title: A Novel Phenotype of Familial Hyperaldosteronism Type III: Concurrence of Aldosteronism and Cushing's Syndrome.
abstract: To date, all the familial hyperaldosteronism type III (FH-III) patients reported presenting with typical primary aldosteronism (PA), without showing other adrenal hormone abnormalities.
  
  
  
  This study characterized a novel phenotype of FH-III and explored the possible pathogenesis.
  
  
  
  A male patient presented with severe hypertension and hypokalemia at the age of 2 years and developed Cushing's syndrome at 20 years. He was diagnosed with PA and Cushing's syndrome on the basis of typical biochemical findings. He had massive bilateral adrenal hyperplasia and underwent left adrenalectomy. KCNJ5 was sequenced, and secretion of aldosterone and cortisol were observed both in vivo and in vitro.
  
  
  
  A heterozygous germline p.Glu145Gln mutation of KCNJ5 was identified. ARMC5, PRKAR1A, PDE8B, PDE11A, and PRKACA genes and β-catenin, P53 immunoactivity were normal in the adrenal. CYP11B2 was highly expressed, whereas mRNA expression of CYP11B1, CYP17A1, and STAR was relatively low in the hyperplastic adrenal, compared with normal adrenal cortex and other adrenal diseases. In the primary cell culture of the resected hyperplastic adrenal, verapamil and nifedipine, two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol and the mRNA expression of CYP11B1, CYP11B2, CYP17A1, and STAR.
  
  
  
  We presented the first FH-III patient who had both severe PA and Cushing's syndrome. Hypersecretion of cortisol might be ascribed to overly large size of the hyperplastic adrenal because CYP11B1 expression was relatively low in his adrenal. Like aldosterone, synthesis and secretion of cortisol in the mutant adrenal may be mediated by voltage-gated Ca2+channels.
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Anli
authors.initials: A
authors.lastname: Tong
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Dianxi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology (A.T., F.W.), Key Laboratory of Endocrinology, Ministry of Health, and Departments of Urology (G.L., Y.Z.) and Clinical Laboratory (D.Z.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; The Key Laboratory of Genome Sciences and Information (J.J.), Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Department of Endocrinology (Z.Y.), Affiliated Hospital of the Inner Mongolia Medical University, Hohhot 010050, China; and Hypertension Center (J.C.), Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000328:Adult; D003480:Cushing Syndrome / Q000175:diagnosis*; D006801:Humans; D006929:Hyperaldosteronism / Q000145:classification / Q000175:diagnosis*; D008297:Male; D010641:Phenotype; D055815:Young Adult