scholarly journals Differentiating Between CAH and PCOS Using Hormone Levels and LC-MS/MS

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A127-A127
Author(s):  
Zane Z Hauck ◽  
David W Kimball ◽  
David T Zava
Keyword(s):  
Case Reports ◽  
Treatment Protocol ◽  
Hydroxysteroid Dehydrogenase ◽  
Hydroxylase Deficiency ◽  
Full Spectrum ◽  
Classic Cah ◽  
Hydroxy Progesterone ◽  
21 Hydroxylase Deficiency ◽  
Low Cortisol

Abstract Introduction: PCOS is one of the most common endocrine issues affecting women today, with almost 10% of women suffering from this condition. CAH is a rarer disease that affects both men and women at a rate of around 1:1000 people. The problem with these two disorders arises in the fact that variants of these conditions may have very similar clinical presentations. This makes a proper diagnosis and treatment protocol difficult. Both PCOS and CAH present with high androgens but differ in that the former usually presents with high cortisol/insulin resistance, and the latter with low cortisol and aldosterone. Another difficulty in diagnosis is due to CAH presenting itself in 4 variants; 21-hydroxylase deficiency, the most common with over 95% prevalence, 11-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase type 2 deficiency, and 17α-hydroxylase deficiency. We have developed and validated an LC-MS/MS assay using a first morning saliva that measures a full panel of steroids necessary to clearly differentiate PCOS from all 4 variants of CAH. This full spectrum of steroids includes precursors of the active steroids (pregnenolone sulfate, DHEA, androstenedione) as well as parent steroids (progesterone, testosterone, estradiol, cortisol, aldosterone) and their precursors (17-OH progesterone) and downstream metabolites (11-hydroxycortisol, corticosterone) that differentiate PCOS from CAH and define the 4 variants of CAH. Clinical Case: We will present several example case reports showing that PCOS presents with high androgens and normal to high cortisol and aldosterone, and in sharp contrast, classic CAH presents with high androgens and 17-hydroxy progesterone, but very low steroids distal to 21-hydroxylase deficiency (i.e low 11-deoxycortisol, cortisol, cortisone, corticosterone, and aldosterone). In contrast the more rare variant of 11-hydroxylase deficiency shows a typical pattern of low cortisol and cortisone and elevated 11-deoxycortisol. 3β-hydroxysteroid dehydrogenase type 2 deficiency is extremely rare to see in an adult as most babies born with this condition do not survive. 17α-hydroxylase deficiency is also very rare but shows elevated progesterone, 11-deoxycorticosterone, corticosterone, and aldosterone. For all these cases aldosterone can be tricky to interpret as there are multiple mechanisms at which aldosterone is produced and thus should not be used as a definitive marker for CAH.

Partial 3β-hydroxysteroid dehydrogenase type 2 deficiency: Diagnosis of a novel mutation after positive newborn screening for 21-hydroxylase deficiency

2016 ◽  
Vol 146 (2) ◽  
pp. 92-93
Author(s):  
M. Pilar Bahíllo-Curieses ◽  
Lourdes Loidi Fernández de Trocóniz ◽  
Agustín del Cañizo López ◽  
María José Martínez-Sopena
Keyword(s):  
Newborn Screening ◽  
Novel Mutation ◽  
Hydroxysteroid Dehydrogenase ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment

2017 ◽  
Vol 176 (4) ◽  
pp. R167-R181 ◽  
Author(s):  
Anne Bachelot ◽  
Virginie Grouthier ◽  
Carine Courtillot ◽  
Jérôme Dulon ◽  
Philippe Touraine
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Management Strategies ◽  
The United States ◽  
Fertility Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency ◽  
And Control

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge.

scholarly journals Failure of Cortisone Acetate Treatment in Congenital Adrenal Hyperplasia because of Defective 11β-Hydroxysteroid Dehydrogenase Reductase Activity*

1999 ◽  
Vol 84 (4) ◽  
pp. 1210-1213 ◽  
Author(s):  
Anna Nordenström ◽  
Claude Marcus ◽  
Magnus Axelson ◽  
Anna Wedell ◽  
E. Martin Ritzén
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Reductase Activity ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Cortisone Acetate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genetic Lesion ◽  
21 Hydroxylase Deficiency ◽  
Very High

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2·day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient’s inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11β-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11β-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency.

scholarly journals Delayed Diagnosis of Congenital Adrenal Hyperplasia with Salt Wasting Due to Type II 3β-Hydroxysteroid Dehydrogenase Deficiency

2005 ◽  
Vol 90 (4) ◽  
pp. 2076-2080 ◽  
Author(s):  
Trine H. Johannsen ◽  
Delphine Mallet ◽  
Harriet Dige-Petersen ◽  
Jørn Müller ◽  
Katharina M. Main ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Hydroxysteroid Dehydrogenase ◽  
Type Ii ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

Abstract Classical 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare cause of congenital adrenal hyperplasia. We report two sisters presenting with delayed diagnoses of classical 3β-HSD, despite salt wasting (SW) episodes in infancy. Sibling 1 was referred for premature pubarche, slight growth acceleration, and advanced bone age, whereas sibling 2 had no signs of virilization. At referral, increased 17α-hydroxyprogesterone associated with premature pubarche at first suggested a nonclassical 21-hydroxylase deficiency. Sequencing of the CYP21 gene showed both girls only heterozygotes (V281L mutation). This result, combined with SW in infancy, suggested a 3β-HSD deficiency because of increased dehydroepiandrosterone sulfate levels. Further hormonal studies showed markedly elevated Δ5-steroids, in particular 17α-hydroxypregnenolone greater than 100 nmol/liter (the clue to the diagnosis) and elevated Δ5-/Δ4-steroid ratios. Sequencing of the type II 3β-HSD gene documented that both girls were compound heterozygotes for T181I and 1105delA mutations. Retrospectively, elevated levels of 17α-hydroxyprogesterone were found on blood spots from Guthrie’s test. There is no previous report of the combination of SW and premature pubarche due to mutations in the type II 3β-HSD gene. Because neonatal diagnosis could have prevented life-threatening crises in these girls, this report further supports the benefits for neonatal screening for congenital adrenal hyperplasia whatever the etiology.

scholarly journals Classic CAH Presenting in Adulthood: Experience From a Tertiary Care Hospital in Eastern India

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A124-A124
Author(s):  
Ipsita Mishra ◽  
Rukma Narkar ◽  
Vaibhav Pathak ◽  
Arun Kumar Choudhury ◽  
Anoj Kumar Baliarsinha
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Serum Testosterone ◽  
Pubic Hair ◽  
Care Hospital ◽  
Eastern India ◽  
Classic Cah ◽  
Biochemical Evaluation ◽  
Hydroxy Progesterone ◽  
21 Hydroxylase Deficiency

Abstract Classic CAH presenting in adulthood: Experience from a tertiary care hospital in Eastern India: Congenital adrenal hyperplasia(CAH) is one of the most common genetic disorders transmitted as an autosomal recessive trait. Of the various forms CAH due to 21-hydroxylase deficiency is most common. Based on the clinical phenotype CAH can be classified as classic and non-classic form. It is very rare for classic CAH to present in adulthood. We describe 3 patients with classic CAH presenting in adulthood. Case 1: 21 year old female presented with complaint of not attaining menarche. She had features of virilisation t with a modified Ferriman Gallwey(FG) score of 18/36, pubic hair stage 4 and atrophied breasts. Genital examination revealed clitoromegaly (CI-100 mm2) with Prader stage 2. Biochemical evaluation revealed elevated levels of serum testosterone (257.2 ng/dl), 17-hydroxy progesterone(332 ng/ml), DHEAS(417 µg/dl) and PRA of 34ng/ml/hr. Case 2: 30 year old female presented with complaint of primary infertility for 5 years. She had history of delayed menarche at 20 years and oligomenorrheic cycles since last 10 years. On examination there was hirsutism with a modified FG score of 15/36, pubic hair stage 5 with atrophied breasts. Genital examination revealed symmetrical genitalia with nonpalpable gonads, clitiromegaly(CI=135mm2) and a single urogenital opening (Prader stage 3). Biochemical evaluation revealed elevated levels of serum testosterone (812ng/dl), 17-hydroxy progesterone (164.8 ng/ml), DHEAS (503 µg/dl) and PRA of 42ng/ml/hr. Case 3: 26 year old female presented with complaint of noticing excessive hair growth in androgen dependent areas. On examination there was short stature,modified FG score 16/36, pubic hair stage 5 with atrophied breasts. Genital examination revealed clitoromegaly (CI=75mm2) with Prader stage 2. Biochemical evaluation revealed elevated levels of serum testosterone (254.2 ng/dl), 17-hydroxy progesterone (351.8 ng/ml), DHEAS (296.2 µg/dl) and PRA of 30ng/ml/hr. Karyotype in all the three patients was 46,XX. All our patients had serum testosterone values in tumorous range, however imaging studies didnot reveal any evidence of malignancy in the adrenals except for occurrence of a single right adrenal nodule of size 2×2.1cm with precontrast HU of <10 and absolute contrast washout of >60% in case 2. Based on clinical and biochemical findings a diagnosis of classic CAH was made. They were started on corticosteroid and mineralocorticoid replacement. In all of the above three patients none of them had been evaluated for the presenting complaints prior to visiting our centre. Failure of implementation of neonatal screening for CAH in many centres in India and the social stigma associated with genital ambiguity are contributory to the delay in diagnosis of CAH.

scholarly journals Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

2016 ◽  
Vol 174 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Brigitte Odenwald ◽  
Uta Nennstiel-Ratzel ◽  
Helmuth-Günther Dörr ◽  
Heinrich Schmidt ◽  
Manfred Wildner ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hospital Admissions ◽  
Discharge Summary ◽  
Severe Illness ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Classic Congenital Adrenal Hyperplasia ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

ObjectiveTo evaluate adrenal crises after the start of treatment up to the age of 6 years in children with classic congenital adrenal hyperplasia (CAH).DesignAnalysis of data extracted from a population-based prospective long-term follow-up study of children detected in neonatal screening.MethodsData of 102 Bavarian children with classic CAH due to 21-hydroxylase deficiency were analyzed, using parental questionnaires and medical reports. Parent-reported hospital admissions of children diagnosed with acute health impairment were included in the analysis if salt loss (hyponatremia) or hypoglycemia was documented in the discharge summary.ResultsA total of 74 children (72.5%) had no report of hospital admissions with salt loss or hypoglycemia during the observational period. However, in 27.5% of the children, 22 salt-wasting crises (seven of these also with low blood glucose) and 16 hypoglycemic episodes without salt loss were reported. Furthermore, the cumulative incidence for seizures was elevated; 13 children experienced seizures during hyponatremia or hypoglycemia. Most adrenal crises were triggered by infections, often with inappropriate emergency management, but in 11 cases hypoglycemia occurred unexpectedly, without evidence of severe illness and without any management errors. Frequency of adrenal crises was 6.5 per 100 patient years (95% CI: 4.6–8.8).ConclusionsCrisis prevention remains a permanent challenge for families and physicians caring for children with classic CAH. Expert care and compliance with emergency recommendations are crucial. Further research on the interactions among glucocorticoid deficiency, adrenomedullary dysfunction, and glucose metabolism is necessary for the prevention of hypoglycemia, especially in young CAH patients.

scholarly journals Nonvirilized Genitalia in 3 Female Newborns With the Salt-Wasting Congenital Adrenal Hyperplasia Phenotype

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Lauren Yauch ◽  
Allison Mayhew ◽  
Veronica Gomez-Lobo ◽  
Kim Shimy ◽  
Kyriakie Sarafoglou
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Cortisol Secretion ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Newborn Screen ◽  
Classic Cah ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a form of primary adrenal insufficiency characterized by impaired cortisol secretion and elevated androgen production, is the leading cause of atypical genitalia in the female newborn. Females with classic CAH, either salt-wasting or simple-virilizing form, usually present at birth with atypical genitalia ranging from clitoromegaly to male-appearing genitalia, due to in utero to elevated androgens (androstenedione and testosterone). Females with mild nonclassic CAH usually present with typical genitalia. Proving the importance of always keeping an open mind for exceptions to the rule, we report on 3 female newborns who presented with the nonvirilized genitalia, salt-wasting CAH phenotype and genotype most consistent with simple-virilizing CAH. It is only through a positive newborn screen identifying the females with CAH that they were diagnosed before developing adrenal and/or salt-wasting crisis.

scholarly journals Pitfalls of Prenatal Diagnosis guiding Postnatal Management in Congenital Adrenal Hyperplasia(CAH)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A150-A151
Author(s):  
Deepa Badrinath Murthy ◽  
Melissa Kaori Litao ◽  
Bina Cherryl Shah ◽  
Brenda Kohn ◽  
Emily Nicole Breidbart
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Urogenital Sinus ◽  
High Dose ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Postnatal Management ◽  
Genotype Phenotype Correlation ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

Abstract Background: 21-hydroxylase deficiency is the most common form of CAH and is associated with a variety of clinical phenotypes (salt wasting SW, simple virilizing SV and non-classic NCCAH). Commonly, there is a strong genotype-phenotype correlation for SW and NCCAH, but this is less predictable with the SV forms. We present a case with prenatal diagnosis of classic CAH which demonstrated genotype-phenotype discordance. Clinical Case: Ex 39 weeker female born to non-consanguineous parents was prenatally diagnosed with CAH based on routine genetic screen. Mother was noted to be a carrier for Intron 2G and father was a carrier of p.I172N both known to be pathogenic variants on CYP21A2. At 23 weeks gestational age, DNA analysis revealed fetus was compound heterozygous for both mutations which is most commonly associated with either SV or SW phenotype. At birth, infant had mild edema of the labia majora which resolved; the clitoris was not enlarged. There was no genital virilization or urogenital sinus. Newborn screen sent at 15 hours of life:17 OHP 132 ng/ml, repeat on DOL 3:77 ng/ml and DOL 13:59.9 ng/ml. High dose cosyntropin stim test on DOL 3 at 0 min: Cortisol not done, 17 OHP 1279 ng/dl; 60 min: Cortisol 12.3mcg/dl, 17OHP 3394 ng/dl. DOL 5 at 0 min: Cortisol 2.7 mcg/dl, ACTH 164.5 pg/ml, 17OHP 803.7 ng/dl; 60 minute: Cortisol 7.6mcg/dl, 17OHP 5920 ng/dl. Using available 17OHP normograms, the infant’s stimulated 17 OHP levels were not consistent with classic CAH. Unstimulated testosterone on DOL 3: 25ng/dl, DOL 5: 14 ng/dl. Ultrasound showed adrenal gland thickness 4mm bilaterally (upper limit of normal). Hydrocortisone (HC) was started on DOL 5 at 35 mg/m2/day after the stim test. On DOL 7, HC was increased to 100 mg/m2/day; fludrocortisone 0.1 mg twice daily and NaCl 0.5 g/day were started (Na 131, K 6.5, plasma renin activity 80.2). Upon discharge (DOL 13), infant was on HC 35 mg/m2/day, Fludrocortisone 0.1mg twice daily and NaCl 2g/day. Doses were adjusted accordingly during outpatient follow up. Currently infant is 4 months of age, thriving and remains on HC 11.3 mg /m2/day, Fludrocortisone 0.05 mg twice daily and NaCl 750 mg daily. Postnatal genetic analysis confirmed prenatal genotype. Conclusion: In general, genotype-phenotype correlation has 80–90% concordance. However clinicians should be aware of genotype/phenotype discrepancies that exist in order to carefully guide postnatal management based on prenatal genetic analysis. Our patient’s 17-ohp was done by LC/MS, which is standard now for most specialized endocrine laboratories. However, the 17-ohp nomograms for CAH, which are frequently used for subtype categorization, are based on RIA levels. Further studies would be helpful in creating an updated normogram using LCMS specifically for the neonatal period, as confirmatory screening of CAH will become more common with the rise in parental prenatal carrier screening.

scholarly journals Case Report:clinical experience of bilateral giant pediatric Testicular adrenal rest tumors with 3 Beta-Hydroxysteroid Dehydrogenase-2 family history

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lingyun Yu ◽  
Pengyu Chen ◽  
Wenbin Zhu ◽  
Junjie Sun ◽  
Shoulin Li
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Tumor Size ◽  
Hydroxysteroid Dehydrogenase ◽  
Endocrine Treatment ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Testicular Adrenal Rest Tumors ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

Abstract Background We reported a patient with Testicular adrenal rest tumors(TARTs) caused by congenital adrenal hyperplasia(CAH). TARTs occur frequently in CAH population with 21-hydroxylase deficiency(21-OHD). There are few reports of TARTs with 3β-hydroxysteroid dehydrogenase deficiency-2 (3β-2HSD).Furthermore,gaint TARTs are rarely mentioned in reported cases involving affected siblings. Case presentation A 14-year-old male patient was admitted by congenital adrenal hyperplasia with progressively increasing bilateral testicular masses.The Patient and his elder brother had been performed mutational and chromosome analysis and biopsy. Hormonal and anthropometric measurements were performed during endocrine treatments. We successfully performed surgery and excised two 83mm×46mm×44mm and 74mm×49mm×31mm tumors. Our pathology and immunochemistry tests have proven TARTs in patient. At first, both siblings received regular doses of hydrocortisone and fludrocortisones and tumor size regressed. During the one-year irregular intake due to Covid-19 pandemic, endocrine treatment became insensitive and tumor size slowly increased. The gene analysis reported two novel mutations C.776 C>T and C.674 T>A. The C.776 C>T is from father and has been reported. The C.674 T>A inherited from mother and cannot found in gene library and may related to TARTs. Conclusions This case illustrates inadequate hormone therapy could cause tumor enlargement. It is essential to seek for ultrasound examination once suspected scrotal mass occurred.It is necessary to adjust endocrine medicine or adopt surgery in refractory gaint TARTs. And presence of tunica vaginalis cavity may indicate the severity of TARTs in surgery.

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