Endocrine Abstracts

Introduction: Cushing’s disease (CD) is a very rare cause of obesity in children. Typical features seen in adults with CD may be absent and clinical investigations may not give a definitive diagnosis. We present a case of CD, highlighting the challenges of diagnosis and the dilemmas encountered in managing such patients.

Case report: A ten-year-old girl was referred with a five-year history of weight gain. At presentation BMI was +3.66 SD and she had a plethoric complexion. Despite signs of puberty, height velocity was 4 cm/yr. Investigations including repeated 24 h urinary free cortisols (UFC) and a midnight cortisol of 515nmol/l suggested increased cortisol secretion. A low-dose dexamethasone suppression test (DST) however demonstrated suppression of cortisol (<22nmol/l), with subsequent 48hr DST showing 48hr cortisol <22nmol/l, ACTH 36.7ng/l. A 3mm lesion in the pituitary gland, consistent with a pituitary microadenoma, was identified on MRI scan, therefore Cushing’s disease was diagnosed. The patient underwent a transsphenoidal resection of her microadenoma. Surgical evaluation and MRI imaging suggested complete resection. Post-operative cortisol levels fell to 126-231nmol/l in a 24 hr period. Clinically the patient lost weight, height velocity improved and she became less plethoric. One year later however, height velocity slowed and weight loss tailed off. Investigations initially showed an inconclusive picture. Over time, 24 h UFC and salivary cortisol and cortisone measurements became persistently elevated, consistent with recurrence of CD. Treatment with metyrapone was instigated, using cortisol day profiles to titrate the dose and monitor for adrenal axis suppression. Subsequently hydrocortisone was added to the block and replace regime. On treatment the patient has regained her normal appearance, benefited from an improved quality of life and achieved significant weight loss (BMI currently 91^st-98^th centile).

Conclusions: This case highlights a number of important learning points in diagnosing and managing CD. Linear growth failure in association with obesity is a key feature of CD in children and monitoring of growth parameters may alert the clinician to disease recurrence. We will discuss the role of post-operative cortisol measurements in predicting likelihood of disease recurrence, the challenges of surgical management and the role of medical therapy.