Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients.
BACKGROUND
The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results.


OBJECTIVE
We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients.


METHODS
We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement.


RESULTS
In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid.


CONCLUSIONS
GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement.
Agha
Amar
A
William Harvey Research Institute, Queen Mary University of London, London, UK. a.agha@qmul.ac.uk
Walker
Dorothy
D
Perry
Les
L
Drake
William M
WM
Chew
Shern L
SL
Jenkins
Paul J
PJ
Grossman
Ashley B
AB
Monson
John P
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000097:blood
D019382:Human Growth Hormone; D013974:Thyroxine