Spontaneous Hypokalemia Research Articles

6606 Connshing Syndrome: An Uncommon Presentation Of Bilateral Adrenal Mass

Abstract Disclosure: C.S. Botero Suarez: None. N. Meda: None. K. Lamar: None. S.K. Suryanarayanan: None. Introduction: Mild autonomous hypersecretion of cortisol in the underlying setting of hyperaldosteronism has been described before and coined the term Connshing Syndrome. Even though it was described in 1979, recently W. Arlt et al in 2017 revived interest in the topic of Connshing Syndrome represents a distinct entity among PA (primary hyperaldosteronisms). We present a case of bilateral adrenal mass associated with mild autonomous hypersecretion of cortisol as well as the development of primary aldosteronism. Case Description: A 62-year-old male with a medical history of hyperlipidemia, hypertension, spontaneous hypokalemia, and T2DM was referred to the clinic due to concerns for hyperaldosteronism. Exam was unremarkable for signs of hypercortisolism. Blood pressure in the clinic was 143/88 mmHg, pulse 81 bpm, weight 105.4 Kg (231.8 lbs.), and a BMI of 28 kg/m2. A non-contrast abdominal CT performed, showed a 2.9 x.1.4 cm right adrenal lipid-rich adenoma with -3.7 HU, as well as a left adrenal lipid-rich adenoma of 1.8 x 1.3 x cm and -7.7 HU. A hormonal workup showed normal plasma metanephrines, an aldosterone of 39 ng/dL, plasma renin activity 0.16 ng/mL/h, and aldosterone/PRA ratio of 243. The patient underwent 1 mg dexamethasone suppression test which resulted in an ACTH <5 pg/mL, dexamethasone level of 288 ng/dL, and cortisol of 1.9 mcg/dL. AVS with Cosyntropin was performed (see Table 1). Right sided adrenalectomy is being considered but the identification of possible lateralization of cortisol is being considered. Discussion: Surgical management is usually preferred treatment modality for both unilateral PA and MACS, but identification of lateralization of both cortisol and aldosterone can be difficult. Although identifying lateralization of aldosterone with Cosyntropin-stimulated AVS is well understood, lateralization of cortisol production is not well understood. Johnson et. all have suggested the use of adrenal venous sampling with dexamethasone suppression as well as measurement of epinephrine levels to identify the source of hypercortisolism. They demonstrated identification of cortisol lateralization with adrenal vein sampling with specificity of 95 – 100% for unilateral disease utilizing a AV/IVC cortisol ratio > 9 and a cortisol lateralization ratio (CLR) of > 2.3. Although our case had a Cosyntropin-stimulated AVS showing clear lateralization of aldosterone production to the right adrenal, the lateralization of cortisol production is yet unknown and AVS with dexamethasone suppression is being considered. Although the treatment considerations are traditionally utilizing the guidelines for both PA and Cushing Syndrome guidelines respectively, very little is known when there are divergence of autonomous secretion amongst the bilateral adrenal masses and more studies are needed to clarify the long-term treatment considerations. 1 Presentation: 6/3/2024

Sparing confirmatory testing in primary aldosteronism (SCIPA): a multicenter retrospective diagnostic accuracy study

BackgroundThe diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed “simplified confirmatory pathway” that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia.MethodsThis is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218.ResultsOf the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 – 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38)ConclusionA hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as “overt primary aldosteronism confirmed” and may not need to proceed with dynamic confirmatory testing.Protocol registration numberSRCTN34186253

THU588 Sparing Confirmatory Testing In Primary Aldosteronism: The Combination Of Renin, Aldosterone And Potassium Levels

Abstract Disclosure: A.C. Ong Lopez: None. D.M. Dimayuga: None. L.E. Tiu: None. O.C. Dampil: None. E. Mendoza: None. M.L. Villa: None. A.M. Macabuag-Oliva: None. Background and Objective: The diagnosis of primary aldosteronism (PA) is comprehensive which includes case-detecting testing, case confirmation followed by subtype classification. In certain instances, one may not proceed with further confirmatory testing in the setting of spontaneous hypokalemia, suppressed renin, and PAC &amp;gt; 15 ng/dL. However, this quality of evidence is very low. This study sought to determine the optimal laboratory combination patterns that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various combination settings and correlating to the recent evidence and clinical practice guidelines. Methodology: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study with a sampling total of 116 participants aged 18 years and above who underwent saline infusion test between January 2010 to March 2023. The main outcome measures comprise the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia) which include the sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.0.0 &amp; MedCalc 20.218. Results: Of the 116 patients who underwent saline infusion test, 76 (65.52%) were diagnosed with PA. A PAC of &amp;gt; 25 ng/dL plus PRA &amp;lt; 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 89.11%, 100.00%) and positive predictive value at 100% (95% CI 82.35, 100.00%). The optimal combination criteria with the best balance of the diagnostic performance indices were determined to be a PAC of &amp;gt; 20 ng/dL plus PRA &amp;lt; 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has a sensitivity of 34.72% (95% CI 23.88% , 46.86%), specificity of 93.75% (95% CI 79.19%, 99.23%), positive predictive value (PPV) of 92.59% (95% CI 75.71%, 99.09%), negative predictive value (NPV) of 38.96% (95% CI 28.05%, 50.75%), positive likelihood ratio (LR+) of 5.56 (95% CI 1.40, 22.06), negative likelihood ratio (LR-) of 0.70 (95% CI 0.58, 0.84), and a diagnostic accuracy of 52.88% (95% CI 42.85%, 62.75%). Conclusion: Hypertensive patients with spontaneous hypokalemia who had initial screening test results of PAC &amp;gt; 20 ng/dL and PRA &amp;lt; 0.6 ng/ml/hr can be diagnosed as overt primary aldosteronism and may not proceed with dynamic confirmatory testing. This is in line with the 2016 Endocrine Society Clinical Practice Guideline recommendation. Presentation: Thursday, June 15, 2023

FRI122 Determinants Of Primary Aldosteronism Screening In The US: A Nationwide Physician Survey Study

Abstract Disclosure: A.F. Turcu: None. Z. Salman: None. S.M. Konzen: None. L. Zhang: None. H. Liu: None. L. Zhao: None. T. Suzer Gurtekin: None. M. Papaleontiou: None. Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA contributes to cardiovascular and renal morbidity and mortality, via mechanisms additive to hypertension. Early detection and targeted therapy of PA mitigate the risk of such complications. Despite this, only a minute fraction of patients at risk are ever screened for PA. Objective: To ascertain triggers and barriers for PA screening across US practices. Methods: Physicians treating hypertension, including internists, family practitioners, cardiologists, nephrologists, and endocrinologists, were randomly selected from active members of the American Medical Association. Physicians were surveyed on their practice of PA screening. Multivariable logistic regression was performed to determine factors associated with PA screening. Results: Of 633 response-eligible physicians, 425 (67%) completed the survey, including 32.4% family practitioners, 26.9% internists, 13.2% cardiologists, 12.2% endocrinologists, and 11.8% Nephrologists. Of the respondents, 230 (55.2%) were men; 63% identified as White, 24% Asian, and 6% Black. Most participants reported that resistant hypertension (84.5%), and hypertension and spontaneous hypokalemia (81.4%) prompt them to screen for PA. Conversely, a minority reported diuretic-induced hypokalemia (26%), obstructive sleep apnea (10%), or atrial fibrillation (6.2%) as triggers for PA screening. Compared with internists, endocrinologists and nephrologists were more likely, and family practitioners were less likely to screen for PA in patients with hypertension and hypokalemia, early-onset hypertension, or adrenal nodules. Barriers to PA screening included clinic visit time constraints (37.4%), poor ancillary support (28.1%), testing logistic concerns (26.2%), ability to control hypertension with medications (20.5%), and belief that PA is rare (20.2%). Female physicians and family practitioners were more likely to report not being familiar with results’ interpretation and next steps, and not having time to keep abreast with expert guidelines; private practitioners were most likely to report reimbursement concerns. Conclusions: Heterogeneity in screening for PA exists among physicians at the frontline of hypertension care. Increasing awareness and developing tools to facilitate PA screening are crucial for the recognition and adequate care of millions of patients with hypertension. Presentation: Friday, June 16, 2023

Pitfalls in the diagnosis and treatment of a hypertensive patient with unilateral primary aldosteronism and contralateral pheochromocytoma: a case report

BackgroundPrimary aldosteronism (PA) is a common cause of secondary hypertension, whereas pheochromocytoma is a rare cause of it. Thus, concomitant PA and pheochromocytoma is a very rare condition.Case presentationA 52-year-old woman was admitted to our hospital with suspected PA based on the presence of hypertension, spontaneous hypokalemia, and a high aldosterone-to-renin ratio. She had no catecholamine excess symptoms other than hypertension. Abdominal computed tomography (CT) showed a right lipid-rich adrenal mass and a left lipid-poor adrenal mass. PA was diagnosed by the captopril challenge test. The 24-h urinary fractionated metanephrines were slightly elevated. Adrenal vein sampling (AVS) confirmed that the right adrenal gland was responsible for aldosterone hypersecretion. Medical therapy with eplerenone was started because the patient refused surgery. Five years later, she requested surgery for PA. The second AVS confirmed right unilateral hyperaldosteronism, as expected. Repeated abdominal CT showed the enlargement of the left adrenal mass. The 24-h urinary fractionated metanephrines had risen to the diagnostic level. 123I- metaiodobenzylguanidine (MIBG) scintigraphy showed a marked tracer uptake in the left adrenal mass with no metastatic lesion. After preoperative management with α-blockade, laparoscopic left partial adrenalectomy was performed. Immunohistochemical examination of the tumor showed chromogranin A positivity leading to the diagnosis of left pheochromocytoma.ConclusionsWe report an extremely rare case of concomitant unilateral PA and contralateral pheochromocytoma. When diagnosing unilateral PA by AVS, especially in cases with a lipid-poor adrenal mass, clinicians should rule out the possibility of the presence of pheochromocytoma before proceeding to undergo unilateral adrenalectomy. Although there is no standard treatment for this rare condition, it is essential to select personalized treatment from the perspective of conserving the adrenal gland.

PS-R03-2: UNILATERAL PRIMARY ALDOSTERONISM AND CONTRALATERAL GROWING ADRENAL MASS: GROWING CONCERN FOR PHEOCHROMOCYTOMA

Concomitant unilateral primary aldosteronism (PA) and pheochromocytoma is extremely rare. A 52-year-old previously healthy woman with no family history of endocrine disease was admitted to our hospital with suspected PA based on high blood pressure, spontaneous hypokalemia, and a high aldosterone-to-renin ratio. She had no catecholamine excess symptoms other than hypertension. Abdominal computed tomography (CT) showed a right lipid-rich adrenal mass and a left lipid-poor adrenal mass. PA was diagnosed by the captopril challenge test. The 24-h urinary fractionated metanephrines were slightly elevated. Adrenal vein sampling (AVS) confirmed that the right adrenal gland was responsible for aldosterone hypersecretion. Medical therapy with eplerenone was started because the patient refused surgery. Five years later, she requested surgery for PA. The second AVS confirmed right unilateral hyperaldosteronism, as expected. Repeat abdominal CT showed the enlargement of the left adrenal mass. The 24-h urinary fractionated metanephrines had risen to the diagnostic level. 123I-MIBG scintigraphy showed a marked accumulation in the left adrenal tumor with no metastatic lesion. After preoperative management of alpha-blockade, laparoscopic left partial adrenalectomy was performed. Immunohistochemical examination of the tumor showed chromogranin A positivity leading to the diagnosis of left pheochromocytoma. One year after surgery, blood pressure and serum K levels remain well controlled. No surgical treatment for the right adrenal mass has been performed, and PHEO has not recurred. This case highlights the potential pitfalls in the treatment and diagnosis of unilateral primary aldosteronism with contralateral pheochromocytoma. In cases of unilateral PA with contralateral lipid-poor adrenal mass, clinicians should rule out if the contralateral adrenal mass is pheochromocytoma to proceed to undergo unilateral adrenalectomy for the treatment of PA.

PS-R07-7: USE OF GADOLINIUM CONTRAST MEDIUM ENABLES ADRENAL VEIN SAMPLING IN A FLORID PRIMARY ALDOSTERONISM PATIENT WITH IODINE ALLERGY

Case: A 35-year-old woman was allergic to iodine contrast medium and was diagnosed with primary aldosteronism (PA) based on functional confirmatory tests. She was suspected to have unilateral PA because of marked hypertension, spontaneous hypokalemia, high plasma aldosterone, reduced plasma renin activity, and a right hypodense adrenal tumor. She wanted to become pregnant and requested adrenalectomy instead of medical treatment with mineralocorticoid receptor antagonists. Localization of PA by adrenal vein sampling (AVS) was necessary, but angiography with iodine contrast medium was not possible because of her allergy. AVS was performed using gadolinium contrast agent (gadoterate meglumine) instead of iodine, in combination with computed tomography angiography (CTA) because the American College of Radiology manual does not recommend prior steroid administration for high-risk patients who have already exhibited adverse reactions to iodine contrast medium. In AVS, before and after adrenocorticotropic hormone (ACTH) loading, 12 blood samples were drawn from the right adrenal vein, left adrenal central vein, left adrenal common duct, left and right renal veins, and the lower inferior vena cava with only 5 mL of gadolinium medium. There were no complications during AVS. Examination revealed an elevated aldosterone/cortisol ratio on the right side, lateralized ratio of 7.4, and contralateral ratio of 0.76; the patient was diagnosed with right unilateral PA. She underwent right adrenalectomy and showed improvements in aldosterone level from 312.4 pg/mL to 83.0 pg/mL, potassium from 3.0 mEq/L to 3.9 mEq/L, and systolic blood pressure from 138 mmHg to 117 mmHg. She is currently off her medications. Conclusion: In PA patients with iodine allergy, AVS can be performed safely and precisely using gadolinium contrast combined with CTA.

PS-BPR01-7: CONCURRENT SOMATIC MUTATIONS IN CTNNB1 AND GNA11 IN AN ALDOSTERONE-PRODUCING ADENOMA

Background: Aldosterone-producing adenoma (APA) is a major subtype of primary aldosteronism (PA), a common form of secondary hypertension. In the past decade, there has been significant progress in the determination of genetic causes of APA. The use of next-generation sequencing (NGS) has led to the identification of somatic mutations in APA that cause excess aldosterone production. Most of the affected genes encode ion channels or transporters. Somatic activating mutations in CTNNB1 (β;-catenin) have also been detected in 2–5% of APA. As a possible pathogenesis, an association of CTNNB1-mutated APA with pregnancy and menopause has been proposed. A recent study reported double somatic mutations in CTNNB1 and GNA11/Q in APA. However, due to its rare incidence, characteristics of APA with these mutations are not well determined. Herein, we report a case of APA harboring somatic CTNNB1 and GNA11 mutations. Case presentation: A 46-year-old Japanese woman presented with hypertension and spontaneous hypokalemia. She had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation. Endocrine testing showed elevated plasma aldosterone concentration (677.5 pg/mL) under suppressed renin (plasma renin activity, 0.3 ng/mL/h). Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling indicated excess aldosterone production from the right adrenal gland. NP-59 scintigraphy further demonstrated increased tracer uptake in the right adrenal lesion. She underwent right laparoscopic adrenalectomy. Histologic diagnosis of the resected tumor was adrenocortical adenoma based on the Weiss criteria. Notably, Ki-67 labeling index was high (6% at hotspots). After surgery, her blood pressure and serum potassium both normalized. Based on the PASO (the primary aldosteronism surgical outcome) study criteria, PA remained clinically and biochemically cured at follow-up 18 months after surgery. Methods: Formalin-fixed, paraffin-embedded adrenal tumor tissue was used for immunohistochemical and genetic analysis. Results: Immunohistochemistry (IHC) showed high and diffuse expression of CYP11B2 (aldosterone synthase) within the tumor, whereas 11β;-hydroxylase (CYP11B1, a steroidogenic enzyme for cortisol biosynthesis) was mostly negative. VSNL1, a marker for the zona glomerulosa where physiologic aldosterone biosynthesis occurs, was highly expressed within the tumor. CYP11B2 IHC-guided targeted NGS identified concurrent somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations with similar variant allele frequencies (29.5% and 29.7%, respectively). Conclusions: To best of our knowledge, this is the first Asian case of APA with CTNNB1 and GNA11 mutations. Detailed clinical and histologic examination would provide useful information for better characterization of patients with PA due to these rare mutations.

JS-NG-8: CASE REPORT: POSSIBLE NEW CHANNELOPATHY ASSOCIATED WITH ELEVATED ALDOSTERONE LEVELS

Background: Potassium channelopathies are associated with prolonged QT cardiac syndrome. New potassium channelopathies in somatic cells, including KCNJ5 mutations, also underlie some forms of primary hyperaldosteronism. We present a first-in-human report of an association between a KCNQ1 loss of function mutation manifesting with life threatening-ventricular tachycardia (VT), severe hypokalemia and presumed hyperaldosteronism. Case Presentation: The patient is a 51-year-old Asian woman known for obesity, Wolff-Parkinson-White post ablation, and recurrent syncopal episodes with polymorphic VT due to prolonged QTc, requiring an implantable cardioverter defibrillator. On initial presentation for syncope, spontaneous hypokalemia was discovered at 3.1 mmol/L. She had multiple hospitalizations for torsade storms and persistent hypokalemia resistant to aggressive potassium supplementation until addition of spironolactone. Investigations revealed a suppressed plasma renin activity &lt; 0.05 ng/L/s, serum aldosterone concentration at 302 pmol/L, and an aldosterone to renin ratio (ARR) &gt; 6040. Repeated ARR was &gt; 10980. Confirmatory saline suppression testing or adrenal vein sampling were not performed due to risk of recurrent VT associated with spironolactone cessation. A comprehensive evaluation for the etiology of this patient's clinical presentation revealed a mutation in the KCNQ1 gene type 1. Literature review: The voltage-dependent K(+) channel responsible for activating delayed K(+) current is composed of pore-forming KCNQ1 and regulatory KCNE1/3 subunits which loss of function predispose to sustained torsade de pointes. Animal models demonstrate that KCNQ1 and KCNE1 mRNAs are expressed in the zona glomerulosa of adrenal glands where potassium channels directly participate in the control of aldosterone production. Although KCNE3 is not expressed in mouse adrenals, its deletion is thought to cause activation of lymphocytes targeting adrenal glands, leading to hyperaldosteronism. Furthermore, administration of spironolactone to KCNE3 knockout mice ameliorates their QT prolongation and predisposition to VT. There have been no case reports of an association between KCNQ1/E1/E3 loss of function and hyperaldosteronism in humans. Conclusion: This raises the question if this mechanism can also be a component of human KCNQ1 and KCNE1/3-linked arrhythmogenesis and hyperaldosteronism. Alternatively, we can further speculate that patients with hyperaldosteronism who develop malignant arrhythmias during hypokalemia are subjects with impaired repolarization reserve as a consequence of variants in genes known to cause long QT syndrome. The variants, leading to subclinical ion channel dysfunction, are typically silent until unmasked by electrolytes abnormalities such as hypokalemia. To our knowledge, this case is a first report of a potentially novel channelopathy associated with hyperaldosteronism in humans. These findings are hypothesis generating and require further investigations.

ODP144 Cushing Syndrome and Primary Hyperaldosteronism due to Synchronic Bilateral Adrenal Adenomas with Exclusive Production of Cortisol on the Right and Aldosterone on the Left

Abstract Female patient, 37 years old, coming from China, with a history of resistant arterial hypertension since the age of 25 years old associated with spontaneous hypokalemia and classic ACTH-independent Cushing's syndrome. Radiological imaging exams showed bilateral adrenal nodules. Diagnosed primary hyperaldosteronism (Baseline aldosterone 103ng/dL (2.5-39.2), Renin 2.7uUI/mL (4.4 - 46.1), Aldo/renin ratio 38.1 and K 3.3) and confirmed laboratory hypercortisolism (Cortisol after 1mg of dexamethasone overnight 17.9mcg/Dl (&amp;lt; 1.8), salivary cortisol at midnight 0.466mcg/dL (&amp;lt;0.274), ACTH &amp;lt;2pg/mL, basal serum cortisol 19.4 (3.7–19.4). Abdominal CT identified bilateral adrenal nodules, one on the right and two on the left, with &amp;lt;10 HU, suggestive of adenomas. In the pandemic, we proposed the same surgical treatment for primary adrenocortical macronodular hyperplasia (total adrenalectomy of the largest gland and with greater uptake in PET-FDG and subtotal of the smallest and with less uptake). The patient was therefore submitted to total videolaparoscopic adrenalectomy on the left and subtotal on the right. The anatomopathological evaluation showed bilateral adenomas (Weiss 1) being the immunohistochemistry of the right adrenal nodule diffusely positive for CYP11B1 and negative for CYP11B2, inferring only cortisol production. In contrast, left adrenal nodules were positive only for CYP11B2, inferring exclusive aldosterone production. However, we also found bilateral subcapsular cell clusters with positivity for CYP11B2. This may infer a possibility of hyperaldosteronism recurrence. The patient developed secondary adrenal insufficiency postoperatively, requiring replacement with hydrocortisone, and cure of hyperaldosteronism with normalization of potassium and release of renin. Six months after the operation, there was no need for antihypertensive drugs. Currently, it is using only one class of antihypertensive, amlodipine 5mg a day, and it still needs to be replaced with hydrocortisone 20mg on waking up and 10mg at 2 pm with still undetectable serum cortisol concentrations, despite the ACTH being unblocked (17.3 pg /ml). Now we are working on genetic background of this case report. Presentation: No date and time listed

Surgical Outcomes of Aldosterone-Producing Adenoma on the Basis of the Histopathological Findings.

IntroductionPrevious studies on the surgical outcomes of aldosterone-producing adenoma (APA) patients were mainly based on the histopathological diagnosis of HE staining or adrenal venous sampling (AVS) instead of the functional pathology. The aim of the present study was to evaluate the surgical outcomes of APA patients based on the functional pathological diagnosis of APA according to HISTALDO (histopathology of primary aldosteronism) consensus.MethodsClinical data of 137 patients with suspected APA were analyzed retrospectively. All patients had hypertension and spontaneous hypokalemia. In all patients, CT showed a unilateral solitary hypodense adrenal lesion, and a contralateral adrenal gland of normal morphology. Tumors were removed and immunostained for CYP11B2, and their pathology were identified based on HISTALDO consensus. Patients were followed up 6 to 24 months after operation.ResultsAmong 137 cases of presumptive APA diagnosed by CT, 130 (95%) cases were pathologically diagnosed with classical pathology, including 123 APA(90%) and 7 aldosterone-producing nodule (APN) (5%). 7 cases (5%) had non-functioning adenoma (NFA) with aldosterone-producing micronodule (APM) or multiple aldosterone-producing micronodule (MAPM) in the surrounding adrenal tissue. In all 137 patients, hypertension was complete or partial clinical success postoperatively. Complete clinical success was achieved in 73 (53%), and partial clinical success was achieved in 64 (47%) cases. Serum potassium level recovered to normal in all. In 123 patients with APA, complete clinical success was reached in 67 (54%), and partial clinical success was reached in 56 (46%) cases. Gender, duration of hypertension and the highest SBP were significant independent predictors for cure of APA after surgery. A multiple logistic regression model integrating the three predictors was constructed to predict the outcome, which achieved a sensitivity of 72.4% and a specificity of 73.1%.ConclusionThe specificity of CT in the diagnosis of APA and APN patients with hypokalemia was 95%. All patients achieved complete or partial clinical success after surgery. Gender, duration of hypertension and the highest SBP were independent predictors for the postoperative cure of APA.

A Case of Primary Hyperaldosteronism Presenting as Hemorrhagic Stroke

Background: Primary aldosteronism (PA) is the most common form of secondary hypertension. Patients with PA are more likely to suffer from end-organ damage compared to matched controls with essential hypertension. We present a case of PA identified in a patient who presented with hypertensive emergency and hemorrhagic stroke. Clinical Case: A 52-year-old man with hypertension and chronic kidney disease presented with sudden onset left-sided weakness. He had a ten year history of hypertension and was taking carvedilol, losartan, and hydralazine prior to presentation. On arrival, his blood pressure was 263/142 mmHg. He had 3/5 grade weakness in the left upper and lower extremities. Laboratory analysis showed a potassium level of 2.8 mmol/L (n = 3.5–5 mmol/L) and a bicarbonate level of 33 mmol/L (n = 21–29 mmol/L). Screening labs for PA were drawn after potassium repletion. CT Head without contrast revealed an acute 2.5-centimeter intracerebral hemorrhage of the right basal ganglia. He was admitted to the intensive care unit and was started on a nicardipine drip with an improvement of blood pressure. His weakness improved and he was discharged home on carvedilol, hydralazine, nifedipine, and losartan.Screening for PA revealed a plasma aldosterone concentration (PAC) of 22.8 ng/dL (n < 16 ng/dL) and a plasma renin activity (PRA) of 0.1 ng/ml/hr (n = 0.2–1.6 ng/ml/hr). The PAC/PRA ratio was therefore extremely elevated at 228. The presence of spontaneous hypokalemia, very low renin, and PAC >20 ng/dL confirmed the diagnosis of primary aldosteronism. He underwent an adrenal MRI which revealed two left adrenal nodules, the largest measuring 10 mm, and a 7.3 mm right adrenal nodule, consistent with bilateral adrenal adenomas. The patient did not desire surgery, therefore adrenal vein sampling was deferred. His hypertension improved with the addition of a mineralocorticoid receptor antagonist. Eight weeks after his stroke the patient was readmitted due to chest pain. He was found to have severe multi-vessel coronary artery disease and underwent a four vessel coronary artery bypass. Conclusion: Patients with PA have higher rates of adverse cardiovascular events compared to age-, sex-, and blood pressure-matched controls with essential hypertension. Studies demonstrate that aldosterone excess has blood pressure independent proinflammatory and profibrotic effects on the vessel wall which leads to endothelial dysfunction and thus accelerated atherosclerosis. Appropriate treatment can eliminate the excess cardiovascular risk associated with PA. This case highlights the importance of including PA in the differential diagnosis of secondary hypertension, particularly among patients presenting with spontaneous hypokalemia, severe uncontrolled hypertension and early onset cardiovascular or cerebrovascular disease.

Levetiracetam Treatment Causing False Negative Screening Test in a Woman With Aldosterone Producing Adenoma

Background: Endocrine hypertension accounts for 5–10% of hypertensive population, with primary hyperaldosteronism being the most frequently encountered diagnosis. Biochemical tests are subject to interference with many drugs that may lead to false positive or negative results.We present a case of aldosterone producing adenoma associated with false negative screening test due to Levetiracetam use. Clinical Case: A 30 year-old Middle Eastern woman was referred to endocrinology clinic for evaluation of secondary hypertension and persistent hypokalemia. Six years ago, she presented to emergency room during the 3rd trimester of her second pregnancy with severe preeclampsia and seizure. Postpartum, she was discharged on Levetiracetam (Keppra) 500 mg orally BID. Upon follow up visits, she continued to have persistent elevation of blood pressure readings with spontaneous hypokalemia ranging 2.5–3.2 mEq/L. She was started on Perindopril 10 mg daily and potassium supplement. Amlodipine 5 mg daily was added shortly later on. Clinically, she had regular menstrual cycle. She did not have plethora, central obesity, easy bruising, or proximal muscle weakness. Her review of systems including thyroid-related symptoms were normal. There was no family history of hypertension or adrenal tumors. On examination, BP 180/110, pulse rate 78, weight 58 kg and BMI 25. Her physical examination was otherwise unremarkable. After holding Perindopril for 4 weeks, biochemical tests showed creatinine 0.52 mg/dL (0.49–1.1), urea 16.8 mg/dL, potassium 2.9 mEq/L (3.5–5.2), direct renin concentration (DRC) 100.6 pg/mL, aldosterone 54.25 ng/dL. Plasma fractionated metanephrines were normal and morning cortisol level after 1 mg overnight dexamethasone suppression test was 0.72 mcg/dL. Renal arterial doppler showed normal renal blood flow without any significant stenosis. Despite increasing potassium supplement she continued to have hypokalemia. As levetiracetam was reported by literature review to cause severe hypokalemia, it was stopped after discussion with neurology. Four weeks later, repeated DRC was suppressed 4.0 pg/mL with elevated aldosterone 62.73 ng/dL. Furthermore, primary hyperaldosternism was confirmed after normal saline suppression test revealed unsuppressed aldosterone 15 ng/dL. An Adrenal CT scan showed a small hypodense right adrenal lesion measuring 11x9 mm with a pre-contrast density of 7 HU and post contrast absolute washout more than 60%. Patient elected to undergo right adrenalectomy. 24 hours post surgery, aldosterone level dropped to 4.0 ng/dL and potassium increased to 5 mEq/L. Fortunately, hypertension and hypokalemia have both resolved after surgery. Conclusion: We are first to report that Levetiracetam can cause unsuppressed direct plasma rennin concentration (DRC) and potentially could result in a false negative screening test for primary hyperaldosteronism.

Primary Hyperaldosteronism in Pregnancy: A Case Report

Background: Primary aldosteronism (PA) is a renin-independent hypersecretion of aldosterone that remains an underdiagnosed etiology of hypertension. Less than 50 cases of primary hyperaldosteronism in pregnancy have been reported in literature that are associated with pregnancy complications including preeclampsia. Clinical Case: A 41-year-old female G9P4 at 32 weeks gestation was admitted for suspected preeclampsia due to elevated blood pressure during a routine prenatal visit. Her comorbidities include type 2 diabetes, uncontrolled hypertension, and preeclampsia in a previous pregnancy. Home medications included Lisinopril 10 mg once daily which was discontinued upon pregnancy and switched to Labetalol 400 mg twice daily and Nifedipine ER 30 mg daily. She was on a total of 220 units of insulin daily.On presentation, patient complained of anxiety but denied any headache, nausea, visual disturbances, chest pain, palpitations, muscle cramps, or fatigue. Her blood pressure was 180/100 mmHg with heat rate of 73. Laboratory values was notable for potassium: 2.8 mmol/L (n 3.5–5 mmol/L), bicarbonate: 28 mmol/L (n 24–31 mmol/L), and magnesium: 1.4 mEq/L (n 1.3–1.9 mEq/L). Liver function test and platelet count were normal. Spot protein-creatinine ratio was 0.3 (n 0–0.2). ECG was normal sinus rhythm with a heart rate of 82 without decreased T wave amplitude or U waves. She received three doses of oral 40 mEq potassium chloride over twelve hours and potassium level post repletion was 3.0 mmol/L.Initially, her hypokalemia was attributed to high insulin dose requirements. Despite down titration of insulin, patient continued to have hypokalemic episodes (nadir 2.7 mmol/L) refractory to oral and parenteral potassium supplementation. She remained hypertensive despite Labetalol 600 mg every 8 hours, Nifedipine ER 30 mg every 12 hours, with as needed hydralazine 10 mg IV pushes, and underwent urgent cesarean delivery. Uncontrolled hypertension persisted postpartum with recurrent episodes of hypokalemia. Further investigations revealed a plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels of 43.5 ng/dL (n <10 ng/dL) and 1.67 ng/mL/hr (n 0.17–5.38 ng/mL/hr) respectively, potassium at time of testing was 3.6 mmol/L. PAC to PRA ratio was greater than 20:1 with an absolute PAC greater than 15 ng/dL, which is highly suggestive of PA. Conclusion: We present a case of suspected PA with spontaneous hypokalemia potentially masked by the use of ACE inhibitors uncovered during pregnancy. Given the changes to the renin-angiotensin-aldosterone system (RAAS) during pregnancy, the diagnosis of PA is difficult to establish during gestation. Still, little is known on how to optimally treat these patients. Reference: Morton, A., 2015. Primary Aldosteronism and Pregnancy. Pregnancy and hypertension. An International Journal of Women’s Cardiovascular Health, Volume 5 Issue 4, 259–262.

PREVALENCE OF PRIMARY ALDOSTERONISM AND HYPOKALEMIA IN 5,100 PATIENTS REFERRED TO A TERTIARY HYPERTENSION UNIT

Objective: Primary aldosteronism (PA) was considered a rare disorder almost always associated with hypokalemia. After the introduction of aldosterone-to-renin ratio, the widespread screening of hypertensive patients unveiled a higher prevalence of normokalemic PA, which now represents the prevailing phenotype. Many studies have described the prevalence of hypokalemia in patients with PA, conversely the prevalence of PA in patients with hypokalemia is unknown. In this retrospective observational study, we define the prevalence of hypokalemia in referred patients with hypertension and the prevalence of PA in patients with hypokalemia and hypertension. Design and method: For each patient, medical records were reviewed by three independent reviewers, who were blinded to patients’ identification and diagnosis. Hypokalemia was defined for potassium levels lower than 3.7 mmol/L. PA was diagnosed according to the Endocrine Society guideline. Multivariate logistic regression analysis was used to assess the association of hypokalemia and PA with cardiovascular risk indicators. Results: Hypokalemia was present in 15.8% of 5,100 patients with hypertension whereas 76.9% of these patients were normokalemic. PA prevalence in this cohort was significantly higher than in a cohort of 1,672 unselected patients with hypertension in primary care from the PATO study (7.8% vs. 5.9%, P = 0.011). The prevalence of PA in patients with hypokalemia was 28.1% and increased with decreasing serum potassium concentrations up to 88.5% of patients with spontaneous hypokalemia and serum potassium concentrations below 2.5 mmol/L. A multivariate regression analysis demonstrated the association of hypokalemia with the occurrence of cardiovascular events independent of PA diagnosis. An association of PA with the occurrence of cardiovascular events and target organ damage independent of hypokalemia was also demonstrated. Conclusions: Our results confirm that PA is a frequent cause of secondary hypertension in patients with hypokalemia and the presence of hypertension and spontaneous hypokalemia are strong indications for a diagnosis of PA. Finally, we show that PA and hypokalemia are associated with an increased risk of cardiovascular events.

Hypertension Editors' Picks: Hyperaldosteronism.

Hypertension Editors' Picks: Hyperaldosteronism.

Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA. MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018. ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups. ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.

Significance of aldosterone gradient within left adrenal vein in diagnosing unilateral subtype of primary aldosteronism.

The success rate of cannulation of the right adrenal vein is limited. The aldosterone gradient within the same adrenal vein branch is specific for aldosterone-producing adenoma. This study was performed to investigate whether the absolute aldosterone gradient within the left adrenal vein (left-AV absolute aldosterone gradient) indicates unilateral excess aldosterone. A retrospective cross-sectional study in a single referral centre. In total, 123 consecutive patients with primary aldosteronism who had successful adrenal vein sampling (AVS) data were examined. The left-AV absolute aldosterone gradient was considered significant when a gradient of >4:1 in the aldosterone-to-cortisol ratio between the common trunk vein and central vein was found. The prevalence of the unilateral subtype in patients with a significant left-AV absolute aldosterone gradient. The prevalence of the unilateral subtype was higher in patients with than without a significant left-AV absolute aldosterone gradient (88.2% [15/17] vs 21.7% [23/106], P<.001). Of 60 patients with spontaneous hypokalemia, left unilateral disease on computed tomography, or both, a significant left-AV absolute aldosterone gradient was present only in patients with the unilateral subtype on AVS (42.9% [15/35]), but not in those with the bilateral subtype (0.0% [0/25]). These data were validated in an external cohort. The presence of a significant left-AV absolute aldosterone gradient can be used to diagnose the left unilateral subtype of primary aldosteronism on AVS in patients with spontaneous hypokalemia, left unilateral disease on computed tomography or both.

Taiwan mini-frontier of primary aldosteronism: Updating detection and diagnosis

To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.

Seizure and coma secondary to Conn\u2019s syndrome: a case report

BackgroundConn’s syndrome is a curable condition if identified properly. It is characterized by autonomous secretion of aldosterone from the adrenal gland cortex. Its morbidity is related to the increased risk of cardiovascular diseases.Case presentationWe report the case of a 48-year-old man of African descent presenting with generalized tonic-clonic seizure and coma secondary to hypertensive encephalopathy. A biochemical evaluation revealed a very high aldosterone level and an undetectable renin level, both are compatible with primary aldosteronism. The presentation of the following confirms the diagnosis of primary aldosteronism: spontaneous hypokalemia, an undetectable renin level, and a high aldosterone level. Abdominal computed tomography revealed a left adrenal adenoma. Adrenal venous sampling confirmed lateralization of aldosterone excretion from the left adrenal gland. Our patient underwent left laparoscopic adrenalectomy that confirmed a left functional adrenal adenoma. After 12 months of follow up, his hypertension was controlled on only one antihypertensive drug which was down from four drugs preoperatively.ConclusionConn’s syndrome, in this case, was complicated by coma secondary to seizure. Adrenalectomy normalized the hypokalemia and improved resistant hypertension. Potassium supplementation and several antihypertensives were discontinued as our patient became normokalemic and normotensive on one antihypertensive agent.