title: Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine.
abstract: OBJECTIVE
  Achieving optimal thyroid hormone replacement is more difficult in TSH deficiency compared to primary hypothyroidism because of the inability to be guided by serum TSH levels. A combination of clinical symptoms and free thyroxine levels (fT4) are typically used to make a diagnosis and monitor replacement. We investigated the diagnosis of TSH deficiency in patients with pituitary disease and the adequacy of levothyroxine replacement compared with primary thyroid disease.
  
  
  METHODS
  Using our department's clinical information system, we identified all patients with a diagnosis of any type of pituitary tumour who had been seen in clinic over a 2-year period. We divided the patients into those at high risk and low risk of TSH deficiency based on the presence of macroadenoma and/or intervention by surgery or radiotherapy. We compared fT4 values in these patients with values in patients with primary thyroid disease in our thyrotoxicosis shared-care scheme (TSC) and hypothyroid register within the same timescale, assessing only those samples considered euthyroid in which TSH was in the normal range.
  
  
  RESULTS
  A database query identified 525 patients with a pituitary tumour of whom 344 were considered at high risk of TSH deficiency. A free T4 (fT4) value was found for 514 patients (97·9%). TSC and thyroid register databases revealed fT4 values for comparison with simultaneous normal TSH in patients on no treatment (n = 3777 samples) or on levothyroxine alone (n = 11,805). fT4 levels overall were lower in pituitary patients than in equivalent controls. Of the high risk group not taking levothyroxine 17% had a free T4 ≤ 11 pmol/l compared to only 8·4% of untreated controls. Furthermore, 38·9% of patients on levothyroxine had a free T4 ≤ 13 pmol/l compared to 9·5% of controls on levothyroxine with previous thyrotoxicosis and 13·4% of controls with primary hypothyroidism. Median fT4 in controls on levothyroxine was 16 pmol/l and 20-80th centile range was 14-19 pmol/l.
  
  
  CONCLUSIONS
  Levothyroxine doses were generally under-replaced in pituitary patients compared to primary thyroid disease and the data imply that some untreated patients were actually TSH deficient. The distribution of fT4 in patients with primary thyroid disease on levothyroxine may guide optimum replacement levels in pituitary disease.
authors.affiliation: Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester, UK.
authors.forename: Olympia
authors.initials: O
authors.lastname: Koulouri
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Auldin
authors.forename: Ravi
authors.initials: R
authors.lastname: Agarwal
authors.forename: Veronica
authors.initials: V
authors.lastname: Kieffer
authors.forename: Carole
authors.initials: C
authors.lastname: Robertson
authors.forename: James
authors.initials: J
authors.lastname: Falconer Smith
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Levy
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Howlett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013959:Thyroid Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013972:Thyrotropin / Q000097:blood / Q000172:deficiency*; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013972:Thyrotropin; D013974:Thyroxine