A Case With Adult GH Deficiency Complicated With Osteogenesis Imperfecta: Effect of GH Replacement on Bone Mineral Density

Background: Osteogenesis imperfecta (OI) is an inherited connective tissue disorder with many phenotypic presentations. Bisphosphonates are the mainstay of pharmacologic fracture prevention therapy, although they aren’t officially approved for the treatment of OI. Clinical Case: The patient was born by breech delivery. After he had multiple fractures at the age of two years, he was diagnosed with osteogenesis imperfecta (OI) type I by genetic analysis (c.1299 + 1G> A mutation in the COL1A1 gene). On the growth curve, his height fell below -2SD at the age of six years. When he was 12 years old, he visited another hospital because of short stature (Hight 119 cm: -2.7SD). Pituitary MRI revealed pituitary stalk disruption and pituitary atrophy. Endocrinological examinations (ITT, TRH, LHRH, arginine stimulation tests) showed severe GH deficiency. Growth hormone replacement therapy was started. At the age of 16 years, he was diagnosed to have central hypothyroidism and central diabetes insipidus, and levothyroxine and DDAVP were started. His bone mineral density of the lumbar spine was 0.546 g/cm(2), and alendronate was started. At the age of 17, central hypogonadism was diagnosed by LHRH stimulation test, and HCG injections were initiated. His bone mineral density continued to increase by GH replacement, HCG injections and bisphosphonate and reached 0.820 g/cm(2) (Z-score: -0.27) by the age of 18 years. GH replacement was discontinued (final height 180 cm). At that age, his bone mineral density declined to 0.717 g/cm(2) at the age of 25 years, although he stayed on an alendronate and HCG injections. At that time, total testosterone 890 ng/dL (142<n<923 ng/dL) was within normal range, but IGF-1 level was below the lower limit (44 ng/mL; -4.6SD, 225<n<337 ng/mL). He was referred to our hospital for transition to adult endocrine care. Endocrinologic evaluation revealed low serum cortisol level in the early morning (2.26 µg/dL, 7.07<n<19.6 μg/dL). GH-releasing peptide-2 stimulation test revealed severe GH deficiency (peak GH 0.18 ng/mL, n> 15 ng/mL (1)) and replacements with GH and hydrocortisone were initiated. After the GH replacement, the bone mineral density started to increase to 0.954 g/cm(2) (Z-score: -0.5). Conclusion: So far as we know, this is the first case report of OI with panhypopituitarism treated with GH and bisphosphonate. This case suggests that bisphosphonate alone is not sufficient to maintain bone mineral density complicated with both OI and severe GHD. GH replacement therapy was inevitable to increase bone mineral density in this patient. Reference: (1) Kazuo Chihara et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Eur J Endocrinol.2007;157;19-27.