SUN-195 Bilateral Aldosterone-Producing Adenomas: A New Subtype of Bilateral Primary Aldosteronism?

Abstract Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) < 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test <13 mUI/L). Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression [cortisol (C)= 2.9 μg/dL and dexamethasone= 701 (˃130 ng/dL)], and normal urinary free cortisol, midnight salivary cortisol, plasma DHEAS and ACTH levels. Computed tomography demonstrated bilateral adrenal nodules without adrenal thickening: 3.5 cm right nodule (pre-contrast density of 7UH density; absolute wash-out of 71%) and 2.5 cm left nodule (pre-contrast density of 8UH density; absolute wash-out of 78%). Sequential adrenal venous (AV) sampling (AVS) under continuous cosyntropin infusion showed a lateralization index of 3.4 (bilateral disease <4). Then, the patient underwent right adrenalectomy and left nodulectomy. In the postoperative period, she presented normalization of K+ levels and complete HT remission. She remained under hydrocortisone replacement for 2 months. After 2 months, biochemical evaluation revealed normal basal cortisol levels (13.3 µg/dL) and biochemical cure of PA (A= 3.1 ng/dL and R= 15.3 mUI/L). Currently, she doesn’t have symptoms of adrenal insufficiency after discontinuation of hydrocortisone. Anatomopathological analysis showed bilateral adenomas (Weiss score of 0) in both sides without adjacent hyperplasia. CYP11B2 immunohistochemistry displayed a strong staining in 50% of cells in the right adenoma and in 30% of cells in the left adenoma. Few aldosterone-producing cell clusters (APCC) were identified in the right zona glomerulosa, which is a frequent finding in normal adrenals. Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.

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SAT-560 Usefulness of Contralateral Suppression in Adrenal Venous Sampling to Define Lateralization in Primary Aldosteronism

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.941 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Thaís C Freitas ◽

Ana Alice Wolf Maciel ◽

Leticia Assis Pereira Vilela ◽

Marcela Rassi-Cruz ◽

Janaina Petenuci ◽

...

Keyword(s):

Primary Aldosteronism ◽

Vena Cava ◽

High Sensitivity ◽

Contralateral Suppression ◽

Endocrine Hypertension ◽

Tertiary Center ◽

Standard Parameter ◽

Unilateral Disease ◽

Biochemical Cure ◽

The Right

Abstract Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA subtypes include bilateral hyperplasia and unilateral PA, typically aldosterone-producing adenomas. Adrenal venous (AV) sampling (AVS) is a key step to define PA subtype and guide PA management. According current PA guidelines, most PA patients should undergo AVS, which is a challenging procedure, especially in terms of successfully cannulating the right AV. The aim of this study was to report a single tertiary center experience with AVS in PA patients. We retrospectively evaluated 84 AVS from 1984 to 2019. Sequential AVS was performed by an experienced interventional radiologist. AV and inferior vena cava (IVC) samples were obtained under cosyntropin continuous infusion. Successful catheterization was defined by a selectivity index [SI= AV/IVC cortisol (C) concentrations] ≥5. Unilateral disease was defined by a lateralization index [LI= aldosterone (A)/C ratio in the dominant AV divided by A/C in the non-dominant AV] ≥4. The relative aldosterone secretion index (RASI= A/C ratio in AV divided by A/C in IVC) was calculated in each side. A RASI <1 was defined as contralateral suppression (CS). In patients with unsuccessful AV catheterization (mostly right AV) or undetermined LI (3-4), CS was used to indicate adrenalectomy. The biochemical cure of PA after adrenalectomy was defined as the gold standard parameter to confirm unilateral disease. Successful bilateral AV catheterization was achieved in 75% of the cases. After 2015, the use of intra-procedural rapid cortisol assay improved angiographer experience and increased AVS successful rate from 52 to 80%. LI revealed unilateral and bilateral aldosterone excess in 68 and 32% of the cases, respectively. A LI ≥4 had a sensitivity of 100% and specificity of 98% to define unilateral PA among patients with successful catheterization. In addition, RASI in the non-dominant AV was significantly lower in unilateral PA according the LI when compared to bilateral cases [0.12 (0.03 to 1.18) vs. 1.1 (0.04 to 4.56), p= 0.0001]. RASI in the non-dominant AV was inversely correlated with LI (r= -0.81, p= 0.0001). A CS index ≤0.5 had a high sensitivity (90%) and specificity (94%) to define unilateral aldosterone excess. In conclusion, the LI is the most valuable parameter in AVS for PA subtyping. Additionally, CS (cut-off of 0.5) is very useful to define lateralization and can be used in cases of borderline LI or unsuccessful AV catheterization.CAPES Grant to Freitas TC.

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Primary Aldosteronism Associated with Multiple Adrenocortical Micronodules in a Patient with Renal Cell Carcinoma

Case Reports in Endocrinology ◽

10.1155/2020/2808101 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Kazuhito Oba ◽

Yuko Chiba ◽

Yoko Matsuda ◽

Takeshi Kumakawa ◽

Rie Aoyama ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Primary Aldosteronism ◽

Renal Cell ◽

Zona Glomerulosa ◽

Adrenocortical Adenoma ◽

Loading Test ◽

Cell Renal Cell Carcinoma ◽

Aldosterone To Renin Ratio ◽

The Right

A 47-year-old woman with a history of diabetes mellitus (DM) and obesity was admitted to our hospital for glucose control. She was detected to have hypertension (HT) and diagnosed with primary aldosteronism (PA) based on the high level of aldosterone to renin ratio and the results of the upright furosemide-loading test according to the criteria of the Japanese Society of Hypertension (JSH) guidelines. Computed tomography revealed left renal tumor and adrenocortical adenoma. She underwent left nephrectomy and adrenalectomy. The pathological findings were clear-cell renal cell carcinoma (RCC) and nonfunctional adrenocortical adenoma. Her nonneoplastic adrenal tissue histologically revealed CYP11B2-positive multiple adrenocortical micronodules (MNs) and concomitant paradoxical hyperplasia of the zona glomerulosa. Therefore, MNs were thought to be responsible for PA in this patient. After surgery, HT was improved, and the result of upright furosemide-loading test after 12 months of surgery did not fulfill the criteria of PA according to the JSH guidelines. However, the adrenocorticotrophic hormone stimulation test was positive; considering the possibility of slight aldosterone overproduction from the right adrenal gland, the administration of spironolactone was started. Herein, we report a rare case of RCC in conjunction with PA histologically associated with MNs.

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Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism

Endocrine Related Cancer ◽

10.1530/erc-20-0384 ◽

2021 ◽

Vol 28 (1) ◽

pp. 1-13

Author(s):

Marcela Rassi-Cruz ◽

Andrea G Maria ◽

Fabio R Faucz ◽

Edra London ◽

Leticia A P Vilela ◽

...

Keyword(s):

Primary Aldosteronism ◽

Early Onset ◽

Zona Glomerulosa ◽

Unilateral Adrenalectomy ◽

Transfected Cells ◽

Functional Studies ◽

Protein Levels ◽

Whole Exome ◽

Hyperplastic Tissue ◽

Bilateral Adrenal Hyperplasia

Abstract Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, ‘sporadic’ bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

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SUN-178 Clinical and Anatomopathological Characteristics of Two Atypical Aldosterone-Producing Adenomas

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1384 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Tatiana Silva Goldbaum ◽

Marcelo L Balancin ◽

Felipe L Ledesma ◽

Ana Alice Wolf Maciel ◽

Thaís Castanheira de Freitas ◽

...

Keyword(s):

Computed Tomography ◽

Ct Scan ◽

Somatic Mutations ◽

Histologic Examination ◽

Confirmatory Testing ◽

Clear Cells ◽

R Ratio ◽

Free Cortisol ◽

Biochemical Cure ◽

Biochemical Evaluation

Abstract Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small (<2 cm in diameter) benign appearing nodules on computed tomography (CT). Up to 70% of APAs may harbor KCNJ5 somatic mutations. Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol <3 μg/dL. He presented biochemical cure of PA and improvement in HT control. Histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 1 (clear cells <25%). CYP11B2 staining was positive in 10% and Ki67 in 5% of tumor cells. Case 2. A 58 yr-old woman was referred to investigate an adrenal mass. She had resistant HT and hypokalemia since 2010. Biochemical evaluation revealed hypokalemia (2.8 mEq/L), A of 16.9 ng/dl, renin <1.6 mUI/L and A/R ratio of 10.6. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation was negative. CT scan showed a heterogeneous solid mass in the right adrenal, measuring 5.5 cm with pre-contrast density of 30 HU and absolute wash-out of 77%. After laparoscopic right adrenalectomy, histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 2 (clear cells < 25% and > 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases. Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.

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Angiotensin II Type 1 Receptor Autoantibodies in Primary Aldosteronism

Hormone and Metabolic Research ◽

10.1055/a-1120-8647 ◽

2020 ◽

Vol 52 (06) ◽

pp. 379-385

Author(s):

Lucie S. Meyer ◽

Siyuan Gong ◽

Martin Reincke ◽

Tracy Ann Williams

Keyword(s):

Angiotensin Ii ◽

Primary Aldosteronism ◽

Functional Role ◽

Adrenal Hyperplasia ◽

Endocrine Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Aldosterone Producing Adenoma ◽

Agonistic Autoantibodies

AbstractPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1R-Abs) have been described in transplantation medicine and women with pre-eclampsia and more recently in patients with PA. Any functional role of AT1R-Abs in either of the two main subtypes of PA (aldosterone-producing adenoma or bilateral adrenal hyperplasia) requires clarification. In this review, we discuss the studies performed to date on AT1R-Abs in PA.

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Proton Stereotactic Radiotherapy for Persistent Adrenocorticotropin-Producing Adenomas

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1220 ◽

2008 ◽

Vol 93 (2) ◽

pp. 393-399 ◽

Cited By ~ 82

Author(s):

Joshua H. Petit ◽

Beverly M. K. Biller ◽

Torunn I. Yock ◽

Brooke Swearingen ◽

John J. Coen ◽

...

Keyword(s):

Stereotactic Radiotherapy ◽

Complete Response ◽

Urinary Free Cortisol ◽

X Rays ◽

Normal Tissues ◽

Secondary Tumors ◽

Free Cortisol ◽

Biochemical Cure ◽

Corticotroph Adenomas

Abstract Context: Radiation therapy is a potentially curative treatment for corticotroph adenomas refractory to surgery. Protons have an advantage over photons (x-rays) by depositing energy at the target with no exit dose, providing a lower dose to adjacent normal tissues. Until recently, proton stereotactic radiotherapy (PSR) was available at only two U.S. centers; use will increase as proton facilities are under development. Objective: Our objective was to evaluate the efficacy and safety of PSR for persistent Cushing’s disease (CD) and Nelson’s syndrome (NS). Design: This was a retrospective review of 38 patients (33 with CD and five with NS) treated between 1992 and 2005. Participants: All patients had transsphenoidal surgery without biochemical cure. Four had previous irradiation with photons. The patients with NS underwent bilateral adrenalectomy 29–228 months (median 40) before PSR. Intervention: Single-fraction PSR was delivered at a median dose of 20 Cobalt Gray Equivalents (range 15–20) on 1 treatment day. Main Outcome Measures: Complete response (CR) was defined as sustained (≥3 months) normalization of urinary free cortisol off medical therapy. CR in NS was based on normalization of plasma corticotropin. Results: At a median follow-up of 62 months (range 20–136), CR was achieved in five patients (100%) with NS and 17 (52%) patients with CD. Among all patients with CR, median time to CR was 18 months (range 5–49). No secondary tumors were noted on follow-up magnetic resonance imaging scans, and there was no clinical evidence of optic nerve damage, seizure, or brain injury. There were 17 patients (52%) who developed new pituitary deficits. Conclusions: PSR is effective for patients with persistent corticotroph adenomas with low morbidity after a median follow-up of 62 months; longer follow-up is warranted for late radiation-related sequelae.

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MON-295 Desmopressin Test in Silent Corticothoph Pituitary Adenomas, a Preliminary Study - a Comparison with Cushing Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1736 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Martha Katherine Huayllas ◽

Marilena Nakaguma ◽

Mirela Costa de Miranda ◽

Christiane Gruetmacher ◽

Priscila Rosada Montebello Cardoso ◽

...

Keyword(s):

Pituitary Adenomas ◽

Preoperative Evaluation ◽

Pituitary Tumors ◽

Immunohistochemical Analysis ◽

Urinary Free Cortisol ◽

High Recurrence Rate ◽

Cushing Disease ◽

Basal Cortisol ◽

Free Cortisol ◽

Cortisol Increase

Abstract Introduction: Silent corticothop adenomas (SCAs) account for 9 to 19% of nonfunctioning pituitary adenomas and behave as the most agressive pituitary tumors with more invasiveness and high recurrence rate. The identification of these patients during the preoperative stage could predict better surgery results. Some authors refer to high basal ACTH level in the preoperative evaluation as the only marker but until this date, there are no clinical and hormonal markers that could predict its occurrence. The aim of this study is to evaluate the response to desmopressin test and the presence of silent corticothoph tumors. Patients and methods: Among 475 patients with pituitary lesion, which underwent surgery, 332 were pituitary adenomas, (82 were acromegaly, 40 Cushing disease, 178 nonfunctioning adenomas). Twenty-three patients, 17 with Cushing disease, (CD), mean age: 31 y, 13 female and 4 male) and 6 patients with SCA (mean age: 47 y, 5 female and 1 male) had positive ACTH confirmed by immunohistochemical analysis. Clinical characteristics: in the CD group, 53% had hypertension (9/17), 42% diabetes (7/17), 100% dyslipidemia, BMI was 30.7 kg/m2. Among SCA group, 67% hypertension, 50% diabetes, 50% dyslipidemia, BMI was 28 kg/m2. All patients were evaluated with basal ACTH and DHEAS before surgery. Patients with SCA underwent desmopressin test and were compared to CD. Dexamethasone suppression test (DST 1 mg) and 24-hour free urinary test was performed in patients with CD and in two patients with SCA. Response to desmopressin test was considered positive when increase in cortisol was above 20% and in ACTH of 35% using chemiluminescence assay (Immulite 2000). Results: Among CD group, the median (med) basal ACTH was 75.9 pg/mL (30.9 to 211), the med basal cortisol was 22.5 µg/dL (14.5 to 43.5), the med DHEAS was 170 µg/dL (33 to 465), the med 24h urinary free cortisol of 454.5 µg/24 h (149 to 1673) and med basal cortisol after DST 1mg of 15.4 µg/dL (4.7 to 31.5). Among SCA, med basal ACTH was 19.4 pg/mL (9.5 to 65.5), the med basal cortisol was 9.5 µg/dL (7.8 to 16.4) and the med DHEAS was 104.5 µg/dL (82 to 127). Only 4 patients with CD had macroadenomas. All of them responded with ACTH increase (med increase of 98%, 31.6 to 377%), and only 4 did not respond to cortisol increase (med increase of 54.4%, 0 to 167%). All patients with SCA had macroadenomas. Only one patient did not respond to ACTH increase (med increase of 123.5%, 9.5 to 1522%, 9.5 to 1522%), and 3 patients did not respond to cortisol increase (med increase of 17.9%, 0 to 234%). Discussion: SCA are invasive tumors, with high recurrence and tests predicting their occurrence are missing. We hypothesized that as ACTH is present in the adenoma a response to desmopressin test could exist (like CRH). Conclusion: The desmopressin test can be a useful tool in the evaluation of SCA and can predict pathological phenotype in preoperative tumors.

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Ectopic ACTH-Producing Pheochromocytoma as a Rare Cause for Rapid Progressing Cushing Syndrome: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.258 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A128-A128

Author(s):

Daniela Salazar ◽

Cláudia Fernandes Costa ◽

Joana Oliveira ◽

Liliana Violante ◽

Ana Luísa Cunha ◽

...

Keyword(s):

Adrenal Gland ◽

Cushing Syndrome ◽

Somatostatin Receptors ◽

Osteoporotic Fractures ◽

Urinary Free Cortisol ◽

Hand Tremor ◽

Ectopic Acth ◽

Late Night ◽

Free Cortisol ◽

The Right

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N < 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N < 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol < 0,0544 µg/dL (N < 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.

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Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology

Endocrinology ◽

10.1210/en.2017-00637 ◽

2017 ◽

Vol 158 (12) ◽

pp. 4129-4138 ◽

Cited By ~ 11

Author(s):

Leticia Aragao-Santiago ◽

Celso E Gomez-Sanchez ◽

Paolo Mulatero ◽

Ariadni Spyroglou ◽

Martin Reincke ◽

...

Keyword(s):

Mouse Models ◽

Primary Aldosteronism ◽

Genetic Basis ◽

Plasma Renin ◽

Adrenal Hyperplasia ◽

Endocrine Hypertension ◽

Bilateral Adrenal Hyperplasia ◽

Human Disorder ◽

Aldosterone Producing Adenoma ◽

Functional Mechanisms

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension that is characterized by the excessive production of aldosterone relative to suppressed plasma renin levels. PA is usually caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been identified in several genes that encode ion pumps and channels that may explain the aldosterone excess in over half of aldosterone-producing adenomas, whereas the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number of mouse models of hyperaldosteronism have been described that recreate some features of the human disorder, although none replicate the genetic basis of human PA. Animal models that reproduce the genotype–phenotype associations of human PA are required to establish the functional mechanisms that underlie the endocrine autonomy and deregulated cell growth of the affected adrenal and for preclinical studies of novel therapeutics. Herein, we discuss the differences in adrenal physiology across species and describe the genetically modified mouse models of PA that have been developed to date.

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SUN-LB96 Basal Contralateral Aldosterone Suppression Is Rare in Lateralized Primary Aldosteronism and Can Be Useful in Predicting Surgical Outcome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2048 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Marie-Josée Desrochers ◽

Matthieu St-Jean ◽

El Ghorayeb Nada ◽

Isabelle Bourdeau ◽

Benny So ◽

...

Keyword(s):

Primary Aldosteronism ◽

Surgical Outcome ◽

Clinical Cure ◽

Suppression Ratio ◽

Postoperative Outcome ◽

Roc Curves ◽

Zona Glomerulosa ◽

Unilateral Adrenalectomy ◽

Biochemical Cure ◽

Surgical Cure

Abstract Background: Adrenal venous sampling (AVS) is performed to distinguish between unilateral or bilateral source of aldosterone in primary aldosteronism (PA). Unilateral aldosteronomas should lead to suppression of renin and contralateral (CL) aldosterone secretion, assessed by the CL suppression ratio. We recently found that CL aldosterone suppression was relatively rare using the ratio of basal aldosterone concentration of the opposite adrenal vein/periphery (AOPP/AP) in contrast to the traditional cortisol-corrected aldosterone ratio ((A/C)OPP(A/C)P). Pathology studies showed frequent zona glomerulosa (ZG) hyperplasia adjacent to a dominant aldosteronoma, which could also indicate probable ZG hyperplasia in the CL adrenal. The ratio of basal CL suppression could be a usefull parameter to predict cure following unilateral adrenalectomy (UA), but controversy remains in the literature. Objectives: 1. To evaluate the prevalence of basal CL suppression using the AOPP/AP ratio as compared to the (A/C)OPP/(A/C)P ratio at previously established cut-offs. 2. To determine the best cut-off to predict clinical and biochemical surgical cure in two Canadian referral centers. 3. To compare the accuracy of the AOPP/AP ratio to the basal lateralization ratio (LR) and the post-ACTH LR in predicting the surgical outcome. Methods: 330 patients with PA and successful bilateral simultaneous basal and post-ACTH stimulated AVS (selectivity index >2 basally and >5 post-ACTH) were included; 124 patients found to be lateralized underwent UA. The follow-up data were evaluated for clinical and biochemical cure at 3 and 12 months using the PASO criteria. Results: Using AOPP/AP and (A/C)OPP/(A/C)P at the cut-off of 1, the prevalence of CL suppression is 6% and 45%, respectively. The median CL suppression ratio is 2.3 (1.3-5.1) in lateralized cases of PA using AOPP/AP. Using ROC curves, the AOPP/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)OPP/(A/C)P is associated with biochemical cure only. The cut-offs for AOPP/AP offering the best sensitivity and specificity for clinical and biochemical cures at 12 months are 2.15 (Se 63% and Sp 71%) and 6.15 (Se 84% and Sp 77%), respectively. Basal LR and post-ACTH LR are associated with clinical cure but only the post-ACTH LR is associated with biochemical cure. Conclusions: Basal CL suppression defined by the AOPP/AP ratio is rare and incomplete compared to the traditional (A/C)OPP/(A/C)P ratio in lateralized cases of PA. This may reflect the frequent micronodular hyperplasia adjacent to dominant aldosteronomas and possibly in the CL adrenal. Basal CL aldosterone suppression may predict clinical postoperative outcome, but with modest accuracy.

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