Chronic Adrenal Insufficiency Research Articles

Fingerprints of increased susceptibility to adrenal crisis in patients with chronic adrenal insufficiency

Fingerprints of increased susceptibility to adrenal crisis in patients with chronic adrenal insufficiency

Early recognition of the APECED rash can accelerate the diagnosis of APECED

Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) is a monogenic autoimmune disease most often resulting from biallelic loss-of-function variants in the autoimmune regulator (AIRE) gene. Although typically characterized by the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, we have recently reported that the clinical spectrum of the syndrome is far broader that previously described and that incorporation of an adjunct triad of APECED rash, autoimmune enteritis-associated intestinal dysfunction, and enamel hypoplasia in the classic triad manifestations could lead to earlier diagnosis. Among the adjunct triad manifestations, APECED rash occurs in 66 % of American APECED patients by age 3, most often developing in the first year of life. Here, we describe the clinical and histological features of protracted APECED rash manifesting together with recurrent mucocutaneous candidiasis as the first two disease components of APECED in a 10-month-old girl.

Long-diagnosed primary adrenal insufficiency in the setting of Werlhof’s disease. A clinical case report

Chronic adrenal insufficiency is an endocrine disease caused by insufficient secretion of adrenal hormones due to dysfunction of one or more links of the hypothalamic-pituitary-adrenal axis. The highest prevalence has been documented in Scandinavian countries: 15–22 people per 100,000 population, while other European countries report 10 cases per 100,000 population. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in adults, and it can be either alone (40 %) or a component of autoimmune polyglandular syndromes (60 %). The etiologic factors of primary adrenal insufficiency include tuberculosis or AIDS. These causes of adrenal cortical insufficiency are particularly relevant in Ukraine. The article describes a clinical case of a patient with both primary adrenal insufficiency and Werlhof’s disease. The prevalence of adrenal insufficiency and etiologic factors of primary adrenal insufficiency are highlighted. A detailed differential diagnosis of primary adrenal insufficiency with other diseases that could cause clinical symptoms such as hypoglycemic states, severe weight loss, hypotension, severe muscle weakness, hyponatremia, hyperkalemia is performed. The basic principles of diagnosis, treatment, and prognosis in primary adrenal insufficiency are discussed. Despite typical, specific manifestations of adrenal insufficiency, diagnosis in real clinical practice is difficult. Awareness and vigilance of doctors regarding the symptoms of adrenal insufficiency is necessary. Late detection of chronic adrenal insufficiency can lead to complications. Timely diagnosis and treatment of chronic adrenal insufficiency improves disease prognosis and quality of life.

Morbidity in Patients with Chronic Adrenal Insufficiency - Cardiovascular Risk Factors and Hospitalization Rate Compared to Population Based Controls.

Patients with adrenal insufficiency (AI) have been found to have increased cardiovascular morbidity, partly associated with nonphysiologic glucocorticoid replacement. We included two separate cohorts (cohort 1 n=384 patients, cohort 2 n=180 patients) of patients with chronic primary and secondary AI under standard replacement therapy and compared them to two age- and sex-matched population-based studies (SHIP-TREND/DEGS). Odds ratios with 95% CI for hypertension, hyperlipidemia/HLP, type 2 diabetes/T2DM, obesity, and hospitalization with adjustment for confounders were evaluated by logistic regression. Patient cohort 1 had significantly lower ORs for obesity [0.4 (0.3-0.6), p<0.001] and hypertension [0.5 (0.3-0.6), p<0.001] compared to SHIP-TREND and for obesity [0.7 (0.5-0.9), p=0.01], hypertension [0.4 (0.3-0.5), p<0.001] and HLP [0.4 (0.3-0.6), p<0.001] compared to DEGS. In cohort 2, ORs were significantly lower for HLP compared to both SHIP-TREND [0.4 (0.2-0.7), p=0.001] and DEGS [0.3 (0.2-0.5), p<0.001] and for hypertension [0.7 (0.4-0.9), p=0.04] compared to SHIP-TREND. In patients with SAI from cohort 2, ORs for DM2 [2.5 (1.3-4.9) p=0.009], hypertension [2.5 (1.4-4.5), p=0.002] and obesity [1.9 (1.1-3.1), p=0.02] were significantly higher compared to DEGS, whereas ORs for HLP were significantly lower compared to both SHIP [0.3 (0.1-0.6), p=0.002] and DEGS [0.3 (0.1-0.6), p<0.001]. In most of our AI patients treated with conventional glucocorticoid doses, the risk for T2DM, obesity, hypertension, and HLP was not increased. The number of hospitalizations was significantly higher in AI patients compared to controls, which might reflect increased susceptibility but also a more proactive management of concomitant diseases by physicians and patients.

Predisposing factors for adrenal crisis in chronic adrenal insufficiency: a case-control study.

This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI). A case-control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study). Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11β-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma-renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires. Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement. Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability.

FRI054 Partial Lipodystrophy As A Manifestation Of Autoimmune Polyglandular Syndrome 1

Abstract Disclosure: S. Agarwal: None. C. Xing: None. M.S. Anderson: Stock Owner; Self; Medtronic Diabetes, Merck. A. Garg: None. Background: Autoimmune polyglandular syndrome 1 (APS1) is a rare autosomal recessive disorder due to mutations in AIRE gene that manifests mainly with chronic mucocutaneous candidiasis, primary hypoparathyroidism and adrenal insufficiency. We report an extremely rare APS1 patient who developed partial lipodystrophy during adulthood. Clinical Case: This 39-year-old white female developed frequent diaper rashes, oral thrush and tetany at the age of one year due to candidiasis and hypoparathyroidism. At 6 years, she developed hypothyroidism. At 11 years, she developed fatigue, excessive thirst, and anorexia due to primary adrenal insufficiency. At 13 years of age, she had thelarche and adrenarche but never attained menarche. At 14 years, she underwent a sibling matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At 35 years, her serum triglycerides level was 904 mg/dL and loss of subcutaneous fat from the upper and lower extremities and hips was noted but she had increased subcutaneous fat on the chest and abdomen as well as buffalo hump. Thigh skinfold thickness was 8 mm (&amp;lt;10th percentile of normal). A whole-body dual-energy X-ray absorptiometry revealed a total body fat of 38% with lower extremity fat of 25%-27% (&amp;lt;1st percentile of normal). Whole exome sequencing on DNA extracted from saliva revealed two pathogenic variants in AIRE gene; c.83T&amp;gt;C; p.Leu28Pro and c.769C&amp;gt;T; p.Arg257* confirming the diagnosis of APS1. No other pathogenic variants were noted in the known lipodystrophy genes. Serum was negative for anti-perilipin 1 autoantibody. Discussion: Biallelic mutations in the AIRE hinder the process of selective apoptosis of T-cells in the thymic medulla that have a strong affinity to self-antigens leading to autoimmunity manifesting as APS1. Previously, a 5-year-old boy with APS1 was reported to develop generalized lipodystrophy and his serum was positive for anti-perilipin 1 autoantibody. Recently, serum anti-perilipin-1 autoantibodies have also been reported in the Aire gene knock out mice. In contrast, our patient has partial lipodystrophy and was negative for anti-perilipin 1 autoantibody. This suggests that patients with APS1 may harbor many different autoantibodies against adipocyte expressed proteins and develop different patterns of autoimmune lipodystrophies. Presentation: Friday, June 16, 2023

Morbidity in patients with chronic adrenal insufficiency - cardiovascular risk factors and hospitalization rate compared to population based controls

Morbidity in patients with chronic adrenal insufficiency - cardiovascular risk factors and hospitalization rate compared to population based controls

Fingerprints of increased susceptibility to adrenal crises in patients with chronic adrenal insufficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SARS-CoV-2-induced adrenal crisis in a patient with autoimmune polyglandular syndrome type 1: case report.

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison's disease as the obligatory component is potentially life threatening.Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia.Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

APECED SYNDROME (FAMILY OBSERVATION)

Introduction: APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) is an autosomal recessive disease characterized by the association of autoimmune endocrine involvement, mucocutaneous candidiasis and ectodermal tissue involvement. Observation: We report the case of 2 brothers from a 2nd degree consanguineous marriage with a history of 2 deaths in the siblings for whom the diagnosis of APECED syndrome was retained on clinical and biological criteria (genetic study in progress).The eldest had candidous onychomycosis of the hands and feet, generalized mucocutaneous candidiasis, profound hypocalcemia with tetany crisis, autoimmune hepatitis, Biermers anemia and ADDISONs disease. Meanwhile the youngest had onychomycosis, vitiligo, atrophy of the tongue, alopecia and adrenalinsufficiency. Discussion:Autoimmune polyglandular syndrome type 1 (APS-1) is classically characterized by at least two of the three components of Whitakers triad: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and chronic adrenal insufficiency. If a sibling is affected, only one component of the triad is necessary to make the diagnosis. Conclusion: This syndrome requires a multidisciplinary approach, without forgetting the importance of genetic counseling for this autosomal recessive disease.

Chronic stress induced loudness hyperacusis, sound avoidance and auditory cortex hyperactivity

Hyperacusis, a debilitating loudness intolerance disorder, has been linked to chronic stress and adrenal insufficiency. To investigate the role of chronic stress, rats were chronically treated with corticosterone (CORT) stress hormone. Chronic CORT produced behavioral evidence of loudness hyperacusis, sound avoidance hyperacusis, and abnormal temporal integration of loudness. CORT treatment did not disrupt cochlear or brainstem function as reflected by normal distortion product otoacoustic emissions, compound action potentials, acoustic startle reflexex, and auditory brainstem responses. In contrast, the evoked response from the auditory cortex was enhanced up to three fold after CORT treatment. This hyperactivity was associated with a significant increase in glucocorticoid receptors in auditory cortex layers II/III and VI. Basal serum CORT levels remained normal after chronic CORT stress whereas reactive serum CORT levels evoked by acute restraint stress were blunted (reduced) after chronic CORT stress; similar changes were observed after chronic, intense noise stress. Taken together, our results show for the first time that chronic stress can induce hyperacusis and sound avoidance. A model is proposed in which chronic stress creates a subclinical state of adrenal insufficiency that establishes the necessary conditions for inducing hyperacusis.

Relapses of pain syndrome in patients with polymyalgia rheumatica during reduction of glucocorticoid therapy

An analysis of causes leading to pain recurrence in patients with polymyalgia rheumatica (PR) after tapering down the dose of glucocorticosteroids (GCS) is presented. True exacerbations resulting from the main disease recurrence and pseudo-exacerbations when the resumption of pain syndrome is not due inflammation but because of other causes – steroid myopathy or chronic adrenal insufficiency (AI) are identified. The experience of using tocilizumab, an inhibitor of interleukin-6 receptors, as steroid-sparing agent in patients with PR is considered. The factors contributing to pain syndrome development, which can mimic exacerbations of PR (associated myofascial pain, vitamin D deficiency, etc.) are indicated. The methodology for AI diagnosis in patients receiving GCS therapy is discussed in detail. Recommendations for the rational AI therapy including acute cases are given.

Self-management and hospitalization in 615 Swedish patients with Addison's disease during the COVID-19 pandemic - a retrospective study.

Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. The aim of this study was to investigate the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and co-morbidities, focusing on the pre-vaccine phase. Among the 615 included patients with AAD, COVID-19 was reported by 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients 85% increased their glucocorticoid dosage during sickness. Older age (p=0.002) and hypertension (p=0.014) were associated with an increased risk of hospital care while younger age (p<0.001) and less worry about infection (p=0.030) correlated with a higher risk of COVID-19. In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one fifth of the cohort contracted COVID-19 few patients required hospital care. A majority of the patients applied general recommended sick-rules despite reporting limited communication with healthcare during the pandemic.

Офтальмологические проявления эндокринных заболеваний

The review provides a detailed description of ophthalmic disorders associated with the most common endocrine diseases — diabetes mellitus, hypo- and hyperthyroidism, chronic adrenal insufficiency, Cushing syndrome, and obesity. Specific characteristics of ocular disorders co-occurring with these diseases are highlighted in the article. In diabetes mellitus, there is a lesion of both the periorbital region — inflammatory processes of the eyelids and conjunctiva, xanthelasm of the eyelids, and intraocular structures — the retina, macula, lens and cornea. Ophthalmological changes in thyroid pathology are manifested by a combination of various "ocular" symptoms, the most famous of which are exophthalmos, dilation of the ocular slit, eye shine, convergence disorder. However, the first complaints of patients may be unstable diplopia, swelling of the eyelids (mainly in the morning), a feeling of "clogging", dryness, lacrimation and/or photophobia, spontaneous retrobulbar pain, pain when moving the eyes, redness of the eyelids, conjunctival injection, redness and swelling of the semilunar fold and lacrimal meat, hyperpigmentation of the eyelids — a symptom Jellineka, swelling and meniscus-like drooping of the eyelids are a symptom of a Singer. Some endocrine diseases may cause symptomatic arterial hypertension, e.g. Cushing disease (syndrome), primary hyperaldosteronism (Conn's disease), acromegaly, and pheochromocytoma. Early signs of the above diseases may include eye disorders which develop prior to other manifestations due to the onset of hypertensive retinopathy. The adequate assessment of the disorders of eyes and paraorbital tissues in patients with endocrine diseases may facilitate more accurate diagnosis and timely treatment. The publication could potentially benefit ophthalmologists, therapists, endocrinologists, pediatricians and general practitioners. Keywords: ophthalmic manifestations, diabetes mellitus, hyperthyroidism, hypothyroidism, adrenal insufficiency, endocrine diseases. For citation: Gazdanova A.A., Knyazeva S.A., Marakhovskaya A.A., Protopopova Yu.V., Sedova A.A., Rakhimov J.B., Salmanov A.F., Magomedova S.A. Ophthalmic manifestations of endocrine diseases. Russian Medical Inquiry. 2023;7(9) (in Russ.). DOI: 10.32364/2587-6821-2023-7-9-4.

Abstract #1316116: A Novel AIRE Gene Mutation Presenting With Autoimmune Polyglandular Syndrome Type 1 and End-Stage Renal Disease: A Case Report

Autoimmune polyendocrine syndrome type is a rare disease with autosomal recessive pattern of inheritance. Mutations in the autoimmune regulator gene (AIRE) lead to this disease. Medullary thymic epithelial cells which contribute significantly to central tolerance; thus preventing autoimmunity and production of autoantibodies. Autoimmune polyendocrine syndrome type 1 is characterized by the development of at least 2 of 3 cardinal components during childhood; chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency (Addison disease) Other classic components are less frequent.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey.

To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.

ODP019 A Case Study of the Association of Autoimmune Polyglandular Syndrome and Pulmonary Artery Hypertension

Abstract We report a patient with combined pulmonary arterial hypertension (PAH) and autoimmune polyglandular syndrome (APS) type 2. A 41 y/o woman with hypothyroidism presented for right heart (RHC) in the work up of PAH. Pt had a medical history of PAH diagnosed by transthoracic echocardiogram (TTE) and hypothyroidism. She reported symptoms of fatigue, shortness of breath with increased pigmentation of her skin progressive for several years. Preadmission lab found hyponatremia of 126 and potassium of 6.6. She was admitted and treated with IV insulin with D50, kayexalate, IV fluids. A random 11 AM cortisol was 0.57 mcg/dl N: AM: 6. 0–30. 0 mcg/dl; PM: 3. 0–16. 0 mcg/dl. Acosyntropin test was ordered. Pt failed the stimulation test (baseline 0.39, 30 min 0.49, 60 min 0.50, with an ACTH at baseline of 1423 pg/ml N: 7.2-63.3). Pt was started on hydrocortisone 20 mg AM/10 mg PM with fludrocortisone 0.1mg. On follow up at 2 weeks, her energy, mood, appetite and breathing tolerance had improved. Follow up RHC in 4 weeks found normalization of right heart pressures. APS is a collection of autoimmune diseases. Type I APS, caused by a defect in the autoimmune regulator (AIRE) gene, is diagnosed with two of three conditions, chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal cortical insufficiency. Type II APS (formally "Schmidt's Syndrome"), associated with HLA haplotypes DR3 (DQB*0201) and DR4 (DQB1*0302), is diagnosed with chronic autoimmune adrenal insufficiency with either Type 1 DM or chronic autoimmune thyroid disease (commonly Hashimotos but can be Graves). It typically presents later in life compared to APS I, age 30-40s. The association between PAH is rare but has been noted in several case studies. It has been associated with APS I in Korniszewski et al. and Bhansali et al. For APS II, the first association was reported by Barrou et al. of a patient with hypothyroidism, hypogonadism, and adrenal insufficiency who later developed PAH. Two cases reported by García-Hernández et al found PAH with positive adrenal antibodies without adrenal insufficiency. In 2009 Walid R. et al. reported a case of severe adrenal insufficiency (hypotension, hypokalemia) with PAH. She improved with steroids, but her PAH was present on TTE four years after treatment started. Pt in that case declined RHC. The patient in this case study proceeded with a RHC which did show normalization of right heart pressures, the first reported case to document normalization of PAH with replacement steroid treatment. Presentation: No date and time listed

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency.

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3βHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients’ age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also—mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing’ syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison’s disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem–mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as “novel pathogenic mutation” (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3βHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1.

Autoimmune polyendocrine syndrome type-1 (APS-1) is a rare inherited monogenic autoimmune disease characterized by the presence of at least two of three following major clinical features: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Mutations in autoimmune regulator (AIRE) gene have been found to contribute to APS-1. In the present study, we reported a 36-years-old male APS-1 patient who presented with hypoparathyroidism and Addison’s disease. The proband underwent complete clinical examinations and mutation screening was performed by Sanger sequencing on AIRE gene. A novel homozygous mutation in exon 9 of the AIRE gene (c.1024C>T) was identified. Based on sequencing findings, HEK293T cell-based assays were conducted to analyze the subcellular localization and mutant transcript processing. Our results revealed that p.Q342X mutant localized in nuclear speckles and exerted a dominant-negative effect on wildtype AIRE function. We reported the c.1024C>T mutation of AIRE gene for the first time, which enriched the AIRE mutation database and contributed to further understanding of APS-1.

Coping strategies in parents of children with chronic Adrenal insufficiency

IntroductionBeing the parent of a child followed for a chronic pathology can require different resources and coping skills.Objectivesto determine the adaptation strategies of the parents of children monitored for adrenal insufficiency in the face of their children’s pathologyMethodsWe conducted a descriptive cross-sectional study carried out with parents of children with Adrenal Insufficiency followed at the pediatric outpatient clinic in Taher Sfar Mahdia University Hospital between February 2019 and April 2020. We used a pre-established questionnaire collecting sociodemographic data and the strategies of coping using the Brief-COPE Board.ResultsA total of 38 parents of children with adrenal insufficiency and 38 control parents participated in the study. The Brief-Cope board’s study of Coping strategies revealed that the strategies most used by parents of children with Adrenal insufficiency were, in descending order: religion (92.1%), support emotional (73.7%), distraction (63.9%), behavioral disengagement and acceptance (57.9%), instrumental support (52.6%), expression of feelings (50%), positive reinterpretation (39.5%), blame (38.9%), denial and humor (36.8%), active coping and planning (36.1%). On the other hand, those used by the control population were in descending order: religion (94.4%), distraction (84.2%), blame (78.9%), acceptance (72.2%) %), emotional support (69.4%), humor (63.9%), behavioral disengagement (61.1%), active coping (47.2%), expression of feelings (44 , 7%), planning (41.7%), instrumental support (30.6%), positive reinterpretation (22%), denial (19.4%).ConclusionsPsychological support for the parents of children with chronic illnesses would be necessary to prevent parental burnout and improve their ability to adapt to their experiencesDisclosureNo significant relationships.