Abstract 37
Authors: Agarwal Khushboo , Elizabeth Kripa , Kapoor Cherian Nitin , Paul Thomas 
Published: February 2023

Introduction: Growth hormone (GH) is important for linear growth as well as maintaining bone mineral density and microarchitecture throughout life, especially during the period of linear growth. We present a comparative analysis of bone microarchitecture and body composition analysis of 3 siblings: 2 with varying degrees of congenital GH deficiency and one with normal stature.

Case Presentation: We present three of five siblings born out of second-degree consanguineous marriage. Two siblings have proportional short stature, rest have normal height. There is no evidence of any other pituitary hormonal deficiency. There was no history of any perinatal complications or chronic illness and both the siblings have good academic performance. Mid-parental height (MPH) for the siblings is 143 cm.
Case 1 is a 24-year-old girl with severe GH deficiency. She had a height of 104 cm (SDS) and weight of 20.3 kg (SDS). Her IGF 1 was < 15 ng/ml and her 8 am cortisol was 21.1 mg/dL. LH was 34.4 mIU/ml. TSH was 1.768 mIU/ml with T4/fT4 levels of 11.9 mg% and 1.61 ng%.
Case 2 is 19-year-old boy with GH deficiency. He had a height of 124 cm (SDS) and weight of 27.5 kg (SDS). His IGF 1 was 20.2 ng.ml and testosterone was 338 ng/ml. He also had normal thyroid profile with TSH 2.559 mIU/ml and T4/fT4 of 8 mg% and 1.2 ng%. Case 3 is their normal statured sibling with IGF 1 levels of 194 ng/ml. Other biochemical evaluation revealed mild dyslipidemia in cases 1 and 2. The body composition showed 61.7% fat in Case 1 and 44.1% fat in case 2 in comparison to 36.8% in the control (case 3). Appendicular lean weight/height2 was 2.47 kg/m2 in Case 1 and 3.76 kg/m2 in Case 2 while it was 4.7 kg/m2 in Case 3. The trabecular bone score was 1.19 in Case 1 and 1.236 in Case 2 while it was 1.287 in Case 2. BMD showed significant osteoporosis in Cases 1 and 2 with Z score -6.3 and -5.0 respectively while it was in normal range for Case 3. Case 1 and 2 show low values of CSA, CSMI and Z and a high BR which are indicative of poor hip strength and a higher tendency to fracture.

Discussion: GH and IGF-1 accelerate bone remodelling and stimulates linear growth via action on epiphyseal prechondrocytes. GH deficiency also results in low muscle mass (sarcopenia) through loss of anabolic action. It contributes to cortical bone loss as periosteal expansion due to muscle drive is lost. As GH is also a lipolytic hormone its deficiency can result in visceral adiposity. Major factors which determine the bone quality in GH deficiency are age of onset, duration and severity of GH deficiency. No information on bone microarchitecture is available from childhood-onset GH deficiency. Cases 1 and 2 show lower TBS compared to the normal sibling. There is no information available about proximal hip geometry assessed by DXA in subjects with childhood-onset GH deficiency. We studied three regions: narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS).

Conclusion: This comparative analysis using DXA between three siblings provides a unique insight into action of GH on bone and body composition. It also highlights need for starting treatment as early as possible and need for GH even after epiphyseal closure.