Effect of hydrocortisone dose schedule on adrenal steroid secretion in congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive disorders caused by a reduced or absent enzymatic activity at one of the stages of adrenal steroid biosynthesis. Prenatal exposure to androgens leads to external genital masculinization of the affected female child. In pregnancy, the provider may be optimizing care for the woman with CAH or targeting treatment to reduce virilization in the affected unborn child. For the affected adult woman the goals of therapy in pregnancy are to prevent adrenal insufficiency, reduce fetal exposure to androgens and glucocorticoids and to avoid damage to reconstructed genitalia. For prenatal therapy for prevention of virilization of possibly affected female children, dexamethasone is used. However, questions remain about the efficacy and safety of exposing 7/8 unaffected children in the first trimester. Prenatal treatment should only be undertaken after careful discussion with the parents of the risks and benefits in an experienced centre or as part of a research protocol.

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THE ADRENAL SUPPRESSIVE EFFECT OF HYDROCORTISONE IN CONGENITAL ADRENAL HYPERPLASIA (CAH) IS NOT AFFECTED BY VARYING THE DOSE SCHEDULE

Pediatric Research ◽

10.1203/00006450-198404001-00521 ◽

1984 ◽

Vol 18 ◽

pp. 180A-180A

Author(s):

J Winterer ◽

G P Chrousos ◽

D L Loriaux ◽

G B Cutler

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Dose Schedule ◽

Suppressive Effect ◽

Adrenal Hyperplasia

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Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2019-00547 ◽

2019 ◽

Vol 104 (11) ◽

pp. 5065-5072 ◽

Cited By ~ 5

Author(s):

Manon Engels ◽

Karijn J Pijnenburg-Kleizen ◽

Agustini Utari ◽

Sultana M H Faradz ◽

Sandra Oude-Alink ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Clinical Signs ◽

Adrenal Hyperplasia ◽

Blood Concentrations ◽

Adrenal Steroid ◽

17 Hydroxyprogesterone ◽

Cortisol Deficiency ◽

Steroid Precursor

Abstract Context and Objective We describe the clinical features and biochemical characteristics of a unique population of severely affected untreated patients with congenital adrenal hyperplasia (CAH) from an Indonesian population with proven cortisol deficiency but without clinical signs of cortisol deficiency. We evaluated the in vitro glucocorticoid activity of all relevant adrenal steroid precursors occurring in patients with CAH. Design Cross-sectional cohort study and translational research. Intervention/Main Outcome Measures Adrenal steroid precursor concentrations before and 60 minutes after ACTH administration to 24 untreated patients with CAH (3 to 46 years) with proven cortisol deficiency (<500 nmol/L post-ACTH) measured by liquid chromatography–tandem mass spectrometry were compared with six control patients (Mann-Whitney U test). Glucocorticoid receptor (GR) activation was determined by dual-luciferase assays in human embryonic kidney cells transfected with the GR and exposed to increasing amounts of adrenal steroid precursors for 24 hours. Results Blood concentrations of the steroid precursors 11-deoxycortisol (457 nmol/L, P = 0.003), 11-deoxycorticosterone (55 nmol/L, P = 0.003), 17-hydroxyprogesterone (610 nmol/L, P < 0.001), progesterone (29 nmol/L, P < 0.001), and 21-deoxycortisol (73 nmol/L) were strongly elevated compared with control subjects. The GR was activated with comparable potency to cortisol by corticosterone and 21-deoxycortisol or with 4 to 100 times lower potency by 11-hydroxyprogesterone, 11-deoxycortisol, aldosterone, 11-deoxycorticosterone, progesterone, and 17-hydroxyprogesterone. Conclusions We identified strongly elevated adrenal steroid precursor concentrations in blood from untreated patients with CAH and demonstrated glucocorticoid activity of these adrenal precursors in vitro, suggesting a possible role of these precursors in the clinical phenotype of these patients. Further studies are necessary to evaluate the role of these precursors in more detail.

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Reproductive outcome of a patient with congenital adrenal hyperplasia: case report

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20184171 ◽

2018 ◽

Vol 7 (10) ◽

pp. 4297

Author(s):

Bhagyashree A. ◽

Shylaja A. S. ◽

Yashaswini Srikonda

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Autosomal Recessive ◽

Prenatal Testing ◽

Perioperative Period ◽

Adrenal Hyperplasia ◽

Androgen Excess ◽

Adrenal Steroid ◽

History Of ◽

Stress Dose

Congenital Adrenal Hyperplasia are a group of inherited autosomal recessive enzymatic defects of adrenal steroid biosynthesis. Low pregnancy rate has been reported in women with CAH. Several factors have been suggested to contribute to this subfertility such as androgen excess, adrenal progesterone hyper secretion, consequences of genital reconstructive surgery, secondary PCOS and psychosexual factors. In contrast to this subfertility, pregnancies are normal and uneventful. During pregnancy, maternal & fetal problems are confined to these deficiencies. Adequate glucocorticoid therapy and improvement of surgical and psychological management could contribute to optimize fertility in CAH. The interposition of the placenta on the HPA axis & other endocrine changes during pregnancy impact considerably on the clinical evaluation of CAH. A 21 years old Primigravida presented to us at 13 weeks of gestation with history of CAH on treatment and vaginoplasty done in the childhood. Endocrinologist opinion was taken, and steroids continued. Advised to meet genetist and follow up for prenatal testing. But patient denied. Antenatal period was uneventful. Patient underwent Emergency LSCS in view of CPD in labour at 36+6 weeks of gestation. Pre-op stress dose of steroid given. A girl baby of birth weight 2.13 kg was born with good Apgar scores. Perioperative period uneventful. Preconception health, including hormonal, psychosexual and anatomical barriers to fertility should be addressed early in women with CAH. This review provides fertility outcome and pregnancy issues of a woman with CAH.

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The Incidence of Associated Anomalies in 105 Patients with Congenital Adrenal Hyperplasia

PEDIATRICS ◽

10.1542/peds.49.4.608 ◽

1972 ◽

Vol 49 (4) ◽

pp. 608-610 ◽

Cited By ~ 1

Author(s):

Rebecca T. Kirkland ◽

John L. Kirkland ◽

Leon Librik ◽

George W. Clayton

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Failure To Thrive ◽

Ambiguous Genitalia ◽

Associated Anomalies ◽

Adrenal Hyperplasia ◽

Electrolyte Metabolism ◽

Developmental Anomalies ◽

Adrenal Steroid ◽

Common Defect

A survey of 105 patients with defective adrenal steroid 21-hydroxylation, the most common defect in congenital adrenal hyperplasia, has been carried out to determine the presence of additional congenital or developmental anomalies. The following is a report of this survey. The diagnosis of congenital adrenal hyperplasia was suspected in infants who presented with ambiguous genitalia or with defect in electrolyte metabolism manifested by failure to thrive, vomiting and dehydration with hyponatremia and hyperkalemia. Measurement of elevated levels of urinary 17-ketosteroids, 11-keto pregnantriol and pregnantriol confirmed the diagnosis. Seventy-two (68.6%) of the 105 patients surveyed demonstrated defects in electrolyte metabolism and 39 of these were males.

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High aldosterone and cortisol levels in salt wasting congenital adrenal hyperplasia: a clinical conundrum

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0166 ◽

2017 ◽

Vol 30 (12) ◽

Cited By ~ 2

Author(s):

Sirisha Kusuma Boddu ◽

Sheeja Madhavan

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Cross Reactivity ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Adrenal Steroid ◽

Wasting Syndrome ◽

Serum Aldosterone ◽

Diagnostic Confusion ◽

Cortisol Levels ◽

17 Hydroxyprogesterone

AbstractBackground:Salt wasting syndrome (hyponatremia, hyperkalemia, dehydration, metabolic acidosis) in early infancy could be caused by either mineralocorticoid deficiency as in congenital adrenal hyperplasia (CAH) and adrenal insufficiency or mineralocorticoid resistance as in pseudohypoaldosteronism (PHA). In salt wasting CAH, serum aldosterone and cortisol levels are expected to be low. Cross reactivity between high levels of adrenal steroid precursors and aldosterone has recently been reported resulting in elevated aldosterone levels in CAH, leading to difficulty in differentiating between CAH and PHA.Case presentation:We report four such cases of salt wasting CAH, where high aldosterone levels and high normal cortisol levels led to initial diagnostic confusion with PHA. Diagnosis of CAH was later established on the basis of significantly elevated adrenocorticotropic hormone (ACTH) stimulated 17-hydroxyprogesterone (17-OHP) values.Conclusions:By reporting these cases we draw attention to the possibility that high levels of adrenal steroid precursors can cross react with aldosterone and cortisol, and underscore the significance of ACTH stimulated 17-OHP values in differentiating CAH and PHA.

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