17-hydroxyprogesterone Levels Research Articles

Hyperinsulinemic-Euglycemic Clamp Strengthens the Insulin Resistance in Nonclassical Congenital Adrenal Hyperplasia.

Insulin sensitivity evaluation by hyperinsulinemic-euglycemic clamp in nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxilase deficiency. Cross-sectional study at university hospital outpatient clinics. NC-CAH patients (25 females, 6 males; 24 ± 10 years) subdivided into C/NC (compound heterozygous for 1 classical and 1 nonclassical allele) and NC/NC (2 nonclassical alleles) genotypes were compared to controls. At diagnosis, C/NC patients presented higher basal and adrenocorticotropin-stimulated 17-hydroxyprogesterone and androstenedione levels than NC/NC genotype. Patients and controls presented similar weight, body mass index, abdominal circumference, and total fat body mass. NC-CAH patients showed higher waist-to-hip ratio, lower adiponectin and lower high-density lipoprotein cholesterol levels with no changes in fasting plasma glucose, glycated hemoglobin, homeostatic model assessment for insulin resistance, leptin, interleukin 6, tumor necrosis factor alpha, C-reactive protein, and carotid-intima-media thickness. All patients had used glucocorticoid (mean time of 73 months). Among the 22 patients with successful clamp, 13 were still receiving glucocorticoid-3 patients using cortisone acetate, 9 dexamethasone, and 1 prednisone (hydrocortisone equivalent dose of 5.5mg/m²/day), while 9 patients were off glucocorticoid but had previously used (hydrocortisone equivalent dose of 5.9mg/m2/day). The NC-CAH patients presented lower Mffm than controls (31 ± 20 vs 55 ± 23µmol/min-1/kg-1, P = 0.002). The Mffm values were inversely correlated with the duration of glucocorticoid treatment (r = -0.44, P = 0.04). There was association of insulin resistance and glucocorticoid type but not with androgen levels. Using the gold standard method, the hyperinsulinemic-euglycemic clamp, insulin resistance was present in NC-CAH patients and related to prolonged use and long-acting glucocorticoid treatment. Glucocorticoid replacement and cardiometabolic risks should be monitored regularly in NC-CAH.

The results of therapy of congenital adrenal hyperplasia in children in perm region

Background. Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. About 90% of all children with CAH have 21-hydroxylase deficiency which is required for the synthesis of glucocorticoids and mineralocorticodes. The salt-wasting form of CAH develops with a deficiency of both types of hormones. This form of CAH results in infant death if not treated, therefore early disease detection and start of treatment are very important.
 Aim of research is to study the clinical features of the course of the disease and evaluate the treatment efficacy of children with salt-wasting form of CAH in the Perm region.
 Materials and methods. We conducted an analysis of the clinical features of the salt-wasting form of CAH in 40 children of the Perm region. To evaluate the treatment efficacy following symptoms were analyzed: salty food craving, hyperpigmentation of skin, hirsutism, delayed or accelerated growth, etc. and parameters of water-electrolytic balance, the level of 17-hydroxyprogesterone, adrenocorticotropic hormone, renin.
 Results and discussion. Despite the modern possibilities of diagnosing and treating CAH, the complete control of the disease cant be achieved in all children. Almost all the children examined had either symptoms of replacement therapy failure or overdose symptoms. Hormonal imbalance disorders were performed by a few children without any symptoms of the disease.
 Conclusion. During our research we concluded that young children often have issues with an overdose of hormonal drugs and frequent occurrence of salt-wasting crises against the background of associated diseases, while for teenagers, problems associated with an insufficient dose of glucocorticoid drugs are relevant. Also, significant difficulties in the treatment of children with CAH are associated with the short action of hydrocortisone. One way to solve these problems is to organize a school for parents of children with CAH. Creating motivation, explaining the principles of treatment and importance of regular taking of drugs, as well as algorithm in medical emergency is an important step in achieving control for the disease.

The Effect of Glucocorticoid therapy on Bone Mineral Density in Children and Adolescents with Congenital Adrenal Hyperplasia

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases caused by a deficiency in adrenal enzymes that lead to changes in cortisol and aldosterone levels. Objective: This study aimed to assess the bone mineral density of the spine and femoral head in children and adolescents aged 5 and 20 years, suffering from different types of congenital adrenal hyperplasia and treated with corticosteroids and to study the associated factors. Materials and method: We studies 44 patients, 26 girls and 18 boys, who were treated with corticosteroids with a physiological dose of 15-20 mg/m2 since infancy. A questionnaire was completed by patients and their parents admitted to the Endocrinology Clinic of Imam Reza Hospital of Mashhad. The patients' bone density was then measured, and the association with different factors, such as age, gender, height, weight, type of CAH, type and duration of receiving corticosteroids, the 17-hydroxyprogesterone level, bone activity markers, vitamin D level, and puberty stage, was analyzed, using SPSS software. Result: No significant correlation between the bone density level and variables such as the duration and dose of corticosteroid consumption, age, sex, time of diagnosis, 17-hydroxyprogesterone level, calcium, and phosphorus, was found. Other variables such as height, weight, puberty stage, and vitamin D levels were found to play a significant role in determining the bone density level.Conclusion: It is highly recommended to consider the side effects and complications when starting treatment with corticosteroids in patients with CAH. Bone densitometry should regularly be done, osteoporosis prophylaxis should be considered using weight-bearing exercises and calcium and vitamin D supplements, and the level of vitamin D should be monitored.

Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia

Children with salt-wasting congenital adrenal hyperplasia (CAH) have an impaired function of steroid synthesis pathways. They require therapy with glucocorticoid (GC) and mineralocorticoid hormones to avoid salt-wasting crisis and other complications. Most commonly, children receive hydrocortisone thrice daily with the highest dose in the morning, mimicking the regular physiology. However, reverse circadian treatment (RCT) had been suggested previously. In this study, we aimed to determine the efficacy of RCT in prepubertal children with CAH by comparing the salivary 17-hydroxyprogesterone (s17-OHP) levels individually. In this retrospective study, we analyzed the records of children with classical CAH and RCT who were monitored by s17-OHP levels. The study included 23 patients. We identified nine prepubertal children with RCT schemes (three boys and six girls) and compared the s17-OHP levels in the morning, afternoon, and evening. The objective of this study was to demonstrate the non-effectiveness of RCT in terms of lowering the morning s17-OHP concentration. In addition, we compared s17-OHP day profiles in six patients on RCT and non-RCT therapy (intraindividually). Eight of nine children with RCT showed higher s17-OHP levels in the morning compared to the evening. In addition, none of the children showed a significant deviation of development. Three children were overweight. No adrenal crisis or pubertal development occurred. Comparison of RCT and non-RCT regimens showed no difference in 17-OHP profiles. Our data do not support the use of RCT schemes for GC replacement in children with CAH due to lack of benefits and unknown long-term risks.

Некласична вроджена гіперплазія кори надниркових залоз унаслідок дефіциту 21-гідроксилази: лабораторні критерії діагностики й контролю ефективності лікування (частина 2)

Некласична вроджена гіперплазія кори надниркових залоз (НВГКНЗ) унаслідок дефіциту 21-гідроксилази є однією з актуальних причин гіперандрогенних проявів у різні вікові проміжки часу. Своєчасна діагностика цього захворювання потребує обов’язкового включення визначення базальних рівнів 17-оксипрогестерону (17-ОПГ) у комплексне обстеження пацієнтів різних вікових груп із клінічними проявами надлишку андрогенів. Особливо це важливо при обстеженні дівчаток-підлітків і жінок репродуктивного віку з клінікою гіперандрогенії. В обов’язковий комплекс обстеження жінок при встановленні діагнозу синдрому полікістозних яєчників має входити виключення некласичної ВГКНЗ відповідно до всіх світових рекомендацій. При отриманні рівнів 17-ОПГ у діапазоні 2–10 нг/мл необхідно провести пробу з козинтропіном, що визнана у світі як стандарт діагностики ВГКНЗ. Діагностичним порогом постановки діагнозу ВГКНЗ унаслідок дефіциту 21-гідроксилази є рівень 17-ОПГ, базальний чи стимульований у пробі, понад 10 нг/мл. Проведення генетичного тестування — визначення мутацій у гені CYP21A2 — є важливим і необхідним інструментом не тільки підтвердження діагнозу, але й визначення тактики лікування пацієнта з діагнозом некласичної ВГКНЗ і виявлення ризиків появи класичної форми в майбутньої дитини за наявності алелі, пов’язаної з класичною формою вродженої дисфункції кори надниркових залоз у майбутніх батьків. За основу лабораторних критеріїв постановки діагнозу взято рекомендації останнього керівництва Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline, 2018.

Некласична вроджена гіперплазія кори надниркових залоз унаслідок дефіциту 21-гідроксилази: лабораторні критерії діагностики й контролю ефективності лікування

Некласична вроджена гіперплазія кори надниркових залоз (НВГКНЗ) унаслідок дефіциту 21-гідроксилази є однією з актуальних причин гіперандрогенних проявів у різні вікові проміжки часу. Своєчасна діагностика цього захворювання потребує обов’язкового включення визначення базальних рівнів 17-оксипрогестерону (17-ОПГ) у комплексне обстеження пацієнтів різних вікових груп із клінічними проявами надлишку андрогенів. Особливо це важливо при обстеженні дівчаток-підлітків і жінок репродуктивного віку з клінікою гіперандрогенії. В обов’язковий комплекс обстеження жінок при встановленні діагнозу синдрому полікістозних яєчників має входити виключення некласичної ВГКНЗ відповідно до всіх світових рекомендацій. При отриманні рівнів 17-ОПГ у діапазоні 2–10 нг/мл необхідно провести пробу з козинтропіном, що визнана у світі як стандарт діагностики ВГКНЗ. Діагностичним порогом постановки діагнозу ВГКНЗ унаслідок дефіциту 21-гідроксилази є рівень 17-ОПГ, базальний чи стимульований у пробі, понад 10 нг/мл. Проведення генетичного тестування — визначення мутацій у гені CYP21A2 — є важливим і необхідним інструментом не тільки підтвердження діагнозу, але й визначення тактики лікування пацієнта з діагнозом некласичної ВГКНЗ і виявлення ризиків появи класичної форми в майбутньої дитини за наявності алелі, пов’язаної з класичною формою вродженої дисфункції кори надниркових залоз у майбутніх батьків. За основу лабораторних критеріїв постановки діагнозу взято рекомендації останнього керівництва Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline, 2018.

Management of Fully Pubertal Girls With Nonclassical Congenital Adrenal Hyperplasia: Glucocorticoids Versus Oral Contraceptives

ObjectiveTo compare clinical outcomes of 3 treatment regimens—glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both—administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved. MethodsA retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit. ResultsAt baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P < .001), testosterone (P < .01), and 17-hydroxyprogesterone (P < .01) levels was observed only in the OC group. ConclusionIn girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.

The validity of the Bayley-Pinneau method in predicting final adult height at the onset of puberty in patients with classic congenital adrenal hyperplasia.

The final adult height (FAH) of patients with congenital adrenal hyperplasia (CAH) is often lower than the predicted adult height (PAH) using the Bayley-Pinneau (B&P) method. The aim of the current work was to test the validity of B&P in predicting FAH from a bone age (BA) measurement performed at onset of puberty. This was a retrospective longitudinal observational convenience single-centre study. The study included 54 patients (male and female) with classic CAH, whether salt-wasting (SW) or simple virilising (SV), who had reached FAH. The results of auxological measurements and hormonal data around the time of puberty were retrieved from files. Predicted adult height (PAH) was calculated from a BA taken at onset of puberty and compared with FAH. The median PAH SDS at the onset of puberty (-1.5) was significantly greater than the median FAH SDS (-2.2) (p < 0.001). The median target height SDS (-0.8) was significantly higher than the median FAH SDS (-2.2) (p < 0.001). FAH and FAH SDS were significantly worse in females (150.36 ± 7.23; -2.05 ± 1.13) than in their male counterparts (162.86 ± 3.30; -1.53 ± 0.51) (p value < 0.001; 0.048). In patients with good control, there was no difference between PAH SDS (-1.7) and FAH SDS (-1.5) (p value = 0.37). In patients with poor control (over- or under-treated) FAH SDS (-2.1) was significantly lower than PAH SDS (-1.4) (p value < 0.001). The B&P method was able to accurately predict FAH in children with classic CAH, who were medically well controlled (based on 17-hydroxyprogesterone levels), but overestimated it by a significant 0.7 SD in poorly-controlled patients.

Disorders of Sex Development.

Disorders of Sex Development.

Genetic aetiology of primary adrenal insufficiency in Chinese children

BackgroundPrimary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.MethodsSeventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.ResultsAmong the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein.ConclusionsWe found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.

Congenital adrenal hyperplasia in men: classical form. Clinical case

Recently, in the foreign scientific literature there have been reports that boys and young men with the classic virile form of congenital adrenal hyperplasia or congenital dysfunction of the adrenal cortex as a result of inadequate glucocorticoid therapy in 21–28% of cases have testicular adrenal rest tumors, which increases under the influence of excessive production of adrenocorticotropic hormone (ACTH). This benign formation up to 2 cm in diameter and larger is detected by palpation and ultrasound. The formations can press on the testicular tissue and lead to hypogonadism. Such individuals may have low testosterone levels due to decreased Leydig cell function. Testicular adrenal rest tumors usually decrease after treatment optimization. Unreasonable surgery is sometimes performed in suspected cancer. A clinical case is presented of the classic form of congenital adrenal hyperplasia, manifested itself in isosexual precocious puberty, cryptorchidism and testicular adrenal rest tumors rare, increased under the influence of excessive ACTH production as a result of inadequate glucocorticoid replacement therapy. Formations detected during ultrasound decrease when treatment is optimized. Observation of the patient in the dynamics showed that ones of the main diagnostic hormonal tests are blood levels of ACTH and 17-hydroxyprogesterone, which at the time of disease detection were excessively high. Continuous glucocorticoid replacement therapy maintains the level of these indicators within the reference values. Timely diagnosis of the nature of the pathology, constant corrective hormone therapy ensured the patient’s ability to adapt to life and society in accordance with his status. Clinical manifestations of hypocorticism and/or hyperandrogenism in the parents of our patient were not detected, which indicates autosomal recessive inheritance of congenital adrenal hyperplasia. In the future, it is important to provide genetic counseling to expectant parents, especially with manifestations of hyperandrogenism, to assess the possible development of such pathology in their offspring.

Is there an association between prostate-specific antigen and androgen levels in 46, XX patients with congenital adrenal hyperplasia?

Congenital adrenal hyperplasia (CAH), a genetic disease characterized by defective cortisol synthesis and excessive levels of sex hormones, can cause precocious puberty in both sexes in untreated individuals and virilization in female patients with a 46, XX karyotype. The female paraurethral (Skene's) gland has been reported as prostate analogous. Growth of prostate tissue is associated with androgen production; therefore, prostate-specific antigen (PSA) levels may represent a marker of virilization in 46, XX patients with CAH. To describe PSA levels in 46, XX patients and evaluate whether higher PSA levels are associated with androgenization and the severity of the disease. Sixty-six patients with CAH and a 46, XX karyotype were included, irrespective of age. Serum PSA, testosterone, 17-hydroxyprogesterone (17-OHP) and androstenedione levels were measured. Patients' age, age at diagnosis, forms of the disease, Prader classification, bone age assessment, sex of rearing, surgery, and the presence of clinical complications were obtained from their medical records. The mean age of patients was 11.45±10.74 years. Forty-three patients (65%) were diagnosed neonatally at a median of 0.08 years (mean 1.47±2.34 years), with registers of 17-OHP measurements (Guthrie test) being available in 51%. Testosterone, 17-OHP and androstenedione were significantly high. PSA was detectable in 25% of cases (levels >0.01ng/ml), with a mean of 0.03±0.09ng/ml, and only in patients over five years of age. A correlation was found between PSA and age (p<0.001), age at diagnosis (p=0.002), testosterone (p=0.001) and androstenedione (p=0.023). There was no correlation between PSA and the forms of CAH or Prader classification. A sub-analysis of the patients over five years of age in whom PSA was detectable also showed that there was a correlation between PSA (p<0.05) and age at analysis, age at diagnosis, testosterone and androstenedione levels. Limitations of this study include the small sample size due to the rareness of the disease, its retrospective nature, the absence of a control group, the fact that the sample was selected at two referral centers, which could have resulted in a selection bias, and the use of different reference values in the different laboratories conducting the PSA tests. PSA is detectable in 25% of 46, XX patients with CAH, only after five years of age. PSA level increases significantly with age, age at diagnosis, and testosterone and androstenedione levels, confirming a correlation between PSA levels and elevated androgen levels.

Virilization Secondary to an Ovarian Leydig Cell Tumor

A 60-year-old female presented with a three-year history of virilizing symptoms including facial hirsutism and deepening of voice. Her medical history was significant for renal transplantation with immunosuppressive therapy consisting of mycophenolate, cyclosporine, and low-dose prednisone. She was noted to have temporal balding and darkly pigmented terminal hair on the upper lip, cheeks, chin, shoulders, and sternum. Pelvic examination revealed clitoromegaly. Menarche occurred at age 12 with regular menstrual cycles until menopause which occurred at age 50. She had two pregnancies: a miscarriage followed by a successful pregnancy.Labs revealed an elevated total testosterone of 530 ng/dL (< 60 ng/dL), free testosterone 14.8 ng/dL (<0.87 ng/dL), androstenedione 2140 ng/dL (<200 ng/dL), and 17-hydroxyprogesterone 704 ng/dL (<285 ng/dL). LH, FSH, and estradiol were inappropriately normal in this post-menopausal female. Prolactin, TSH, DHEA-S, IGF-1 were within normal limits. Transvaginal ultrasound found a 2 cm hypoechoic right ovarian mass which was confirmed on MRI. MRI also revealed a 5 mm right adrenal nodule. Tumor markers including CA-125, Inhibin A, Inhibin B, HCG, and AFP were within normal limits. Dexamethasone suppression testing did not lower the testosterone level. 17-hydroxyprogesterone level after cosyntropin stimulation testing was 704 ng/dL (<1000 ng/dL). The patient underwent laparoscopic bilateral oophorectomy and salpingectomy, pelvic washout and omental biopsy. Pathology was consistent with a benign Leydig cell tumor. Following oophorectomy there was complete normalization of the total testosterone level (15 ng/dL, n< 60 ng/dL).A thorough history and physical exam is vital in determining the cause of hirsutism. Medications, including over-the-counter and herbal formulations should be carefully reviewed. Although cyclosporine has been associated with hirsutism, patients typically present with vellus hair formation in the affected areas rather than darkly pigmented terminal hair. In this case, hirsutism progressively worsened following menopause and physical examination was significant for virilization. Hirsutism in a combination with virilization is typically neoplastic in nature. Endogenous androgen production can originate from either the adrenal glands or ovaries. In our patient, with workup showing both ovarian and adrenal as potential sources of endogenous androgen production, an adrenal cause was excluded due to a normal DHEA-S level at baseline and a lack of suppression of testosterone after dexamethasone suppression testing. As a result, the source was localized to the ovary. While excessive androgen production resulting in virilization is seen with ovarian tumors, Leydig stromal cell tumors are extremely rare and account for less than 0.1% of all ovarian tumors.

What Cut-off Value of 17-Hydroxyprogesterone Should Be an Indication to Perform a 250 µg Cosyntropin Stimulation Test When NCCAH Is Suspected? - a Retrospective Study

The Nonclassic Congenital Adrenal Hyperplasia (NCCAH) is a less severe form of CAH in which the activity of the 21-hydroxylase is estimated at about 20% to 50%. Cosyntropin stimulation test is the gold diagnostic standard used to test for this condition. The study was aimed at verifying the currently accepted threshold of 17-hydroxyprogesterone (17OHP) level (≥2.0 ng/mL) at which cosyntropin stimulation test should be performed. Material and methods. The study included 343 patients (328 females and 15 males) referred for a cosyntropin stimulation test due to suspected NCCAH. The median age at the time of evaluation was 27 years. Serum 17-OHP was measured with ELISA assay using Ledect96 Microplate Reader. The NCCAH diagnosis was made if cosyntropin-stimulated 17OHP level exceeded 10.0 ng/mL. The ROC curve was determined, and the cut-off point with the highest sensitivity and specificity was established. The study was approved by the Ethics Board of JUMC. Results:. Symptoms, which prompted testing for NCCAH, most often were: hirsutism in 187 patients, irregular menstrual cycles in 178 patients, and acne in 138 patients. A total of 79 patients (77 females and two males) were diagnosed with NCCAH based on cosyntropin stimulation test results. Seventy-one of them had baseline levels of 17OHP≥2.0 ng/mL. The mean age of patients with confirmed NCCAH was 28.86 years. The baseline 17OHP cut-off value that qualified patients best for testing was 2.79 ng/mL in our group, with sensitivity and specificity of 77.2% and 91.3%, respectively. The sensitivity and specificity for a guideline-recommended cut-off point (17OHP ≥2.0 ng/mL) was 86.1% and 76%, respectively. In five of six patients with secondary amenorrhea and a baseline level of 17OHP ≥2.0 ng/mL, NCCAH was confirmed in a cosyntropin stimulation test. Conclusions:. Our results suggest considering an upward shift in the 17OHP threshold at which patients suspected for NCCAH should be referred for further evaluation. This may reduce the number of unnecessary cosyntropin stimulation tests, mainly that patients with mild phenotype (or asymptomatic) frequently may not require any treatment. However, attention should be paid to patients with coexisting secondary amenorrhea and 17OHP levels ≥2.0 ng/mL, which may be a clinical predictor of NCCAH.

Large Bilateral Adrenal Myelolipomas in the Setting of Congenital Adrenal Hyperplasia

Adrenal myelolipomas (AMLs) are rare benign adrenal tumors containing adipose and hematopoietic tissue, with a reported incidence of 0.08 to 0.4% on autopsy. AMLs are the second most common primary adrenal incidentaloma. Congenital adrenal hyperplasia (CAH) is associated with 10% of analyzed AML cases, half of which are bilateral in CAH patients.This is a 40-year old male with CAH diagnosed shortly after birth, due to 21-hydroxylase deficiency. He was doing well on a maintenance dose of hydrocortisone 20mg PO qAM and 10mg PO qPM and fludrocortisone 0.2mg PO daily until two years ago when he was incidentally found to have large bilateral AMLs while undergoing abdominal MRI and CT scans. These measured 6.6x3.6x7.7cm on the right (R) and 12.3x8.4x6.8cm on the left (L) at the time. He was asymptomatic, denying flank and abdominal pain. Follow up adrenal CT a year later revealed his AMLs increased in size to 8.7x4.2x6.6cm (R) and 13.9x6x8cm (L). Repeat CT another year later showed further rapid enlargement of his AMLs, measuring 11.1x6.1x7.9cm (R) and 17.1x7.8x10.8cm (L). He also exhibited a rising 17-hydroxyprogesterone level of 11,547ng/dL, despite an increased hydrocortisone dose (20mg BID). Although he remained asymptomatic, due to the precipitous growth of the masses and his increasing steroid requirement, a surgical approach was recommended. Open bilateral adrenalectomy was performed by an experienced endocrine surgeon and patient was discharged from the hospital with maintenance hydrocortisone and fludrocortisone therapy as well as strict sick day instructions.AMLs were first described in 1905 by Gierke. In the past, they were often discovered on autopsies, but more recently, due to the increase in imaging, have been incidentally diagnosed on more patients. Mostly, they occur unilaterally and are small (<4 cm) in size. Individuals with hormonal dysfunction such as those with Cushing’s Syndrome, Conn’s syndrome and CAH, particularly with difficult-to-control corticotropin levels, may be at a greater risk of developing AMLs concurrently, however this phenomenon is still not well understood. Small asymptomatic AMLs can be monitored with serial imaging over time. Spontaneous rupture of AMLs was found in 4.5% of cases, mostly occurring in tumors > 10cm, some resulting in retroperitoneal hemorrhage or even hemorrhagic shock. Although there is no clear consensus on surgery, development of symptoms or significant growth (to >10cm), as in our case, is a reason to pursue surgical evaluation especially in a young, otherwise relatively healthy adult.

Clinical features and sex hormone profile in male patients with frontal fibrosing alopecia: A multicenter retrospective study with 33 patients

Clinical features and sex hormone profile in male patients with frontal fibrosing alopecia: A multicenter retrospective study with 33 patients

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) in adult males: Clinical presentation, hormone function and the detection of adrenal and testicular adrenal rest tumors (TARTs)

Introduction21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia (CAH). In adulthood, most studies are reported in females. By contrast, data on adult males are scarce. ObjectiveTo describe a series of adult males with classic 21-OHD and to assess the presence of adrenal masses and testicular adrenal rest tumors (TARTs). Material and MethodsEight males (21–42 years) were included. We evaluated clinical presentation, 17-Hydroxyprogesterone (17-OHP), Testosterone (T), Δ4Androstenedione (Δ4A) ACTH, LH, FSH and plasma renin activitiy (PRA) levels at consultation. Molecular studies of the CYP21A2 gene, testicular ultrasound (US), semen analysis and adrenal computed tomography (CT) scan were performed. Treatment and compliance were assessed. ResultsBasal 17-OHP levels were >20ng/ml in all patients. At consultation, median 17OH-P was 11.5 (2.3–81) ng/ml, FSH: 3 (0.3–4) mUI/ml, LH: 1.1 (0.1–6) mUI/ml, T: 4.3 (1.7–8) ng/ml, Δ4A: 5.7 (1.4–16) ng/ml, ACTH: 86.4 (76–334) pg/ml, PRA: 9.5 (1.3–23.6) ng/ml/h. Semen analysis was performed in 5/8 patients, showing azoospermia in two. Molecular genetic analysis was performed in 4/8 patients. TARTs were found in 5/6, being bilateral in four. Adrenal masses were found in 4/6. In the 7 patients diagnosed in childhood, their follow-up was referred to as irregular, both in their attendance at consultations and in compliance with the indicated treatment. ConclusionsTo our knowledge, this is the first series on adult males with classic 21-OHD which concomitantly assesses clinical presentation, molecular biology, adrenal and testicular imaging studies, semen analysis and compliance to treatment. A high prevalence of adrenal masses and TARTs was observed, possibly associated with poor treatment compliance leading to elevated ACTH and increased proliferation. Our findings on TARTs agree with reports in international publications of CAH in males, with adrenal imaging being added in our group. Although we are aware that further studies with a larger sample size and more data are needed, we consider that our findings contribute to the clinical management of classical 21-OHD in the male population.

Kongenitalna adrenalna hiperplazija

Congenital adrenal hyperplasia is a disease in which a gene mutation, which is inherited in an autosomal recessive manner, causes a disorder in the synthesis of enzymes that create glucocorticoids, mineralocorticoids, or sex steroids from adrenal cholesterol. The incidence of the classic form of the disease ranges from 1:14000 to 1:18000 births. In the majority of cases, the disease is caused by mutations in the CYP21A2 gene that participates in the synthesis of the 21 Alpha-hydroxylase. Due to the lack of enzymes, the synthesis of cortisol is blocked with the accumulation of sex hormones. The classic form of the disease, or a simple virilizing form in which patients lose salt, is diagnosed in the infant period. In the non-classical or mild form of the disease, with late-onset, patients may be asymptomatic or with a milder form of virilization postnatally. The diagnosis is made based on 17-hydroxyprogesterone levels, in order to determine the deficiency of the 21 Alpha-hydroxylase enzyme. Common complications of the disease are adrenal crisis, hypoglycemia, infertility, and premature entry into puberty. Prenatal therapy is referred to as experimental treatment, while the basis of care is hydrocortisone replacement. In severe forms of the disease, patients are unable to produce enough cortisol in response to stress from gastroenteritis, surgery, trauma, or fever, requiring higher doses of hydrocortisone. In certain cases of genital uncertainty, surgical treatment is necessary. A multidisciplinary team of experts is necessary for adequate surveillance of the disease, in both childhood and adulthood.

Gas chromatography-mass spectrometry-based metabolic profiling of androgens, progestins and glucocorticoids in women with polycystic ovary syndrome

Hypothesis/aims of study. Polycystic ovary syndrome (PCOS) is a common disease. Depending on the diagnostic criteria, the disease is seen in 10-20% of women of reproductive age and accounts for 70-80% of all forms of hyperandrogenic syndrome. PCOS is a heterogeneous condition of multifactorial etiology characterized by various clinical, endocrine and metabolic disorders. Therefore, it is important to clarify the specific features of steroid hormone biosynthesis and metabolism and steroidogenesis enzyme activity, as well as to search for new laboratory criteria for early diagnosis and prompt treatment. The aim of this study was to perform metabolic profiling of androgens, progestins and glucocorticoids using gas chromatography-mass spectrometry (GC-MS) in obese and non-obese women with PCOS.&#x0D; Study design, materials and methods. We examined 53 women of reproductive age diagnosed with PCOS. The first group included 30 women aged 22 to 29 years with normal body weight. The second group comprised 23 obese patients aged 25 to 33 years with an average body mass index (BMI) of 35.3 0.4 kg/m2. The control group consisted of 25 healthy women aged 26 0.6 years having a normal BMI without clinical and biochemical signs of hyperandrogenism. Immunoassay methods were used to determine the serum levels of luteinizing hormone, follicle-stimulating hormone, free testosterone, 17-hydroxyprogesterone, and sex hormone-binding globulin. A glucose tolerance test was performed to determine glucose and insulin levels before and after load. Urine steroid profiles were studied by GC-MS with the optimization of the sample preparation schedule. Statistical data processing was performed using the STATISTICA for WINDOWS software system (version 10). The main quantitative characteristics of the patients are presented as the median (Me), the 25th percentile and the 75th percentile (Q25Q75). To compare the results obtained in the study groups, the nonparametric Mann-Whitney test was used. The 95% confidence interval was considered statistically significant.&#x0D; Results. The article presents a metabolomics analysis of androgens, glucocorticoid hormones and progestins in women with PCOS compared to the control group. It was revealed that non-obese patients with PCOS had increased urinary excretion of androstenedione metabolites, dehydroepiandrosterone and its metabolites, 17-hydroxypregnanolone, pregnantriol, and 5-ene-pregnenes, while obese patients with PCOS had increased that of androsterone and dehydroepiandrosterone metabolites (16-oxo-androstenediol and androstenediol-17) compared to the control group findings. Decreased ratios of cortisol and cortisone tetrahydro metabolite amount to the levels of 11-oxo-pregnanetriol, pregnanetriol and 17-hydroxypregnenolone, when compared to the control group, was obtained in non-obese patients with PCOS, which indicates 21-hydroxylase deficiency. In obese patients with PCOS, four signs of increased 5-reductase activity were obtained, and in PCOS patients with a normal BMI, three signs were obtained, which indicates varying 5-reductase activity in PCOS patients depending on the BMI.&#x0D; Conclusion. Quantitative evaluation of androgen and progestin metabolites, as well as 5- and 5-metabolites of androstenedione and glucocorticoids in the study of urine steroid profiles by GC-MS method opens new opportunities for PCOS diagnostics.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) in adult males: Clinical presentation, hormone function and the detection of adrenal and testicular adrenal rest tumors (TARTs)

Introduction21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia (CAH). In adulthood, most studies are reported in females. By contrast, data on adult males are scarce. ObjectiveTo describe a series of adult males with classic 21-OHD and to assess the presence of adrenal masses and testicular adrenal rest tumors (TARTs). Material and MethodsEight males (21–42 years) were included. We evaluated clinical presentation, 17-Hydroxyprogesterone (17-OHP), Testosterone (T), Δ4Androstenedione (Δ4A) ACTH, LH, FSH and plasma renin activitiy (PRA) levels at consultation. Molecular studies of the CYP21A2 gene, testicular ultrasound (US), semen analysis and adrenal computed tomography (CT) scan were performed. Treatment and compliance were assessed. ResultsBasal 17-OHP levels were >20ng/ml in all patients. At consultation, median 17OH-P was 11.5 (2.3–81) ng/ml, FSH: 3 (0.3–4) mUI/ml, LH: 1.1 (0.1–6) mUI/ml, T: 4.3 (1.7–8) ng/ml, Δ4A: 5.7 (1.4–16) ng/ml, ACTH: 86.4 (76–334) pg/ml, PRA: 9.5 (1.3–23.6) ng/ml/h. Semen analysis was performed in 5/8 patients, showing azoospermia in two. Molecular genetic analysis was performed in 4/8 patients. TARTs were found in 5/6, being bilateral in four. Adrenal masses were found in 4/6. In the 7 patients diagnosed in childhood, their follow-up was referred to as irregular, both in their attendance at consultations and in compliance with the indicated treatment. ConclusionsTo our knowledge, this is the first series on adult males with classic 21-OHD which concomitantly assesses clinical presentation, molecular biology, adrenal and testicular imaging studies, semen analysis and compliance to treatment. A high prevalence of adrenal masses and TARTs was observed, possibly associated with poor treatment compliance leading to elevated ACTH and increased proliferation. Our findings on TARTs agree with reports in international publications of CAH in males, with adrenal imaging being added in our group. Although we are aware that further studies with a larger sample size and more data are needed, we consider that our findings contribute to the clinical management of classical 21-OHD in the male population.