Endocrine Abstracts

Case presentation: A 67-year old diabetic and hypertensive female, with no significant family history, first underwent total thyroidectomy, with a histological and immunohistochemical result of both papillary thyroid carcinoma (PTC) T3Nx stage III and medullary thyroid carcinoma (MTC), with additional radioiodine treatment for PTC, showing excellent response to therapy at follow-ups (stimulated thyroglobulin <0.2 ng/ml, normal CEA and calcitonin). Almost 10 years later, the patient presented for the first time with elevated total serum calcium (12.5 mg/dl) and elevated PTH (82.2 pg/ml). A 99mTc-pertechnetat/99mTc-sestamibi scintigram was performed, showing a left superior parathyroid adenoma, for which she underwent parathyroidectomy, with constant normal PTH and total serum calcium after surgery. At that point, a thorough laboratory and genetic examination was performed. Pheochromocytoma was not confirmed. Screening for genetic mutations of the RET gene for exons 5, 8, 10, 11, 13, 14, 15 and 16 were all negative. Unfortunately, sequencing the entire RET coding region was not possible. During this extensive endocrine evaluation, an abnormal overnight 1 mg dexamethasone suppression test (13.4 mg/dl) raised the possibility of an associated Cushing syndrome. A low ACTH level (1.7 pg/ml) and an elevated midnight plasma cortisol (7.9 mg/dl) confirmed the ACTH-independent Cushing syndrome. The abdominal computed tomography (CT) showed bilateral macronodular adrenal hyperplasia. Adrenal vein sampling not being available at that time in Romania, we carried on with initial left adrenalectomy (being the largest of the two glands). At 6 months postoperative, the patient presented with persistent hypercortisolemia: ACTH= 14.9 pg/ml, basal plasma cortisol= 19.95 mg/dl, midnight plasma cortisol= 9.2 mg/dl, overnight 1 mg dexamethasone suppression test cortisol= 10 mg/dl. The patient had a second adrenalectomy and received prompt glucocorticoid (GC) and mineralocorticoid (MC) substitution. Interestingly, the patient’s main complaint was persistent proximal muscle weakness, with persistent cushingoid features, persistent diabetes and hypertension. After gradual withdrawal of GC substitution, a high-dose Synacthen test confirmed residual endogenous glucocorticoid secretion (cortisol at 30′= 27 mg/dl, 60′= 32 mg/dl) with a normal 2×2 mg dexamethasone suppression test (0.95 mg/dl). The abdominal CT described an 8 mm nodule most likely a residue of the right adrenal gland.

Conclusion: Our case portrays an interesting association of ACTH-independent Cushing syndrome with normal endogenous cortisol secretion after bilateral adrenalectomy in a patient with prior PTC, MTC and primary hyperparathyroidism (a suspected MEN type 2A without genetic confirmation)- a constellation of rather rare endocrine disorders showcasing the importance of in-depth genetic studies.