Challenges in the Diagnosis, Treatment and Follow-up of Patients with Primary Macronodular Adrenal Hyperplasia Pmah Experience of a Large Cohort from a Single Tertiary Center

Presentation Number: SUN 388
Date of Presentation: April 2nd, 2017

Patricia Queilla Souza Lima de Almeida*1, Madson Q. Almeida2, Beatriz M P Mariani3, Mirian Y Nishi4, Maria Claudia N Zerbini3, Victor Srougi5, Fabio Y. Tanno3, Maria Adelaide Albergaria Pereira6, Jose Luiz Chambo4, Berenice Bilharinho Mendonça7 and Maria Candida Barisson Villares Fragoso8
1Clinicas Hospital, University of Sao Paulo, School of Medicine, Av. Dr. Enéas de Carvalho Aguiar, 155 bloco 6, 2Hospital das Clínicas & Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 3Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 4Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 5Faculdade de Medicina da Universidade de São Paulo, São Paulo, 6Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, SAO PAULO, Brazil, 7Disciplina de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular/ LIM42, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil, 8Hospital das Clinicas, University of Sao Paulo, School of Medicine, Sao Paulo, BRAZIL


Background: PMAH is a cause of Cushing's syndrome (CS), characterized by adrenal macronodules and cortisol secretion, causing since subclinical CS (SCS) to overt CS1. Germline mutations in armadillo repeat containing 5 (ARMC5) have been described in families and in apparently sporadic cases (ASC) of PMAH. Nevertheless, no positive correlation was described between genotype and phenotype inter and intra familial cases. The suspicious of PMAH is based in screening for CS when the patients present clinical features of hypercortisolism independent of pituitary ACTH; and/or by the present of bilateral adrenal nodular nodules incidentaloma and by familial genetic screening for ARMC5. The diagnosis in mild presentation is a challenge and consequently its treatment. In addition, the association of PMAH with meningioma and a higher cardiovascular risk to require a specific protocol to precocious diagnosis to improve outcome3,4. Objective: This study aims to characterize epidemiological, clinical, laboratory, radiological imaging and molecular the data from a large cohort of patients with PMAH from tertiary single Hospital (1980-2016). Methods and patients: Data from 56 patients were analyzed. All of them were submitted to hormonal evaluation and abdominal CT/MRI, 51/56 had done cranial CT/MRI. Results: Female:male 42:14 (rate 3). Eight no related families were diagnosed (34 individuals), 22 ASC. The average age at diagnosis was 53 years (range 27 to 69). The median serum level of F after DST (midnight orally 1 mg dexamethasone) was 10 µg/dL (range 0.32 to 33 µg/dL). Eighteen/56 (32%) have CS and 38/56 (67.8%) SCS. Sixteen distinct ARMC5 germline mutations were identified 75% (34 familial cases and 8 ASC). Abdominal CT showed bilateral and unilateral adrenal involvement in 80.4% and 19.6% respectively. Intracranial meningiomas were detected in 11/51 (21.6%) and 6/56 presented others tumors. Thirty six patients were submitted to surgical proceed (17 with CS and 19 with SCS, associated with metabolic syndrome (MS), 20 patients maintain clinical observation and they did not present any clinical reason for surgical treatment such as: MS, osteoporosis, heart failure follow-up (range 1-12 yrs). Conclusion: The present study contributes with a detailed database of the large cohort of familial and ASC of PMAH associated with or without ARMC5 mutations. Although many questions remain: Why is the clinical presentation is so dissimilar, even among members of the same family? How can we follow the patients and the asymptomatic relative carriers of germline ARMC5 mutations? Which other tumors are associated with ARMC5 defect? When should a surgical procedure be indicated? Are overt Cushing´s syndrome and/or subclinical hypercortisolism related to a slightly increased cardiovascular risk? We hope a collaborative study from different cohorts could provide advance in the management of patients with PMAH.