The Pathogenetic Spectrum of Bartter's Syndrome Principal Discussant: JAY H
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Familial Hyperaldosteronism
Familial hyperaldosteronism Description Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Aldosterone helps control the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the body's fluid levels and blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure (hypertension), often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure. Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. In most individuals with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected individuals have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement. There are other forms of hyperaldosteronism that are not familial. These conditions are caused by various problems in the adrenal glands or kidneys. In some cases, a cause for the increase in aldosterone levels cannot be found. -
Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm
Kidney360 Publish Ahead of Print, published on July 23, 2020 as doi:10.34067/KID.0000922020 Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic Paradigm Michael R Lattanzio(1), Matthew R Weir(2) (1) Division of Nephrology, Department of Medicine, The Chester County Hospital/University of Pennsylvania Health System (2) Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD Correspondence: Matthew R Weir University of Maryland Medical Center Division of Nephrology 22 S. Greene St. Room N3W143 Baltimore, Maryland 21201 [email protected] 1 Copyright 2020 by American Society of Nephrology. Abbreviations PA=Primary Hyperaldosteronism CVD=Cardiovascular Disease PAPY=Primary Aldosteronism Prevalence in Hypertension APA=Aldosterone-Producing Adenoma BAH=Bilateral Adrenal Hyperplasia ARR=Aldosterone Renin Ratio AF=Atrial Fibrillation OSA=Obstructive Sleep Apnea OR=Odds Ratio AHI=Apnea Hypopnea Index ABP=Ambulatory Blood Pressure AVS=Adrenal Vein Sampling CT=Computerized Tomography MRI=Magnetic Resonance Imaging SIT=Sodium Infusion Test FST=Fludrocortisone Suppression Test CCT=Captopril Challenge Test PAC=Plasma Aldosterone Concentration PRA=Plasma Renin Activity MRA=Mineralocorticoid Receptor Antagonist MR=Mineralocorticoid Receptor 2 Abstract Nearly seven decades have elapsed since the clinical and biochemical features of Primary Hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly since an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. -
Original Article Clinical Characteristics and Mutation Analysis of Two Chinese Children with 17A-Hydroxylase/17,20-Lyase Deficiency
Int J Clin Exp Med 2015;8(10):19132-19137 www.ijcem.com /ISSN:1940-5901/IJCEM0013391 Original Article Clinical characteristics and mutation analysis of two Chinese children with 17a-hydroxylase/17,20-lyase deficiency Ziyang Zhu, Shining Ni, Wei Gu Department of Endocrinology, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China Received July 25, 2015; Accepted September 10, 2015; Epub October 15, 2015; Published October 30, 2015 Abstract: Combined with the literature, recognize the clinical features and molecular genetic mechanism of the disease. 17a-hydroxylase/17,20-lyase deficiency, a rare form of congenital adrenal hyperplasia, is caused by muta- tions in the cytochrome P450c17 gene (CYP17A1), and characterized by hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism. We presented the clinical and biochemical characterization in two patients (a 13 year-old girl (46, XX) with hypokalemia and lack of pubertal development, a 11 year-old girl (46, XY) with female external genitalia and severe hypertension). CYP17A1 mutations were detected by PCR and direct DNA sequencing in patients and their parents. A homozygous mutation c.985_987delTACinsAA (p.Y329KfsX418) in Exon 6 was found in patient 1, and a homozygous deletion mutation c.1459_1467delGACTCTTTC (p.Asp487_Phe489del) in exon 8 in patient 2. The patients manifested with hypertension, hypokalemia, sexual infantilism should be sus- pected of having 17a-hydroxylase/17,20-lyase deficiency. Definite diagnosis is depended on mutation analysis. Hydrocortisone treatment in time is crucial to prevent severe hypertension and hypokalemia. Keywords: 17a-hydroxylase/17,20-lyase deficiency Introduction patients with 17a-hydroxylase/17,20-lyase defi- ciency, and made a confirmative diagnosis by Deficiency in cytochrome p450c17 (MIM mutation analysis of CYP17A1. -
High and Non-Suppressible Plasma Renin Activity in a Patient with Aldosterone Producing Adenoma: Pathophysiologic and Diagnostic Implications
Journal of Human Hypertension (1999) 13, 75–78 1999 Stockton Press. All rights reserved 0950-9240/99 $12.00 http://www.stockton-press.co.uk/jhh CASE REPORT High and non-suppressible plasma renin activity in a patient with aldosterone producing adenoma: pathophysiologic and diagnostic implications E Shyong Tai and PHK Eng Department of Endocrinology, Singapore General Hospital, Singapore We describe a case of primary aldosteronism due to an possible pathophysiological causes of a rise in PRA in aldosterone producing adenoma with high and non-sup- this clinical setting and suggest that underlying arteri- pressible plasma renin activity (PRA). She had sup- olar disease due to prolonged hypertension may be the pressed PRA at initial diagnosis. This rose above the cause of increased and non-suppressible PRA in pri- reference range for normal individuals over a period of mary aldosteronism. 7 years with untreated hypertension. We discuss the Keywords: primary aldosteronism; plasma renin activity; diagnosis Introduction Case report Primary aldosteronism is classically associated with Our patient was a 34-year-old woman who was hypertension, hypokalaemia and suppressed plasma found to have hypertension during the fifteenth renin activity (PRA). Most cases are due to an aldo- week of pregnancy. Plasma aldosterone was sterone producing adenoma (APA). We present a 2039 pmol/l, PRA Ͻ0.15 g/l/h and a diagnosis of case of prolonged, untreated, primary aldosteronism primary aldosteronism was made. Following the due to an APA. She had suppressed PRA at the time delivery of her child, she defaulted follow-up and of diagnosis, which became elevated and non-sup- was not treated with any antihypertensives nor pot- pressible by intravenous salt loading. -
Congenital Hypoaldosteronism Developmental Delay
CASE REPORTS Congenital Hypoaldosteronism developmental delay. She had an episode of generalized seizures at 3 months of age. At presentation she weighed 4 kg with a head VANATHI SETHUPATHI, circumference of 35 cm and was severely VIJAYAKUMAR M dehydrated. Blood pressure was in the normal range LALITHA JANAKIRAMAN* for the age. She had partial head control with no NAMMALWAR BR grasp or social smile. Fundoscopy was normal. Liver was enlarged. External genitalia were normal. Initial hematological and biochemical values are shown in Table I. Urine metabolic screen, blood ammonia, ABSTRACT serum lactate, thyroid function, immunoglobulin, Congenital hypoaldosteronism due to an isolated complement levels and chest X-ray were normal. aldosterone biosynthesis defect is rare. We report a 4 Blood and urine cultures were negative. month old female infant who presented with failure to Ultrasonogram of the abdomen showed mild thrive, persistent hyponatremia and hyperkalemia. hepatomegaly with normal echotexture. Investigations revealed normal serum 17 hydroxy progesterone and cortisol. A decreased serum aldosterone Hyponatremia, hypercalemia and low serum and serum 18 hydroxy corticosterone levels with a low 18 bicarbonate was treated with intravenous calcium hydroxy corticosterone: aldosterone ratio was suggestive gluconate, sodium bicarbonate and oral sodium of corticosterone methyl oxidase type I deficiency. She was polystyrene sulfonate. During follow-up, serum started on fludrocortisone replacement therapy with a sodium continued to remain at around 125 mEq/L, subsequent normalization of electrolytes. Further molecular analysis is needed to ascertain the precise potassium varied between 6.2 and 7.2 mEq/L with nature of the mutation. bicarbonate around 18 mEq/L. The child was hospitalized twice subsequently for dehydration, Key words: Congenital hypoaldosteronism, CMO I defi- hyponatremia and hyperkalemia. -
A Case of Gitelman's Syndrome with Decreased Angiotensin II–Forming Activity
545 Hypertens Res Vol.29 (2006) No.7 p.545-549 Case Report A Case of Gitelman’s Syndrome with Decreased Angiotensin II–Forming Activity Kimika ETO1), Uran ONAKA1), Takuya TSUCHIHASHI1), Takashi HIRANO2), Masaru NAKAYAMA2), Kosuke MASUTANI3), Hideki HIRAKATA3), Hidenori URATA4), and Minoru YASUJIMA5) Gitelman’s syndrome (GS) is a variant of Bartter’s syndrome (BS) characterized by hypokalemic alkalosis, hypomagnesemia, hypocalciuria and secondary aldosteronism without hypertension. A 31-year old Japa- nese man who had suffered from mild hypokalemia for 10 years was admitted to our hospital. He had met- abolic alkalosis, hypokalemia and hypocalciuria. Since he had two missense mutations (R261C and L623P) in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), he was diagnosed as having GS. He showed hyperreninism and a high angiotensin I (Ang I) level, whereas his angiotensin II (Ang II) and aldo- sterone levels were not elevated. His angiotensin converting enzyme (ACE) activities were normal, and administration of captopril inhibited the production of Ang II and aldosterone. We evaluated the Ang II–form- ing activity (AIIFA) of other enzymes in his lymphocytes. Interestingly, chymase-dependent AIIFA was not detected in the lymphocytes. Together, these results suggest that the lack of chymase activity resulted in the manifestation of GS without hyperaldosteronism. (Hypertens Res 2006; 29: 545–549) Key Words: Gitelman’s syndrome, angiotensin II, aldosterone, chymase several TSC gene mutations have been reported (5–10). Introduction Moreover, GS is characterized by sodium wasting, low blood pressure, and secondary hyperaldosteronism. Here, we report In 1966, Gitelman et al. reported three adult patients with a case of GS with hyperreninism and high angiotensin I (Ang intermittent episodes of muscle weakness and tetany, I) but without elevated angiotensin II (Ang II) or hyperaldos- hypokalemia, and hypomagnesemia, but no history of poly- teronism. -
Primary Hyperaldosteronism: a Case of Unilateral Adrenal Hyperplasia with Contralateral Incidentaloma Sujit Vakkalanka,1 Andrew Zhao,1 Mohammed Samannodi2
Unexpected outcome (positive or negative) including adverse drug reactions CASE REPORT Primary hyperaldosteronism: a case of unilateral adrenal hyperplasia with contralateral incidentaloma Sujit Vakkalanka,1 Andrew Zhao,1 Mohammed Samannodi2 1University at Buffalo, Buffalo, SUMMARY palpitations or any difficulty breathing in the past. New York, USA Primary hyperaldosteronism is one of the most common She was being managed in an outpatient setting for 2Department of Medicine, Buffalo, New York, USA causes of secondary hypertension but clear hypokalaemia and hypertension since 2009. She differentiation between its various subtypes can be a has been taking three antihypertensives (amlodi- Correspondence to clinical challenge. We report the case of a 37-year-old pine, benazepril and labetalol) and supplemental Dr Mohammed Samannodi, African-American woman with refractory hypertension potassium (2 tablets of 10 mEq three times a day) [email protected] who was admitted to our hospital for palpitations, but was very recently switched to hydralazine, ver- Accepted 28 June 2016 shortness of breath and headache. Her laboratory results apamil and doxazosin mesylate, and two potassium showed hypokalaemia and an elevated aldosterone/renin tablets of 20 mEq three times a day. ratio. An abdominal CT scan showed a nodule in the left On physical examination, her heart rate was adrenal gland but adrenal venous sampling showed 110 bpm while the blood pressure was 170/ elevated aldosterone/renin ratio from the right adrenal 110 mm Hg. Cardiac, abdominal, neurological and vein. The patient began a new medical regimen but musculoskeletal examinations were unimpressive declined any surgical options. We recommend with no signs of clubbing or oedema. -
Monogenic Forms of Mineralocorticoid Hypertension: Insights Into the Pathogenesis of ‘Essential’ Hypertension?
Journal of Human Hypertension (1998) 12, 7–12 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 REVIEW ARTICLE Monogenic forms of mineralocorticoid hypertension: insights into the pathogenesis of ‘essential’ hypertension? M Petrelli and PM Stewart Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK Keywords: hyperaldosteronism; mineralocorticoid; Liddle’s syndrome; inheritance; cortisol; 11-hydroxysteroid dehydrogen- ase Hypertension is a common condition, which, mary aldosteronism due to an adrenocortical tumour depending on its definition, affects 10–25% of the (Conn’s Syndrome).1 Both subjects had a mineral- population. Because it is an established risk factor ocorticoid excess syndrome, characterised by pot- for coronary and cerebrovascular disease, hyperten- assium deficiency, suppressed plasma renin activity sion has, quite rightly, been targeted as an important (PRA) and increased aldosterone secretion rate, factor in determining the health of the nation. which, in contrast to tumorous aldosteronism, Despite this we can explain the underlying cause of responded to treatment with the synthetic glucocort- a patient’s hypertension in Ͻ5% of cases; the icoid, dexamethasone. Shortly afterwards, an remainder are labelled ‘essential’ hypertension, an additional, well-documented case was described, elegant way of stating that the aetiology is unknown. confirming the existence of this new ‘glucocorticoid As a result, in the vast majority of cases treatment remediable’ aldosteronism syndrome.2 Sub- is given on an empirical basis. sequently it was shown to be inherited in an autoso- In the last 5 years, significant advances have been mal dominant fashion and approximately 100 cases made in our understanding of the pathogenesis of were reported in the world literature up to the early hypertension with the characterisation of three 1990’s.3–9 forms of inherited hypertension. -
Prevalence of Primary Hyperaldosteronism Assessed by Aldosterone/Renin Ratio and Spironolactone Testing
I ORIGINAL PAPERS Prevalence of primary hyperaldosteronism assessed by aldosterone/renin ratio and spironolactone testing Sue Hood, John Cannon, Roger Foo and Morris Brown ABSTRACT – Recent studies have suggested that Aldosterone-secreting adenomas were long consid- Sue Hood RGN primary hyperaldosteronism may be present in ered a rare cause of hypertension, with bilateral Research Sister more than 10% of patients with hypertension. We micronodular hyperplasia accounting for a similarly *John Cannon MB aimed to estimate the prevalence in unselected small proportion – less than 2% – of all hyperten- FRCGP General patients in primary care, and investigate the sion.1 But recent studies have suggested that primary Practitioner influence of current drug treatment upon the hyperaldosteronism (PHA) may be present in at least Roger Foo MD aldosterone/renin ratio (ARR) and its prediction 10% of patients.2–5 These studies have used biochem- MRCP Specialist of blood pressure response to spironolactone. We ical measures of autonomous aldosterone secretion, Registrar measured blood pressure, plasma electrolytes, usually the ratio of plasma aldosterone to renin and Morris Brown MSc renin activity and aldosterone in 846 patients the failure of aldosterone to suppress during treat- MD FRCP FMedSci, Professor of with hypertension. Spironolactone 50 mg was ment with salt supplementation. However, as often Clinical prescribed for one month to patients with blood occurs when the arbiter for diagnosis changes – here, Pharmacology pressure ≥130/85 mmHg and ARR ≥400. The from anatomical to biochemical – the question arises primary outcome measure was to discover the whether the definition of the condition has also Clinical Pharmacology Unit, proportion of patients with plasma aldosterone changed. -
Adrenal Insufficiency Immunodeficiency Sy in a Patient Ndrome
Endocrine Journal 1994, 41(1), 13-18 Adrenal Insufficiency in a Patient with Acquired Immunodeficiency Sy ndrome KoIcHI FUJII, IsAO MORIMOTO, ATSUSHIWAKE, YOHSUKEOKADA, NoBUo INOKUCHI, OsAMUISHIDA, YOIcHIRONAKANO, SUSUMUODA, ANDSUMIYA ETO First Departmento f Internal Medicine,University of Occupational and EnvironmentalHealth, Kitakyushu807, Japan Abstract. A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insuffi- ciency due to a CMV infection in patients with AIDS. Key words: Acquired Immunodeficiency Syndrome (AIDS), Cytomegalovirus infection, Adrenal Insuffi- ciency, Addison's Disease. (Endocrine Journal 41:13-18,1994) AUTOPSY reports of acquired immunodeficiency syndrome (AIDS) patients have noted adrenal de- Methods structive lesions associated with a cytomegalovirus (CMV) infection [1-5]. These reports indicate that Plasma aldosterone [8] and plasma renin activity more than 50% of AIDS patients have a various de- (PRA) [9] were measured with a radioimmunoas- grees of CMV adrenalitis. However, few cases say (RIA) kit (Daichi Radioisotope Ltd., Tokyo, Ja- have shown presented clinical and biochemical pan). -
Failing Hormones
PHoto qu iZ failing hormones F.L. Opdam1*, B.E.P.B. Ballieux2, H. Guchelaar3, A.M. Pereira1 Departments of 1Internal Medicine and Endocrinology, 2Clinical Chemistry, 3Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands, *corresponding author: e-mail: [email protected] Case reP ort A 70-year-old female patient presented to the outpatient Sodium concentration was 126 mmol/l, potassium 4.9 clinic with general malaise, salt craving, and hypotension. mmol/l, creatinine 59 umol/l and plasma osmolality She had been treated for severe asthma with 15 mg 244 mOsm/kg. Urinary sodium concentration was 43 prednisone daily without interruptions for at least ten mmol/l. ACTH was suppressed (<5 ng/l), with a normal years. This treatment was complicated by the development afternoon cortisol level (0.293 mg/l). Plasma renin activity of diabetes mellitus and severe osteoporosis. In addition, was undetectable (<0.10 mg/l/hour), and aldosterone she suffered from generalised myopathy and skeletal pain, concentration was low (0.13 nmol/l, reference range 0.0 to for which she took naproxen 500 mg three times a day. 0.35 nmol/l). The transtubular potassium gradient (TTPG = (Urine potassium/ (urine osmol/serum osmol))/ serum On clinical examination, a wheel-chair dependent, 71-year- potassium)) was 3.7 (reference >7) old woman was seen with a moon face, buffalo hump, abdominal fat accumulation, and severe muscle atrophy (figure 1). Her blood pressure, however, was low (110/60), WHat is yo Ur dia Gnosis? both in supine and in upright position. See page 532 for the answer to this photo quiz. -
Glucocorticoid-Remediable Aldosteronism
CME Review Article #18 0021-972X/2001/1104-0263 The Endocrinologist Copyright © 2001 by Lippincott Williams & Wilkins CHIEF EDITOR’S NOTE: This article is the 18th of 36 that will be published in 2001 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned appear following the Table of Contents. Glucocorticoid-Remediable Aldosteronism Robert G. Dluhy, M.D.* Glucocorticoid-remediable aldosteronism (GRA) eralocorticoid-excess state. GRA is caused by a represents a rare, heriditary form of primary aldos- chimeric gene duplication that results from unequal teronism which is inherited in an autosomal domi- crossing over between the highly homologous 11- nant fashion. GRA is characterized by early onset hydroxylase (CYP11B1) and aldosterone synthase of moderate-to-severe hypertension and suppressed (CYP11B2) genes. The chimeric gene represents a plasma renin activity. The family history is often fusion of the 5'adrenocorticotropin-responsive reg- positive for a history of early hemorrhagic stroke. ulatory region of the 11-hydroxylase gene and the However, the clinical and biochemical features that 3' coding sequence of the aldosterone synthase define mineralcorticoid excess states, such as hy- gene. This results in ectopic expression of aldos- pokalemia, are not consistently present in GRA. terone synthase activity in the zona fasciculata, the Accordingly, recognition of this syndrome can be zone of the adrenal gland that normally secretes difficult. In GRA, aldosterone secretion is solely cortisol. This mutation explains the physiology and regulated by adrenocorticotropin. As a result, the genetics of GRA and provides the basis for a simple administration of exogenous glucocorticoids will direct genetic test for this disorder.