P-50 WE KNOW YOU ARE THERE: MISSING MASS
Authors: Salva Hazal , Ustay Ozlem 
Published: January 2025

Abstract

Introduction
Diagnosing neoplastic Cushing's Syndrome (CS) can be quite challenging. Activation of the hypothalamic-pituitary-adrenal axis may also be influenced by various conditions such as psychiatric disorders, alcoholism, obesity, or polycystic ovary syndrome. Here we present a case where Cushing's Disease (CD) or CS is evident but the mass could not be identified.

Clinical Case
A 40-year-old female patient was evaluated for difficulty in weight loss and uncontrolled diabetes. She had bipolar disorder, type 2 diabetes mellitus, initially detected during pregnancy and continuing postpartum, and hypertriglyceridemia (HTG). Despite treatment with fenofibrate and omega-3, she experienced five episodes of pancreatitis. Lipopheresis was performed every 21 days, and attacks have not recurred. Genetic testing for HTG was negative. Due to worsening obesity, orlistat was added. She was receiving 107 units of insulin daily, along with lithium, oxcarbazepine, lamotrigine, quetiapine, aripiprazole, metformin. Family history was unremarkable, and she did not smoke or consume alcohol. Physical examination showed weight of 85 kg, height of 1.55 m, and Body Mass Index of 35.38 (second-degree obesity). She had male-pattern hair loss and abdominal obesity. There was no purple striae. Buffalo hump, moon face, plethora, and supraclavicular fat pads were observed. (Figure-1)
Laboratory evaluation showed 1 mg Dexamethasone Suppression Test at 7.5 ng/dl and 2.2 ng/dl (&lt;1.8), HbA1c was 8.2% (4-5.6), triglycerides were 2000 mg/dl (&lt;150), and microalbuminuria was 57 mg/day. Additional results included 24-hour urine cortisol of 203, 288, and 255 nmol/day, midnight cortisol levels of 14.3 ng/dl and 8.6 ng/dl, and ACTH levels of 12.5 pg/ml, 29 pg/ml, 70 pg/ml. Imaging revealed osteoporosis (L1-4 Z-score: -2.6, 0.764), and pituitary Magnetic Resonance Imaging (MRI) (3 Tesla) showed no mass lesion. Abdominal Computed Tomography indicated no adrenal mass lesion. Intravenous Desmopressin stimulation test (Inferior Petrosal Sinus Sampling-IPSS) was administered to differentiate CD from ectopic CS. IPSS showed CD. Despite controlled psychiatric periods, she had a 10-year history of hypercortisolism symptoms. Elevated midnight cortisol and high urine cortisol confirmed CD through IPSS. No additional evaluation for pseudo-cushing was deemed necessary.
Metyrapone 2x250 mg was initiated, with pituitary MRI monitoring every six months. HTG treatment was adjusted to include gemfibrozil, omega-3, and medium-chain fatty acids. With dietary changes, triglyceride levels dropped to 300 mg/dl, and the patient lost 12 kg, aiding in managing triglycerides and diabetes. Ramipril was started for microalbuminuria, and atorvastatin was planned.
During follow-up, 24-hour urine cortisol was 18.7 and 17.7 nmol/day.

Conclusion
In the case of a mass in CD that cannot be detected despite investigations, as in this patient, Metyrapone can be an option that saves time and helps reduce the patient’s complaints.Figure 1:Abdominal obesity, buffalo hump, moon face, plethora, and supraclavicular fat pads Table 1:IPSS results of the patient