Donatella Capalbo1, Cristina Moracas2, Marco Cappa3, Antonio Balsamo4, Mohamad Maghnie5,6, Malgorzata Gabriela Wasniewska7, Nella Augusta Greggio8, Federico Baronio4, Carla Bizzarri3, Giusy Ferro3, Alessandra Di Lascio9, Marianna Rita Stancampiano9, Sara Azzolini8, Giuseppa Patti5,6, Silvia Longhi10, Mariella Valenzise7, Giorgio Radetti10, Corrado Betterle11, Gianni Russo9, Mariacarolina Salerno2. 1. Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy. 2. Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Endo-ERN Center for Rare Endocrine Conditions, Naples, Italy. 3. Unit of Endocrinology, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy. 4. Pediatric Unit, Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, Endo-ERN Center for Rare Endocrine Conditions, Bologna, Italy. 5. Department of Pediatrics, IRCCS Istituto Giannina Gaslini, University of Genova, 16147 Genova, Italy. 6. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy. 7. Unit of Pediatrics, Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy. 8. Department of Women's and Children's Health of Padua, Pediatric Endocrinology and Adolescence Unit, Endo-ERN Center for Rare Endocrine Conditions, Padua, Italy. 9. Department of Pediatrics, Endocrine Unit, IRCCS San Raffaele Scientific Institute, Endo-ERN Center for Rare Endocrine Conditions, Milan, Italy. 10. Department of Pediatrics, Regional Hospital, Bolzano, Italy. 11. Unit of Endocrinology, Department of Medicine (DIMED) University of Padua, Padua, Italy.
Abstract
CONTEXT: Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children. OBJECTIVE: To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. PATIENTS AND METHODS: Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. RESULTS: The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was -0.70 ± 1.20 standard deviation score. CONCLUSIONS: We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.
CONTEXT: Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children. OBJECTIVE: To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. PATIENTS AND METHODS: Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. RESULTS: The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was -0.70 ± 1.20 standard deviation score. CONCLUSIONS: We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.
Authors: Stefan Pilz; Michael Krebs; Walter Bonfig; Wolfgang Högler; Anna Hochgerner; Greisa Vila; Christian Trummer; Verena Theiler-Schwetz; Barbara Obermayer-Pietsch; Peter Wolf; Thomas Scherer; Florian Kiefer; Elke Fröhlich-Reiterer; Elena Gottardi-Butturini; Klaus Kapelari; Stefan Schatzl; Susanne Kaser; Günter Höfle; Dietmar Schiller; Vinzenz Stepan; Anton Luger; Stefan Riedl Journal: J Klin Endokrinol Stoffwechs Date: 2022-03-02
Authors: Federica Buonocore; Avinaash Maharaj; Younus Qamar; Katrin Koehler; Jenifer P Suntharalingham; Li F Chan; Bruno Ferraz-de-Souza; Claire R Hughes; Lin Lin; Rathi Prasad; Jeremy Allgrove; Edward T Andrews; Charles R Buchanan; Tim D Cheetham; Elizabeth C Crowne; Justin H Davies; John W Gregory; Peter C Hindmarsh; Tony Hulse; Nils P Krone; Pratik Shah; M Guftar Shaikh; Catherine Roberts; Peter E Clayton; Mehul T Dattani; N Simon Thomas; Angela Huebner; Adrian J Clark; Louise A Metherell; John C Achermann Journal: J Endocr Soc Date: 2021-05-11