Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia

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Aim: Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are frequent. The determinants of them have not yet been established. Objective: To establish the prevalence of adverse outcomes and to find determining factors for each of them. Design, patients, and methods: Cross-sectional monocentric study of 104 patients with childhood onset of CAH (71 women, 33 men). Analysis established first the determinants of clinical, hormonal, genetic variables and second a composite criterion for some of the outcomes and determinants. Results: BMI was above 25 kg/m 2 in 44% of the cohort, adrenal hyperplasia and/or nodules were present in 45% of the patients, and irregular menstrual cycles and hyperandrogenism were found in 50 and 35% of the women respectively. In univariate analysis, the determinants of these outcomes were all linked to disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione concentrations. Low weight was a determinant of abnormal bone mineral density (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36% of the men). Total cumulative glucocorticoid dose was a determinant of BMI and TART, whereas fludrocortisone dose was a determinant of TART (PZ0.03). In men, the composite criterion was associated with androstenedione concentration and CF. In women, the composite criterion was associated with total testosterone concentration. Conclusion:The present study confirms the high prevalence of adverse outcomes in CAH patients. These are, most often, related to disease control. The impaired health status of adults with CAH could therefore be improved through the modification of treatment.

Section: Discussionsupporting

confidence: 88%

Determining clinical and biological indicators for health outcomes in adult patients with childhood onset of congenital adrenal hyperplasia

Bachelot¹,

Golmard²,

Jérôme³

et al. 2015

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“…However, high progesterone levels could contribute to female infertility 35 . In a case-control study of 16 women with classic CAH, those patients with a low LH pulse amplitude and frequency had higher progesterone levels and worse hormonal control than those with LH pulsatility similar to normal controls 36 . Further studies investigating the relevance of high progesterone in CAH and its impact on fertility are needed.…”

Section: Discussionmentioning

confidence: 93%

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Debono

Mallappa

Gounden

et al. 2015

Objectives The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing’s syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods Twenty-four hour serum sampling for corticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, dehydroepiandrosterone (DHEA), testosterone, progesterone and 24-hour urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration were calculated. Results A significant rhythm was confirmed for ACTH (r2 0.95;P<0.001), 17OHP (r2 0.70; P=0.003), androstenedione (r2 0.47;P=0.043), androsterone (r2 0.80;P<0.001), testosterone (r2 0.47;P=0.042) and progesterone (r2 0.64;P=0.006). The mean (SD) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone [4.3(2.3) and 9.7(3.5) hours], evening prednisone [4.5(2.0) and 10.3(2.4) hours], and daily dexamethasone [9.2(3.5) and 16.4(7.2) hours]. AUC0-24hr progesterone, androsterone and 24-hour urine pdiol were significantly related to 17OHP. Conclusion In CAH patients adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.

“…Several factors (androgen and progesterone overproduction and prenatal exposure to sexual steroid) are suspected to disturb the reproductive axis in CAH females. A recent study has described LH pulsatility in women with classic CAH (35). No differences have been observed between patients and controls in terms of mean LH levels, LH pulse amplitude or LH frequency.…”

Section: Female Fertilitymentioning

confidence: 94%

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

Bachelot

Grouthier

Courtillot

et al. 2017

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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.