{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:42:09Z","timestamp":1788964929094,"version":"build-2803163510"},"reference-count":15,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg\/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 \u03bcg\/d), epinephrine (66 \u03bcg\/d), and calcium (558 mg\/d). Baseline serum cortisol was 23.9 \u03bcg\/dl and decreased to 12.9 and 4.5 \u03bcg\/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg\/ml and decreased to 75 and 24 pg\/ml after dexamethasone. Bone density t-score was \u22124.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg\/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 \u03bcg\/d), epinephrine (0 \u03bcg\/d), and calcium (281 mg\/d) but not plasma ACTH (125 pg\/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg\/ml) and ACTH by 91% (125 to 11 pg\/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng\/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing\u2019s syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.<\/jats:p>","DOI":"10.1210\/jc.2002-021796","type":"journal-article","created":{"date-parts":[[2003,10,13]],"date-time":"2003-10-13T17:42:51Z","timestamp":1066066971000},"page":"4565-4568","source":"Crossref","is-referenced-by-count":33,"title":["Cushing\u2019s Syndrome Due to Medullary Thyroid Carcinoma: Diagnosis by Proopiomelanocortin Messenger Ribonucleic Acid in Situ Hybridization"],"prefix":"10.1210","volume":"88","author":[{"given":"R. C.","family":"Smallridge","sequence":"first","affiliation":[{"name":"Division of Endocrinology (R.C.S.), Jacksonville, Florida 32224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Bourne","sequence":"additional","affiliation":[{"name":"Orlando Diabetes and Endocrine Specialists (K.B.), Orlando, Florida 32835"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. W.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology (B.W.P.), Mayo Clinic, Jacksonville, Florida 32224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"van Heerden","sequence":"additional","affiliation":[{"name":"Department of General Surgery (J.A.v.H.), Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. C.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology, Metabolism, and Nutrition (P.C.C., W.F.Y.), Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. F.","family":"Young","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology, Metabolism, and Nutrition (P.C.C., W.F.Y.), Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071617561498500_R1","first-page":"752","article-title":"Ectopic adrenocorticotropic hormone syndrome.","volume":"15","author":"Wajchenberg","year":"1994","journal-title":"Endocr Rev"},{"key":"2020071617561498500_R2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2265.1994.tb02468.x","article-title":"ACTH precursors characterize the ectopic ACTH syndrome.","volume":"40","author":"Stewart","year":"1994","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071617561498500_R3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1365-2265.1998.00451.x","article-title":"ACTH precursors: biological significance and clinical relevance.","volume":"48","author":"White","year":"1998","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071617561498500_R4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF02739974","article-title":"The immunophenotype of pituitary adenomas.","volume":"7","author":"Lloyd","year":"1996","journal-title":"Endocr Pathol"},{"key":"2020071617561498500_R5","first-page":"479","article-title":"Analysis of endocrine active and clinically silent corticotropic adenomas by in situ hybridization.","volume":"137","author":"Lloyd","year":"1990","journal-title":"Am J Pathol"},{"key":"2020071617561498500_R6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00022744-200103000-00012","article-title":"In situ hybridization detection of calcitonin mRNA in routinely fixed, paraffin-embedded tissue sections: a comparison of different types of probes combined with tyramide signal amplification.","volume":"9","author":"Qian","year":"2001","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"2020071617561498500_R7","first-page":"849","article-title":"[Cushing syndrome associated with metastatic medullary carcinoma of the thyroid. 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