Context:Patients with congenital adrenal hyperplasia (CAH) often suffer from long-term complications secondary to chronic glucocorticoid therapy and suboptimal treatment regimens.Objective: The aim of the study was to describe clinical characteristics of a large cohort of pediatric and adult CAH patients. Design and Setting:We conducted a cross-sectional study of 244 CAH patients [183 classic, 61 nonclassic (NC)] included in a Natural History Study at the National Institutes of Health. Main Outcome Measure(s):Outcome variables of interest were height SD score, obesity, hypertensive blood pressure (BP), insulin resistance, metabolic syndrome, bone mineral density, hirsutism (females), and testicular adrenal rest (TART). Results:The majority had elevated or suppressed androgens, with varied treatment regimens. Mean adult height SD score was Ϫ1.0 Ϯ 1.1 for classic vs. Ϫ0.4 Ϯ 0.9 for NC patients (P ϭ 0.015). Obesity was present in approximately one third of patients, across phenotypes. Elevated BP was more common in classic than NC patients (P Յ 0.01); pediatric hypertensive BP was associated with suppressed plasma renin activity (P ϭ 0.001). Insulin resistance was common in classic children (27%) and adults (38% classic, 20% NC); 18% of adults had metabolic syndrome. The majority (61%) had low vitamin D; 37% of adults had low bone mineral density. Hirsutism was common (32% classic; 59% NC women). TART was found in classic males (33% boys; 44% men). There is a wide spectrum of phenotypes determined by the residual 21-hydroxylase activity, with a continuum between the classic or severe form and the mild nonclassic (NC) form. The incidence of classic CAH ranges from 1 in 10,000 to 20,000 live births worldwide and is subclassified into salt-wasting (SW) and simple virilizing (SV), re- Conclusions

Extensive genetic analysis beyond targeted CYP21A2 mutational detection is often required to accurately determine genotype in patients with CAH due to the high frequency of complex genetic variation.

Photobiomodulation (PBM) is a clinically accepted tool in regenerative medicine and dentistry to improve tissue healing and repair and to restore the functional disability. The current in vitro study aimed to investigate the photobiomodulatory effects of 980 nm wavelength (the real energy at the target: ~0.9 W, ~0.9 W/cm 2 , 60 s, ~55 J/cm 2 and a single energy ~55 J in CW) on MC3T3-E1 pre-osteoblast, delivered with flattop profile in comparison to the standard profile. The laser groupings and their associated energies were: Group 1 - once per week (total energy 110 J); Group 2 - three times per week (alternate day) (total energy 330 J); Group 3 - five times per week (total energy 550 J). The metabolic activity and the osteoblasts maturation were analyzed by alkaline phosphatase assay, alizarin red S histological staining, immunoblot and/or double immunolabeling analysis for Bcl2, Bax, Runx-2, Osx, Dlx5, osteocalcin, and collagen Type 1. Our data, for the first time, prove that laser irradiation of 980 nm wavelength with flat-top beam profile delivery system, compared to standard-Gaussian profile, has improved photobiomodulatory efficacy on pre-osteoblastic cells differentiation. Mechanistically, the irradiation enhances the pre-osteoblast differentiation through activation of Wnt signaling and activation of Smads 2/3-βcatenin pathway.