost under increasing l-T(4) doses. Ninety-five per cent confidence intervals for FT(3) and FT(4), when assessed in defined TSH concentration bands, differed significantly for l-T(4)-treated compared with untreated patients. Higher doses were often needed to restore FT(3) levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2.
  
  
  CONCLUSIONS
  The data reveal disjoints between FT(4)-TSH feedback and T(3) production that persist even when sufficient T(4) apparently restores euthyroidism. T(4) treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.
authors.affiliation: Department of Nuclear Medicine, Klinikum Luedenscheid, Paulmannshoeher Street 14, D-58515 Luedenscheid, Germany. rudolf.hoermann@gmail.com
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hoermann
authors.forename: John E M
authors.initials: JE
authors.lastname: Midgley
authors.forename: Rolf
authors.initials: R
authors.lastname: Larisch
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Dietrich
mesh_terms: D000328:Adult; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010902:Pituitary Gland / Q000503:physiopathology*; D012189:Retrospective Studies; D013972:Thyrotropin / Q000032:analysis*; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine