The Diagnostic Challenges in ACTH Dependent Cushing’s Disease

Objective: To discuss the difficulties in the diagnostic workup and management of ACTH dependent Cushing’s syndrome.
Methods: We report the case of a patient with ACTH dependent Cushing’s syndrome, in whom the identification of the source of ACTH production was a challenge.
Results: A 26-year-old man presented with a weight gain of 20kg, hypertension (250/160 mmHg), hypokalemia, purple stretch marks and severe proximal muscle weakness 6 months of evolution. He also had 4 episodes of pneumonia requiring hospitalization. ACTH-dependent hypercortisolism (cortisol 32ng/dl, ACTH 135pg/ml) was diagnosed. The severe clinical presentation suggested the possibility of ectopic ACTH production. The dexamethasone suppression test (DST) showed no inhibition of cortisol. Whole body octreotide scintigraphy and gallium-68 PET-CT did not show any evidence of ectopic tumor. A pituitary MRI was reported as normal. Bilateral inferior petrosal sinus sampling was carried out and was essential in establishing a diagnosis of Cushing’s disease. In a second MRI, a pituitary microadenoma on the left side was identified. The patient underwent transsphenoidal resection. Postoperatively, hypercortisolism persisted, and since the patients clinical condition deteriorated further, bilateral adrenalectomy was successfully performed, providing a definitive cure for the life threatening hypercortisolism.
Conclusion: The diagnosis and management of ACTH dependent Cushing´s syndrome remains a challenge. The results of dexamethasone suppression tests should be evaluated in the context of the patient. These tests have a high negative predictive value; however in the context of critical illness (pneumonia) may alter the hypothalamic-pituitary-adrenal axis response. This case confirms the need for a bilateral IPS sampling in order to establish diagnosis.