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

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.

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Sodium Chloride Supplementation Is Not Routinely Performed in the Majority of German and Austrian Infants with Classic Salt-Wasting Congenital Adrenal Hyperplasia and Has No Effect on Linear Growth and Hydrocortisone or Fludrocortisone Dose

Hormone Research in Paediatrics ◽

10.1159/000481775 ◽

2017 ◽

Vol 89 (1) ◽

pp. 7-12 ◽

Cited By ~ 5

Author(s):

Walter Bonfig ◽

Friedhelm Roehl ◽

Stefan Riedl ◽

Jürgen Brämswig ◽

Annette Richter-Unruh ◽

...

Keyword(s):

Sodium Chloride ◽

Congenital Adrenal Hyperplasia ◽

Routine Care ◽

Sodium Content ◽

Adrenal Crisis ◽

First Year ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

First Year Of Life ◽

Oral Sodium

Introduction: Sodium chloride supplementation in salt-wasting congenital adrenal hyperplasia (CAH) is generally recommended in infants, but its implementation in routine care is very heterogeneous. Objective: To evaluate oral sodium chloride supplementation, growth, and hydrocortisone and fludrocortisone dose in infants with salt-wasting CAH due to 21-hydroxylase in 311 infants from the AQUAPE CAH database. Results: Of 358 patients with classic CAH born between 1999 and 2015, 311 patients had salt-wasting CAH (133 females, 178 males). Of these, 86 patients (27.7%) received oral sodium chloride supplementation in a mean dose of 0.9 ± 1.4 mmol/kg/day (excluding nutritional sodium content) during the first year of life. 225 patients (72.3%) were not treated with sodium chloride. The percentage of sodium chloride-supplemented patients rose from 15.2% in children born 1999–2004 to 37.5% in children born 2011–2015. Sodium chloride-supplemented and -unsupplemented infants did not significantly differ in hydrocortisone and fludrocortisone dose, target height-corrected height-SDS, and BMI-SDS during the first 2 years of life. Conclusion: In the AQUAPE CAH database, approximately one-third of infants with salt-wasting CAH receive sodium chloride supplementation. Sodium chloride supplementation is performed more frequently in recent years. However, salt supplementation had no influence on growth, daily fludrocortisone and hydrocortisone dose, and frequency of adrenal crisis.

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Adverse Effects of Ramadan Fasting in a Girl with Salt-Losing Congenital Adrenal Hyperplasia

Case Reports in Endocrinology ◽

10.1155/2020/6688927 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3

Author(s):

Valeria Calcaterra ◽

Francesco Bassanese ◽

Andrea Martina Clemente ◽

Rossella Amariti ◽

Corrado Regalbuto ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Insufficiency ◽

Treatment Plan ◽

Management Plan ◽

Hormonal Control ◽

Adrenal Crisis ◽

Adrenal Hyperplasia ◽

Ramadan Fasting ◽

Salt Wasting ◽

Classic Form

Objective. Congenital adrenal hyperplasia (CAH) is the most common cause of adrenal insufficiency in pediatrics. Chronic glucocorticoid replacement is the mainstay of treatment in the classic forms of CAH, and mineralocorticoid replacement therapy is mandatory in the salt-wasting form. Fasting is a mild stressor, which can expose to dehydration, hypotension, hypoglycemia, and acute adrenal crisis in patients with adrenal insufficiency. Case. We report the case of an adolescent affected by the classic form with salt-losing CAH, who observed Ramadan for 30 days, without individualized therapeutic management plan. After Ramadan, a dramatic increase of ACTH level (1081 pg/ml, n.v. 6–57), reduced cortisolemia, tendency to hypotension, and weight loss were recorded. She experienced insomnia, intense thirst, asthenia, and headache. The symptoms disappeared restarting the previous therapy schedule and increasing the total hydrocortisone daily dose with progressive restoring of hormonal control. Conclusion. Our case confirms that patients with CAH are vulnerable, especially during fasting in Ramadan, with a higher risk of acute adrenal crisis. CAH patients should reform and individualize their treatment plan and be submitted to careful monitoring.

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Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0540 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ilja Dubinski ◽

Susanne Bechtold Dalla-Pozza ◽

Martin Bidlingmaier ◽

Nicole Reisch ◽

Heinrich Schmidt

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Pubertal Development ◽

Adrenal Crisis ◽

Adrenal Hyperplasia ◽

Glucocorticoid Treatment ◽

Steroid Synthesis ◽

Prepubertal Children ◽

Salt Wasting ◽

17 Hydroxyprogesterone

Abstract Objectives Children with salt-wasting congenital adrenal hyperplasia (CAH) have an impaired function of steroid synthesis pathways. They require therapy with glucocorticoid (GC) and mineralocorticoid hormones to avoid salt-wasting crisis and other complications. Most commonly, children receive hydrocortisone thrice daily with the highest dose in the morning, mimicking the regular physiology. However, reverse circadian treatment (RCT) had been suggested previously. In this study, we aimed to determine the efficacy of RCT in prepubertal children with CAH by comparing the salivary 17-hydroxyprogesterone (s17-OHP) levels individually. Methods In this retrospective study, we analyzed the records of children with classical CAH and RCT who were monitored by s17-OHP levels. The study included 23 patients. We identified nine prepubertal children with RCT schemes (three boys and six girls) and compared the s17-OHP levels in the morning, afternoon, and evening. The objective of this study was to demonstrate the non-effectiveness of RCT in terms of lowering the morning s17-OHP concentration. In addition, we compared s17-OHP day profiles in six patients on RCT and non-RCT therapy (intraindividually). Results Eight of nine children with RCT showed higher s17-OHP levels in the morning compared to the evening. In addition, none of the children showed a significant deviation of development. Three children were overweight. No adrenal crisis or pubertal development occurred. Comparison of RCT and non-RCT regimens showed no difference in 17-OHP profiles. Conclusions Our data do not support the use of RCT schemes for GC replacement in children with CAH due to lack of benefits and unknown long-term risks.

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Increased Frequency of Acute Illness and Hospitalizations in Infants and Toddlers with Congenital Adrenal Hyperplasia

10.1101/19005462 ◽

2019 ◽

Author(s):

Teresa Tseng ◽

Amy Seagroves ◽

Christina M. Koppin ◽

Madison Keenan ◽

Elana Putterman ◽

...

Keyword(s):

High Risk ◽

Congenital Adrenal Hyperplasia ◽

Acute Illness ◽

Adrenal Crisis ◽

Infants And Toddlers ◽

Adrenal Hyperplasia ◽

Tertiary Center ◽

Ed Visits ◽

The Impact ◽

Stress Dose

AbstractPurposeInfants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for adrenal crisis and associated sequelae. To better understand acute illness at this early age, we determined the frequency and severity of acute illness and hospitalizations between 0-4 years of age, both within CAH and compared to controls. We also evaluated the impact of pre-hospital stress-dose hydrocortisone on Emergency Department (ED) visits and hospitalizations.MethodsWe performed a retrospective study of 40 CAH youth and 27 age-matched controls at a tertiary center. Characteristics of acute illnesses during the first 4 years of life were recorded, including fever, vomiting, diarrhea, ED visits, hospitalizations, abnormal electrolytes, and stress-dose hydrocortisone usage.ResultsCAH youth had more frequent illnesses requiring stress-dosing when they were younger than 2 years old [4.0 (1.0-6.0)] compared to when they were 2-4 years old [3.0 (1.0-4.0), P < 0.05], with the most illnesses during their first year of life. As well, CAH infants and toddlers had more hospitalizations younger than 2 years old compared to 2-4 years old (36 vs 2). 25% (3/12) of CAH youth with abnormal electrolytes in the ED did not receive any stress-dosing (oral/IM) prior to the ED, and only 25% (3/12) had received intramuscular hydrocortisone at home. CAH youth had more frequent ED visits (7.4 times as many) and hospitalizations (38 to 0) compared to controls.ConclusionsVery young children with classical CAH are at high risk for acute illness and hospitalizations during their first 2 years of life, and do not receive adequate stress-dosing prior to the ED despite appropriate education. Our findings underscore the need for earlier recognition of acute illness in this vulnerable population and improved education regarding administration of stress-dose hydrocortisone to prevent morbidity.

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Congenital Adrenal Hyperplasia (CAH) and Gitelman Syndrome (GS): Overlapping Symptoms in an Uncommon Association

Case Reports in Pediatrics ◽

10.1155/2021/6633541 ◽

2021 ◽

Vol 2021 ◽

pp. 1-3

Author(s):

Valeria Calcaterra ◽

Giulia Roberto ◽

Anna La Rocca ◽

Beatrice Andrenacci ◽

Federico Rossi ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Gitelman Syndrome ◽

Blood Levels ◽

Adrenal Hyperplasia ◽

Case Presentation ◽

Salt Wasting ◽

Life Saving ◽

Neonatal Diagnosis ◽

Natural Tendency ◽

Recessive Transmission

Background. Classical salt-wasting (SW) congenital adrenal hyperplasia (CAH) and Gitelman syndrome (GS) are two genetic conditions in which dyselectrolytemia may occur. No association between the two conditions has been previously described. Case Presentation. We present the case of a boy with a neonatal diagnosis of SW-CAH who showed low potassium blood levels from the age of 15 years. This electrolytic alteration was, at first, attributed to an excessive action of mineralocorticoid drugs. Due to persistence of hypokalemia, SLC12A3 whole genome sequencing was performed, showing a heterozygous C to T base pair substitution at position 965 in gene SLC12A3. This mutation is related to Gitelman syndrome with autosomal recessive transmission. Conclusions. SW-CAH and GS determine opposite values of potassium in the absence of specific therapy, with a natural tendency to compensate each other. The symptom overlap makes diagnosis difficult. Organic causes of hypokalemia in patients undergoing life-saving therapy should not be excluded.

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Increased Mortality in Patients With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2957 ◽

2014 ◽

Vol 99 (12) ◽

pp. E2715-E2721 ◽

Cited By ~ 61

Author(s):

Henrik Falhammar ◽

Louise Frisén ◽

Christina Norrby ◽

Angelica Lindén Hirschberg ◽

Catarina Almqvist ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Neonatal Screening ◽

Causes Of Death ◽

Population Based ◽

Personal Identification ◽

Adrenal Crisis ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Salt Wasting ◽

21 Hydroxylase Deficiency

Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: This study sought to study mortality and causes of death in CAH. Design, Setting, and Participants: We studied patients with CAH (21-hydroxylase deficiency, n = 588; CYP21A2 mutations known, >80%), and compared them with controls (n = 58 800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: Mean age of death was 41.2 ± 26.9 years in patients with CAH and 47.7 ± 27.7 years in controls (P < .001). Among patients with CAH, 23 (3.9%) had deceased compared with 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3 (1.2–4.3) in CAH males and 3.5 (2.0–6.0) in CAH females. Including only patients born 1952–2009, gave similar total results but only patients with salt wasting (SW) or with unclear phenotype had an increased mortality. The causes of death in patients with CAH were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter, all except one were deceased before the introduction of neonatal screening in 1986, and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The SW phenotype also seemed to have worse outcome in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.

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MON-158 Rates of Illnesses in Patients with Congenital Adrenal Hyperplasia

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1156 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Ashwini Mallappa ◽

Ninet Sinaii ◽

Diala El-Maouche ◽

Padmasree Veeraraghavan ◽

Elizabeth Joyal ◽

...

Keyword(s):

At Risk ◽

Congenital Adrenal Hyperplasia ◽

Incidence Rate ◽

Adrenal Crisis ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Life Threatening ◽

Tract Infections ◽

21 Hydroxylase Deficiency ◽

Stress Dose

Abstract Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency during childhood and patients are at risk for life-threatening adrenal crisis. In a recent study from our group, we reported gastrointestinal and upper respiratory tract infections as the two most common precipitating events for adrenal crises and hospitalizations across all ages. We also reported 11 incidents of life-threatening hypoglycemic events in children, sometimes accompanied by seizures. Objective: To evaluate the annual rates of illnesses in patients with CAH. Methods: We retrospectively reviewed longitudinally collected data over 23 years from 156 CAH patients enrolled in our CAH natural history study (www.clinicaltrials.gov #NCT00250159). Incidence of illnesses and occurrence of stress-dose days were computed per person-years. Incidence rate ratio (IRR) with 95% confidence intervals (CI) were calculated for comparisons. Results: A total of 2298 visits (1909 for children and 389 for adults) were available for evaluation among the 156 patients (21-OHD: 97.4%). A total of 1870 illness events (1664 in children) were observed in 143 patients (121 children) and 2710 stress-dose days (2460 in children) were observed in 141 patients (120 children) during the study period. The incidence rate of illnesses was higher in children than adults (1.5 vs. 0.5 illnesses/person-years, IRR = 3.1, 95% CI 2.7 - 3.6; P<.0001) with incidence highest in young patients: 2.5 illnesses/person-years in <3 year olds. Similarly, the stress-dose days were higher in children than adults (2.2 vs. 0.6 days/person-years, IRR = 3.8, 95% CI 3.3 - 4.3; P<.0001). Conclusions: Patients with CAH do not appear to have higher rates of infectious illnesses than expected, but remain at risk for life-threatening adrenal crises. As expected, illness rates are higher during childhood than adulthood. Prevention of adrenal crisis is crucial and is best accomplished through repeated age-specific education of patients and caregivers. Acknowledgement: This research was supported by the Intramural Research Program at the National Institutes of Health (NIH), Bethesda, Maryland.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0170 ◽

2015 ◽

Vol 28 (5-6) ◽

Cited By ~ 6

Author(s):

Hale Unver Tuhan ◽

Gonul Catli ◽

Ahmet Anik ◽

Huseyin Onay ◽

Bumin Dundar ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenocorticotropic Hormone ◽

Cross Reactivity ◽

Clinical Findings ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Subsequent Investigation ◽

Glucocorticoid Deficiency ◽

Pseudohypoaldosteronism Type

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

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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.

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