MON-486 Unmasking Nelson’s Syndrome-Like Phenomenon in Addison’s Disease: A Rare Pituitary Puzzle

Abstract Disclosure: S. Ramadan: None. J.A. Pallotta: None. M. Flores: None. Nelson’s syndrome, characterized by an ACTH secreting pituitary adenoma following bilateral adrenalectomy, is a rare complication of Cushing’s disease. However, similar cases have been described in patients with Addison’s disease, where chronic pituitary stimulation from inadequate adrenal insufficiency management leads to progressive hyperpigmentation and elevated ACTH levels, mimicking Nelson’s syndrome. We present a 35 year old male with Addison’s disease who developed clinical and biochemical features resembling Nelson’s syndrome and its successful management. Case: A 35-year-old male with a medical history of esophagitis, pernicious anemia, vitamin D deficiency, and celiac disease was diagnosed with Addison’s disease in 2014 after presenting with fatigue, muscle weakness, orthostasis, and electrolyte imbalances. His workup revealed low morning cortisol (1.4 μg/dL), elevated plasma renin (18 ng/mL/hr), low aldosterone (4 ng/dL), and a failed cosyntropin stimulation test (cortisol: 1.3 → 1.5 μg/dL). ACTH levels were markedly elevated (>5401 pg/mL), and 21-hydroxylase antibodies were positive. CT imaging showed no adrenal abnormalities. Treatment with hydrocortisone (10 mg AM, 5 mg at noon, 5 mg PM) and fludrocortisone (0.1 mg daily) achieved symptom control without any adrenal crises. In 4/2024, he presented with worsening hyperpigmentation, low mood, and difficulty gaining weight and muscle mass despite adherence to his prescribed glucocorticoid and mineralocorticoid regimen. He denied dizziness, orthostasis, or blood pressure fluctuations. Lab tests revealed elevated ACTH (1442 pg/mL, up from prior levels of 18-551 pg/mL) despite adequate cortisol levels (20.7 μg/dL). The pituitary panel was otherwise normal. MRI revealed a 4 mm pituitary microadenoma, raising suspicion of either Nelson’s syndrome like pathology or primary pituitary ACTH hypersecretion coexisting with Addison’s disease. Persistent ACTH elevation despite adequate glucocorticoid therapy made the latter more likely, with chronic ACTH stimulation being the cause of hyperpigmentation. In 5/2024, bedtime dexamethasone (0.25 mg) was initiated to suppress ACTH secretion. The patient experienced significant improvement in hyperpigmentation and gained 8 pounds. By 8/2024, ACTH levels had decreased to 11 pg/mL, with cortisol within normal limits, reflecting adequate glucocorticoid replacement. Conclusion: This case highlights that Nelson’s syndrome like features can develop in Addison’s disease without adrenalectomy. Possible mechanisms include inadequate ACTH suppression by conventional glucocorticoid therapy, autoimmune driven pituitary adenoma formation, or secondary pituitary hyperplasia from insufficient adrenal hormone replacement. While dexamethasone effectively manages ACTH hypersecretion, long term glucocorticoid side effects necessitate ongoing monitoring Presentation: Monday, July 14, 2025