Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia

AbstractDuring the first weeks of life, salt-wasting crisis, hyperkalemia, acidosis, hypoglycemia, and shock are the main findings of congenital adrenal hyperplasia (CAH). Pseudohypoaldosteronism type 1 (PHA1) is a rare disease of mineralocorticoid resistance, which is characterized with high aldosterone levels, hyponatremia and hyperkalemia without clinical findings of glucocorticoid deficiency. Patients with PHA1 are often initially diagnosed with CAH; however, it is unusual that a CAH patient is misdiagnosed as PHA1. In this report, we describe two cases with severe salt-losing crisis, hyperkalemia, and mild acidosis, which were initially diagnosed with PHA1, due to the high aldosterone levels along with normal adrenocorticotropic hormone and cortisol levels. However, subsequent investigation and genetic analysis led to the diagnosis of CAH with a homozygous I2 splice mutation in both alleles of the

Download Full-text

Graves’ Thyrotoxicosis Leading to Adrenal Decompensation and Hyperandrogenemia in a Pediatric Patient with Salt-Wasting Congenital Adrenal Hyperplasia

Case Reports in Endocrinology ◽

10.1155/2018/2359205 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3

Author(s):

Meghan E. Fredette ◽

Lisa Swartz Topor

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Crisis ◽

Adrenal Hyperplasia ◽

Free T4 ◽

Adrenal Androgens ◽

Case Presentation ◽

Adrenal Hormones ◽

Salt Wasting ◽

Glucocorticoid Deficiency ◽

Stress Dose

Introduction. Thyroid hormone is known to accelerate glucocorticoid turnover. In a thyrotoxic state, individuals with adrenal insufficiency are unable to increase endogenous cortisol production to compensate for increased turnover, placing them at risk for symptoms of glucocorticoid deficiency and adrenal crisis. In patients with salt-wasting congenital adrenal hyperplasia (SW-CAH), hyperandrogenemia is a measurable reflection of relative glucocorticoid insufficiency. Case Presentation. A 12-year-old girl with SW-CAH reported 3 recent episodes of vomiting without diarrhea, and accompanying tachycardia, responsive to stress dose steroids. In the previous 9 months, she unintentionally lost 2.6 kg. She had tachycardia and new thyromegaly. Labs showed suppressed TSH, elevated free T4 and total T3, and elevated thyroid stimulating immunoglobulin (TSI) consistent with Graves’ disease. Adrenal androgens were markedly elevated. Maintenance hydrocortisone dose was 25 mg/m2/day and was not changed. Methimazole was initiated. Four weeks later, free T4 and adrenal androgens normalized. She had no further vomiting episodes. Conclusions. Thyrotoxicosis must be included in the differential diagnosis of individuals with SW-CAH who present with episodes concerning for adrenal crises, escalating hydrocortisone requirements, and/or inadequate suppression of adrenal hormones.

Download Full-text

Systemic pseudohypoaldosteronism-1 with episodic dyslipidemia in a Sudanese child

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-21-0010 ◽

2021 ◽

Vol 2021 ◽

Author(s):

Asmahan Abdalla ◽

Mohammed Abdulrahman Alhassan ◽

Reem Tawfeeg ◽

Ayman Sanad ◽

Hasan Tawamie ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Respiratory Symptoms ◽

Na Channel ◽

List Type ◽

Adrenal Hyperplasia ◽

Laboratory Findings ◽

Genetic Syndrome ◽

First Case ◽

Pseudohypoaldosteronism Type

Summary Systemic pseudohypoaldosteronism type 1 (PHA1) is a rare genetic syndrome of tissue unresponsiveness to aldosterone caused by mutations affecting the epithelial Na channel (ENaC). The classical presentation is life-threatening neonatal/infantile salt-losing crises that mimic congenital adrenal hyperplasia (CAH). Consistently, extra-renal manifestations, including respiratory symptoms that resemble cystic fibrosis, are well reported. Clinical diagnosis is made by the presence of hyponatremia, hyperkalemia, metabolic acidosis, respiratory symptoms, evidence of high renal and extra-renal salt loss in addition to high plasma renin and aldosterone levels. We herein report a novel manifestation of PHA1: episodic dyslipidemia in a 7-month-old Sudanese boy that occurred during the salt-losing crises. Whole exome sequencing of the patient revealed one homozygous missense variant c.1636G>A p.(Asp546Asn) in the SCNN1B gene, confirming our clinical and laboratory findings that were compatible with PHA1. This report aims to highlight the possible explanation of dyslipidemia in PHA1 and its expected consequences in the long term. Learning points A child presenting with features that mimic salt-losing congenital adrenal hyperplasia (CAH) crises that do not respond to glucocorticoid and mineralocorticoid therapy should alert the pediatricians to the possibility of end-organ resistance to aldosterone. Pseudohypoaldosteronism type 1 (PHA1) can be diagnosed even in the absence of advanced laboratory investigations. To our knowledge, this is the first case of systemic PHA1 to have a documented episodic dyslipidemia (primarily as marked hypertriglyceridemia).

Download Full-text

High aldosterone and cortisol levels in salt wasting congenital adrenal hyperplasia: a clinical conundrum

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0166 ◽

2017 ◽

Vol 30 (12) ◽

Cited By ~ 2

Author(s):

Sirisha Kusuma Boddu ◽

Sheeja Madhavan

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Cross Reactivity ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Adrenal Steroid ◽

Wasting Syndrome ◽

Serum Aldosterone ◽

Diagnostic Confusion ◽

Cortisol Levels ◽

17 Hydroxyprogesterone

AbstractBackground:Salt wasting syndrome (hyponatremia, hyperkalemia, dehydration, metabolic acidosis) in early infancy could be caused by either mineralocorticoid deficiency as in congenital adrenal hyperplasia (CAH) and adrenal insufficiency or mineralocorticoid resistance as in pseudohypoaldosteronism (PHA). In salt wasting CAH, serum aldosterone and cortisol levels are expected to be low. Cross reactivity between high levels of adrenal steroid precursors and aldosterone has recently been reported resulting in elevated aldosterone levels in CAH, leading to difficulty in differentiating between CAH and PHA.Case presentation:We report four such cases of salt wasting CAH, where high aldosterone levels and high normal cortisol levels led to initial diagnostic confusion with PHA. Diagnosis of CAH was later established on the basis of significantly elevated adrenocorticotropic hormone (ACTH) stimulated 17-hydroxyprogesterone (17-OHP) values.Conclusions:By reporting these cases we draw attention to the possibility that high levels of adrenal steroid precursors can cross react with aldosterone and cortisol, and underscore the significance of ACTH stimulated 17-OHP values in differentiating CAH and PHA.

Download Full-text

Pseudohypoaldosteronism Type 1 Newborn Patient with a Novel Mutation in SCNN1B

Journal of Pediatric Intensive Care ◽

10.1055/s-0039-1700950 ◽

2020 ◽

Vol 09 (02) ◽

pp. 145-148

Author(s):

Muhammed Seyhanli ◽

Ozkan Ilhan ◽

Evren Gumus ◽

Meltem Bor ◽

Meryem Karaca

Keyword(s):

Metabolic Acidosis ◽

Neonatal Intensive Care ◽

Adrenocorticotropic Hormone ◽

Novel Mutation ◽

The Novel ◽

Feeding Problems ◽

Adrenal Hyperplasia ◽

Pseudohypoaldosteronism Type ◽

Made In

AbstractPseudohypoaldosteronism is a rare disease characterized by resistance to aldosterone-targeted organs, hyponatremia, hyperkalemia, metabolic acidosis, and severe salt loss in hyperaldosteronism. Homozygous mutations in SCNN1A, SCNN1B, and SCNN1G genes were found to be responsible for the etiology. About 80 cases with molecular basis have been reported to date. In this case, a newborn patient admitted to our neonatal intensive care unit due to feeding problems was examined. The parents of the patient had a consanguineous marriage, and they had lost their three sons due to hyperkalemia. Since she had hyponatremia and hyperkalemia, congenital adrenal hyperplasia was primarily considered. Although the initial evaluation was made in this direction, the patient was diagnosed as pseudohypoaldosteronism type 1 with the findings obtained during the process such as dehydration, cortisol levels, adrenocorticotropic hormone levels, and negative CYP21A2 analysis result. This clinical diagnosis was confirmed by the novel homozygous frame-shift variant c.1245_1246insC (p.N416Qfs*35) in SCNN1B shown by gene analysis. In this report, we seek to emphasize that aldosterone deficiency should be one of the first diagnoses to be considered in neonatal patients with hyponatremia, hyperkalemia, metabolic acidosis, and dehydration.

Download Full-text

Concurrence of Meningomyelocele and Salt-Wasting Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Case Reports in Pediatrics ◽

10.1155/2015/196374 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Heves Kırmızıbekmez ◽

Rahime Gül Yesiltepe Mutlu ◽

Serdar Moralıoğlu ◽

Ahmet Tellioğlu ◽

Ayşenur Cerrah Celayir

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Growth Retardation ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Salt Wasting ◽

Significant Regression ◽

One Year ◽

The One ◽

21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of inherited defects of cortisol biosynthesis. A case of classical CAH due to 21-hydroxylase deficiency (21-OHD) with early onset of salt waste and concurrence of meningomyelocele (MMC) was presented here. The management of salt-wasting crisis which is complicated by a postrenal dysfunction due to neurogenic bladder was described. Possible reasons of growth retardation in the one-year follow-up period were discussed. A significant regression of the phallus with proper medical treatment was also mentioned.

Download Full-text

Aldosterone Synthesis in Salt-Wasting Congenital Adrenal Hyperplasia with Complete Absence of Adrenal 21-Hydroxylase

New England Journal of Medicine ◽

10.1056/nejm199101173240302 ◽

1991 ◽

Vol 324 (3) ◽

pp. 145-149 ◽

Cited By ~ 66

Author(s):

Phyllis W. Speiser ◽

Levon Agdere ◽

Hajime Ueshiba ◽

Perrin C. White ◽

Maria I. New

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Hyperplasia ◽

Salt Wasting

Download Full-text

The role of imaging in congenital adrenal hyperplasia

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003371 ◽

2014 ◽

Vol 58 (7) ◽

pp. 701-708 ◽

Cited By ~ 6

Author(s):

Sara Reis Teixeira ◽

Paula Condé Lamparelli Elias ◽

Marco Túlio Soares Andrade ◽

Andrea Farias Melo ◽

Jorge Elias Junior

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Tumors ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Testicular Adrenal Rest Tumors ◽

High Incidence ◽

Adrenal Rest ◽

Hormonal Evaluation

Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

Download Full-text

High Reliability of Neonatal Screening for Congenital Adrenal Hyperplasia in Switzerland

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-012093 ◽

2002 ◽

Vol 87 (9) ◽

pp. 4106-4110 ◽

Cited By ~ 29

Author(s):

Michael Steigert ◽

Eugen J. Schoenle ◽

Anna Biason-Lauber ◽

Toni Torresani

Keyword(s):

Positive Predictive Value ◽

Congenital Adrenal Hyperplasia ◽

Predictive Value ◽

Neonatal Screening ◽

Screening Program ◽

High Reliability ◽

Dried Blood Spots ◽

Recall Rate ◽

Adrenal Hyperplasia ◽

Salt Wasting

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children’s Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.

Download Full-text