Successful Treatment of Pediatric Cushing’s Syndrome

An 11-year-old girl presented at an endocrinology clinic in November 2008 for evaluation of short stature. She had also gained weight and her face had become more rounded. Laboratory tests included chromosome blood analysis, chemistry, thyroid tests and cortisol measurement. All results were normal, including her serum cortisol level (13.8 μg/dL). Following the clinic visit, the patient’s growth retardation decreased from the 10th percentile to the 1st percentile, and her central weight gain worsened. Consequently, she was seen by a second endocrinologist in January 2009. At that time, she did not have other striking Cushingoid features (e.g., striae, easy bruising, proximal myopathy). Her 24-hour urine cortisol level was elevated at 91 mcg/day (normal: 1 – 21), but a repeated test was normal. Pituitary magnetic resonance imaging (MRI) was also normal. Based on an abnormal growth hormone stimulation test, she was started on growth hormone replacement therapy, but linear growth was suboptimal despite dose escalation over the course of two years. At this point, bedtime salivary cortisol was found to be elevated, and the patient was referred to Emory.

At the Emory Pituitary Center, neurosurgeon Nelson Oyesiku, MD, PhD, FACS, collaborated with neuroendocrinologist Adriana Ioachimescu, MD, PhD, FACE, and Children’s Healthcare of Atlanta pediatric endocrinologist Briana Patterson, MD, who performed additional workup, including a combined low-dose dexamethasone suppression corticotropin-releasing hormone (LDDST-CRH) test, multiple paired adrenocorticotropic hormone (ACTH)-cortisol tests and a high-dose dexamethasone suppression test (HDDST). The hormonal workup suggested ACTH-dependent Cushing’s syndrome of pituitary origin. MRI was repeated with a dynamic sella protocol and revealed at 4 mm x 5 mm pituitary hypodense lesion.

In October 2011, at age 13 years and 11 months – and nearly three years after the onset of her symptoms – the patient underwent transsphenoidal surgery. The postoperative course was uncomplicated, and her immediate postoperative serum cortisol level was lower than 2 mcg/dL. At a three-month postsurgical followup, she was on hydrocortisone replacement therapy and exhibited favorable changes in weight and appearance. MRI did not show a postoperative residual tumor.

Cushing’s syndrome is rare in children, and pituitary disease is very rarely responsible for this diagnosis before the onset of puberty. The diagnostic workup for Cushing’s syndrome is more challenging in children than adults. A decrease in height percentile as well as weight percentile warrants further workup even in the absence of typical clinical signs of hypercortisolemia encountered in adults. Collaboration between adult and pediatric endocrinologists is essential in these cases. Early diagnosis is key to achieve normal pubertal and bone development, as well as an acceptable adult height. Surgical removal of the tumor is very difficult as children have very small corridors for surgical access to the base of the brain. Furthermore, finding these very small tumors can also be extremely difficult and requires very meticulous exploration by an experienced pituitary surgeon. Surgical excision of the pituitary adenoma is the most effective and rapid means of curing Cushing’s syndrome. Remission of Cushing’s syndrome is a life transforming event in children and adults.