• Journal of Genetic Medicine
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• 제10권2호
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• pp.81-87
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• 2013

Pseudohypoaldosteronism (PHA), a rare syndrome of systemic or renal mineralocorticoid resistance, is clinically characterized by hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels with either renal salt wasting or hypertension. PHA is a heterogeneous disorder both clinically and genetically and can be divided into three subgroups; PHA type 1 (PHA1), type 2 (PHA2) and type 3 (PHA3). PHA1 and PHA2 are genetic disorders, and PHA3 is a secondary disease of transient mineralocorticoid resistance mostly associated with urinary tract infections and obstructive uropathies. PHA1 includes two different forms with different severity of the disease and phenotype: a systemic type of disease with autosomal recessive inheritance (caused by mutations of the amiloride-sensitive epithelial sodium channel, ENaC) and a renal form with autosomal dominant inheritance (caused by mutations of the mineralocorticoid receptor, MR). In the kidneys, the distal nephron takes charge of the fine regulation of water absorption and ion handling under the control of aldosterone. Two major intracellular actors necessary for the action of aldosterone are the MR and the ENaC. Impairment of the intracellular aldosterone signal transduction pathway results in resistance to the action of mineralocorticoids, which leads to PHA. Herein, ion handling the distal nephron and the clinico-genetic findings of PHA are reviewed with special emphasis on PHA type 1.

• 대한임상독성학회지
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• 제21권2호
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• pp.151-155
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• 2023

Licorice is a perennial herb belonging to the legume family that mainly grows in northeastern China, Mongolia, Siberia, and other regions. It is used in traditional medicine in the form of dried roots in the East and the West. The main active component of licorice, glycyrrhizin, is known to produce mineralocorticoid effects when consumed chronically, which can lead to apparent mineralocorticoid excess syndrome. Herein, we present the case of a 72-year-old woman who was admitted to the emergency room with severe generalized weakness and difficulty keeping her neck upright, which had developed after daily consumption of licorice-infused water for the past 2 months. Blood tests revealed metabolic alkalosis and severe hypokalemia, and an electrocardiogram showed ventricular bigeminy. The patient was treated with daily potassium and spironolactone supplements, leading to a significant improvement in muscle strength after a week. One week later, the patient was discharged, showing rare ventricular premature contractions on electrocardiography, but with no specific complaints. Chronic licorice ingestion leading to hypokalemia and muscle weakness can be life-threatening, necessitating the discontinuation of the causative agent, close monitoring, and cautious supplementation of potassium and spironolactone as treatment.

• Toxicological Research
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• 제18권3호
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• pp.301-309
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• 2002

Licorice has been wed in clinical medicine for thousands of years. However it is only in recent times that we have been able to employ scientific methods to prove its efficacy and to give us a better understanding of its mechanism of action. One of important mechanisms for its efficacy is related to mineralocorticoid activity increased by glycyrrhizic acid, the active ingredient in licorice. Also the main undesirable side-effects of Licorice relate to is mineralocorticoid activity resulting in a state of apparent mineralocorticoid excess (AME). These therapeutic and undesirable effects are explained by the inhibition of 11-$\beta$-hydroxysteroid dehydrogenase (11-$\beta$-HSD) activity. Recently, the reduction of serum testosterone in men by licorice was reported which would have important health implications in the context of fertility and sexual dysfunction. Here, health implication of licorice were reviewed In term of its pharmacodynamic and toxicodynamic mechanism.

• Clinical and Experimental Pediatrics
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• 제54권2호
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• pp.90-93
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• 2011

Pseudohypoaldosteronism type 1 (PHA1) is a rare form of mineralocorticoid resistance characterized in newborns by salt wasting with dehydration, hyperkalemia and failure to thrive. This disease is heterogeneous in etiology and includes autosomal dominant PHA1 owing to mutations of the NR3C2 gene encoding the mineralocorticoid receptor, autosomal recessive PHA1 due to mutations of the epithelial sodium channel (ENaC) gene, and secondary PHA1 associated with urinary tract diseases. Amongst these diseases, autosomal dominant PHA1 shows has manifestations restricted to renal tubules including a mild salt loss during infancy and that shows a gradual improvement with advancing age. Here, we report a neonatal case of PHA1 with a NR3C2 gene mutation (a heterozygous c.2146_2147insG in exon 5), in which the patient showed failure to thrive, hyponatremia, hyperkalemia, and elevated plasma renin and aldosterone levels. This is the first case of pseudohypoaldosteronism type 1 confirmed by genetic analysis in Korea.

• BMB Reports
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• 제40권2호
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• pp.180-188
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• 2007

In vivo studies have demonstrated that aldosterone is an independent contributor to glomerulosclerosis. In the present study, we have investigated whether aldosterone itself mediated glomerulosclerosis, as angiotensin II (Ang II) did, by inducing cultured renal mesangial cells to produce plasminogen activator inhibitor-1 (PAI-1), and whether these effects were mediated by aldosterone-induced increase in transforming growth factor $\beta_1$ (TGF-$\beta_1$) expression and cellular reactive oxygen species (ROS) activity. Quiescent rat mesangial cells were treated by aldosterone alone or by combination of aldosterone and spironolactone, Ang II, neutralizing antibody to TGF-$\beta_1$ or antioxidant Nacetylcysteme (NAC). This study indicate that aldosterone can increase PAI-1 mRNA and protein expression by cultured mesangial cells alone, which is independent of aldosterone-induced increases in TGF-$\beta_1$ expression and cellular ROS. The effects on PAI-1, TGF-$\beta_1$ and ROS generation were markedly attenuated by spironolactone, a mineralocorticoid receptor antagonist, which demonstrate that mineralocorticoid receptor (MR) may play a role in mediating these effects of aldosterone.

• Childhood Kidney Diseases
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• 제24권1호
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• pp.58-61
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• 2020

Pseudohypoaldosteronism type 1 (PHA1) is a rare salt-wasting disorder caused by resistance to mineralocorticoid action. PHA1 is of two types with different levels of disease severity and phenotype as follows: systemic type with an autosomal recessive inheritance (caused by mutations of the epithelial sodium channel) and renal type with an autosomal dominant inheritance (caused by mutations in the mineralocorticoid receptor). The clinical manifestations of PHA1 vary widely; however, PHA1 commonly involves hyponatremia, hyperkalemia, metabolic acidosis and elevated levels of renin and aldosterone. The earliest signs of both type of PAH1 also comprise insufficiency weight gain due to chronic dehydration and failure to thrive during infancy. Here, we report a case of renal PAH1 in a 28-day-old male infant harboring a novel heterozygous mutation in NR3C2 gene (c.1341_1345dupAAACC in exon 2), showing only failure to thrive without the characteristic of dehydration.

• Annals of Clinical Neurophysiology
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• 제3권1호
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• pp.50-52
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• 2001

Licorice is widely used as a Chinese(herbal) medicine. The glycyrrhizin, a main ingredient of the natural licorice, has a potent mineralocorticoid effect which may cause severe hypokalemia and muscle paralysis. We present a 60-year-old woman, who had been ingesting one or two spoonful of licorice powder daily for about one year, developed acute flaccid quadriparesis with high levels of serum muscle enzymes and the typical features of mineralocorticoid excess such as severe hypokalemia and metabolic alkalosis. Both plasma renin activity and serum aldosterone level were below the normal values. This case indicates that licorice-induced hypokalemic myopathy should be considered in the differential diagnosis of a patient with acute quadriparesis and hypokalemia.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.190.2-191
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• 2003

Production of prostaglandins involved in renal salt and water homeostasis is modulated by regulated expression of the inducible form of cyclooxygenase-2 (COX-2) at restricted sites in the rat kidney. COX-2 expression in the kidney is regulated by dietary salt intake, but the mechanism of its action is not fully understood. We have previously that high salt regulates COX-2 expression in rat kidney. (omitted)

• 한국임상수의학회지
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• 제22권2호
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• pp.130-135
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• 2005

A retrospective study was performed with 9 cases of spontaneous canine hypoadrenocorticism presented to the Veterinary Medical Teaching Hospital of Seoul National University. The disease occurred mostly in young to middle­aged dogs. Most dogs had chronic nonspecific signs such as episodic anorexia, lethargy and vomiting, but 3 dogs were brought to the hospital with an acute adrenal crisis. Serum biochemical analysis revealed azotemia, abnormal concentration of sodium, potassium, and chloride in almost all the patients. Diagnoses were made based on lack of adrenocortical response to exogenous adrenocorticotropic hormone(ACTH). Most dogs have been responded well with mineralocorticoid and glucocorticoid replacement except for a dog which died during treatment for adrenal crisis. Three dogs treated with fludrocortisone acetate(final median dosage, $31.0{\mu}g/kg/day$) for mineralocorticoid supplementation showed some adverse effects, such as excessive appetite and polyuria/polydipsia. In this study, it was suggested that clinicians should also consider hypoadrenocorticism when they diagnose a patient showing nonspecific gastrointestinal signs with unknown cause or laboratory findings which mimic primary renal diseases.

• Journal of Genetic Medicine
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• 제20권1호
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• pp.25-29
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• 2023

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.