We hypothesized that they may interfere with mineralocorticoid signaling and fludrocortisone therapy in patients with congenital adrenal hyperplasia (CAH) without effective glucocorticoid replacement and ACTH suppression.
A standard dose adrenocorticotropic hormone (ACTH) test revealed an inadequate cortisol response and high 17-hydroxy progesterone levels, suggesting simple virilising congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.
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).
A 23-year-old woman with CAH (21-hydroxyase deficiency) untreated for the past 5 years presented with a pelvic mass and elevated serum testosterone (1433 ng/dL) and plasma ACTH (1117 pg/mL).
Congenital adrenal hyperplasia (CAH) is a group of genetic disorders of adrenal steroidogenesis that impair cortisol synthesis, with compensatory increases in ACTH leading to hyperplastic adrenals.
To avoid giant CAH-associated adrenal myelolipomas in adults, it is important to identify CAH early so appropriate treatment can be initiated to interrupt the chronic adrenal hyperstimulation resulting from increased ACTH.
Carriers of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) demonstrate increased secretion of cortisol precursors following ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic corticotropin-releasing hormone (CRH) secretion.
The low adrenal cortisol levels associated with CAH affects the hypothalamic-pituitary-adrenal negative feedback system leading to increased pituitary adrenocorticotropic hormone (ACTH) production, which overstimulates the adrenal cortex in an attempt to increase cortisol production resulting in a hyperplastic adrenal cortex.
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.
Interestingly, the bilateral giant myelolipoma associated with CAH that had high androgen and ACTH levels but lacked MC2R and AR overexpression presented a significantly shorter AR allele compared with other tumors.
ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients.
Diagnosis of classical CAH is confirmed by follow-up serum 17-hydroxyprogesterone and/or the adrenocorticotropin stimulation test; however, neither test definitively distinguishes between the classical subtypes.
Traditional treatment of CAH consists of the suppression of ACTH through glucocorticoid replacement, in an attempt to reduce excessive androgen production.
ACTH stimulation test is widely used as a basic diagnostic method for non-classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD).
In congenital adrenal hyperplasia (CAH), decreased production of cortisol leads to increased secretion of ACTH from the pituitary, resulting in hyperplasia of the adrenals.
After ACTH testing, 13 out of the 32 (41%) cases displayed higher 17-hydroxyprogesterone (17-OHP) levels than normal but less than those found in patients affected by nonclassical adrenal hyperplasia (CAH); these levels were similar to those observed in obligate heterozygotes for CAH due to 21-hydroxylase deficiency (21-OHD).
The ACTH-stimulated delta 5-17P levels and delta 5-17P/F ratios in the PP children without type II 3 beta HSD gene mutation were exceedingly lower than the respective reported hormonal data for children with 3 beta HSD deficiency CAH with proven type II 3 beta HSD gene mutation.
The general feature of CAH, which results from an enzymatic block at any stage in the synthesis of cortisol, is increased serum adrenocorticotropin and thus stimulated adrenal synthesis of steroids proximal to the block.
In addition, the iv ACTH stimulation test revealed that the mother and the other unaffected sibling also carried an allele for an attenuated form of CAH.