Adrenal insufficiency in a man with non-classical 21-hydroxylase deficiency: Consequence or coincidence?

1994 ◽  
Vol 17 (8) ◽  
pp. 665-670 ◽  
Author(s):  
Allan R. Glass ◽  
S. G. Jackson ◽  
R. S. Perlstein ◽  
H. Linton Wray
Keyword(s):  
Adrenal Insufficiency ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals Bilateral adrenal myelolipomas presenting as acute adrenal insufficiency in an adult with congenital adrenal hyperplasia

2019 ◽  
Vol 12 (2) ◽  
pp. bcr-2018-226826 ◽  
Author(s):  
Sakolwan Suchartlikitwong ◽  
Rahul Jasti ◽  
Joaquin Lado-Abeal ◽  
Ana Marcella Rivas Mejia
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Insufficiency ◽  
Reproductive Organs ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Abdominal Ct ◽  
Acute Adrenal Insufficiency ◽  
Rare Tumours ◽  
21 Hydroxylase Deficiency ◽  
Stress Dose

Adrenal myelolipomas are relatively rare tumours composed of adipocytes and myeloid cells that arise in response to chronic adrenocorticotropic hormone stimulation. We present the case of bilateral adrenal myelolipomas in a 39-year-old man with untreated congenital adrenal hyperplasia (CAH) presenting with acute adrenal insufficiency and severe virilisation. Phenotypically, he is a man of short stature and has hyperpigmentation of the skin, gingiva and nail beds. Genital examination revealed micropenis and no palpable testes. Laboratory testing was consistent with primary adrenal insufficiency. An abdominal CT showed bilateral adrenal myelolipomas. An MRI of the pelvis revealed female reproductive organs. Chromosome study showed a karyotype of 46,XX. A CYP21A2 gene mutation confirmed diagnosis of CAH with 21-hydroxylase deficiency. The patient was treated with stress dose corticosteroids, subsequently tapered to physiological doses. We review previously reported cases and discussed diagnosis and treatment, including hormonal therapy and psychological approach.

scholarly journals Real-World Estimates of Adrenal Insufficiency–Related Adverse Events in Children With Congenital Adrenal Hyperplasia

2020 ◽  
Vol 106 (1) ◽  
pp. e192-e203
Author(s):  
Salma R Ali ◽  
Jillian Bryce ◽  
Houra Haghpanahan ◽  
James D Lewsey ◽  
Li En Tan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Congenital Adrenal Hyperplasia ◽  
Adrenal Insufficiency ◽  
Real World ◽  
Median Number ◽  
Adrenal Hyperplasia ◽  
Real World Data ◽  
Hydroxylase Deficiency ◽  
Middle Income ◽  
21 Hydroxylase Deficiency

Abstract Background Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. Methods Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. Results A total of 518 children—with a median of 11 children (range 1, 53) per center—had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. Conclusions The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency–related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.

scholarly journals Genetic defects in pediatric-onset adrenal insufficiency in Japan

2017 ◽  
Vol 177 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Naoko Amano ◽  
Satoshi Narumi ◽  
Mie Hayashi ◽  
Masaki Takagi ◽  
Kazuhide Imai ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Phenotypic Variability ◽  
Rational Approach ◽  
Genetic Defects ◽  
Molecular Testing ◽  
Japanese Children ◽  
Hydroxylase Deficiency ◽  
Male Patients ◽  
21 Hydroxylase Deficiency ◽  
Pediatric Onset

Context Most patients with pediatric-onset primary adrenal insufficiency (PAI), such as 21-hydroxylase deficiency, can be diagnosed by measuring the urine or serum levels of steroid metabolites. However, the etiology is often difficult to determine in a subset of patients lacking characteristic biochemical findings. Objective To assess the frequency of genetic defects in Japanese children with biochemically uncharacterized PAI and characterize the phenotypes of mutation-carrying patients. Methods We enrolled 63 Japanese children (59 families) with biochemically uncharacterized PAI, and sequenced 12 PAI-associated genes. The pathogenicities of rare variants were assessed based on in silico analyses and structural modeling. We calculated the proportion of mutation-carrying patients according to demographic characteristics. Results We identified genetic defects in 50 (85%) families: STAR in 19, NR0B1 in 18, SAMD9 in seven, AAAS in two, NNT in two, MC2R in one and CDKN1C in one. NR0B1 defects were identified in 78% of the male patients that received both glucocorticoid and mineralocorticoid replacement therapy and had normal male external genitalia. STAR defects were identified in 67% of female and 9% of male patients. Seven of the 19 patients with STAR defects developed PAI at age two or older, out of whom, five did not have mineralocorticoid deficiency. Conclusions Molecular testing elucidated the etiologies of most biochemically uncharacterized PAI patients. Genetic defects such as NR0B1 defects are presumed based on phenotypes, while others with broad phenotypic variability, such as STAR defects, are difficult to diagnose. Molecular testing is a rational approach to diagnosis in biochemically uncharacterized PAI patients.

A case of silent 21-hydroxylase deficiency with persistent adrenal insufficiency after removal of an adrenal incidentaloma

1996 ◽  
Vol 44 (1) ◽  
pp. 111-116 ◽  
Author(s):  
Shoichiro Nagasaka ◽  
Ken Kubota ◽  
Takashi Motegi ◽  
Eiji Hayashi ◽  
Manabu Ohta ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenal Incidentaloma ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

Etiology of primary adrenal insufficiency in children: a 29-year single-center experience

2019 ◽  
Vol 32 (6) ◽  
pp. 615-622 ◽  
Author(s):  
Melati Wijaya ◽  
Ma Huamei ◽  
Zhang Jun ◽  
Minlian Du ◽  
Yanhong Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
Adult Population ◽  
Adrenal Crisis ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

Abstract Background Primary adrenal insufficiency (PAI) in children is a rare condition and potentially lethal. The clinical characteristics are non-specific. It may be manifested as a chronic condition or crisis. The etiologies of PAI in children are different from the adult population. Therefore, diagnostic investigation becomes challenging. Methods A retrospective study was conducted at The First Affiliated Sun Yat Sen University Pediatric Endocrine unit between September 1989 and July 2016. Results A total of 434 patients (237 males, 197 females) were identified as having PAI. Congenital adrenal hyperplasia (CAH) was the most frequent etiology (83.4%, n = 362, male:female = 174:188), of which 351 (97.2%) were 21-hydroxylase deficiency (21-OH) CAH. Non-CAH etiology accounted for 11.3% (n = 49, male:female = 47:2), of which 46 (93.9%) were of non-autoimmune. The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). The etiology was not identified for 23 patients (5.3%, male:female =16:7). Clinical symptoms were in accordance with the incidence of genital ambiguity (42.6%), digestive symptoms (vomiting and diarrhea) (35.5%), failure to thrive (26.5%), gonadal-associated symptom (premature puberty, sexual infantilism and amenorrhea) (21.2%), hyperpigmentation (9.7%), adrenal crisis (AC; 4.1%), neurological symptoms (3.2%), fatigue (2.5%) and prolonged jaundice (2.1%). Through physical examination, 58.5% were found to have hyperpigmentation. Conclusions This study spanned 29 years at our institution. The etiology of PAI in children was mostly of congenital forms, which exhibits a wide spectrum of clinical characteristics. For etiological diagnosis, chromosomal karyotyping is recommended for female phenotype patients.

scholarly journals Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency

2016 ◽  
Vol 174 (5) ◽  
pp. 601-609 ◽  
Author(s):  
Adina F Turcu ◽  
Aya T Nanba ◽  
Robert Chomic ◽  
Sunil K Upadhyay ◽  
Thomas J Giordano ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Cytochrome B5 ◽  
Vena Cava ◽  
Adrenal Vein ◽  
Serum Samples ◽  
Hydroxylase Deficiency ◽  
Men And Women ◽  
Liquid Chromatography Tandem Mass ◽  
21 Hydroxylase Deficiency ◽  
Immunohistochemical Studies

Abstract Objective To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. Design Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3–59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. Methods We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. Results Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3–4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. Conclusions All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess.

scholarly journals Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children

2020 ◽  
Author(s):  
Zhuo Chang ◽  
Wei Lu ◽  
Zhu-Hui Zhao ◽  
Li Xi ◽  
Xiao-Jing Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Testosterone Levels ◽  
Novel Variants ◽  
Novel Variant ◽  
Threatening Condition ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Background Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. Results Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p. 279GfsX17) and c.651 + 2T > G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p. 108S > X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399 + 1G > A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein. Conclusions We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.

Adrenal Insufficiency

2015 ◽  
Author(s):  
D. Lynn Loriaux
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenocorticotropic Hormone ◽  
Deficiency Syndrome ◽  
Relative Adrenal Insufficiency ◽  
Hydroxylase Deficiency ◽  
Addison Disease ◽  
Laboratory Confirmation ◽  
Pituitary Secretion ◽  
21 Hydroxylase Deficiency ◽  
Clinical Pictures

Adrenal insufficiency (Addison disease) can be categorized as primary or secondary; the former results from adrenal cortex destruction, whereas the latter is caused by disruption of pituitary secretion of adrenocorticotropic hormone. The clinical pictures are the same, and their signs can be differentiated only by the presence of hyperpigmentation and vitiligo in autoimmune disease. Diagnosing both chronic and acute syndromes requires laboratory confirmation; however, the only available diagnostic test for adrenal insufficiency is cosyntropin stimulation. Relative adrenal insufficiency is a hypothetical situation stemming from misinterpretation of this test, and there is no pathophysiologic evidence of its existence. The most common form of congenital adrenal hyperplasia is the 21-hydroxylase deficiency syndrome. This module contains 1 highly rendered figure, 2 tables, 4 references, and 5 MCQs.

Adrenal Insufficiency

2018 ◽  
Author(s):  
D. Lynn Loriaux
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenocorticotropic Hormone ◽  
Deficiency Syndrome ◽  
Relative Adrenal Insufficiency ◽  
Hydroxylase Deficiency ◽  
Addison Disease ◽  
Laboratory Confirmation ◽  
Pituitary Secretion ◽  
21 Hydroxylase Deficiency ◽  
Clinical Pictures

Adrenal insufficiency (Addison disease) can be categorized as primary or secondary; the former results from adrenal cortex destruction, whereas the latter is caused by disruption of pituitary secretion of adrenocorticotropic hormone. The clinical pictures are the same, and their signs can be differentiated only by the presence of hyperpigmentation and vitiligo in autoimmune disease. Diagnosing both chronic and acute syndromes requires laboratory confirmation; however, the only available diagnostic test for adrenal insufficiency is cosyntropin stimulation. Relative adrenal insufficiency is a hypothetical situation stemming from misinterpretation of this test, and there is no pathophysiologic evidence of its existence. The most common form of congenital adrenal hyperplasia is the 21-hydroxylase deficiency syndrome. This module contains 1 highly rendered figure, 2 tables, 4 references, and 5 MCQs.

scholarly journals Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children

2020 ◽  
Author(s):  
Zhuo Chang ◽  
Wei Lu ◽  
Zhu-Hui Zhao ◽  
Li Xi ◽  
Xiao-Jing Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Information ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Testosterone Levels ◽  
Novel Variants ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Background: Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.Methods: Seventy children were enrolled. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.Results: Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p.279GfsX17) and c.651+2T>G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p.108S>X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399+1G>A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399+1G>A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein.Conclusions: We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.

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