Cushing disease as possible cause of persistent growth failure despite growth hormone therapy in a small for gestational age male MaryKathleen Heneghan Æ Ramin Alemzadeh Published online: 22 September 2009 Ó Springer Science+Business Media, LLC 2009 Abstract Growth hormone (GH) therapy in children with small for gestational age (SGA) has been shown to be of significant therapeutic benefit. We report the case of an 11- year-old Caucasian male who developed early adrenarche, hypertension and insulin resistance on GH therapy for SGA and profound short stature (ht -5 SD). This patient dem- onstrated a poor response to GH therapy and developed physical and biochemical findings of insulin resistance responsive to metformin therapy. He remained hyperten- sive, however, and continued to have elevated serum dehydroepiandrosterone sulfate levels. Urinary free cortisol excretion was subsequently found to be elevated. The diagnosis of Cushing’s disease was confirmed with inferior petrosal sinus sampling and pituitary MRI. The patient underwent partial adenohypophysectomy with resulting normalization of plasma cortisol levels and associated symptoms. Our patient’s diagnosis of Cushing’s disease was complicated by his past history of poor growth since birth and history of SGA. The signs of Cushing’s disease did not overtly appear until GH therapy was initiated to help treat severe short stature. It is possible that the met- abolic effects of GH therapy unmasked the presence of underlying Cushing’s disease. Keywords Cushing’s disease Á Pituitary adenoma Á Short stature Á Small for gestational age Á Growth hormone Introduction Use of growth hormone (GH) for patients born small for gestational age (SGA) who remain below 2 standard deviations (SD) for height and weight is a well recognized therapeutic approach [1]. Studies have demonstrated that SGA can be associated with a multitude of morbidities in late childhood and adulthood including insulin resistance and hypertension [2–4]. In addition, GH treatment can be associated with alterations in a child’s metabolic profile which may mimic some features of metabolic syndrome and hypercortisolism [5]. Cushing’s syndrome is an uncommon endocrine disorder in young children and its clinical features may be exacerbated by metabolic effects of ongoing GH therapy. Case report Our patient was a healthy Caucasian male who was initially referred to our clinic at 3.5 years of age for evaluation of short stature. He was born at 26 weeks and SGA at 662 g. The review of his growth records indicated that height, weight and head circumference were consistently below the 3rd percentile (-4.0 SD) but with interval growth (see Fig. 1). The patient spent 18 weeks in the neonatal inten- sive care unit (NICU) requiring nasogastric feeding tube. His parents reported normal attainment of developmental milestones, a good energy level with appropriate appetite and no hospitalizations or surgeries since discharge from the NICU. His midparental height was determined to be at the 30th percentile (173.4 cm) and physical examination revealed a healthy appearing toddler. His skeletal age was estimated at 2.5 years and GH therapy for SGA indication was discussed along with careful follow up. M. Heneghan Á R. Alemzadeh (&) Section of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA e-mail: ralemzad@mcw.edu 123 Pituitary (2011) 14:409–413 DOI 10.1007/s11102-009-0201-3