Decreased Cortisol Secretion in Nonclassical 21-Hydroxylase Deficiency Before and During Glucocorticoid Therapy

Abstract

Objective: The Cortisol response in patients with nonclassical 21-hydroxylase deficiency (NC210HD) was assessed before and during hydrocortisone therapy and the findings were related to genotype. Design: Comparative study. Methods:The study sample comprised 41 patients (10 males) with NC210HD, divided into two groups according to the genetic analysis of the CYP21 gene: Group A carried two mild mutations (n = 29), and Group Β were compound heterozygotes for one mild and one severe mutation (n = 12). The 250 μg short ACTH test was performed at diagnosis. To evaluate the degree of treatment-induced suppression of adrenal function, 31 patients also underwent the 1 μg/1.73 m 2 ACTH test during hydrocortisone therapy. Basal and stimulated Cortisol levels and the increment in Cortisol response were compared between Groups A and Β and between the whole patient sample and healthy controls (32 subjects for the 250 μg test and 29 for the 1 μg/1.73 m 2 test). Results: The basal, stimulated, and incremental Cortisol levels were similar in Groups A and B; therefore, all the patients were considered together. At diagnosis, the basal Cortisol levels were similar in the patients and controls, but the stimulated and incremental Cortisol levels were significantly lower in the patients (p <0.001 for both). During hydrocortisone therapy, the patients had slightly higher basal Cortisol levels than the controls (p = 0.04), but significantly lower stimulated and incremental Cortisol levels (p <0.001 for both). Conclusions: Cortisol levels in NC210HD are similar in patients carrying two mild mutations and in compound heterozygotes for one mild and one severe mutation. Stimulated and incremental Cortisol levels in response to the short ACTH test might be decreased not only during but also before hydrocortisone therapy. Therefore, coverage with a stress dose of hydrocortisone during serious intercurrent illness or surgery is recommended in patients with NC210HD, especially those previously treated with corticosteroids. KEY WORDSCortisol, ACTH test, nonclassical 21-hydroxylase deficiency VOLUME 15, NO. 7, 2002 985 Brought to you by |

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

“…By suppressing ACTH production, glucocorticoids can normalise the excessive androgen production, also when it cannot be explained by cortisol deficiency, but rather the changed enzyme kinetics (80). The androgen levels may even be subnormal in both males and females (81,82).…”

Diseases associated with the low copy number of the <i>C4B</i> gene encoding C4, the fourth component of complement

“…On the other hand, even heterozygous carriers of 21-hydroxylase deficiency (healthy parents of CAH patients) exhibit a significantly lower mean 24-hour urinary free cortisol secretion than control subjects (Charmandari et al, 2004). The same observation was made for patients with non-classical 21-hydroxylase deficiency (Weintrob et al, 2002).…”

Clinical analysis of 78 patients with nonclassical 21-hydroxylase deficiency

“…In infertile patients with NC21OHD, dexamethasone is used to induce fertility before pregnancy. The goal of treatment is not glucocorticoid replacement (37), but rather to effectively suppress early morning ACTH and 17OHP concentrations to correct irregular menstrual cycles and other symptoms of adrenal androgen excess, such as acne, hirsutism, and infertility. Furthermore, serum 17OHP and androstenedione (A4) are the most commonly used indicators to evaluate the adequacy of glucocorticoid treatment in CAH, and 17OHP and androsterone levels in treated patients are generally recommended to remain above normal or slightly elevated (11).…”