Case history: A 49-year-old teacher presented to his GP with lethargy and lower limb weakness. He had noticed polydipsia and polyuria, and had experienced weight loss albeit with an increase in central abdominal fat mass. He had previously undergone cholecystectomy and colonic polypectomy. He took no regular medications.
Investigations: He had hypercalcaemia 3.34 mmol/l with PTH of 356 ng/l and hypokalaemia 2.7 mmol/l and was admitted for intravenous fluid therapy and potassium replacement. Renal function was normal and phosphate level measured low at 0.42 mmol/l. A contrast enhanced CT Chest/Abdomen/Pelvis imaging revealed a well-encapsulated anterior mediastinal mass measuring 1742 cm × 1142 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 242 cm right inferior parathyroid lesion. The patient underwent biopsy of the mediastinal lesion and immunohistochemistry was positive for synaptophysin and CD56 with weak patchy staining for PAX8; Ki67 was 3%. Histology was consistent with an atypical carcinoid-likely thymic. His serum cortisol was 2612 nmol/l. Inadequate cortisol suppression to 575 nmol/l from an ODST was demonstrated and ACTH was elevated at 67 ng/l. Pituitary MRI was normal and remaining anterior pituitary biochemistry was unremarkable. On review of the previous CT imaging, the adrenals appeared normal but a pancreatic lesion was noted adjacent to the uncinate process with internal calcification. The admission was further complicated by an increase in urine output, to 10l/24 hrs with significant thirst, for which a water deprivation test was conducted. Desmopressin was administered at 1700 hrs without significant response.
|Serum osmolality (mOsm)||300||301||304||304||298||301||294||291|
|Urine osmolality (mOsm)||253||275||377||348||391||412||355||304|
|Serum Na+ (mmol/l)||150|
A 18FDG-PET demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga-DOTA-PET, the mediastinal mass was moderately avid, and the pancreatic mass showed marked uptake with additional peripancreatic lesions likely representing lymph node involvement.
Treatment: Intravenous fluids successfully treated hypercalcaemia. Metyrapone was initiated at 250 mg QDS and uptitrated to 500 mg QDS, with therapeutic cortisol concentration aimed between 100–200 nmol/l. Genetic testing due to MEN-1 phenotype was requested and he was referred urgently for thoracic MDT review and surgery.
Conclusions/Discussion: The underlying unifying diagnosis is clinical MEN-1 with concurrent paraneoplastic Cushing’s syndrome most likely secondary to the large thymic neoplasm, complicated further by nephrogenic DI due to multiple electrolyte disturbances.