Endocrine Abstracts

Introduction: Medullary thyroid carcinoma (MTC) accounts for 3-9% of all thyroid cancers and only 0.7% develop paraneoplastic Cushing’s syndrome. However, incidence of endogenous Cushing’s syndrome is also low (1–3/million population/year), with a female preponderance, pituitary mediated ACTH production being responsible for up to 80% of these cases.

Aim: To present the difficulties in the differential diagnosis of ACTH dependent hypercortisolism in a patient with previous medullary thyroid carcinoma.

Patient and methods: A 53 year old woman with thyroidectomy for MTC in 2009 (preoperative calcitonin levels >2000 pg/ml; negative CEA), without biochemical or imagistic evidence of recurrence 9 years after, presented in our department for significant weight gain, peripheral edema and high blood pressure (SBP~190 mmHg).

Methods: TSH, FT4 and calcitonin were measured by chemiluminescence. Serum cortisol and plasma ACTH were measured by electrochemiluminescence. We also performed: 1-mg overnight dexamethasone suppression test (1-mg DST) and 48-h, 2mg/d low-dose DST (LDDST) ; immunohistochemistry of thyroid tumor for calcitonin, CEA, SSTR2, SSTR5, TTF1, Ki67 and ACTH; pituitary and adrenal imaging by MRI, cervical and thoracic imaging by CT scan.

Case report: Clinical examination showed gynoid obesity (BMI = 41.95 kg/m²), BP = 175/100 mmHg, normal visual field, but no purple striae or hirsutism; galactorrhea or extremities enlargement were absent. There were no palpable cervical masses. Hormonal assessment revealed increased 8 AM serum cortisol (22.38 µg/dl) and plasmatic ACTH (72.66 pg/ml), loss of nocturnal nadir of serum cortisol at 11 PM (9.76 µg/dl), without adequate suppression of 8 AM serum cortisol either after 1-mg DST (3.93 µg/dl) or LDDST (4.59 µg/dl), normal prolactin and IGF1. ACTH dependent Cushing’s syndrome was therefore diagnosed. There was no diabetes or osteoporosis. MRI showed a pituitary adenoma (9.5/5.5/6.5 mm) and bilateral adrenal hyperplasia. IPSS was not technically available, but there wasn’t any sign of recurrence of MTC (persistent normal calcitonin and CEA, negative ACTH immunohistochemistry of the thyroid tumor, negative imaging study for local regrowth/distant metastases–ultrasonography, CT scan), neuroendocrine markers were normal (Cromogranin A, 5-HIA, plasmatic metanephrines and normetanephrines) and there were no pulmonary nodules on CT scan. Therefore, Cushing’s disease was the most probable diagnosis. Treatment with 2 mg/week of Cabergoline was started. Pituitary surgery is pending.

Conclusion: The reported case is uncommon because previous MTC (with high rates of recurrence/metastases and probability to develop paraneoplastic Cushing’s syndrome) was later associated with pituitary ACTH secreting microadenoma. Immunohistochemistry of pituitary adenoma and hormonal postoperative assessment are mandatory for diagnosis confirmation.