17-hydroxyprogesterone Levels Research Articles

Comparison of modified-release hydrocortisone capsules versus prednisolone in the treatment of congenital adrenal hyperplasia.

Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone. Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study. The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline. At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years). MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

Investigating the potential neuroprotective benefits of taurine and Dihydrotestosterone and Hydroxyprogesterone levels in SH-SY5Y cells.

Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer's disease (AD) is a commonly occurring type of dementia, which becomes more prevalent as people age. This experiment aimed to assess the neuroprotective effects of taurine on SH-SY5Y cells by examining its impact on Dihydrotestosterone (DHT), Dihydroprogesterone (DHP), as well as the expression of miRNA-21 and miRNA-181. The effects of various taurine concentrations (0.25, and 0.75 mg/mL), and LPS (0.1, and 12 mg/mL) on the SH-SY5Y cell line were assessed using the MTT assay. The levels of DHT and DHP were quantified using an ELISA kit. Additionally, the expression levels of miRNA-181 and miRNA-21 genes were examined through Real-Time PCR analysis. The results of the MTT assay showed that treatment with taurine at concentrations of 0.25, and 0.75 mg/mL reduces the toxicity of LPS in SH-SY5Y cells. ELISA results indicated that taurine at a concentration of 0.25, and 0.75 mg/mL significantly elevated DHT and DHP hormones in the SH-SY5Y cell line compared to the untreated group (p < 0.01). The expression levels of IL-1β and IL-6 were decreased under the influence of LPS in SH-SY5Y cells after taurine treatment (p < 0.01). Gene expression analysis revealed that increasing taurine concentration resulted in heightened expression of miRNA-181 and miRNA-21, with the most significant increase observed at a concentration of 0.75 mg/mL (p < 0.001). Our study findings revealed that the expression of miRNA-181 and miRNA-21 can be enhanced by taurine. Consequently, exploring the targeting of taurine, miRNA-181, and miRNA-21 or considering hormone therapy may offer potential therapeutic approaches for treating AD or alleviating severe symptoms. Nonetheless, in order to fully comprehend the precise mechanisms involved, additional research is required.

Maternal Steroid Hormone Levels in Early Pregnancy and Autism in the Offspring: A Population-Based, Nested Case-Control Study

BackgroundA role for prenatal steroid hormones in the etiology of autism has been proposed, but evidence is conflicting. MethodsHere, we examined serum levels of maternal estradiol, testosterone, 17-hydroxyprogesterone (OHP), and cortisol from the first trimester of gestation (mean = 10.1 weeks) in relation to the odds of diagnosed autism with and without co-occurring intellectual disability (ID) in the offspring (n = 118 autism with ID, n = 249 autism without ID, n = 477 control). Levels of maternal hormones were measured using highly sensitive liquid chromatography tandem mass spectrometry, standardized according to gestational timing of sample collection, and analyzed with restricted cubic spline logistic regression models adjusting for child’s sex and maternal health, demographic, and socioeconomic factors. ResultsWe observed significant nonlinear associations between maternal estradiol, 17-OHP, and cortisol with autism, which varied with the presence of co-occurring ID. Compared to mean levels, lower levels of estradiol were associated with higher odds of autism with ID (odds ratio for concentrations 1 SD below the mean = 1.66; 95% CI, 1.24–2.11), while higher cortisol levels were associated with lower odds (odds ratio for 1 SD above the mean = 0.55; 95% CI, 0.36–0.88). In contrast, higher 17-OHP was associated with increased odds of autism without ID (odds ratio for 1 SD above the mean = 1.49; 95% CI, 1.11–1.99). We observed no evidence for interaction with sex of the child. ConclusionsThese findings support the notion that the maternal steroid hormonal environment in early pregnancy may contribute to autism, but also emphasize the complex relationship between early-life steroid exposure and autism.

Physician and Adolescent Hirsutism Score Ratings and Their Concordance to Androgen Levels [ID 2683618

INTRODUCTION: Hirsutism affects 5–15% of reproductive-aged women. The gold standard for quantifying hirsutism is the modified Ferriman–Gallwey (mFG) score. This study explores whether adolescent and physician ratings of hirsutism using the mFG score, correlate with androgen levels in the setting of confounders like depilation. METHODS: Hispanic adolescent females with irregular menstruation and suspected polycystic ovary syndrome (PCOS) were recruited from obstetrics and gynecology clinics at TTUHSC El Paso between September 2021 and May 2023. Patients completed an intake questionnaire, completed PCOS laboratory testing, and rated their hair growth using the mFG visual scoring method. Providers used same the methods for rating hirsutism during the same visit. We estimated Lin’s concordance correlation and Bland–Altman agreement between patient and provider mFG ratings. Linear regression explored factors affecting score changes. Statistical analysis was done by STATA 17.0. RESULTS: Forty females participated in this study. The average age at enrollment was 16.19 with a mean (SD) mFG score of 10.55 (5.95) (physicians) and 18.29 (5.78) (adolescents). Adolescents reported higher mean mFG scores than physicians. There is a low level of agreement between the two groups (−7.95; 95% CI: −23.02, 7.12). Specifically, physicians underrated hirsutism scores for arm hair. Using unadjusted linear regression, DHEAS and 17-hydroxyprogesterone levels demonstrate the hormonal influence on hirsutism. CONCLUSION: Preliminary findings indicate discordance between physicians’ and patients’ mFG scores, possibly influenced by examination precision and patient perception. Physician-scored mFG, and evaluation of androgen levels, may serve as precise hirsutism markers for Hispanic adolescents.

A CASE REPORT ON ATYPICAL PRESENTATION OF CONGENITAL ADRENAL HYPERPLASIA

We report a case of 52-day old infant presented to casualty with complaint of failure to gain weight,10-day history of regurgitation of feeds, poor acceptance of feed and lethargy from one day, not passed urine in last 8hours. On examination baby had tachycardia with signs of dehydration, blood gas shows metabolic acidosis with serum sodium- 124meq/l, serum potassium- 6.2meq/l. A probable diagnosis of failure to thrive with severe sepsis, inborn errors of metabolism (IEM), and CAH was considered and baby was treated with intravenous fluids, antibiotics, calcium gluconate, salbutamol nebulisation and hydrocortisone. Following the above interventions, babys hydration status and ECG changes improved. The diagnosis of CAH was considered as 17- hydroxyprogesterone levels were elevated. Genetic analysis was not done due to patients economic constraints and baby was discharged with oral Hydrocortisone, Fludrocortisone and table salt (Nacl). Currently baby is thriving well with adequate weight gain.

Syndrome of hyperandrogenism in adolescent girls

The diagnosis of hyperandrogenism may be based on clinical manifestations or on determining the blood level of androgens. Causes of hyperandrogenism in the peripubertal period are polycystic ovary syndrome (PCOS), non-classical forms of congenital adrenal hyperplasia (NCCAH), androgen-producing tumors, obesity, idiopathic hirsutism, and other rare causes. Physiological hyperandrogenism of peripubertal period passes within 2 years. PCOS affects from 4 to 21% of women of reproductive age and from 6 to 18% of adolescent girls. To date, there is no consensus on the diagnostic criteria for PCOS in teenage girls. At least, three symptoms are necessary: menstrual disorders, clinical and biochemical hyperandrogenism and polycystic ovaries. Diagnosis of NCCAH includes measurement of the level of 17-hydroxyprogesterone and a test with adrenocorticotropic hormone. The purpose of the treatment of these diseases is to reduce the manifestations of hyperandrogenism, regulate the menstrual cycle and improve the quality of life. Effective methods of pharmacotherapy are combined oral contraceptives and antiandrogens. An important stage is lifestyle changes in PCOS and obesity patients.

Prevalence of endocrine disorders in 304 premenopausal women referred with oligomenorrhoea.

We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population. The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 μg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed. The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030). We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.

Steroid metabolites producing adenoma: a case report

Hyperandrogenism is the most prevalent cause of menstrual cycle abnormalities and infertility in women. Here, we present a case of a 32-year-old woman with a 7-year history of menstrual irregularity and infertility. Laboratory test results revealed elevated 17-hydroxyprogesterone, progesterone 21-deoxycortisol. Abdominal computed tomography found a 3,9х2,9х2,6 cm left adrenal tumor. Non-classic congenital adrenal hyperplasia was diagnosed initially, however, treatment with supraphysiological doses of dexamethasone proved ineffective and progesterone and 17-hydroxyprogesterone levels remained high. Genetic testing revealed no 21-hydroxylase deficiency. Laparoscopic adrenalectomy was performed with subsequent pathological report being compatible with an adrenal cortical adenoma. 17-hydroxyprogesterone, progesterone 21-deoxycortisol levels returned to the normal range postoperatively and the patient’s menstrual cycle normalized without additional medication. Steroid metabolites producing adenomas are also extremely rare with only a few cases found in patients without previous CAH diagnosis. When a patient with clinically and biochemically diagnosed NCCAH demonstrate no typical features and shows poor response to steroid therapy, the patient should receive multisteroid LC–MS/MS assay for glucocorticoids and androgens, adrenal and ovarian imaging and undergo CYP21A2 gene mutation analysis.

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells.

Endocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS). NCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR. Cell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11-deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11-deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix. In cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality.

Congenital Adrenal Hyperplasia with Concomitant Mullerian Agenesis: A Rare Occurrence in 46 Xx Disorders of Sexual Development

The most common cause of 46 XX DSD is due to congenital adrenal hyperplasia with varying degrees of virilization. Females with CAH do not produce an anti-mullerian hormone (AMH), therefore the internal genitalia, which are Mullerian derivatives, develop normally. We report a unique case of CAH with aplasia of the uterus and upper vagina. The clinical, laboratory, and imaging findings of the patient are presented with a review of the literature. We report an ongoing case of a 20-year-old patient with ambiguous genitalia and primary amenorrhea. On physical examination, we found that she had an underdeveloped breast and clitoral virilization with separate urethral and vaginal openings. We performed a G-banded chromosome analysis, with 46 XX results. Laboratory test showed her 17-hydroxyprogesterone level was immensely elevated, while her FSH, LH, and estradiol level was below normal. Ultrasound imaging revealed the absence of uterus and cervix. Nevertheless, we found a diminutive uterine remnant during diagnostic laparoscopy with normal ovaries and fallopian tubes. On vaginoscopy examination, we found her vagina to be 5 cm long with blind end. In the presence of primary amenorrhea in patients with CAH, it is important to investigate for possible associated mullerian anomalies.

The Impact of Maternal Hypothyroidism during Pregnancy on Minipuberty in Boys.

Minipuberty is a period of increased reproductive axis activity in infancy, which seems to be implicated in the postnatal development of male genital organs. Impaired thyroid function during pregnancy is associated with an increased risk of prenatal, perinatal, and postnatal complications. The aim of this study was to investigate whether the presence of hypothyroidism during pregnancy modulates the course of male minipuberty. We compared three matched groups of male infants: sons of women with hypothyroidism uncontrolled or poorly controlled during pregnancy (group A), male offspring of women treated over the entire pregnancy with adequate doses of levothyroxine (group B), and sons born to women with no evidence of thyroid disease (group C). Salivary levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol, progesterone, and 17-hydroxyprogesterone, as well as urine concentrations of FSH and LH, were assessed once a month in the first 6 months of life, and once every two months between months 6 and 12. Gonadotropin and testosterone levels during the first 6 months of life were lower in group A than in groups B and C. Differences in testosterone and gonadotropin levels were accompanied by similar differences in penile length and testicular volume. Concentrations of the remaining hormones did not differ between the study groups. The obtained results suggest that untreated or undertreated maternal thyroid hypofunction in pregnancy has an inhibitory effect on postnatal activation of the hypothalamic-pituitary-testicular axis and genital organ development in their male offspring.

The correlation of intratesticular testosterone with body mass index and smoking

Intratesticular testosterone plays a crucial role in male reproductive function and overall health. Body Mass Index (BMI) and smoking are known lifestyle factors that can influence hormonal balances. Elevated BMI has been associated with alterations in testosterone levels, impacting male fertility and endocrine function. The aim was to examine the concurrent relationships between intratesticular testosterone, BMI, and smoking habits. Biopsies of the testicles were taken from 32 patients with non-obstructive azoospermia. Testicular sperm extraction (TESE) under spinal or general anesthesia was performed after a comprehensive history, physical examination, and investigations. After performing a minced biopsy and centrifuging the fluid, testicular fluid was extracted. The highest intratesticular testosterone levels were in normal patients and lowest levels in over weight patient; on the contrary the highest serum 17-hydroxyprogesterone levels were found in over weight patient and lowest levels in normal weight patients; There were insignificantly higher both intratesticular testosterone and 17- hydroxyprogesterone levels in non-smokers. In conclusion, the statistical analysis revealed that there is an insignificantly low correlation between intratesticular testosterone levels, BMI, and smoking.

THU620 Metastatic Adrenocortical Carcinoma Arising From A Testicular Rest Tumor

Abstract Disclosure: L.E. Chozet: None. J.M. Bruder: None. R. Flores: None. S. Hackman: None. K. highes: None. L. Vasquez: None. G. Le: None. T. cortez: None. M.A. Escobar Vasco: None. Background: Congenital adrenal hyperplasia (CAH) involves a range of autosomal recessive disorders characterized by abnormalities in the adrenal biosynthesis pathway. Testicular adrenal rest tumors (TARTs) are a complication mostly seen in male patients with congenital adrenal hyperplasia which can lead to infertility. These tumors are known to have benign characteristics. We present a unique case of a male patient with CAH diagnosed with metastatic adrenocortical carcinoma arising from a TART. Clinical Case: A 40-year-old man with poorly controlled congenital adrenal hyperplasia from 21-hydroxylase deficiency and bilateral testicular adrenal rest tumors presented with syncope and worsening left testicular pain for 2 months. Scrotal ultrasound showed enlarged bilateral scrotal masses (left bigger than right). Initial evaluation for his syncopal event included CTA chest which showed an incidental finding of innumerable bilateral solid pulmonary nodules. 17-hydroxyprogesterone levels were elevated at 5273 ng/dL (normal less than 138 ng/dL). Additional biochemical workup of the testicular mass was unremarkable. The patient underwent left radical orchiectomy with pathology showing high-grade carcinoma with adrenocortical differentiation. A right upper lobe lung biopsy was done which demonstrated metastatic carcinoma with adrenocortical differentiation, morphologically similar to the testicular tumor. The initial patient presentation of progressively worsening left testicular pain in the setting of testicular adrenal rest tumors (TARTs) led to the diagnosis of adrenal carcinoma. Conclusion: This case presents a unique presentation of adrenal carcinoma in a patient with congenital adrenal hyperplasia arising in the setting of testicular adrenal rest tumors (TARTs). This case demonstrates a unique presentation of adrenal carcinoma, as malignant degeneration has not been described in patients with TARTs. It also highlights the importance of close monitoring even if these tumors are thought to be of benign origin. Presentation: Thursday, June 15, 2023

FRI192 Serum Steroid Biomarkers For The Differential Diagnosis Of Adrenocortical Carcinoma (ACC) And Adrenocortical Adenoma (ACA)

Abstract Disclosure: D. van Rooyen: None. R. Scheske: None. A.M. Lerario: None. W.E. Rainey: None. R.J. Auchus: None. G.D. Hammer: None. T. Else: None. Background: Adrenal tumors are very common, with the vast majority being benign adrenocortical adenomas (ACA). Adrenocortical carcinomas (ACC) represent only a very small proportion of adrenal tumors. Distinction between the common ACA and rare ACC relies on invasive and costly protocols which are often inconclusive. Research into the use of steroid biomarkers as a non-invasive alternative diagnostic tool has been the focus of various steroid metabolomics studies. In this study, we aimed to identify serum steroid biomarkers to distinguish ACA from ACC. Methods: This study population was comprised of 103 patient samples, including 45 (31 female) and 58 (40 female) respective samples from ACA (age 32-90) and ACC (age 16-77) patients presenting with disease at the time of sampling. No ACC patients studied had been treated with mitotane. Serum steroid levels (4 sulfates and 25 Δ4 steroids) were measured using liquid-chromatography tandem mass spectrometry (LCMS/MS) with comparisons made between steroid profiles in ACA vs ACC and between males and females within each group (ACA and ACC). Data were analyzed to obtain the geometric means with 95% CIs, and statistical significance was determined using a two-tailed Mann-Whitney test. Results: ACC patients were characterized by significantly elevated levels of pregnenolone-sulfate, 17hydroxypregnenolone-sulfate, 11-deoxycorticosterone, 17hydroxyprogesterone, and androstenedione when compared to ACA patients. In addition, steroid levels differed between male and female samples, with dehydroepiandrosterone-sulfate (p&amp;lt;0.01), androstenediol-3-sulfate (p&amp;lt;0.05), 11deoxycortisol (p&amp;lt;0.0001), cortisol (p&amp;lt;0.05) and testosterone (p&amp;lt;0.01) significantly increased in female ACC patients when compared to male counterparts. Conclusion: Significant differences in plasma steroids were observed in ACC vs ACA patients, with more steroids altered in female patients. Serum steroid profiles, particularly steroid sulfates, might serve as an adjunct, easy to obtain diagnostic tool to differentiate ACA and ACC. Presentation: Friday, June 16, 2023

FRI228 Primary Adrenal T-cell Lymphoma: A Case Report

Abstract Disclosure: H. Tabassum: None. S. Xu: None. A. Manavalan: None. Introduction: Primary T-cell adrenal lymphoma (PAL) is exceedingly rare. Adrenal insufficiency (AI) is common in these cases. Here we describe a patient with bilateral, large, T-cell PAL with rapid progression, without adrenal insufficiency. Clinical Case: A 62-year-old male, with coronary artery disease and recent coronary intervention, hyperlipidemia and hypertension presented to the hospital with abdominal pain, fever, night sweats and weight loss for a month. Work up revealed a 5.8 cm left adrenal mass with 14% absolute washout, measuring 34 Hounsfield Units (HU) pre-contrast, 68 HU postcontrast, and 63 HU on delayed images, and a 5.2 cm right adrenal mass with 42% absolute washout, measuring 35 HU pre-contrast, 81 HU postcontrast, and 62 HU on the delayed images with no other suspicious lesions or lymphadenopathy. The patient demonstrated no clinical symptoms or signs of adrenal hormone excess or deficiency. Levels of renin, aldosterone, serum cortisol, ACTH, 24-hour urine free cortisol, serum metanephrines, and thyroid function were normal. Additional tests to rule out adrenal cortical carcinoma (ACC) revealed normal levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and estradiol. Persistent non-significant elevation of 11-deoxycortisol was observed at 51 ng/dL and 63ng/dL (Ref &amp;lt; 42 ng/dL). Adrenal biopsy was suggested but deferred due to the increased risk of hemorrhage given recent coronary revascularization and use of dual antiplatelet therapy. Follow up imaging in a few weeks revealed diffuse, retroperitoneal lymphadenopathy with unchanged adrenal masses. A lymph node biopsy confirmed a diagnosis of peripheral T-cell lymphoma. The left adrenal gland demonstrated an uptake SUV of 22.7 and the right, 19.17 on FDG PET. The patient was initiated on chemotherapy with etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin. Imaging three months later revealed a marked decrease in FDG activity SUV 6.98 g/mL on the left and SUV up to 3.32 g/mL on the right. Adrenal function remained intact on follow up. Conclusion: Peripheral T-cell lymphoma with adrenal involvement is an extremely rare and aggressive disease with rapid progression. Mostly seen in males over the age of 50, it may present with abdominal pain, B symptoms or both. While ACC is usually unilateral, lymphoma and metastatic disease may present bilaterally, however, other imaging features can be similar. AI is expected when 90% of the adrenal glands are destroyed by tumor infiltration, however, this does not always correlate with tumor size. In our patient, AI was not observed on presentation or follow up. As adrenal insufficiency can occur at any time in the disease course and may mimic symptoms of cancer or chemotherapy, the clinician should always be vigilant for its development in these cases. Presentation: Friday, June 16, 2023

THU205 A Case Of Infant With Familial-Male Limited Precocious Puberty (FMPP) Inherited From Father Due To An Activating Mutation Of The Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene

Abstract Disclosure: H. Yoo: None. J. Ha: None. M. Jung: None. Y. Choi: None. E. Yoo: None. We present an extremely rare case of FMPP with an activating mutation of the LHCGR gene in a Korean infant. A 16-month-old-boy was brought to the out-patient clinic with complaints of pubic hair, acne and rapid growth acceleration. His father had become aware of the symptoms 4 month before. His grandfather and father had a family history of precocious puberty and profound short stature (Height of grandfather and father: 148 cm and 158 cm respectively). At physical examination, his height was 83 cm (+1.2 SDS) and his weight was 14.3 kg (+2.8 SDS). The testicular volume was 2 mL and pubic hair was appropriate for Tanner stage 2. Stretched penile length was 7 cm (&amp;gt;2 SDS). He did not have any café au lait spots or hyperpigmentation. His bone age was significantly advanced to that of a 4 year old. Laboratory findings showed abnormally elevated serum testosterone (5.74 ng/mL) and slightly elevated α-fetoprotein (14.1 ng/ml; reference 0-10 ng/mL) with suppressed LH level (&amp;lt;0.07 mIU/mL). Serum levels of β-human chorionic gonadotropin, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone sulfate were within normal range. A gonadotropin releasing hormone (GnRH) stimulation test revealed a prepubertal response(peak LH 0.52). Brain magnetic resonance imaging study was reported to be normal. Ultrasound of the scrotum and adrenal gland were both normal. Due to the patient’s classic presentation and his family history of male-limited precocious puberty, a genetic analysis for LHCGR gene was performed. Molecular genetic analysis identified a pathogenic variant of LHCGR (c.1730 C&amp;gt;T, p.Thr577Ileu), which was previously reported in a FMPP patient. His father and paternal grand father also carry the same mutation. Anti-androgen treatment with bicalutamide (25mg/day) and aromatase inhibition with anastrozole (1mg/day) were initiated. After treatment, there was improvement in pubertal progression, accelerated growth velocity and rate of skeletal maturation without any specific side effects. Presentation: Thursday, June 15, 2023

SAT304 Improved Biochemical Control With Dose Reduction In Chronic Glucocorticoid Therapy: A Phase III Extension Study Of Chronocort (Efmody) In The Treatment Of Congenital Adrenal Hyperplasia (CAH)

Abstract Disclosure: R.J. Ross: Employee; Self; Diurnal, A Neurocrine Biosciences Company. D.P. Merke: None. A. Mallappa: None. W. Arlt: None. A. Brac de la Perriere: None. A.L. Hirschberg: None. A. Juul: None. J.D. Newell-Price: None. C.G. Perry: None. A. Prete: None. A. Rees: None. N. Reisch: None. M. Stikkelbroeck: None. P.A. Touraine: None. N. Aslam: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. H. Coope: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences company. J. Porter: Employee; Self; Diurnal Ltd, a Neurocrine Biosciences Company. Background: Management of congenital adrenal hyperplasia (CAH) involves replacing cortisol deficiency and controlling raised adrenal androgens. Guidelines recommend a target daily hydrocortisone dose of ≤25mg to replace adrenal insufficiency; however, cohort studies show doses &amp;gt;25mg are used to control androgens in CAH patients. Modified-release hydrocortisone (MRHC) capsules, (Efmody, UK), replicate the cortisol diurnal rhythm and improve the control of CAH compared to standard glucocorticoid therapy1. This post-hoc analysis examines total glucocorticoid daily dose and 9am 17-hydroxyprogesterone (17-OHP) levels in MRHC treated patients after 24 months in an ongoing MRHC single-arm extension study. Methods: All patients (n=71) that completed 24 months in the extension study at the time of the interim data cut were reviewed. Patients were recruited predominantly from the 6-month randomised phase III study comparing MRHC to standard glucocorticoid with blind titration of MRHC doses. In this extension phase the dose was titrated by the investigator on the 17-OHP and androstenedione levels at 4, 12, 24 weeks and 6 monthly. Androgen control was defined as 17-OHP &amp;lt;36 nmol/L (&amp;lt;1190 ng/dL). After 24 months, 64 of the patients had 9am 17-OHP data. A Wilcoxon-signed ranks test was performed to assess the change in total MRHC daily dose from baseline to 24 months. A Fisher’s exact test was performed to determine if the number of patients that achieved androgen control on a hydrocortisone (HC) dose ≤25 mg showed a statistically significant increase. Results: The median daily HC dose at baseline was 30mg (Inter-quartile range (IQR) 25-40) and at 24 months had reduced to 20mg (IQR 15-25), p&amp;lt;0.0001.Quadrant analysis revealed the following data: Baseline: &amp;gt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 9/71 (13%). &amp;gt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day18/71 (25%). &amp;lt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 22/71 (31%). &amp;lt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 22/71 (31%). 24 months: &amp;gt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 16/64 (25%). &amp;gt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 2/64 (3%). &amp;lt 36nmol/L 17-OHP &amp; &amp;lt 25mg/day 31/64 (48%). &amp;lt 36nmol/L 17-OHP &amp; &amp;gt 25mg/day 15/64 (23%). 48% of subjects achieved androgen control based on 9am 17-OHP level at a HC dose ≤ 25 mg following 24 months of MRHC treatment compared with 31% at baseline (31% vs 48%, p= 0.03 by Fisher’s exact test). Conclusions: After 24 months of MRHC treatment the median daily HC dose was reduced from a median of 30mg to 20mg and the number of patients achieving androgen control based on 9am 17-OHP while receiving HC ≤25mg/day increased significantly.

THU186 A Case Of 3beta-hydroxysteroid Dehydrogenase Type2 Deficiency Diagnosed By Whole Genome Sequencing In A Patient With Congenital Adrenal Hyperplasia

Abstract Disclosure: S. Chang: None. C. Kim: None. 3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare type of congenital adrenal hyperplasia (CAH) caused by HSD3B2 gene mutations. The estimated prevalence is less than 0.5% of all CAH and less than 1/1,000,000 at birth. It is a disorder of impaired steroidogenesis and sex steroid deficiency characterized by variable degrees of salt wasting, hypoglycemia, male incomplete masculinization and female virilization. Some newborns with 3βHSD2D have increased level of 17-hydroxyprogesterone (17OHP) that clinicians misdiagnose them as having classic 21-hydroxylase deficiency. A male newborn was referred to our hospital for generalized hyperpigmentation. Laboratory test showed hyponatremia, hyperkalemia and hypoglycemia. Hormonal study showed high level of adrenocorticotropic hormone, 17OHP, progesterone, renin activity, dehydroepiandrosterone (DHEA), androstenedione and low level of aldosterone. Clinically diagnosing with CAH, we administered glucocorticoid and mineralocorticoid replacement. We performed PCR sequencing for CYP21A2 gene mutation to confirm 21 hydroxylase deficiency but revealed normal result. After follow-up for 17 years with replacement treatment, he happened to have the opportunity to perform whole genome sequencing. Whole genome sequencing allowed to detect two pathogenic mutations in the HSD3B2 gene, described in compound heterozygosity (p.Arg249Ter and c.-149_143-1766del). One mutation (c.-149_143-1766del) is inherited from his father and the mother was not done for gene study. While there have been less than 100 cases of 3βHSD2D reported worldwide, in our best knowledge, this is the first case of genetically confirmed 3βHSD2D in Korea. Presentation: Thursday, June 15, 2023

Genotype-Specific Cortisol Reserve in a Cohort of Subjects With Nonclassic Congenital Adrenal Hyperplasia (NCCAH).

Recent guidelines suggest that patients with nonclassic congenital adrenal hyperplasia (NCCAH) stop glucocorticoid therapy after achieving adult height. However, these guidelines do not differentiate between NCCAH genotype groups. Compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation vs subjects with biallelic mild (mild/mild) mutations. Retrospective evaluation of the medical records of 122 patients who presented with postnatal virilization and were diagnosed with NCCAH. Patients underwent standard intravenous 0.25 mg/m2 ACTH stimulation testing. Those with stimulated 17OHP level ≥40 nmol/L were screened for the 9 most frequent CYP21A2 gene mutations followed by multiplex ligation-dependent probe amplification. A stimulated cortisol level below 500 nmol/L was defined as partial cortisol deficiency. Patients were subdivided into 3 genotype groups: 77 carried the mild/mild genotype, mainly homozygous for p.V281L mutation; 29 were compound heterozygous for mild/severe mutation, mainly p.V281L/p.I2Splice, and 16 were heterozygous for p.V281L, and were excluded from statistical evaluation. Stimulated cortisol levels were significantly lower in the mild/severe than in the mild/mild group (mean ± SD, 480 ± 90 vs 570 ± 125 nmol/L, P < .001). The mild/severe group exhibited a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs 28/71, 39%, P = .004). Peak 17OHP was significantly higher in the mild/severe group (198 ± 92 vs 118 ± 50 nmol/L, P < .001). The high rate of partial adrenal insufficiency in the mild/severe group underscores the need to carefully consider the value of glucocorticoid therapy cessation and the importance of stress coverage in this group.

Differences in Hyperandrogenism Related to Early Detection of Non-Classical Congenital Adrenal Hyperplasia on Second Newborn Screen.

Screening for congenital adrenal hyperplasia (CAH) remains heterogenous across geographies-we sought to determine the proportion of non-classical CAH (NCAH) detection by one vs. two newborn screens (NBS) in two U.S. regions. Data were collected at tertiary centers in Houston (HOU) and Los Angeles (LA) on 35 patients with NCAH, comparing patients identified via the NBS vs. during childhood, 17-hydroxyprogesterone (17-OHP) levels, genotype, and phenotype. The NBS filter-paper 17-OHP levels and daily cutoffs were recorded on initial and second screens. In all, 53% of patients with NCAH in the HOU cohort were identified as infants via the second NBS. Patients identified clinically later in childhood presented at a similar age (HOU: n = 9, 5.5 ± 3.1 years; LA: n = 18, 7.9 ± 4 years) with premature pubarche in almost all. Patients in LA had more virilized phenotypes involving clitoromegaly and precocious puberty and were older at treatment onset compared with those identified in HOU by the second NBS (HOU: 3.2 ± 3.9 years; LA: 7.9 ± 4.0 years, p = 0.02). We conclude that the early detection of NCAH could prevent hyperandrogenism and its adverse consequences, with half of the cases in HOU detected via a second NBS. Further studies of genotyping and costs are merited.