Adrenal Insufficiency

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.

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

BMJ Case Reports ◽

10.1136/bcr-2018-226826 ◽

2019 ◽

Vol 12 (2) ◽

pp. bcr-2018-226826 ◽

Cited By ~ 1

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 ◽

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.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa694 ◽

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 ◽

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.

HLA and Hormonal Studies in 5 Patients with Late-Onset 21-Hydroxylase Deficiency Syndrome (210HDS)

Obstetrical & Gynecological Survey ◽

10.1097/00006254-198704000-00016 ◽

1987 ◽

Vol 42 (4) ◽

pp. 249-251

Author(s):

C. SCARONI ◽

E. ORLANDINI ◽

VENTURI C. PASINI ◽

M. GANGEMI ◽

F. MANTERO

Keyword(s):

Late Onset ◽

Deficiency Syndrome ◽

Hydroxylase Deficiency ◽

Genetic defects in pediatric-onset adrenal insufficiency in Japan

Acta Endocrinologica ◽

10.1530/eje-17-0027 ◽

2017 ◽

Vol 177 (2) ◽

pp. 187-194 ◽

Cited By ~ 13

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 ◽

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.

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

Journal of Endocrinological Investigation ◽

10.1007/bf03349683 ◽

1994 ◽

Vol 17 (8) ◽

pp. 665-670 ◽

Cited By ~ 8

Author(s):

Allan R. Glass ◽

S. G. Jackson ◽

R. S. Perlstein ◽

H. Linton Wray

Keyword(s):

Adrenal Insufficiency ◽

Hydroxylase Deficiency ◽

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

Clinical Endocrinology ◽

10.1046/j.1365-2265.1996.631456.x ◽

1996 ◽

Vol 44 (1) ◽

pp. 111-116 ◽

Cited By ~ 16

Author(s):

Shoichiro Nagasaka ◽

Ken Kubota ◽

Takashi Motegi ◽

Eiji Hayashi ◽

Manabu Ohta ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Adrenal Incidentaloma ◽

Hydroxylase Deficiency ◽

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0445 ◽

2019 ◽

Vol 32 (6) ◽

pp. 615-622 ◽

Cited By ~ 6

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 ◽

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.

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

Acta Endocrinologica ◽

10.1530/eje-15-1181 ◽

2016 ◽

Vol 174 (5) ◽

pp. 601-609 ◽

Cited By ~ 76

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 ◽

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.