The presentation of congenital adrenal hyperplasia in an unscreened population

Abstract

Background The aim of this study was to describe the incidence and spectrum of early clinical presentations of congenital adrenal hyperplasia (CAH) in an unscreened population. Methods A national retrospective observational study was undertaken to identify all children diagnosed with CAH in the Republic of Ireland, between January 2005 and December 2019. Reporting clinicians completed anonymized clinical questionnaires. Results There were 103 cases of CAH reported and 69 cases met the study inclusion criteria. The estimated annualized incidence of CAH in the Republic of Ireland was 1:14,754 or 0.07 cases per 1,000 live births. Forty-seven children presented clinically in the first six months of life, but only 17 of these had a confirmed diagnosis by day 10. Of these early presentations, there were 28 infants with salt-wasting, 15 females presented with virilized genitalia and four infants were detected due to a family history of CAH. Female infants presented at a median age of 0 days [IQR 0–1] and males at 14 days [IQR 9–21]. Seventy-eight percent of salt-wasting presentations occurred after day 10. Delays in clinical presentation, biochemical diagnosis and treatment initiation were identified. Conclusions The incidence of CAH is higher in Ireland than in other unscreened populations. In the absence of screening, clinicians should be aware of the possibility of CAH and appropriate investigations should be urgently requested. Life-threatening salt-wasting is the most frequent clinical presentation and many cases could be detected prior to decompensation if newborn screening were introduced.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Prior to inclusion of SCID on the panel earlier this year, a study showing its high prevalence in Ireland and the need for NBS was reported in 2021 [ 849 ]. Studies supporting the addition of other conditions have also been recently published including one on CAH and another on metachromatic leukodystrophy [ 850 , 851 ].…”

International Newborn Screening Practices for the Early Detection of Congenital Adrenal Hyperplasia

“…The value of NBS for CAH has been debated, and despite international endocrine societies recommending its use [2, 48], it is not currently universally adopted [3, 4, 6, 7, 28]. Screening for CAH significantly reduces the time to diagnosis [9, 10, 49] and thus has the potential to reduce mortality and morbidity.…”

“…Where screening programmes account for age at collection times with adjustment of 17OHP cutoffs, the number of early false positives will be reduced [31,32]. Screening later is attractive, as it reduces many of these confounding factors; however, allowing for the turnaround time, there is a risk that infants may present symptomatically if there is a delay in screening result, thereby reducing the potential benefits of NBS [28]. Screening programmes must also take into consideration other conditions within their NBS panel, ease of arranging NBS (e.g., where many infants are discharged early), local infrastructure (for transit of samples), and availability of laboratory resources, in order to appropriately balance the risks of false-positive results and the urgency to detect affected infants in their area.…”

“…In contrast, 17OHP levels progressively increase in affected infants [20]. If samples are collected too early after birth, more false-positive cases will be identified, whereas the value of screening is decreased if taken too late, as infants may present symptomatically [28]. Preterm infants, low birth weight infants, and unwell infants have been shown to have higher mean 17OHP values [20, 22], and for this reason gestational age or birth weight stratification is recommended [2].…”

Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway

“…In addition, enhanced ROS may contribute to the induction of autophagy in the retina. Another mechanism of mitochondrial dysfunction leading to DR is the formation of free radicals[ 14 - 17 ]. These reactive compounds may contribute to a switch in the metabolism, e.g.…”