Endocrine Abstracts

Introduction: Nelson’s syndrome is a rare complication of Cushing’s disease treated with bilateral adrenalectomy. There is no effective medical treatment yet. Nelson’s patients respond to hypothalamic stimuli distinctly from patients with Cushing’s disease and those with Addison’s disease. We describe the responses to standard ACTH stimulation tests in a patient with Nelson’s syndrome.

Case report: A 42-year-old woman presented with ACTH dependent Cushing’s syndrome. Pituitary MRI was suggestive of a lesion on the left side, measuring 4 x 3 mm and an ectopic source of ACTH was excluded. Following an unsuccessful transphenoidal surgery in 2013, she was placed on pasireotide 0.6 mg twice daily for one year. Partial response was seen on pasireotide, but she developed severe hyperglycemia. Fluconazole 200 mg daily was tried for 6 months, in conjunction with cabergoline 1 mg twice weekly, with little benefit. The patient finally had a bilateral adrenalectomy in3/2016 and was replaced with hydrocortisone 20 mg am-10 mg pm and fludrocortisone 0.1 mg/d, while maintaining all other pituitary axes intact. Two years later (2/2018), a pituitary tumor was visible on the right lateral pituitary, which grew further in the next 32 months to 10 mm (10/2020). Gradual skin hyperpigmentation was noticeable since 2018. The patient remained hyperglycemic but managed well with GLP-1R agonist and metformin. Her ACTH levels gradually increased since 2016, reaching am levels of 1886 pg/ml (7-64) and late evening levels of 1235 pg/ml (5-30) in late 2021. The patient had an exaggerated response to desmopressin stimulation with ACTH >2000 pg/ml (dilutions were not performed) to x3 above baseline at 15’, remaining at this level beyond 120’. An exaggerated response was noted following CRH stimulation, with ACTH rising from 1741 pg/ml to >2000 pg/ml at 15’, returning to baseline at 120’. ACTH decreased to 134 pg/ml following overnight suppression with 8 mg dexamethasone.

Conclusions: Abnormal and distinct hypothalamic-pituitary dynamics underlie the pathophysiology of Nelson’s syndrome, which cannot be explained solely on lack of adrenal negative feedback. In patients with otherwise intact pituitary function repeat neurosurgery or radiotherapy are not desirable options and pasireotide use is similarly limited. A case for blockade of CRH receptor blockade can be a rational therapeutic option in this clinical situation.

References: 1 Barber TM et al, European Journal of Endocrinology (2010) 163 495–507

2 Patel J et al, Neurosurg Focus 38 (2):E14, 2015

3 He X & Spencer-Segal JL: Clinical Diabetes and Endocrinology (2020) 6:22 Oldfield EH et al, J Clin Endocrinol Metab 62: 1020,1986