title: Presentation of a medullary endocrine neoplasia 2A kindred with Cushing's syndrome.
abstract: Although medullary thyroid cancer (MTC) can produce adrenocorticotropic hormone (ACTH) in up to 40 per cent of cases as determined by immunohistochemistry, clinical hypercortisolism is rarely seen. We report a medullary endocrine neoplasia 2A (MEN 2A) kindred whose proband case presented with Cushing's syndrome (CS). This 51-year-old woman presented with debilitating weakness, exertional dyspnea, 50 pound weight gain, moon facies, worsening hypertension, striae, and hirsutism. A comprehensive evaluation diagnosed ectopic ACTH production from unresectable metastatic MTC to the liver. Genetic testing revealed a germline RET proto-oncogene mutation at codon 609. Further genetic testing identified six family members with the same mutation. The patient underwent palliative bilateral laparoscopic adrenalectomies with significant improvement in major comorbidities. Overall CS resulting from ectopic ACTH overproduction by MTC is rare, occurring in 0.6 per cent of all patients with medullary thyroid carcinoma. About 50 cases have been previously reported in the literature, but only three in families with MEN 2A. We describe the first case of a MEN 2A kindred presenting with CS from ectopic ACTH production by metastatic medullary thyroid carcinoma. We advocate consideration of early bilateral laparoscopic adrenalectomies in patients with symptomatic hypercortisolism from unresectable metastatic medullary thyroid carcinoma.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6860, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Zaydfudim
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Stover
authors.forename: Susan W
authors.initials: SW
authors.lastname: Caro
authors.forename: John E
authors.initials: JE
authors.lastname: Phay
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000601:surgery; D000315:Adrenalectomy / Q000379:methods; D000324:Adrenocorticotropic Hormone / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D044963:Biopsy, Fine-Needle; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000556:secondary* / Q000601:surgery; D003480:Cushing Syndrome / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D010535:Laparoscopy / Q000379:methods; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000556:secondary* / Q000601:surgery; D000090063:Proto-Oncogene Mas; D013964:Thyroid Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000324:Adrenocorticotropic Hormone