Validation of glucagon stimulation test in establishing GH and ACTH deficiency in hypopituitarism and evaluation of AACE/ACE proposed revised cut-point for diagnosis of adult GH deficiency

Presentation Number: SUN 431
Date of Presentation: April 2nd, 2017

Shariq Rashid Masoodi*1, Zhahid Hassan2, Mahroosa Ramzan2, Raiz A Misgar2, Zafar Amin Shah2, Mohd Ashraf Ganie2 and Sridhar Chitturi3
1Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India, 2Sher-i-Kashmir Institute of Medical Sciences, srinagar, Srinagar, India, 3Royal Darwin Hospital, Darwin, Australia

Abstract

Background: Diagnosis of GH deficiency (GHD) and secondary adrenal insufficiency entails evaluation by multiple dynamic stimulation tests in most cases as insulin tolerance test (ITT), the gold-standard test for evaluation of GHD and hypothalamo-pituitary-adrenal (HPA) axis, carries risks and hence avoided in many institutes. Glucagon stimulation test (GST) is a safe alternative to test for GHD and HPA axis. Hypopituitarism due to Sheehan’s syndrome is a common condition in our Kashmiri population (1). It is of immense clinical value to have a reliable and safe alternative to ITT for testing both GH and ACTH deficiency in this population. Recently American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) have proposed a lower GH cut-point of 1 μg/L in adult GHD in overweight/obese subjects (2).

Objectives: 1) To study the diagnostic performance of GST compared to ITT in adult patients with hypopituitarism and HPA axis suppression. 2) To study the utility of AACE/ACE proposed lower GH cut-point of 1 μg/L for adult GHD.

Subjects: Eighteen adults (16 women) with established hypopituitarism and 2 patients with HPA axis suppression due to exogenous glucocorticoids.

Methods: GST and ITT were performed on consecutive days as per standard protocol. Main outcome measures were the GH and Cortisol response to GST and ITT.

Results: Hypopituitarism was due to Sheehan’s syndrome in 13 patients, pituitary tumors in 4 subjects and empty sella syndrome in 1 patient. Two patients with HPA axis suppression due to exogenous glucocorticoids were also evaluated with both GST and ITT. Sixteen patients had ≥3 pituitary hormone deficiencies. Median age was 38.5 years (range 23 to 70 years), BMI mean±SD was 25.1±3.7 (range 17.8 to 33.6). Eight patients (40%) had BMI of ≥25 kg/m2.

Peak cortisol levels obtained during GST were significantly lower than the values obtained during ITT (5.1±4.8 vs. 6.2±5.7 μg/dl; P = 0.004). Peak GH responses were not significantly different between GST and ITT (0.4±0.7 vs 1.4±3.4 μg/L; P = 0.445). Using ITT as gold standard, GH cut of 3 μg/L in GST had 100% sensitivity, 100% NPV, 89% PPV, and 90% accuracy in diagnosing GHD. Adopting AACE/ACE proposed lower GH cut-point of 1 μg/L did not add further to the diagnostic accuracy of GST in GHD overall or in overweight/obese subjects.

Conclusions: We conclude that GST can be reliably used in the evaluation of GHD as well as HPA axis in hypopituitarism. The lower GH cut-point of 1 μg/L did not enhance the diagnostic accuracy of GHD in the overweight/obese patients with hypopituitarism in our study population.

References: (1) Zargar AH, et al Fertil Steril. 2005 Aug;84. (2):523-8. (2) Yuen KCJ, et al. Endocr Pract 2016 Oct;22(10):1235–44. (3) Hamrahian AH, et al. Pituitary. 2016 Jun;19(3):332–41.

 

Nothing to Disclose: SRM, ZH, MR, RAM, ZAS, MAG, SC