Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity.
OBJECTIVE
The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11beta-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism.


METHODS
Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42-76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR (20-30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve.


RESULTS
At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = -0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = -0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 +/- 6.4 (mean +/- SD) to 3.5 +/- 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 +/- 268 to 431 +/- 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 +/- 0.1 to 0.75 +/- 0.08 (p < 0.03) consistent with increased 11beta-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 +/- 9.0 vs. 33.0 +/- 8.2) or insulin sensitivity (HOMA %S: 37.1 +/- 8.6 vs. 52.8 +/- 33.7).


CONCLUSIONS
Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.
Department of Endocrinology, St Bartholomew's Hospital, King's College Hospital, London, UK.
Giovanni V
GV
Frajese
Norman F
NF
Taylor
Paul J
PJ
Jenkins
G Michael
GM
Besser
John P
JP
Monson
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D000172:Acromegaly / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D009994:Osmolar Concentration
D003692:Delayed-Action Preparations; D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D015282:Octreotide; D006854:Hydrocortisone