Congenital hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency type I in a Portuguese patient - Case report and review of literature

SUMMARY Hyperreninemic hypoaldosteronism due to aldosterone synthase (AS) deficiency is a rare condition typically presenting as salt-wasting syndrome in the neonatal period. A one-month-old Portuguese boy born to non-consanguineous parents was examined for feeding difficulties and poor weight gain. A laboratory workup revealed severe hyponatremia, hyperkaliaemia and high plasma renin with unappropriated normal plasma aldosterone levels, raising the suspicion of AS deficiency. Genetic analysis showed double homozygous of two different mutations in the CYP11B2 gene: p.Glu198Asp in exon 3 and p.Val386Ala in exon 7. The patient maintains regular follow-up visits in endocrinology clinics and has demonstrated a favourable clinical and laboratory response to mineralocorticoid therapy. To our knowledge, this is the first Portuguese case of AS deficiency reported with confirmed genetic analysis.

Diabetes mellitus and hyperkalemic renal tubular acidosis: case reports and literature review / Diabetes mellitus e acidose tubular renal hipercalêmica: relatos de caso e revisão da literatura

ABSTRACT Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.

RESUMO Apesar de comum, o hipoaldosteronismo hiporeninêmico continua a ser uma entidade sub-diagnosticada, com maior prevalência em pacientes com diabetes mellitus. A doença cursa com hipercalemia assintomática acompanhada de acidose metabólica hiperclorêmica sem disfunção renal significativa. O mecanismo fisiopatológico subjacente não é entendido em sua totalidade, mas postula-se que a deficiência de aldosterona (hipoaldosteronismo hiporeninêmico) e/ou a resistência à aldosterona no órgão-alvo (pseudo-hipoaldosteronismo) possam ser responsáveis. O diagnóstico é fundamentado em parâmetros laboratoriais. A estratégia terapêutica varia de acordo com o mecanismo fisiopatológico subjacente e a etiologia, mas seu objetivo é normalizar o potássio sérico. O presente artigo relata dois casos e analisa a literatura relevante sobre o assunto.

Polyglandular Autoimmune Syndrome Type 2 Complicated by Multiple Organ Failure, Empty Sella Syndrome and Aplastic Anemia

Polyglandular autoimmune syndrome (PAS) is a group of syndromes comprised of glandular and extra-glandular disorders characterized by autoimmunity. A 57-year-old woman presented with acute progressive dyspnea and generalized weakness for several months. The patient was assessed to have acute congestive heart failure with cardiomyopathy, chronic renal failure with hyporeninemic hypoaldosteronism, and pancytopenia in addition to primary hypothyroidism and adrenal insufficiency. With the diagnosis of PAS type 2 complicated by multiple organ failure (MOF), medium-dose prednisolone (30 mg/d) was introduced primarily to control the activity of autoimmunity, which triggered MOF over the adrenal insufficiency. Levothyroxine (25 microg/d) was followed for replacement of the thyroid hormone deficiency. However, the symptoms and signs fluctuated, depending on the dosage of prednisolone, and progressively worsened by empty sella syndrome and aplastic anemia. Here, we report on a case of PAS type 2 with MOF and atypical complications, and suggest that recognition, assessment, and control of PAS as a systemic autoimmune disease may be essential.

Management of a 25-day-old Male Presenting with a First Episode of Acute Pyelonephritis, and Persistent Hyperkalemia with Normal Serum Aldosterone

Hyperkalemia is often detected in young infants, particularly in association with acute pyelonephritis or a urinary tract anomaly. Cases of hyperkalemia in this population may also be due to transient pseudohypoaldosteronism, or immaturity of renal tubules in handling potassium excretion. Symptoms of hyperkalemia are non-specific, but are predominantly related to skeletal or cardiac muscle dysfunction, and can be fatal. Therefore, treatment has to be initiated immediately. Administration of fludrocortisone for hyperkalemia is appropriate in cases with hypoaldosteronism, but is challenging in young infants with hyperkalemia due to renal tubular immaturity, without pseudohypoaldosteronism. We report the case of a 25-day-old male presenting with persistent hyperkalemia with normal serum aldosterone, who was admitted with a first episode of pyelonephritis and unilateral high-grade vesicoureteral reflux. The patient was treated successfully with fludrocortisone.

A Case of Myotonic Dystrophy with Electrolyte Imbalance

Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with a multisystem involvement, caused by an abnormal expansion of the CTG sequence of the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being reported. But, Electrolytes imbalance is a very rare condition in patients with DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally elevated serum sodium and potassium. The patient had minimum volume of maximally concentrated urine without water loss. It was only cured by normal saline hydration. The cause of hypernatremia was considered by primary hypodipsia. Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of hyperkalemia.

Maternally-inherited diabetes with deafness (MIDD) and hyporeninemic hypoaldosteronism / Diabetes mitocondrial (MIDD) e hipoaldosteronismo hiporreninêmico

Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G) in the mitochondrial-encoded tRNA leucine (UUA/G) gene. As the name suggests, this condition is characterized by maternally-inherited diabetes and bilateral neurosensory hearing impairment. A characteristic of mitochondrial cytopathies is the progressive multisystemic involvement with the development of more symptoms during the course of the disease. We report here the case of a patient with MIDD who developed hyporeninemic hypoaldosteronism. Arq Bras Endocrinol Metab. 2012;56(8):574-7.

O diabetes mitocondrial (MIDD) é uma forma rara de diabetes monogênico resultante, na maioria dos casos, da mutação mitocondrial A3243G. Essa condição é caracterizada por diabetes de transmissão materna e disacusia neurossensorial. Uma característica das mitocondriopatias é o envolvimento progressivo de outros órgãos ou sistemas, levando ao aparecimento de diversos sintomas durante o curso da doença. Este relato descreve o caso de um paciente com MIDD que, durante o período de acompanhamento, apresentou hipoaldosteronismo hiporreninêmico. Arq Bras Endocrinol Metab. 2012;56(8):574-7.

A Case of Hyperkalemic Periodic Paralysis Induced by Diabetic Nephropathy / 대한내과학회지

Hyperkalemic periodic paralysis is characterized by episodic flaccid paralysis of the skeletal muscles due to an increase in serum potassium concentrations. Primary hyperkalemic periodic paralysis is caused by point mutations in SCN4A, encoding a voltage-gated skeletal muscle sodium channel. However, hyperkalemia-related diseases, such as renal failure, adrenal insufficiency, hypoaldosteronism, and chronic diuretic use, can induce secondary hyperkalemic periodic paralysis. Diagnosis of this disease is based on clinical features, nerve conduction studies, and a DNA sequence analysis. In cases of diagnostic uncertainty, a provocation test can be used to ensure the correct diagnosis. Here, we report a case of secondary hyperkalemic periodic paralysis with hyperkalemia that was induced by diabetic nephropathy, and review the relevant literature.

Disorders of Potassium Metabolism

Hypokalemia usually reflects total body potassium deficiency, but less commonly results from transcellular potassium redistribution with normal body potassium stores. The differential diagnosis of hypokalemia includes pseudohypokalemia, cellular potassium redistribution, inadequate potassium intake, excessive cutaneous or gastrointestinal potassium loss, and renal potassium wasting. To discriminate excessive renal from extrarenal potassium losses as a cause for hypokalemia, urine potassium concentration or TTKG should be measured. Decreased values are indicative of extrarenal losses or inadequate intake. In contrast, excessive renal potassium losses are expected with increased values. Renal potassium wasting with normal or low blood pressure suggests hypokalemia associated with acidosis, vomiting, tubular disorders or increased renal potassium secretion. In hypokalemia associated with hypertension, plasam renin and aldosterone should be measured to differentiated among hyperreninemic hyperaldosteronism, primary hyperaldosteronism, and mineralocorticoid excess other than aldosterone or target organ activation. Hypokalemia may manifest as weakness, seizure, myalgia, rhabdomyolysis, constipation, ileus, arrhythmia, paresthesias, etc. Therapy for hypokalemia consists of treatment of underlying disease and potassium supplementation. The evaluation of hyperkalemia is also a multistep process. The differential diagnosis of hyperkalemia includes pseudohypokalemia, redistribution, and true hyperkalemia. True hyperkalemia associated with decreased glomerular filtration rate is associated with renal failure or increased body potassium contents. When glomerular filtration rate is above 15 mL/min/1.73m2, plasma renin and aldosterone must be measured to differentiate hyporeninemic hypoaldosteronism, primary aldosteronism, disturbance of aldosterone action or target organ dysfunction. Hyperkalemia can cause arrhythmia, paresthesias, fatigue, etc. Therapy for hyperkalemia consists of administration of calcium gluconate, insulin, beta2 agonist, bicarbonate, furosemide, resin and dialysis. Potassium intake must be restricted and associated drugs should be withdrawn.

A Case of Primary Aldosteronism after Renal Transplantation / 대한신장학회지

After renal transplantation, we are more likely to encounter hyperkalemia rather than hypokalemia. We report a case of kidney transplantation recipient with hypokalemia and hypertension secondary to primary aldosteronism. A 48 year-old woman was presented with fatigue and weight loss that had lasted for 3 months. She was diagnosed as autosomal dominant polycystic kidney disease that ultimately progressed to end-stage renal disease. She was operated for renal transplantation before 6 months. She had hypokalemia and hypertension at that time. The ratio of plasma aldosterone over plasma renin activity was 851.7. The computed tomography (CT) revealed 2.4x1.7 cm sized adrenal mass on the right side. The pre-transplantation CT also showed that there had been adrenal mass in the same location even before the transplantation. Right adrenalectomy was performed. After she got discharged, she was again presented with nausea and vomiting. She developed hyperkalemia and was diagnosed as hyporeninemic hypoaldosteronism. She was prescribed with fludrocortisones and recovered from the disease, and resumed the state of normokalemia and normotension.

Congenital hypoaldosteronism.

Congenital hypoaldosteronism due to an isolated aldosterone biosynthesis defect is rare. We report a 4 month old female infant who presented with failure to thrive, persistent hyponatremia and hyperkalemia. Investigations revealed normal serum 17 hydroxy progesterone and cortisol. A decreased serum aldosterone and serum 18 hydroxy corticosterone levels with a low 18 hydroxy corticosterone: aldosterone ratio was suggestive of corticosterone methyl oxidase type I deficiency. She was started on fludrocortisone replacement therapy with a subsequent normalization of electrolytes. Further molecular analysis is needed to ascertain the precise nature of the mutation.

Hiperaldosteronismo hiporreninémico supresible con glucocorticoides. Reporte de un caso y revisión de la literatura / Glucocorticoid-supressible hyporeninemic hyperaldosteronism. A case report and literature review

Se presenta el caso de un paciente de 57 años de edad, hipertenso severo y refractario, tratado sin éxito con 4 drogas antihipertensivas. El cuadro se asociada a debilidad muscular, alcalosis metabólica, hipokalemia severa y kaliuresis aumentada. Después de un exhaustivo estudio y varios ensayos terapéuticos en secuencia, se concluyó que este caso de hiperaldosteronismo hiporreninémico correspondía a la rara patología genética conocida como hiperaldosteronismo supresible con glucocorticoides. Hasta donde el autor sabe este es el primer caso reportado en Centroamérica de esta entidad. Se hace una revisión sobre el tema.

Pseudo-hypo aldosteronism Type II.

A 50-day-old infant diagnosed as meningitis had persistently elevated serum potassium, low serum bicarbonate and normal serum sodium. She had metabolic acidosis with low TTKG, low serum renin and low normal serum aldosterone with no renal failure or extra renal causes of hyperkalemia. Hence a diagnosis of Type II pseudo-hypoaldosteronism was made. She was started on oral thiazide following which her serum electrolytes normalized.

A Case Of Transient Hyporeninemic Hypoaldosteronism After Unilateral Adrenalrectomy for Aldosterone-Producing Adenoma / 대한내분비학회지

Primary aldosteronism is due to either a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex in most cases. A unilateral adrenalectomy in hypertensive and hypokalemic patients, with a well-documented adrenal adenoma, is usually followed by the correction of hypokalemia in all subjects, with the cure of hypertension in 60 to 87% of patients. Here, a unique case, in which a unilateral adrenalectomy for the removal of an adrenal adenoma was followed by severe hyperkalemia, low levels of plasma renin activity and serum aldosterone, suggestive of chronic suppression of the renin-aldosterone axis, is reported. In a follow-up Lasix stimulation test on the 70th day after surgery, the suppression of the renin-aldosterone axis was resolved, indicating the suppression was transient. Patients undergoing a unilateral adrenalectomy for an aldosterone-producing adenoma should be closely followed up to avoid severe hyperkalemia.

Hyperkalemia in Chronic Kidney Disease

Potassium balance and serum potassium level are maintained until very late in chronic kidney disease (CKD), mainly because of an increase in renal and colonic excretion. Hyperkalemia may develop earlier in the course of CKD in patients with hyporeninemic hypoaldosteronism. Hyperkalemia in CKD patients may occur in association with excess dietary potassium intake, constipation or prolonged fasting. It may also be seen with the use of potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and non-steroidal anti-inflammatory drugs. If suspected, pseudohyperkalemia should be excluded to avoid unnessary treatments. Acute treament of hyperkalemia in marked or symptomatic hyperkalemia, particularly in the presence of electrocardiographic changes includes combinations of intravenous calcium gluconate and infusions of glucose and insulin with or without bicarbonate. In patients with kidney failure, dialysis may be required. Either asymptomatic and mild hyperkalemia or chronic hyperkalemia in CKD patients can be treated by potassium restriction, a loop diuretic at high doses, and cation exchange resin.

Clinical Observation on Hyperkalemic Distal Renal Tubular Acidosis / 대한신장학회잡지

PURPOSE: Renal tubular aicdosis (RTA) is a disorder of renal acidification out of porportion to the reduction in glomerular filtration rate. Type IV RTA refers to hyperkalemic metabolic acidosis resulting from aldosterone deficiency or resistance. The incidence of each type RTA has not been reported exactly, however reports on type IV RTA have been recently increasing. METHODS: A retrospective clinical analysis was performed in 50 patients with hyperkalemic distal renal tubular acidosis diagnosed between Jan. 1984 and Feb. 2003 at Department of Internal Medicine, Keimyung University, Dongsan Medical Center. RESULTS: From 1984 to 2003, 50 cases of hyperkalemic distal renal tubular acidosis were diagnosed. The mean age was 50.8+/-19.5 years. The two most common conditions were posttransplantation (28%), and diabetes mellitus (22%), which were followed by hypertension (12%), systemic lupus erythematosus (12%), chronic renal failure (12%), and others (26%). Asymptomatic hyperkalemia (34%), and muscle weakness (28%) were the two most common clinical presentations. All patients demonstrated normal anion gap acidosis with positive urine anion gap. The mean creatinine clearance was 25.6+/-16.4 mL/min. The mean baseline PRA and aldosterone levels were 3.82+/-7.16 ng/mL/hr and 110.02+/-108.2 ng/mL, respectively. Hyperkalemia was well responded to 9-alpha-fludrocortisone, furosemide, K-exchane resin, and combinations of these regimens. CONCIUSION: Type IV RTA is the most common type of RTA in children and adults, and can be an important cause of asymptomatic hyperkalemia. Therefore, type IV RTA should be included in the diffrential diagnosis of unexplained hyperkalemia in various clinical settings.

A case of POEMS syndrome associated with amyloidosis / 대한내과학회지

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal M protein, and skin lesion) is a rare multisystemic disease of unknown cause with varying clinical manifestations. Amyloidosis-associated POEMS Syndrome is also rare condition. We experienced a 63-year-old female who had been suffered from edema and tingling sensation of low extremities. She also had a marked demyelination, axonal degeneration and regeneration of the nerve, hypoaldosteronism, hyperprolactinemia, decreased sexual hormone, monoclonal gammopathy (IgG lambda type), skin change and ascites. The renal biopsy revealed homogenous mesangial widening with a few cell nuclei at the glomerular capillary, and it showed positive apple-green birefringence in Congo-red stain. It's the first report that shows the deposition of amyloid in patients with POEMS syndrome in Korea. Edema and M-spike were improved by use of prednisolone, melphalan, fludrocortisone and colchicine.

Chronic hyponatremia of Sheehan's syndrome / 대한내과학회지

Sheehan's syndrome has been attributed to ischemic damage of the pituitary gland or hypothalamic-pituitary stalk during the peripartum period. Well-described clinical features of Sheehan`s syndrome include hypothyroidism, growth hormone deficiency, hypogonadism, hypoprolactinemia, adrenal insufficiency, and different sodium and water disturbance. The occurrence of sodium and water disturbances associated with Sheehan`s syndrome depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions that also may play a role in sodium and water balance. Chronic hyponatremia is the most common presentation of altered sodium levels in patients with Sheehan`s syndrome. The chronic nature of the presenting hyponatremia suggests more subtle changes of panhypopituitarism or better adaptive mechanism. Although controversial, another mechanism proposed for hyponatremia in the chronic setting involves alternation in the renin-angiotensin/aldosterone system with resulting sodium wasting. We presented a patient with Sheehan`s syndrome associated with hyporeninemic hypoaldosteronism and hyponatremia 53 years old women, who had 4th baby delivery with severe blood loss about 25 years ago, was admitted to hospital because of general weakness. The patient was diagnosis Sheehan`s syndrome with hyponatremia. In addition, we performed hormonal study to find cause of hyponatremia. The results were hypopituitarism and hyporeninemic hypoaldosteronism. Hyponatremia was corrected by hormonal therapy (glucocorticoid,synthyroid,estrogen). The patient felt well-being sensation and was followed up the out-patient department.

Actividad de 11 beta hidroxiesteroide dehidrogenasa tipo 2 en hipertensos chilenos / 11 B-hydroxysteroid dehydrogenase activity in patients with hypertension and low plasma renin activity

Background: Half of hypertensive patients with low plasma renin activity have a primary hyperaldosteronism. Among the remaining half, 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) deficiency plays an important role. This enzyme catalyzes the conversion of cortisol to cortisone, avoiding the interaction of cortisol with the mineralocorticoid receptor. If the enzyme fails, cortisol will stimulate sodium and water reabsorption and increase blood pressure. Aim: To determine biochemical alterations, suggestive of 11ßHSD2 deficiency, in low-renin hypertensive patients. Patients and Methods: Twenty eight hypertensive patients with a plasma renin activity of less than 0.5 ng/ml/h and with a plasma aldosterone of less than 5 ng/dl were studied. Twenty eight normotensive patients were studied as controls. Serum cortisol (RIA), cortisone (ELISA) and the serum cortisol/cortisone ratio were determined in all of them, between 9 and 10 AM. Measurements were confirmed by high pressure liquid chromatography. The serum cortisol/cortisone ratio was considered abnormal when its Ln (cortisol/cortisone) value was over 2 standard deviations of the mean. Results: Serum cortisol was higher in hypertensive subjects than in controls (11.1ñ3.3 and 9.2ñ2.8 µg/dl, respectively; p <0.05). No differences were observed in serum cortisone (3.4ñ1.3 and 3.7ñ1.2 µg/dl, respectively). Four hypertensive subjects had an abnormally high Ln (cortisol/cortisone) value (1.86; 1.73; 2.07 and 2.01, considering a normal value of less than 1.61). Conclusions: Four of 28 hypertensive subjects with low plasma renin activity and aldosterone had biochemical alterations suggestive of 11ßHSD2 deficiency

Transient hyperkalemia and hypoaldosteronism in a patient with acute glomerulonephritis.

The authors describe a 7-year-old boy with acute glomerulonephritis, who developed acute renal failure in the early course of his disease. While the renal function and other clinical manifestations gradually improved, hyperkalemia occurred unexpectedly, and returned to normal level spontaneously after a short period of symptomatic treatment. With the result of a low transtubular potassium gradient (TTKG) level, it was concluded that hypoaldosteronism was the major cause of hyperkalemia in this patient.

Hiperaldosteronismo primário e hipoaldosteronismo primário / Primary hyperaldosteronism and primary hipoaldosteronism

Neste estudo de casos, relatamos duas patologias clínicas de pouca freqüência, em dois pacientes do sexo masculino, de 48 e 55 anos de idade, um com história pregressa de hipertensäo arterial estágio III de difícil controle e outro com hipercalemia importante, hipotensäo arterial e fraqueza generalizada. Tendo sido um abordado terapeuticamente e outro cirurgicamente, obtendo melhora clínica do quadro patológico. No estudo destes dois casos, abordaremos os aspectos clínicos, os principais mecanismos etiológicos e métodos diagnósticos e subsidiários dirigidos e orientados pelo exame clínico e dados dirigidos pela anamnese.