Endocrine Abstracts

Case: A 74-year-old female presenting with central weight gain, proximal myopathy, thin skin and bruising. Clinical examination identified central obesity, round facies, dorso-cervical and supra-clavicular fat pads.

Investigations: Bloods revealed hypokalaemia (3.2mmol/l), elevated cortisol levels (>1000nmol/l) persisted post low dose Dexamethasone suppression test, with a supressed ACTH (<5). Urine free cortisol 1842nmol/24hrs (0-165). CT Chest-Abdomen-Pelvis revealed a large heterogeneous left adrenal mass (5.7x3.7 cm) with no disseminated malignancy. She commenced Metyrapone whilst awaiting surgery.

Management: In July 2021 Laparoscopic left Adrenalectomy was performed. The adrenal was noted to be ragged and distorted, 70x40x38mm weighing 51g. Histology was consistent with an adrenal cortical adenoma, Weiss score 2 (confluent necrosis and capsule invasion). Hydrocortisone replacement was commenced post-operatively. Short Synacthen Test two months later revealed a flat response (Cortisol 90 to 165nmol/l), hydrocortisone was continued. Ten months post-operatively Cushingoid features recurred; bruising, facial and abdominal weight gain, with elevated cortisol (927nmol/l) after 48hrs without Prednisolone. CTCAP revealed disseminated metastatic disease; multiple nodules in the left upper quadrant at the adrenalectomy bed, adjacent to the pancreas and splenic flexure, lung (2.2 cm right lower lobe) and liver metastases. No resectable targets were identified. Metyrapone was re-commenced, she was referred to Cambridge to start Mitotane and EDP Chemotherapy (Etoposide, Doxorubicin, Cisplatin). Urine steroid profile revealed high cortisol metabolites suggestive of Cushing’s recurrence. Repeat urine steroid profile in June 2022 indicated treatment with Metyrapone had improved total cortisol metabolites with a corresponding increase in androgen metabolite levels. The initial histology of the adrenalectomy was re-reviewed in light of the aggressive behaviour clinically. It was found to contain an oncocytic component (dominant) of a higher nuclear grade and more mitotically active than the clear cell component, with resulting challenging assessment of malignant potential. Worrisome features were present; fibrous bands, disruption of reticulin architecture and prominent capsular invasion. Re-review of the initial CT, highlighted a possible tiny lung deposit, suggesting potential metastatic disease prior to the initial operation. Her most recent EDP chemotherapy occurred in October and there has been a partial response. The latest round has been delayed, as she recently presented with expressive dysphasia, an acute right pontine infarct was evident on MRI. Significant hypercholesterolemia (Total Cholesterol 19, LDL 15.5mmol/l) was apparent, likely due to persistent effects of Mitotane on free fatty acid release although stopped for a few months, and Pravastatin was commenced. She is ongoing review to assess regarding the role of further Chemotherapy.