SAT-459 Hypothalamic-Pituitary-Gonadal (HPG) and Hypothalamic-Pituitary-Thyroid (HPT) Axes in Cushing Syndrome (CS): A Retrospective Cohort Study

Abstract

Background: It is well known that persistent hypercortisolemia suppresses thyroid and gonadal function. However, there are few data on the degree and type of derangement or the course of recovery of these axes after cure. To investigate this, we studied the pre- and post-surgical characteristics of the gonadal and thyroid axis hormones in CS patients (pts). Methods: We retrospectively reviewed records of 23 adult CS pts admitted to our protocols from 2010 - 2018 who received curative surgery with follow-up for 6 - 12 months (6M-12M). We recorded morning serum free T4 (fT4) and TSH, and morning LH, FSH, estradiol (E, premenopausal only) or testosterone (T, in men only) values before (0M), and 6M and 12M after definitive surgery. The rate of abnormal values was calculated at each timepoint. Data were analyzed using SPSS 23 software and are shown as percentage, mean ± SD or median(Interquartile Range). Results: Pt age was 45.6 ± 10.8 years; 21 (91%) were female. Before surgery fT4 (Nl: 0.9 - 1.7ng/dL) and TSH (Nl: 0.27 - 4.2mcIU/mL) were low normal. Subnormal values were seen for LH (13%), FSH (9.5%), E (14.2%, Nl: 15 - 350 pg/mL) and T (100%, n=2, Nl: 181-758ng/dL). fT4 increased from 0.96 ± 0.2 at 0M to 1.12 ± 0.13 at 12M (p=0.016), remaining in the lower half of the normal range. TSH increased significantly from 0M (0.98 ± 0.57) to 6M (2.8 ± 1.4) and 12M (2.9 ± 0.13) (p<0.0005 for both). In premenopausal women (n=14), there was a statistically significant (SS) change from 0M to 12M in both serum E (38.9 pg/mL (21.4 - 51) to 132.3 pg/mL (84.2 - 388), p=0.028) and LH levels (2.9 U/L (3.3 - 5.9) to 7.5 (3.6 - 13.6), nl(follicular phase): 1-12 U/L, p=0.019); the change in E, LH and FSH at 6M and in FSH at 12M was not SS. Menses were documented only in 8; resumption of normal cycles occurred 2 - 11 months after surgery. In postmenopausal females(n=7) there were no SS changes in LH or FSH from OM (LH: 21.4+11.1, nl: 11-40 U/L; FSH 54.3+30.5, nl: 22-153 U/L) to 6M or 12M. One man was taking T at 0M and one had a low T level at 0M (88.2 ng/dL) that normalized (357 ng/dL, nl: 181 - 758ng/dL ) at 6M.Conclusions: HPT and HPG axes improved after cure. While the HPT axis may start recovery at 6M, reflected by SS rise in TSH at 6M, HPG axis recovery was more homogeneous. Larger studies are needed to uncover the effects of hypercortisolemia on Hypothalamic-Pituitary-End organ axes and timelines of their recovery after treatment.