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Cureus Jan 2024Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who...
Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who developed signs and symptoms of mineralocorticoid excess while on abiraterone and discuss its pathophysiology and treatment options. The patient developed hypokalemia, metabolic alkalosis, and hypertension, indicative of increased mineralocorticoid activity, confirmed by elevated ACTH, corticosterone, and deoxycorticosterone levels. Abiraterone inhibits cytochrome P450c17 (CYP17A1), thus inhibiting testosterone and cortisol synthesis. Diminished cortisol synthesis, in turn, leads to excessive mineralocorticoid precursor production mediated by ACTH, leading to enhanced sodium absorption and potassium excretion. Abiraterone is often prescribed with low-dose prednisone to suppress ACTH; however, this strategy may not provide physiological glucocorticoid levels, resulting in ACTH-mediated mineralocorticoid excess in some patients. High-dose steroids or mineralocorticoid antagonists may activate mutant androgen receptors in prostate cancer tissue; therefore, amiloride is suggested for managing residual mineralocorticoid activity. This case highlights the importance of being vigilant for the signs and symptoms of mineralocorticoid excess in patients on abiraterone.
PubMed: 38318572
DOI: 10.7759/cureus.51757 -
CEN Case Reports Feb 2024Gitelman syndrome is a rare, autosomal recessively inherited tubulopathy manifesting with hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Common...
Gitelman syndrome is a rare, autosomal recessively inherited tubulopathy manifesting with hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Common symptoms include fatigue, myalgia, reduced performance capacity, tetany, paresthesia, and delayed growth. However, as reported in the literature, diagnosis in some patients is prompted by an incidental finding of hypokalemia. GS develops due to mutations in the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter. Many variants in the SLC12A3 gene causing GS have been reported in literature. A new pathogenic homozygous mutation (c.2612G > T), absence of hypomagnesemia, and accompanying autoimmune thyroiditis are remarkable in our patient. There are a few Gitelman syndrome cases that are complicated with autoimmune thyroiditis in the literature. In this study, we present a case of Gitelman syndrome with a novel homozygous mutation and accompanying autoimmune thyroiditis and review of the literature.
PubMed: 38308744
DOI: 10.1007/s13730-023-00845-z -
CEN Case Reports Feb 2024Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary...
Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary factors, such as lifestyle and /or medicines. Notably, PBS/PGS is more likely to cause renal dysfunction than GS. We report the first case of PBS/PGS due to long-term laxative abuse leading to end-stage kidney disease (ESKD). The patient was a 49-year-old woman with a history of constipation since school, who had used excessive doses of laxatives on her own judgment for nine years at least from 22 years of age. Two years later, blood tests revealed hypokalemia (serum K 3.1 mEq/L), and nine years later, the patient's renal function began to deteriorate (Cr-eGFR 48.7 mL/min/1.73 m). Since abuse of laxatives was suspected as the cause, it was changed to the proper dosage of laxatives. At 33 years, the patient developed acute kidney injury (AKI), due to a urinary tract infection, and required intensive treatment, including hemodialysis. Although the patient was eventually weaned off dialysis, the renal function did not recover to pre-AKI levels. In suspected GS, comprehensive genetic testing for renal disease-related genes was performed; however, no obvious pathogenic variants were identified. Thereafter, despite decreasing the laxative doses and potassium supplementation, her renal function continued to decline. At 49 years, the patient developed ESKD and was started on maintenance hemodialysis. PBS/PGS is a disease that can lead to ESKD. An early diagnosis of PBS/PGS is crucial to prevent renal function deterioration, and the underlying causes should be removed immediately.
PubMed: 38306007
DOI: 10.1007/s13730-024-00851-9 -
BMJ Case Reports Jan 2024Pseudo-Bartter syndrome (PBS) is characterised by hyponatraemic, hypochloraemic metabolic alkalosis that mimics Bartter syndrome, without renal tubular disease. We...
Pseudo-Bartter syndrome (PBS) is characterised by hyponatraemic, hypochloraemic metabolic alkalosis that mimics Bartter syndrome, without renal tubular disease. We present a case of an infant with a positive cystic fibrosis (CF) newborn screening, hospitalised during the summer with dehydration, oliguria and apathy. Blood analysis revealed hypochloraemic metabolic alkalosis, hypokalaemia and hyponatraemia. Urine analysis showed leucocyturia with reduced sodium and chloride excretion fraction, and urinary culture was positive for After antibiotherapy and intravenous rehydration with additional supplementation of sodium and chloride, the patient recovered completely. PBS is one of CF complications that is especially prevalent in infants and young children with increased sweating and/or other causes of additional loss of sodium and chloride. Clinical awareness of this syndrome and its strong clinical suspicion are extremely important for an early diagnosis and treatment of CF, particularly in countries where the universal screening of CF is not routinely performed.
Topics: Infant; Child; Infant, Newborn; Humans; Child, Preschool; Cystic Fibrosis; Bartter Syndrome; Chlorides; Alkalosis; Hyponatremia; Sodium
PubMed: 38296503
DOI: 10.1136/bcr-2023-257348 -
Acute Medicine 2023A 32-year-old lady with a history of bulimia nervosa was noted to have a raised adjusted calcium of 2.94mmol/L associated with high parathyroid hormone (PTH) 17.2pmol/L....
A 32-year-old lady with a history of bulimia nervosa was noted to have a raised adjusted calcium of 2.94mmol/L associated with high parathyroid hormone (PTH) 17.2pmol/L. On review, she had an apparent hypercalcaemia for at least three years, and also had a chronic, severe alkalosis with a bicarbonate up to 81.9mEQ/L. Ionised calcium during that time had actually been low, down to 1.03mmol/L. This case highlights the effects of alkalosis on calcium, as more albumin is available for binding to ionised calcium. This results in a low ionised calcium, which triggers PTH release and overall leads to raised adjusted calcium levels. Clinicians may misdiagnose a similar patient with primary hyperparathyroidism and treatment would cause worsening of true hypocalcaemia.
Topics: Female; Humans; Adult; Calcium; Hyperparathyroidism, Primary; Parathyroid Hormone; Alkalosis
PubMed: 38284639
DOI: No ID Found -
Theriogenology Mar 2024Regulation of intracellular pH (pH) is an important homeostatic function of cells. There are three major pH regulatory mechanisms: the HCO/Cl exchanger (AE), which...
Regulation of intracellular pH (pH) is an important homeostatic function of cells. There are three major pH regulatory mechanisms: the HCO/Cl exchanger (AE), which alleviates alkalosis, and the Na/H exchanger (NHE) and Na,HCO/Cl exchanger (NDBCE), both of which counteract acidosis. NHE activity, which is high at the germinal vesicle stage of oocyte, is inhibited during meiotic maturation, while this inhibition is abolished when the oocyte reaches the pronuclear (PN) stage of the zygote. On the other hand, we have previously found that NDBCE performs complementary regulation against acidosis during meiotic maturation. Additionally, we found that AE activity, which is a defense mechanism against alkalosis, gradually decreases during preimplantation period of embryonic development. Considering that NHE activity is inhibited during meiotic maturation and AE activity gradually decreases during embryonic development stages, we investigated whether NHE and NDBCE activities, both of which act against acidosis, functionally change from the PN zygote to the blastocyst stage of the embryo and identified these pH-regulating proteins at the molecular level in mice of the Balb/c strain. PN zygotes, two-cell (2-c), four-cell (4-c), morula and blastocyst stage embryos were obtained from 5-8-week-old, sexually mature female Balb/c mice by using the classical superovulation procedure. pH was recorded by using the microspectrofluorometric technique on zygotes and embryos simultaneously loaded with the pH-sensitive fluorophore, 2',7'-Bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). The activities of NHE and NDBCE were determined from the recovery curve of induced-acidosis in bicarbonate-free and bicarbonate-containing media, respectively. Specific inhibitors such as cariporide (1 μM), S3226 (1 and 10 μM), EIPA (1, 5, and 25 μM), and amiloride (1 mM) were used to functionally identify NHE isoforms, and the nonspecific inhibitor 4,4'-diisocyanatostilbene-2,2' disulphonic acid, disodium salt (DIDS) was used to confirm NDBCE activity. The isoforms of the pH-regulatory proteins were also identified by molecular biology using real-time PCR. We found that NHE activity was high at all embryonic stages, and differences between stages were not significant. Functional and molecular findings indicated that isoforms of NHE 1 and 5 are present in the blastocyst, whereas isoforms of NHE 1, 3, and 4 are functional at earlier embryonic stages. Although the contribution of NDBCE activity to recovery from induced-acidosis was detected at all embryonic stages, it was significant only in the PN zygote and the 2-c embryo. This finding was confirmed by molecular analysis, which detected the expression of SLC4A8 encoding NDBCE at all embryonic stages. In conclusion, NHE is an active and important defense mechanism against acidosis and is encoded by at least two protein isoforms in all stages of the Balb/c strain of mice. NDBCE has a supportive function in all embryonic stages, especially in the PN zygote and the 2-c embryo. Preimplantation stage embryos have effective mechanisms to defend against acidosis in response to their metabolic end products (increased acid load) and the acidic environment in utero.
Topics: Pregnancy; Mice; Female; Animals; Hydrogen-Ion Concentration; Chloride-Bicarbonate Antiporters; Mice, Inbred BALB C; Acidosis; Sodium-Hydrogen Exchangers; Alkalosis; Protein Isoforms; Defense Mechanisms; Rodent Diseases
PubMed: 38277795
DOI: 10.1016/j.theriogenology.2024.01.021 -
AJP Reports Jan 2024We describe a pregnant patient with severe compulsive water ingestion and vomiting that lead to metabolic alkalosis and preterm delivery. A 21-year-old patient was...
We describe a pregnant patient with severe compulsive water ingestion and vomiting that lead to metabolic alkalosis and preterm delivery. A 21-year-old patient was hospitalized multiple times throughout pregnancy for symptoms initially thought to be related to hyperemesis gravidarum. Overtime, it became apparent that the patient induced vomiting by rapidly drinking large volumes of water. At 32 weeks' gestation, rapid ingestion of water caused 3 days of vomiting with findings of hyponatremia, hypokalemia, hypochloremia, metabolic alkalosis, and compensatory respiratory acidosis. Fetal monitoring showed minimal variability and recurrent decelerations; subsequent biophysical profile score of 2/10 prompted urgent cesarean section. A male newborn was delivered and cord blood gases reflected neonatal metabolic alkalosis and electrolyte imbalances identical to those of the mother. Compensatory hypoventilation in both mother and fetus were treated with assisted ventilation. With saline administration and repletion of electrolytes, metabolic alkalosis resolved for both patients within days. Metabolic alkalosis was transplacentally acquired by the fetus. This case demonstrates the development of metabolic alkalosis in a pregnant woman caused by vomiting severe enough to prompt preterm delivery for nonreassuring fetal status. It also demonstrates fetal dependence on both placenta and mother to maintain physiologic acid-base and electrolyte balance.
PubMed: 38269119
DOI: 10.1055/s-0043-1778113 -
Clinical Journal of the American... May 2024Liddle syndrome was initially characterized by hypertension, hypokalemia, metabolic alkalosis, and suppressed plasma renin and aldosterone, resulting from...
BACKGROUND
Liddle syndrome was initially characterized by hypertension, hypokalemia, metabolic alkalosis, and suppressed plasma renin and aldosterone, resulting from gain-of-function variants in the epithelial Na + channel (ENaC). Efficient treatment with ENaC inhibitors is available, but the phenotypic spectrum of genetically confirmed Liddle syndrome is unknown, and some patients may remain undiagnosed and at risk of inefficient treatment. In this study, we used a reverse phenotyping approach to investigate the Liddle syndrome phenotypic spectrum and genotype-phenotype correlations.
METHODS
Pubmed, Embase, Scopus, and the Human Gene Mutation Database were searched for articles reporting Liddle syndrome variants. The genetic variants were systematically classified to identify patients with genetically confirmed Liddle syndrome. We identified 62 articles describing 45 unique variants within 86 Liddle syndrome families, and phenotypic data were pooled for 268 patients with confirmed Liddle syndrome.
RESULTS
The Liddle syndrome variants localized to exon 13 of SCNN1B and SCNN1G , disrupting the PPPxY motif critical for downregulating ENaC activity. Hypertension sensitive to ENaC inhibition was present in 97% of adults carrying Liddle syndrome variants while hypokalemia, metabolic alkalosis, and plasma renin and aldosterone suppression showed incomplete penetrance. In addition, 95% and 55% of patients had a family history of hypertension or cerebrovascular events, respectively. The genotype had minor phenotypic effects; however, probands compared with relatives showed significant phenotypic discrepancies consistent with selection bias for initial genetic screening.
CONCLUSIONS
Patients with genetically confirmed Liddle syndrome displayed a phenotypic spectrum, with ENaC-sensitive hypertension and family history of hypertension being the most common features. The phenotype seemed independent of the specific gene or variant type involved.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Phenotype; Adult; Genetic Association Studies; Female; Male; Hypertension; Renin; Hypokalemia; Adolescent; Young Adult; Genetic Predisposition to Disease; Child; Mutation
PubMed: 38265765
DOI: 10.2215/CJN.0000000000000430 -
Oxford Medical Case Reports Nov 2023Hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease with a prevalence of...
Hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease with a prevalence of <1:1 000 000, due to variations in the seryl-tRNA synthetase (SARS2) gene encoding SARS on . This study investigated two Palestinian girls from the same village who presented with progressive renal failure during infancy, with atypical clinical manifestations of HUPRA syndrome including leukopenia, anemia, salt wasting, renal failure, marked hyperuricemia, hypercholesterolemia, hyperlactatemia, and hypertriglyceridemia but without pulmonary hypertension or alkalosis. Instead, they showed acidosis on routine follow-up, distinguishing them from previous cases. Using single whole exome sequencing, we identified two homozygous pathogenic variants in the SARS2 gene (c.1175A>G (p.D392G)) and (c.1169A>G (p.D390G)). These cases with their unique phenotypes, expand the SARS2 pathogenic variant spectrum and describe clinical differences between homozygous and compound heterozygous variants.
PubMed: 38264205
DOI: 10.1093/omcr/omad119 -
PloS One 2024The infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious...
The infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious neonatal complications such as necrotizing enterocolitis and sepsis, which can lead to long-term disability. Although many studies have described links between microbiome composition and disease risk, there is a need for biomarkers to identify infants at risk of these complications in practice. In this pilot study, we obtained stool samples from preterm infant participants longitudinally during the first postnatal months, and measured pH and redox, as well as SCFA content and microbiome composition by 16S rRNA gene amplicon sequencing. These outcomes were compared to clinical data to better understand the role of pH and redox in infant gut microbiome development and overall health, and to assess the potential utility of pH and redox as biomarkers. We found that infants born earlier or exposed to antibiotics exhibited increased fecal pH, and that redox potential increased with postnatal age. These differences may be linked to changes in SCFA content, which was correlated with pH and increased with age. Microbiome composition was also related to birth weight, age, pH, and redox. Our findings suggest that pH and redox may serve as biomarkers of metabolic state in the preterm infant gut.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Gastrointestinal Microbiome; Pilot Projects; RNA, Ribosomal, 16S; Oxidation-Reduction; Alkalosis; Biomarkers; Hydrogen-Ion Concentration
PubMed: 38261587
DOI: 10.1371/journal.pone.0290598