Incidentally discovered adrenal masses, referred to as adrenal incidentalomas, are fairly common given the routine use of imaging as part of clinical care in a variety of settings. Adrenal incidentalomas most frequently are benign and hormonally inactive tumors. However, approximately 11% to 15% are hormonally active, which can lead to diagnosis of clinically relevant conditions that affect morbidity and mortality. Thus, all adrenal incidentalomas should be tested for production of hormones at initial diagnosis. A 1-mg dexamethasone suppression test is the initial screening test. Patients then should be referred for appropriate treatment. Among the adrenal mass subtypes, pheochromocytomas are associated with the highest risk of mortality. Every effort should be made to exclude the presence of these tumors. Patients with hypertension and adrenal incidentalomas should be evaluated for aldosterone excess with an aldosterone to renin ratio. Primary malignancy represents a low percentage of adrenal incidentalomas. A minority of adrenal malignancies are primary adrenocortical tumors, which are associated with a poor prognosis and for which management often is palliative.

Metabolic alkalosis defined by the increase of both plasma HCO3- level (>26 mmol/L) and blood arterial pH (>7.43) is quite frequent and usually accompanied by hypokalemia. Its pathogenesis requires both the generation of alkalosis and its maintenance. Generation may be due to excessive hydrogen ion loss by the gastrointestinal tract (e.g. vomiting) or by the kidney (e.g. use of loop diuretics) or may be due to exogenous base gain. Maintenance reflects the inability of the kidney to excrete the excess of bicarbonate because of hypovolemia, chloride depletion, hypokalemia, hyperaldosteronism, renal failure or a combination of these factors. The evaluation of volemic status and measurement of urinary Cl- and plasma levels of renin and aldosterone are crucial to identify the cause(s) of metabolic alkalosis. The cornerstone of treatment is the correction of existing depletions and the prevention of further losses. In vomiting-induced chloride depletion alkalosis, infusion of potassium chloride restores the excretion of bicarbonate by the kidney.

Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist. Compared with primary hypertension, PA causes more end-organ damage and is associated with excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation. Screening is simple and readily available, and targeted therapy improves blood pressure control and mitigates cardiovascular morbidity. Despite these imperatives, screening rates for PA are low, and mineralocorticoid-receptor antagonists are underused for hypertension treatment. After the evidence for the prevalence of PA and its associated cardiovascular morbidity is summarized, a practical approach to PA screening, referral, and management is described. All physicians who treat hypertension should routinely screen appropriate patients for PA.

Hypertension is caused by increased cardiac output and/or increased peripheral resistance. Areas covered: The various mechanisms affecting cardiac output/peripheral resistance involved in development of essential hypertension are covered. These include Genetics, Sympathetic nervous system over activity, Renal mechanisms: Excess sodium intake and pressure natriuresis, Vascular mechanisms: Endothelial cell dysfunction and the Nitric Oxide Pathway, Hormonal Mechanisms: The renin-Angiotensin-Aldosterone system(RAAS), Obesity, Obstructive Sleep Apnea (OSA), Insulin resistance and metabolic syndrome, Uric Acid, Vitamin D, Gender Differences, Racial, Ethnic and Environmental Factors. Increased Left ventricular ejection force and hypertension and its association with- increased basal sympathetic activity- Cortical connections. Expert commentary: Maximum association of hypertension is found with sympathetic over-activity which is directly or indirectly involved in different mechanisms of hypertension including RAS, OSA, obesity etc. It is not overt sympathetic activity; but disturbed basal sympathetic tone. Basal sympathetic tone arises from hypothalamus; possibly affected by cortical influences. Therefore, hypertension is not merely a disease of circulatory system alone. Its pathogenesis involves alteration in ANS (autonomic Nervous System) and likely in cortical -hypothalamic connections. Assessment of ANS and cortical-hypothalamic connections may be required for better understanding of hypertension.

An adrenal incidentaloma is an adrenal mass detected on imaging that was not performed for suspected adrenal disease. The prevalence is approximately 3% and increases up to 10% in older people. The risk of malignancy and a hormone excess have to be evaluated. Approximately 15% of incidentalomas harbor an overproduction of hormones, in particular primary aldosteronism (Conn's syndrome), hypercortisolism (Cushing's syndrome) and pheochromocytoma. Primary aldosteronism is the main cause of endocrine hypertension. It is characterized by an overproduction of aldosterone usually due to a unilateral adenoma or an idiopathic, often bilateral hyperplasia. The aldosterone to renin ratio is an established screening parameter for the diagnosis. If the ratio is elevated a confirmatory test, e. g. saline infusion test, should follow. Usually an adrenal venous catheter has to be used to discriminate between unilateral and bilateral aldosterone overproduction. In the case of unilateral overproduction an adrenalectomy is recommended, otherwise treatment is carried out with an aldosterone antagonist. For the diagnosis of an adrenal Cushing's syndrome a dexamethasone suppression test and a suppressed or in the lower limit of normal ACTH is required. The rare pheochromocytoma is a catecholamine-producing tumor. The diagnosis is carried out by determination of metanephrines in plasma or in 24 h urine samples. Unilateral adrenal tumors leading to clinically significant hormone excess or tumors with suspicion of malignancy should be surgically removed. A minimally invasive adrenalectomy is normally the method of choice in patients with a unilateral adrenal tumor <6 cm and without local tumor invasion. In unilateral, clearly benign, non-functioning, small adrenal tumors (<4 cm) surgery is not required.

Guillain-Barré syndrome (GBS) may be complicated by severe hypertension (HT) and in turns severe HT can occur with neurological damage mimicking a GBS, so that underlying causes should be investigated. We describe a case of a 62-year-old woman presented to the emergency department for hypertensive crisis with symmetric flaccid paralysis, hypotonia and hyporeflexia of both upper and lower limbs. Brain computed tomography, magnetic resonance imaging and lumbar puncture were normal. Laboratory investigations revealed severe hypokalemia, renal failure, liver impairment, rabdomyolysis, metabolic alkalosis, and low plasma renin and aldosterone levels. Continuous potassium replacement led to complete clinical resolution. A detailed history revealed chronic intake of 250 g/day black liquorice. Hypokalaemic muscle weakness may simulate a GBS. When serum potassium level falls below 2.5 mmol/l, rhabdomyolysis may occur. In this clinical case, an apparent mineralocorticoid excess syndrome was induced by chronic ingestion of liquorice. This latter contains the glycyrrhetic acid that inhibits the enzyme 11-β-hydroxysteroid dehydrogenase enzyme type-2 leading an aldosterone-like effect and causing hypertension, hypokalemia, metabolic alkalosis and low renin values. The clinical presentation is similar to that observed in the primary aldosteronism, but in this syndrome plasma aldosterone levels are low rather than elevated as in primary aldosteronism. Liquorice-induced hypertension with severe hypokalemia and rhabdomyolysis is a rare condition and the initial presentation with acute muscle paralysis is still more unusual. Before performing instrumental examinations in middle-aged peoples with hypertension crisis and neurological impairment, a detailed clinical history is mandatory.

Drug-induced hypertension offers the opportunity to further understand pathways involved in the regulation of blood pressure. Posaconazole is an antifungal agent known to induce hypertension and hypokalaemia. In recent months, a flurry of reports has unravelled the metabolic processes involved. In this issue of CKJ, Barton K, Davis TK, Marshall B et al. Posaconazole-induced hypertension and hypokalemia due to inhibition of the 11β-hydroxylase enzyme. Clin Kidney J 2018; 11: 691-693 present convincing evidence of 11β-hydroxylase inhibition resulting in a biochemical syndrome resembling genetic congenital adrenal hyperplasia and characterized by high 11-deoxycorticosterone and 11-deoxycortisol levels as well as androgen levels. This adds to prior evidence supporting inhibition of 11β-hydroxysteroid dehydrogenase 2, the enzyme that inactivates cortisol in aldosterone-sensitive tissues such as the kidneys, yielding a syndrome resembling genetic apparent mineralocorticoid excess or licorice toxicity, characterized by a high cortisol/cortisone ratio.

Somatic KCNJ5 mutations result in excess aldosterone production and are reported to be more common in Asia than elsewhere. To assess the prevalence of somatic KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed the clinical characteristics, treatment outcomes, and biochemistry and histologic differences among patients with and without somatic KCNJ5 mutations. Of the 96 patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient with p.W126R. All patients presented with hypertension. Hypokalemia was documented in 98% of patients. The hypertension cure rate at 1 year after surgery was 35%. Patients with somatic KCNJ5 mutations required more potassium supplementation and had adrenal histology compatible with zona fasciculata-like cells compared with patients without the mutations (all P < 0.05). There were no significant differences in preoperative plasma aldosterone concentration (PAC), plasma renin activity, aldosterone/renin ratio, potassium level, treatment of hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5-mutant and nonmutant groups. In a multivariate analysis, a higher PAC was associated with the presence of somatic KCNJ5 mutations. In summary, the prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand, an Asian country with residents of different ethnic backgrounds, is comparable to previous reports in Asia.