MON-018 - Adrenal Cushing'S Syndrome Followed by Invasive Corticotroph Macroadenoma

Background:
The coexistence of ACTH-independent and ACTH-dependent Cushing syndrome in a single patient is exceedingly rare. In most reported cases, pituitary disease precedes the development of adrenal autonomy as a consequence of prolonged ACTH stimulation of the adrenal cortex. The reverse sequence – autonomous adrenal cortisol secretion suppressing a clinically significant corticotroph adenoma – is exceptionally uncommon and poses major diagnostic challenges.

Case Presentation:
A 60-year-old woman presented with severe Cushing syndrome, including profound hypokalemia (2.3 mmol/L), refractory hypertension and diabetes, hirsutism, proximal myopathy, edema, and venous thrombosis. Biochemical testing showed marked hypercortisolism (DST 18.6 µg/dl, UFC 1059 µg/24h [normal range of 32-243, 4.3× ULN]) with low-normal ACTH (8 pg/mL) and normal DHEA-S (3 µg/mL). Imaging revealed a 4-cm left adrenal mass. She underwent left adrenalectomy with rapid clinical remission.
Two months later, she developed recurrent hyperglycemia and pedal edema with cerebrospinal fluid rhinorrhea. Imaging demonstrated a large destructive sellar mass with cavernous sinus and skull base invasion. Hypercortisolism recurred (morning cortisol 24.33 µg/dL, UFC 324 µg/24 h [4.5× ULN]) with ACTH rising to 98 pg/mL. Biopsy confirmed a densely granulated corticotroph adenoma.
Transsphenoidal resection resulted in clinical improvement with biochemical evidence of hypocortisolism based on a low morning cortisol (3.21 µg/dL). The postoperative course was complicated by transient diabetes insipidus, persistent CSF leak, and meningitis. 8 months after pituitary surgery morning cortisol levels remained low at 4.6 µg /dl and the patient is still under glucocorticoid replacement therapy.

Discussion:
This case illustrates the diagnostic challenges that arise when Cushing syndrome does not conform to classic ACTH-dependent or ACTH-independent patterns.
It is noteworthy that after removal of the adrenal adenoma, not only was the ACTH suppression released, but this may also have unleashed a previously controlled aggressive biological behavior that subsequently manifested clinically with skull base erosion and rhinorrhea.
The temporal relationship between the autonomous adrenal cortisol secretion and pituitary ACTH secretion remains unclear – whether one preceded the other, developed simultaneously, or the adrenal adenoma developed in response to prolonged ACTH stimulation.

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