Clinical characteristics of primary aldosteronism screened from Chinese patients with hypertension: The China primary aldosteronism prospective study.

We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone-to-renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non-diagnosed PA (n = 147) were 4.54 (95% CI: 2.78-7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64-0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63-3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90-4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20-2.86) for a 0.3 mmol/l higher serum high-density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Update on Primary Aldosteronism: Time to Screen All Hypertensives.

Primary aldosteronism (PA), characterized by autonomous renin-independent aldosterone production, is the most common endocrine cause of hypertension.1 PA was initially considered a rare cause of secondary hypertension, as experts described 0.451% prevalence in mild to moderate hypertension when hypokalemia was an essential reason for screening.1 However, recent data suggests that PA may be present even in patients with normokalemia, and 515% of patients in the hypertensive cohort have underlying overt PA.2.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

CONTEXT: Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening. OBJECTIVE: We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. METHODS: Our study included all PA patients with hypokalemia diagnosed between 2001 and 2022. Delayed diagnosis was defined as duration of hypokalemia of more than 1 year from first occurrence to first evaluation by a PA specialist. Patients were reassessed post adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. RESULTS: Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 years (range, 2.4-7.5 years). Patients with delayed diagnosis were older, had longer duration of HT, higher pill burden, lower renal function, and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidemia, and less severe hypokalemia (serum potassium >3.0 mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%) (P < .05). Sixty of 118 (50.8%) nondelayed, and 39 of 122 (32.0%) patients with delayed diagnosis, underwent surgery. CONCLUSION: Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in HT guidelines, and efforts to improve awareness of PA among primary care physicians, are urgently needed.

Treatment of hypokalemia with amiloride unmasked hypercalcemia and hyperparathyroidism: A case report.

Colonic pseudo-obstruction, also called Ogilvie's syndrome, occurs due to impaired intestinal propulsion, and may be caused by electrolyte imbalances such as hypokalemia and some endocrine disorders such as hyperparathyroidism. Secretory diarrhea due to intestinal pseudo-obstruction can cause hypokalemia. Diuretics such as amiloride can be used to treat hypokalemia, however in this case, treatment with amiloride induced hypercalcemia and unmasked hyperparathyroidism. A 73-year-old female with a history of hypertension and parathyroid adenoma presented with recurrent colonic pseudo-obstruction and chronic hypokalemia. Her hypokalemia was treated with amiloride, causing hypercalcemia of 14.4 mg/dL, elevated PTH, and altered mental status. Amiloride was subsequently discontinued with improvement in her symptoms, and her hyperparathyroidism was treated with cinacalcet. To our knowledge, this is the first report of amiloride unmasking hyperparathyroidism and inducing hypercalcemia.

Comprehensive analysis of clinical and laboratory features of 440 published cases of Sjögren's syndrome and renal tubular acidosis.

AIM: To describe the clinical and laboratory features of Sjögren's syndrome (SS) with renal tubular acidosis (RTA) from published literature. METHODS: A systematic search of indexed publications in all languages till December 2021 identified cases of SS with RTA (SS-RTA) and were included if either antibody (anti-SSA/anti-SSB) or salivary gland histopathology were positive. RESULTS: There were 440 cases of SS-RTA (63.9% from Asia, 95.5% women). The median (range) age was 37 (6-78) years. Only 7.7% had a previous diagnosis of SS. Oral or ocular sicca symptoms were present in 63.7%. Positive ocular tests, oral tests, anti-SSA, anti-SSB and salivary gland histopathology were reported in 256/331 (77.3%), 123/128 (96%), 382/407 (93.9%), 298/379 (78.6%), and 246/268 (91.8%), respectively. Hypokalemic paralysis (HP) was the presenting feature in 63.6%; 25% had multiple episodes of HP and 8.4% had respiratory paralysis. Type 1, type 2, combined type 1 & 2, and type 4 RTA was seen in 388, 8, 38, and 3 patients, respectively. Proximal dysfunction and RTA complications were infrequently evaluated. Fanconi syndrome, nephrogenic diabetes insipidus, proteinuria, and low estimated glomerular filtration rate were found in 45, 21, 178, and 157, respectively. Nephrocalcinosis, renal stones, and osteomalacia were reported in 92, 79, and 72, respectively. Tubulointerstitial nephritis was found in 142 out of 152 renal biopsies. CONCLUSION: SS-RTA is an early manifestation of SS characterized by younger age and subclinical sicca symptoms. Although evaluated less frequently, oral sicca signs and salivary gland biopsy have a high positive yield. HP is the most common presentation. RTA is mostly distal; proximal dysfunction and complications were infrequently assessed.

Ascending Flaccid Paralysis Secondary to Hypokalemia in A Cancer Patient using Abiraterone - A Case Report.

BACKGROUND: Prostate cancer (PC) is the most common type of neoplasm in men and the fourth leading cause of mortality in Brazil. The prostate cancer refractory metastatic castration can be treated with abiraterone acetate (AA). CASE PRESENTATION: Its use has been associated with increased survival. However, there are also side effects associated with the use of this drug, such as severe electrolyte disturbances. CONCLUSION: The objective is to report the clinical case of a patient with castration-resistant metastatic prostate cancer who developed ascending flaccid paralysis secondary to severe hypokalemia, probably due to hyperaldosteronism secondary to the use of Abiraterone Acetate, despite the use of Prednisone.

Association between preoperative hypokalemia and postoperative complications in elderly patients: a retrospective study.

BACKGROUND: Hypokalemia is a common form of electrolyte disorder, which has a higher incidence in hospitalized patients and is closely related to perioperative complications and prognosis. Due to decreased skeletal muscle mass which causes total body potassium reduction, and increased comorbidities, the elderly are more susceptible to hypokalemia. OBJECTIVE: To investigate preoperative hypokalemia in elderly patients and its effect on postoperative complications. METHODS: Data were retrospectively collected from the elderly patients who underwent elective surgery from April 2018 to March 2019 and had preoperative blood gas data available. Patients, with age 60 to 100 years, were divided into hypokalemia group (potassium level < 3.5 mmol/L) and normokalemia group (potassium level between 3.5 and 5.5 mmol/L) according to preoperative blood gas analysis. Hypokalemia can be divided into mild (potassium level 3.0 to 3.5 mmol/L), moderate (potassium level 2.5 to 3.0 mmol/L) and severe (potassium level < 2.5 mmol/L), respectively. The risk factors of preoperative hypokalemia and its impact on postoperative complications and prognosis were primary outcomes. Secondary outcomes included postanesthesia care unit (PACU) stay time and hospital length of stay (LOS). RESULTS: Of 987 participants, 436 (44.17%) developed preoperative hypokalemia, among them 357 (81.88%) mild, 87 (16.74%) moderate and 6 (1.38%) severe. Multivariate logistic regression showed that female gender (OR, 1.851; 95% CI, 1.415-2.421), pre-existing hypokalemia at admission (OR, 4.498; 95% CI, 2.506-8.071), and oral laxative twice or more (OR, 1.823; 95% CI, 1.266-2.624) are risk factors of preoperative hypokalemia. Gynecological and biliopancreatic surgery were more common in hypokalemia group than normokalemia group (P <  0.001, P <  0.05). There was no significant difference in postoperative complications, PACU stay time, LOS, and 30-day mortality between the two groups (all P >  0.05). CONCLUSIONS: Female gender, pre-existing hypokalemia at admission, and oral laxative twice or more are independent risk factors for preoperative hypokalemia in elderly patients. However, postoperative complications and 30-day mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.

Primary Aldosteronism Screening Rates Differ with Sex, Race, and Comorbidities.

Background Primary aldosteronism (PA) is a common but under-recognized cause of secondary hypertension. Data directly comparing screening rates across single and overlapping indications are lacking. Methods and Results We conducted a retrospective review of adults with hypertension seen in outpatient clinics at a tertiary referral academic center between January 1, 2017, and June 30, 2020. We included patients with hypertension plus at least one of the following: resistant hypertension; age<35 years; obstructive sleep apnea; hypokalemia; or an adrenal mass. We excluded patients with adrenal insufficiency, severe renal disease, or heart failure, and renovascular hypertension. Of 203 535 patients with hypertension, 86044 (42.3%) met at least 1 PA screening criterion, and of these, 2898 (3.4%) were screened for PA. Screening occurred in 2.7% of patients with resistant hypertension; 4.2% of those with obstructive sleep apnea; 5.1% of those <35 years; 10.0% of those with hypokalemia; and 47.3% of patients with an adrenal mass. Screening rates were higher in patients with multiple risk factors: 16.8% for ≥3, 5.7% for 2, and 2.5% for 1 criterion. Multiple logistic regression showed that the odds of PA screening were higher in patients with hypokalemia: odds ratio (95% CI): 3.0 (2.7-3.3); women: 1.3 (1.2-1.4); Black versus White: 1.5 (1.4-1.7); those with obstructive sleep apnea, chronic renal disease, stroke, and dyslipidemia. Conclusions Consideration for PA is given in a small subset of at-risk patients, and typically after comorbidities have developed.

Hypokalemia-induced rhabdomyolysis as the first symptom of primary aldosteronism: a case report and literature review.

Primary aldosteronism (PA) is a well-documented cause of secondary hypertension, often accompanied by hypokalemia. However, PA with normal blood pressure and hypokalemic rhabdomyolysis (RM) is rare. We report a case of hypokalemia-induced RM as the first symptom of PA. A 65-year-old woman was admitted due to intermittent limb weakness and myalgia. She denied a history of hypertension. Laboratory findings showed profound hypokalemia (1.8 mmol/L) and extreme elevation of creatinine kinase (CK) levels (18,370 U/L), suggestive of hypokalemia-induced RM. She was administered intravenous fluids as well as active oral and intravenous potassium supplements. CK and myoglobin levels gradually decreased, but the serum potassium recovery was poor. Further evaluations strongly suggested PA by an aldosterone-producing adenoma, which was surgically removed. After surgery, the patient recovered well. The systolic blood pressure decreased by approximately 10-20 mmHg and the diastolic blood pressure decreased by approximately 5-10 mmHg. After discontinuation of spironolactone and oral potassium supplementation, the patient had normal serum potassium levels. This case indicates that PA is a cause of hypokalemic RM, even in patients with normal blood pressure. In addition, attention should be paid to changes in serum aminotransferase levels associated with RM. If the patient had no liver disease, it might be a marker for skeletal muscle injury instead of hepatocyte damage.

Localization diagnosis of adrenocorticotrophic hormone-dependent Cushing's syndrome: two case reports and literature review.

BACKGROUND: The common causes of adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome (CS) include Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis and lesion location of CD and EAS often bring great difficulties to clinical diagnosis and treatment. This article reports the localization diagnosis, treatment, and follow-up results of two patients with ACTH-dependent CS with different causes and reviews the literature. CASE DESCRIPTION: Case 1: a 29-year-old female patient attended the clinic because of irregular menstruation, weight gain, and violaceous striae. The low dose dexamethasone suppression test (LDDST) was not suppressed, and the high dose dexamethasone suppression test (HDDST) suggested the results of serum cortisol and 24-h urine free cortisol were contradictory. Magnetic resonance imaging (MRI) indicated pituitary microadenoma, and bilateral inferior petrosal sinus sampling (BIPSS) indicated ACTH was centrally secreted. CD was diagnosed. The patient underwent transsphenoidal surgery, and the symptoms of CS were improved after the operation. A natural pregnancy occurred more than half a year after the surgery, and a healthy baby boy was delivered 9 months later. Case 2: a 29-year-old female patient complained of facial redness and elevated blood pressure. Examination showed refractory hypokalemia and abnormally elevated serum cortisol and ACTH. Androgens also increased. Neither LDDST nor HDDST was inhibited. Chest-to-pelvis computed tomography (CT) scan revealed a soft tissue mass in the anterior mediastinum, considered as a possible thymoma. EAS and thymoma were diagnosed. An anterior mediastinal mass resection was performed, and pathological results suggested thymic carcinoid weakly positive for ACTH. After the operation, hypertension and hypokalemia were relieved, and cortisol, ACTH and androgens returned to normal levels. CONCLUSIONS: The differentiation between CD and EAS should be comprehensively evaluated in combination with the medical history, function tests, pituitary MRI, and other tests. If the function test results are discordant or pituitary MRI shows the lesion diameter is less than 6 mm, BIPSS should be further performed to confirm the diagnosis. The lesions of EAS are complex and diverse, and it is necessary to pay attention to imaging examinations of the neck-to-pelvis to locate lesion and provide direction for subsequent treatment.

Patient with respiratory distress, facial oedema and refractory hypokalaemia.

Small cell lung carcinoma, when associated with co-occurrence of complications such as paraneoplastic syndrome and superior vena cava syndrome, poses a greater management challenge to the clinical team. We report a 56-year-old man who was eventually diagnosed with stage III small cell lung carcinoma, presenting with respiratory distress, facial and upper body oedema, proximal muscle weakness, hypokalaemia, new-onset hypertension and hyperglycaemia. His medical management was complicated by associated superior vena cava syndrome and Cushing's syndrome leading to refractory hypokalemia, immunosuppression and depression. Although the patient improved clinically and biochemically with the chemotherapy and other treatments, the development of neutropenic pneumonia led to his demise. This case highlights the importance of a multidisciplinary approach to achieve better patient care and the need for good clinical vigilance to identify possible humoral manifestations of aggressive malignancies such as small cell carcinoma of the lung to assist their early detection.

Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma.

Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP). Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus. Conclusions: A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.

Retinal vein occlusion as the presenting feature of Cushing's syndrome.

A 53-year-old man presented to his optician with blurring of vision in the right eye and was diagnosed to have branch retinal vein occlusion. Over the following 3 months, he had further progressive visual impairment due to right central retinal vein occlusion (CRVO) and then left CRVO. Soon thereafter, during a hospital admission for infected submandibular gland, he was noted to have secondary hypothyroidism and persistent hypokalaemia which led to the diagnosis of Cushing's syndrome. This case was unusual as the patient did not manifest any classical features of Cushing's syndrome at the time of presentation with bilateral CRVO, and only 3 months later had dramatic weight loss, muscle weakness and acute psychosis. He received intravenous etomidate and underwent emergency transsphenoidal hypophysectomy with dramatic clinical and biochemical improvement and complete visual recovery in the left eye but unfortunately vision in the right eye remained limited to hand movements.