Alterations in the Hypothalamic-Pituitary-Thyroid Axis Following Growth Hormone Replacement May Attenuate Improvements in Quality of Life

Presentation Number: SUN 456
Date of Presentation: April 2nd, 2017

Nigel Glynn*1, Helena Kenny2, Karen McGurren1, David Halsall3, John H McDermott4, Diarmuid Smith1, William Tormey5, Christopher J Thompson1, Donal O'Gorman2 and Amar Agha1
1Beaumont Hospital & RCSI Medical School, Dublin, Ireland, 2Dublin City University, Dublin, Ireland, 3University of Cambridge & Addenbrooke's Hospital, United Kingdom, 4Connolly Memorial Hospital, Dublin 15, Ireland, 5Beaumont Hospital, Dublin, Ireland

Abstract

Growth hormone (GH) replacement is an established component of clinical care for adults with hypopituitarism and shows clear benefits, particularly in health-related quality of life (QOL). However, alterations in the thyroid axis, most commonly a decline in serum free T4, are frequently provoked by GH substitution. We hypothesised that fluctuations in the thyroid axis following GH replacement in adults will attenuate the expected improvement in QOL.

We conducted a prospective, observational study of 20 hypopituitary men receiving GH replacement as part of routine clinical care. Serum TSH and thyroid hormone (free & total T4, free & total T3, reverse T3), insulin like growth factor-1 (IGF-1), testosterone and electrolytes were measured before and after GH substitution. Subjects were also administered generic health-related QOL questionnaires - the Short Form 36 (SF36) and the Nottingham Health Profile (NHP). They also completed the GH deficiency disease-specific Assessment of Growth Hormone Deficiency in Adulthood (AGHDA) questionnaire.

Following GH replacement, serum IGF-1 levels rose significantly, as expected, (+114.4±12.3μg/L, p<0.0001). Serum free T4 concentration declined (-1.09±1.99 pmol/L, p=0.02); free T3 level increased (+0.34±0.15 pmol/L; p=0.03). The baseline median AGHDA score was 16/25 (range 0-24). AGHDA score (median±SD) declined during the study 16±8.7 vs 12±7.9; p=0.003. Subgroup analysis of those in whom serum free T4 fell during the study (n=12) demonstrated a blunted and non-significant decline in AGHDA score. Self-reported scores in the six domains of NHP did not change significantly during the study. In relation to SF-36, there was a significant increase in scores for physical function, vitality and emotional role, indicating an improvement in QOL. However, the rise in these scales did not correlate with either the rise in serum IGF-1 or the increase in freeT3/freeT4 ratio. The improvements in health-related QOL, measured by SF-36, observed in the full cohort were not apparent when subjects who experienced a decline in free T4 were examined separately.

In conclusion, GH replacement is associated with improvements in health-related QOL. However, in patients who experience a decline in serum free T4 concentration following GH substitution, the expected improvement in QOL may be attenuated.

 

Nothing to Disclose: NG, HK, KM, DH, JHM, DS, WT, CJT, DO, AA