Form Of Primary Adrenal Insufficiency Research Articles

Depressive and anxiety disorders and antidepressant prescriptions among insured children and young adults with congenital adrenal hyperplasia in the United States.

Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency. We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States. We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4-25 years enrolled in employer-sponsored or Medicaid health plans. Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers. The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.

Growth alterations in rare forms of primary adrenal insufficiency: a neglected issue in paediatric endocrinology.

Primary adrenal insufficiency (PAI) is an endocrine disorder characterized by direct adrenal failure, with consequent glucocorticoid, and eventually mineralocorticoid, deficiency. In children, the main cause of PAI is congenital adrenal hyperplasia (CAH), due to a loss of function of adrenal steroidogenic enzymes, but also rarer forms, including autoimmune polyglandular syndrome, adrenoleucodistrophy, adrenal hypoplasia congenita, familial glucocorticoid deficiency, and Allgrove's Syndrome, may be observed. In PAI children, growth alterations represent a major issue, as both inadequate and excessive glucocorticoid replacement treatment may lead to reduced growth rate and adult height impairment. However, growth abnormalities are poorly studied in rare forms of paediatric PAI, and specific studies on growth rate in these children are currently lacking. In the present review, the currently available evidence on growth alterations in children with rare PAI forms will be summarized, with a major focus on comorbidities with a potential impact on patients' growth rate.

Prevalence of testicular adrenal rest tumor and factors associated with its development in 6 month to 18 years-old patients with congenital adrenal hyperplasia

Introduction: Congenital adrenal hyperplasia (CAH) is a potentially life-threatening form of primary adrenal insufficiency characterized by cortisol, aldosterone, and epinephrine deficiencies, as well as overproduction of androgen. Infertility is one of the most important complications in male patients with CAH, and testicular adrenal rest tumors (TARTs) are known to be the most important caause of infertility in these patients. In the present study, the prevalence of TART and factors associated with its development were evaluated in patients with CAH. Methods & Materials: This is a descriptive cross-sectional study evaluating 30 males (6 month -18 years) with the classical 21-hydroxylase deficiency (21-OHD) through testicular ultrasonography. Data including age, bone age, puberty, 21-OHD phenotype (salt wasting (SW) or simple virilizing (SV)) and serum levels of 17- hydroxyprogesterone (17-OHP), androstenedione and adrenocorticotropic hormone (ACTH) were records. Results: The prevalence of TART was determined 56.7%, which increased with age with higher prevalence in children >12 (52.9%) year old. The mean age in patients with TART was 12.4 ± 4.18 years. No association was found between TART and 21-OHD phenotype, androstenedione, or 17OHP levels, but an association was found between TART and elevated levels of ACTH (p= 0.049), advanced bone age (p= 0.030) and puberty (p= 0.003). Conclusion: According to the results, TART is very common and can occur in pre-pubertal and young patients, and the disease control could be a factor associated with its development. Therefore, it is suggested to investigate the TART development early in childhood, mainly in poorly controlled 21-OHD patients.

Adrenal cortex development and related disorders leading to adrenal insufficiency

The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation. It consists of three histologically distinct and functionally specialized zones. The fetal adrenal forms from mesodermal material and produces predominantly adrenal C19 steroids from its fetal zone, which involutes after birth. Transition to the adult cortex occurs immediately after birth for the formation of the zona glomerulosa and fasciculata for aldosterone and cortisol production and continues through infancy until the zona reticularis for adrenal androgen production is formed with adrenarche. The development of this indispensable organ is complex and not fully understood. This article gives an overview of recent knowledge gained of adrenal biology from two perspectives: one, from basic science studying adrenal development, zonation and homeostasis; and two, from adrenal disorders identified in persons manifesting with various isolated or syndromic forms of primary adrenal insufficiency.

Beyond the adrenals: Organ manifestations in inherited primary adrenal insufficiency in children.

Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

Objective:Congenital adrenal hyperplasia (CAH) is the most common form of primary adrenal insufficiency in children. Neonatal screening for CAH is effective in detecting the salt-wasting (SW) form and in reducing mortality. In this study, our aim was to estimate the incidence of CAH in Turkey and to assess the characteristics and efficacy of the adopted newborn CAH screening strategy.Methods:A pilot newborn CAH screening study was carried out under the authority of the Turkish Directorate of Public Health. Newborn babies of ≥32 gestational weeks and ≥1500 gr birth weight from four cities, born between March 27-September 15, 2017 were included in the study. Screening protocol included one sample two-tier testing. In the first step, 17α-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood spots (DBS) obtained at 3-5 days of life. The cases with positive initial screening were tested by steroid profiling in DBS using a liquid chromatography-tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol (21-S), cortisol (F), 11-deoxycortisol and androstenedione as a second-tier test. The babies with a steroid ratio (21-S+17-OHP)/F of ≥0.5 were referred to pediatric endocrinology clinics for diagnostic assessment.Results:38,935 infants were tested, 2265 (5.82%) required second-tier testing and 212 (0.54%) were referred for clinical assessment, six of whom were diagnosed with CAH (four males, two females). Four cases were identified as SW 21-hydroxylase deficiency (21-OHD) (two males, two females). One male baby had simple virilizing 21-OHD and one male baby had 11-OHD CAH. The incidence of classical 21-OHD in the screened population was 1:7,787.Conclusion:The incidence of CAH due to classical 21-OHD is higher in Turkey compared to previous reports. We, therefore, suggest that CAH be added to the newborn screening panel in Turkey. The use of steroid profiling as a second-tier test was found to improve the efficacy of the screening and reduce the number of false-positives.

Mutations in SGPL1, encoding sphingosine-1-phosphate lyase, cause a novel form of primary adrenal insufficiency with steroid resistant nephrotic syndrome

Mutations in SGPL1, encoding sphingosine-1-phosphate lyase, cause a novel form of primary adrenal insufficiency with steroid resistant nephrotic syndrome

Mutations in SGPL1, encoding sphingosine-1-phosphate lyase, cause a novel form of primary adrenal insufficiency with steroid resistant nephrotic syndrome

Mutations in SGPL1, encoding sphingosine-1-phosphate lyase, cause a novel form of primary adrenal insufficiency with steroid resistant nephrotic syndrome

Perioperative Severe Hypotension in a Patient with Multiple Endocrine Neoplasia Type IIb and Bilateral Adrenalectomies: Time to Review the Evidence for Stress Dose Steroids.

Multiple endocrine neoplasia type IIb (MEN IIb) is an endocrine disorder which can manifest with tumors such as pheochromocytomas and neuromas. We present the case of a patient with MEN IIb, after bilateral adrenalectomies, on maintenance steroid replacement, who underwent a neuroma resection and developed severe hypotension. There is persistent controversy regarding the general administration of perioperative “stress dose” steroids for patients with adrenal insufficiency. While the most recent literature suggests that stress dose steroids are unnecessary for secondary adrenal insufficiency, the rarer form of primary adrenal insufficiency always requires supplemental steroids, specifically hydrocortisone, when undergoing surgical procedures.

儿童原发性肾上腺皮质功能减退症诊治进展

Primary adrenal insufficiency (PAI) in children is a kind of clinical syndrome, derived from the adrenal cortex diseases caused by abnormal cortical hormone synthesis, which is uncommon but potentially treated. Its clinical manifestations are glucocorticoid secretion deficiency or defect, characterized by abnormal mineralocorticoid, with / without abnormal androgen. The clinical characteristics of PAI in children may be non-specific and acute adrenal crisis is life-threatening. The frequency of the various forms of PAI in children differs substantially from that in the adult population. The various etiologies of PAI can be grouped into three categories as impaired steroidogenesis, adrenal dysgenesis and adrenal destruction, and the genetic forms are more common. Life-long glucocorticoid replacement treatment and education of the patient and the family are necessarily required. The former should be monitored closely in case of insufficient or excessive treatment. New formulations of hydrocortisone are supposed to improve outcome in children with PAI in the near future.

Familial isolated glucocorticoid deficiency: three clinical cases and a brief overview of the current literature

Familial isolated glucocorticoid deficiency (FIGD) is a rare form of primary adrenal insufficiency associated with the resistance of the adrenal cortex to the action of ACTH. This pathology manifests itself in the form of cortisol deficiency despite the normal mineralocorticoid function. Approximately 50% of all FIGD cases are attributable to mutations in two genes (melanocortin 2 receptor gene, MC2R, and melanocortin 2 receptor accessory protein gene, MRAP). In addition, the relationship between FIGD and mutations in nicotinamide nucleotide transhydrogenase gene, NNT, minichromosome maintenance gene, MCM4, and STAR is documented. No genetic defect was found in almost 25% of the cases of isolated deficiency of gucocorticoids. The clinical descriptions of the patients presenting with FIGD including its molecular-genetic diagnostics are of great interest for the understanding of this rare disease.

Adrenal Insufficiency: Causes of Adrenal Insufficiency and Prevention of Adrenal Crisis

Adrenal insufficiency (AI) is defined as the body's inability to produce enough adrenal hormones. Cortisol and aldosterone maintain normal physiologic functions in the body such as blood pressure, glucose levels and sodium/water balance in the body. Adrenal insufficiency can be primary or secondary, congenital or acquired. The most common form of primary adrenal insufficiency in children is congenital adrenal hyperplasia (CAH), with an incidence of about 1 in 15,000. A much more common cause of acute adrenal insufficiency is glucocorticoid withdrawal in patients being treated with chronic pharmacologic doses of steroids. The prevalence of secondary adrenal insufficiency is 150–280 per million. Causes of permanent AI include: Addison disease, CAH, complete removal of pituitary gland, surgical removal of the adrenal gland. Temporary causes are surgical removal of tumor from the pituitary gland, removal of cortisol producing tumors, medical treatments that lower cortisol levels to treat Cushing syndrome, and taking steroids for prolonged periods. The purpose of this poster is to identify and explain the causes of adrenal insufficiency, explain the daily management versus the illness regimen, and review the sick day rules and injection teaching of intramuscular hydrocortisone to prevent adrenal crisis. Nursing interventions to prevent adrenal crisis are to educate parents about sick day rules and provide intramuscular injection teaching to parents of children on glucocorticoid therapy. Even though there are adequate treatments for adrenal crisis, it continues to be a cause of morbidity and mortality in children. Children are at increased risk during times of illness and surgical procedures. There are many children taking glucocorticoid therapy for multiple diseases. Giving exogenous glucocorticoids turns off the body's natural ability to produce extra cortisol in times of physiologic stressors. Prevention of the crisis with correct dosing for physiologic stressors such as fever or trauma is an important goal. Pediatric endocrine nurses can provide patients and their families with the tools to prevent crisis by knowing the symptoms, causes, and tools to use in case of emergency.

Severe loss‐of‐function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt‐losing adrenal hypoplasia

ObjectiveFamilial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency.DesignMutational analysis of MC2R by direct sequencing.PatientsChildren (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1).ResultsMC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time.ConclusionsMC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosis.

Familial adrenocorticotropin unresponsiveness associated with alacrima and achalasia: biochemical and molecular studies in two siblings with clinical heterogeneity.

The syndrome of familial adrenocorticotropin (ACTH) unresponsiveness is a rare form of primary adrenal insufficiency, usually without mineralocorticoid deficiency. It is characterized by elevated plasma ACTH concentrations and undetectable plasma cortisol levels not responding to exogenous ACTH. Alacrima and achalasia have also been occasionally associated with adrenal insufficiency (triple A syndrome). Pathogenetic mutations have been identified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness. Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known. Here we report two siblings with familial ACTH unresponsiveness who were discrepant for skin pigmentation and mineralocorticoid function. In addition, achalasia and alacrima were documented only in the older sibling. The boy, studied at the age of 2 years, was hyperpigmented, in contrast to his normally pigmented sister, studied at the age of 9 years; basal plasma alpha-melanocyte stimulating hormone immunureactivity levels were 79 and 38 pg/ml, respectively (normal < 40 pg/ml). Furosemide-induced diuresis resulted in normal rises of plasma renin activity in both patients; however, plasma aldosterone levels increased only in the boy and not in his sister. Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality. Direct sequencing of the entire coding area of the ACTH receptor gene was also normal. The syndrome of familial ACTH unresponsiveness can vary clinically and biologically within the same family.(ABSTRACT TRUNCATED AT 250 WORDS)