Adrenal Vein Cortisol to Metanephrine Ratio for Localizing ACTH-Independent Cortisol-Producing Adenoma: A Case Report

Context Finding the source of adrenocorticotropic hormone (ACTH)-independent cortisol-producing adenoma in the patients with subclinical Cushing syndrome (SCS) and bilateral adrenal nodules is sometimes challenging. Computed tomography (CT) and positron emission tomography are helpful, but adrenal venous sampling (AVS) is the gold standard approach. However, interpretation of AVS is important to improve the accuracy of decision-making for surgery. We report a case and review of the literature to assess the benefit of using adrenal vein cortisol to metanephrine ratio to determine the source of cortisol production in SCS and bilateral nodules. Evidence Acquisition Three authors searched PubMed for data on patients with SCS who had AVS procedure and measurements of cortisol and catecholamines. Case Description A 51-year-old woman with SCS and hypertension crisis presented to our clinic. Paraclinical investigations revealed that she had an ACTH-independent cortisol-producing adenoma and her CT scan showed bilateral adrenal nodules. After AVS, cortisol (high to low) lateralization ratio could not determine the source of cortisol production but the cortisol to metanephrine ratio localized the source to the left side, which included the larger nodule according to CT measurements. Left adrenalectomy led to clinical and paraclinical improvement. Conclusion There is a possibility of co-secretion of other steroids accompanied with cortisol in the setting of ACTH-independent SCS. Moreover, cortisol measurement alone and interpretation of AVS results based on cortisol values may not help lateralizing the source of cortisol production with bilateral adrenal nodules. Therefore, we suggest applying cortisol to metanephrine ratio with the same gradient (gradient > 2.3, highest to lowest concentration) when the source of cortisol production cannot be determined by cortisol lateralization ratio.

Cardiac Myxoma Caused by Fumarate Hydratase Gene Deletion in Patient With Cortisol-Secreting Adrenocortical Adenoma

Context Germline mutations in fumarate hydratase (FH) gene are known to cause hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and are occasionally accompanied with cutaneous and uterine leiomyoma or cortisol-producing adrenocortical hyperplasia. However, the association between FH mutations and cardiac or adrenocortical tumors has remained unknown. Here, we identified a novel deletion in FH, exhibiting cardiac myxoma and subclinical Cushing syndrome due to adrenocortical tumor. Case Description A 44-year-old man was referred to our hospital for cardiac and adrenal tumor evaluation. He had a history of multiple painful, dermal papules and nodules diagnosed as cutaneous leiomyoma. The surgically resected cardiac tumor was diagnosed as myxoma. The adrenal tumor was clinically diagnosed as subclinical Cushing syndrome. Laparoscopically resected adrenal tumor was pathologically diagnosed as adrenocortical adenoma harboring unique histological findings similar to primary pigmented nodular adrenocortical disease (PPNAD). DNA analysis revealed a germline deletion in FH c0.737delT (p. Phe225Leufs*31) and loss of heterozygosity (LOH) in cardiac myxoma. As a functional analysis of FH in cardiac myxoma, low FH protein expression with elevated 2-succinocysteine (2SC), a marker of FH dysfunction, was immunohistochemically detected. However, in adrenocortical tumor, LOH of FH was not detected, and FH or 2SC expression was not altered. Conclusions This is the first case of HLRCC complicated by cardiac myxoma. LOH of FH deletion and its dysfunction were identified in cardiac myxoma. The association between FH deletion and adrenocortical lesion, however, needs to be further clarified.

SAT-164 Pattern and Spectrum of Adrenal Disorders Seen Among Adults in Southern Iraq. A Tertiary Center Experiences

Background: Adrenal disorders is rare life-threatening conditions needed high awareness for earlier diagnosis. The aim of this study is to see the pattern and spectrum of adrenal disorders in Southern Iraq. Methods: Retrospective electronic database analysis of Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah, the largest tertiary referring Center in the Southern Iraq. Only adults 18 years and above analysed. Results: The total referred patients for presumed adrenal disorders were 5064(6%) of 83473 new patients seen over 11 years for the period of August 2008 to August 2019.The commonest adrenal disease were due to glucocorticoids misuse in 2407/5064 (47.5%),followed by adrenal endocrine hypertension in 883/5064 (17.4%),than adrenal insufficiency in 340/5064 (6.7%), hirsutism in 264/5064 (5.2%), hypopituitarism 85/5064 (1.6%) and congenital adrenal hyperplasia in 78/5064 (1.5%).Rare causes of adrenal disorder were primary aldosteronism in 30/5064 (0.5%), Addison disease in 26/5064 (0.5%), pheochromocytoma in 19/5064 (0.4%), autoimmune polyendocrine syndromes in 19/5064 (0.4%), ACTH independent Cushing syndrome in 17(0.3%), ACTH dependent Cushing syndrome in 4(0.07%), subclinical Cushing syndrome in 4(0.07%), ectopic ACTH syndrome in 1(0.01%), adrenal cyst in 9(0.1%), adrenal myelolipoma in 5(0.09%), adrenocortical carcinoma in 3(0.05%),and paraganglioma in 2(0.04%).One of the paraganglioma were secretory. Patients characteristics for those with glucocorticoids misuse showed that female forming the bulk of cases in 1708/2407 (70.9%), and mean age of 39.5±12.3 years. Urban constitutes 1306/2407 (54.3%),and 629/2407 (26.1%) were illiterates. There were 706/2407 (29.3%) with established type 2 diabetes mellitus(with all the risks of loss of glycemic control) and glucocorticoids misuse causes 105/2407 (4.3%) incident diabetes. Conclusion: Glucocorticoids misuse constituted the bulk of referral for adrenal disorders in Basrah. A lot of work needed to reduce the prevalence of this new high-risk iatrogenic disease.

MON-200 Clinical Characterizations of Aldosterone- and Cortisol-Producing Adrenal Tumors in Primary Aldosteronism

Objective: Aldosterone- and cortisol-producing adrenal tumors (A/CPTs) are considered to be a subtype of primary aldosteronism (PA). The clinical characterizations of these tumors are still unclear, and they are often neglected by clinicians. The aim of this study was to summarize the clinical characterizations of these tumors to reduce the missed diagnosis. Methods: The clinical, imaging and pathological data of patients with PA admitted to our hospital from January 1, 2013 to December 31, 2016 was reviewed. All the PA patients with a combination of a positive aldosterone-to-renin ratio (ARR) and a positive captopril challenge test (CCT), in whom the dexamethasone inhibition test was performed as well, were included in our study. These patients were divided into two groups, A/CPTs group and simple PA group, according to the function of cortisol secretion. The data of the two groups were compared and analyzed with SPSS 23.0. P<0.05 was statistically significant. Results: There were 87 patients with PA included in our study, 32 of whom (36.8%) were diagnosed with A/CPTs. In these 32 A/CPTs patients, 31 patients (96.9%) were combined with subclinical Cushing syndrome. Compared to these in simple PA group (n=55), the patients in A/CPTs group (n=32) were elder (53.81±10.70 ys vs 48.42±10.17 ys, P=0.022), with larger diameter of adrenal tumors (1.50cm vs 1.15cm, P=0.001), higher fasting plasma glucose (5.33mmo/L vs 4.99mmol/L, P=0.047), higher serum cortisol levels and lower serum ACTH levels (all P<0.05). 24 patients in A/CPTs group and 23 patients in simple PA group underwent adrenalectomy. 6 patients (25.0%) in A/CPTs group and 3 patients (13.0%) in simple PA group received glucocorticoid replacement therapy after adrenalectomy. Conclusions:The prevalence of A/CPTs in PA is high. The patients with A/CPTs are mainly combined with subclinical Cushing syndrome, and prone to need glucocorticoid replacement therapy. Therefore, we recommend that all patients with PA should evaluate the function of cortisol secretion, and all patients with A/CPTs should be followed up closely after adrenalectomy to reduce the morbidity of adrenal insufficiency.