Recurrent Atraumatic Pelvic Fractures in a Patient With Cushing’s Disease - Is DEXA Scan Really Useful to Predict the Future Fracture Risk?

Background: Cushing’s disease may present with a variety of clinical features, including osteoporosis and fracture. Due to the inhibitory effects of cortisol on osteoblastic activity and enhancing effects on osteoclastic activity, these patients are more prone to have osteoporotic fractures. We report a case of ACTH dependent Cushing’s disease presenting with recurrent atraumatic pelvic fractures in a woman despite normal bone mineral density for her age. Clinical Case: A 56 year-old-woman was referred to the endocrinology department for suspected Cushing’s syndrome following a recent atraumatic fracture of right pubic ramus. She had a history of weight gain and easy fatigue. On examination, she had subtle changes suggestive of Cushing’s syndrome, including mild truncal obesity, minimal bruising and moon face. She had been taking hormone replacement therapy for 3 years for the post-menopausal symptoms. Her bone mineral density was normal for her age on a recent DEXA scan [femoral neck T score: -0.9, Z score: 0.1, lumbar spine (L1-L4) T score: -1.2, Z score: -0.1]. Her vitamin D, serum calcium and parathyroid hormone levels were normal. Her 24-hour urinary cortisol was 688 nmol/day (reference range: <200 nmol/day), low dose dexamethasone suppression cortisol 525 nmol/L (reference range: <50 nmol/day), ACTH 96 ng/L (reference range: <50 ng/L), indicating ACTH dependent Cushing syndrome. MRI pituitary showed 7 mm right sided hypoenhancing area suggestive of a pituitary microadenoma. CT neck, thorax, abdomen and pelvis did not show any source of ectopic ACTH secretion but did show generalised osteopenia, with old fractures of the ribs and left ilium. She was referred for trans-sphenoidal resection of pituitary tumour. While awaiting pituitary surgery she was treated with metyrapone: at this time she suffered a further atraumatic fracture of the left pubic ramus. Conclusion: Glucocorticoid excess predominantly affects trabecular bones (pelvis, ribs, lumbar spine) as compared to cortical bones. Due to micro-architectural changes, reduction in bone strength is disproportionately greater than would be expected from BMD measured by DEXA. Clinicians should be aware that recurrent fracture of trabecular bones may indicate Cushing’s disease even though other clinical features of cortisol excess are minimal or absent.