scholarly journals Measurement of Salivary Adrenal-Specific Androgens as Biomarkers of Therapy Control in 21-Hydroxylase Deficiency

2019 ◽  
Vol 104 (12) ◽  
pp. 6417-6429 ◽  
Author(s):  
Irina Bacila ◽  
Jo Adaway ◽  
James Hawley ◽  
Sundus Mahdi ◽  
Ruth Krone ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Hormonal Control ◽  
Hydroxylase Deficiency ◽  
Cross Sectional ◽  
Monitoring Strategies ◽  
Liquid Chromatography Tandem Mass ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Monitoring Treatment ◽  
Patient Subgroups

Abstract Background Monitoring of hormonal control represents a key part of the management of congenital adrenal hyperplasia (CAH). Monitoring strategies remain suboptimal because they rely on frequent blood tests and are not specific for adrenal-derived hormones. Recent evidence suggests the crucial role of adrenal-specific 11-oxygenated-C19 androgens in the pathogenesis of CAH. Objective To establish a correlation between plasma and salivary adrenal-specific androgens in CAH as a noninvasive monitoring strategy. Design This prospective cross-sectional study recruited patients between 2015 and 2018. Setting Multicenter study including 13 tertiary centers in the United Kingdom. Participants Seventy-eight children with CAH and 62 matched healthy controls. Methods Using liquid chromatography–tandem mass spectrometry, plasma and salivary concentrations of five steroids were measured: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). The correlation between plasma and salivary steroids was analyzed to assess their use in clinical practice. Results Strong correlations between plasma and salivary steroid concentrations in patients with CAH were detected: 17OHP (rs = 0.871; P < 0.001), A4 (rs = 0.931; P < 0.001), T (rs = 0.867; P < 0.001), 11OH4A (rs = 0.876; P < 0.001), and 11KT (rs = 0.944; P < 0.001). These results were consistent for patient subgroups based on sex and age. Analysis of patient subgroups based on 17OHP concentrations established clear correlations between plasma and salivary concentrations of the adrenal-specific androgen 11KT. Conclusions The current study identified tight correlations between plasma and saliva for the adrenal-derived 11-oxygenated C19 androgen 11KT, as well as 17OHP and A4, which are widely used for monitoring treatment in CAH. This combination of steroid hormones will serve as an improved noninvasive salivary test for disease monitoring in patients with CAH.

scholarly journals Salivary profiles of 11-oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia

2021 ◽  
Author(s):  
Hanna Nowotny ◽  
Matthias K. Auer ◽  
Christian Lottspeich ◽  
Heinrich Schmidt ◽  
Ilja Dubinski ◽  
...  
Keyword(s):  
Diurnal Rhythm ◽  
Area Under The Curve ◽  
Early Morning ◽  
Hydroxylase Deficiency ◽  
Cross Sectional ◽  
Female Patients ◽  
Male Patients ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Monitoring Treatment

AbstractContextSeveral studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD).ObjectiveTo analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.Design, Setting, and ParticipantsCross-sectional single center study including 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age-matched controls (men=15; women=17).Outcome MeasuresSalivary concentrations of the following steroids were analyzed by LC-MS/MS: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT).ResultsSimilar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: male patients Δmean = 79 %; male controls Δmean = 81%; female patients Δmean = 33 %; female controls Δmean = 91 %; 11KT: male patients Δmean = 64 %; male controls Δmean = 60 %; female patients Δmean = 49 %; female controls Δmean = 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male = 0.741**; r(p)female = 0.842****), and 11OHA4 (r(p)male = 0.385n.s.; r(p)female = 0.527*) were observed in patients but not in controls.ConclusionsAdrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a cross-sectional study of factors involved in bone mineral density

2003 ◽  
Vol 21 (6) ◽  
pp. 396-401 ◽  
Author(s):  
Patr�cia Oliveira de Almeida Freire ◽  
Sofia Helena Valente de Lemos-Marini ◽  
Andr�a Trevas Maciel-Guerra ◽  
Andr� Moreno Morcillo ◽  
Maria Tereza Matias Baptista ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Congenital Adrenal Hyperplasia ◽  
Bone Mineral ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Adrenal Hyperplasia ◽  
Mineral Density ◽  
Hydroxylase Deficiency ◽  
Cross Sectional ◽  
21 Hydroxylase Deficiency

scholarly journals Serum Steroid Profiling by Liquid Chromatography–Tandem Mass Spectrometry for the Rapid Confirmation and Early Treatment of Congenital Adrenal Hyperplasia: A Neonatal Case Report

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 284 ◽  
Author(s):  
Ilaria Cicalini ◽  
Stefano Tumini ◽  
Paola Irma Guidone ◽  
Damiana Pieragostino ◽  
Mirco Zucchelli ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Tandem Mass ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of steroid biosynthesis, in 95% of cases due to 21-hydroxylase deficiency. The resulting hormonal imbalances lead to increased 17-hydroxyprogesterone and androgens levels, at the expense of decreased concentrations of glucocorticoids and, in some cases, of mineralocorticoids. A variety of clinical presentations accompany a range of severities, which are described as different forms of CAH, and are the result of these hormonal imbalances. The incidence of CAH worldwide is approximately 1 in 15,000 live births, and is population-dependent; thus, its inclusion in neonatal screening tests is widely discussed. Diagnosis of CAH is based on the quantification of 17-hydroxyprogesterone, usually by immunoassay, which has low specificity and high false-positive rates, resulting in a relatively high demand for a second-tier confirmation test. We report a case of a newborn recognized as female at birth, but showing ambiguous genitalia and other CAH clinical features, including hypernatremia, in the first days of life. In addition to the classical assays, liquid chromatography–tandem mass spectrometry was used to determine the serum steroid profile, allowing for the accurate and simultaneous quantification of seven steroids in the same analysis. Such an application immediately revealed an alteration in the levels of specific steroids related to CAH, leading to an early intervention by hormone replacement therapy. Subsequently, the diagnosis of classic CAH due to 21-hydroxylase deficiency was further confirmed by molecular testing.

scholarly journals Genetic aetiology of primary adrenal insufficiency in Chinese children

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhuo Chang ◽  
Wei Lu ◽  
Zhuhui Zhao ◽  
Li Xi ◽  
Xiaojing Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Information ◽  
Cross Sectional Study ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Cross Sectional ◽  
Salt Wasting ◽  
Novel Variants ◽  
21 Hydroxylase Deficiency

Abstract Background Primary 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. Methods Seventy 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. Results Among 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. Conclusions We 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.

scholarly journals Absence of Testicular Adrenal Rest Tumors in Newborns, Infants, and Toddlers with Classical Congenital Adrenal Hyperplasia

2019 ◽  
Author(s):  
Mimi S. Kim ◽  
Christina M. Koppin ◽  
Pankhuri Mohan ◽  
Fariba Goodarzian ◽  
Heather M. Ross ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hormonal Control ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Young Males ◽  
Testicular Adrenal Rest Tumors ◽  
17 Hydroxyprogesterone ◽  
Adrenal Rest ◽  
21 Hydroxylase Deficiency ◽  
Testicular Adrenal Rest

AbstractINTRODUCTIONTesticular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH.OBJECTIVEWe assessed the prevalence of TART in newborn, infant, and toddler males with classical CAH via scrotal ultrasound.METHODSMales with CAH had scrotal ultrasounds during the first 4 years of life, evaluating testes for morphology, blood flow, and presence of TART. Newborn screen 17-hydroxyprogesterone (17-OHP) and serum 17-OHP at the time of ultrasound were recorded. Bone ages were considered very advanced if ≥ 2SD above chronological age.RESULTSThirty-one ultrasounds in 16 males were performed. An initial ultrasound was obtained in four newborns at diagnosis (6.8 ±2.1 days), six infants (2.2 ±0.9 months), and six toddlers (2.4 ±0.9 years). Eleven males had at least one repeat ultrasound. A large proportion (11/16) were in poor hormonal control with an elevated 17-OHP (325 ±298 nmol/L). One infant was in very poor hormonal control (17-OHP 447 nmol/L) at initial ultrasound, and two toddlers had advanced bone ages (+3.2 and +4.5 SD) representing exposure to postnatal androgens. However, no TART were detected in any subjects.CONCLUSIONSTART were not found in males up to 4 years of age with classical CAH despite settings with expected high ACTH drive. Further research into the occurrence of TART in CAH may elucidate factors which contribute to the detection and individual predisposition to TART.

Pengetahuan Mahasiswi Universitas Al Azhar Indonesia Terhadap Premenstrual Syndrome

2015 ◽  
Vol 2 (3) ◽  
pp. 193
Author(s):  
Riris Lindiawati Puspitasari ◽  
Dewi Elfidasari ◽  
Kun Mardiwati Rahayu
Keyword(s):  
Premenstrual Syndrome ◽  
Population Sample ◽  
Reproductive Organs ◽  
Cross Sectional Study ◽  
Hormonal Control ◽  
P Value ◽  
Cross Sectional ◽  
Knowledge Age ◽  
Physical Changes ◽  
Age Of Menarche

<p><em>Abstrak –<strong> </strong></em><strong>Tahap perkembangan r</strong><strong>emaja ditandai </strong><strong>dengan</strong><strong> perubahan fisik umum </strong><strong>yang di</strong><strong>serta</strong><strong>i</strong><strong> perkembangan kognitif</strong><strong> maupun</strong><strong> sosial.<em> </em>Menstruasi merupakan </strong><strong>proses alamiah organ reproduksi wanita dengan </strong><strong>peng</strong><strong>e</strong><strong>ndalian hormon</strong><strong>. S</strong><strong>alah satu gangguan menstruasi adalah <em>Premenstrual Syndrome</em> </strong><strong>atau</strong><strong> sindrom sebelum haid</strong><strong> atau dikenal juga sebagai </strong><strong>ketegangan sebelum haid</strong><strong>.</strong><strong> </strong><strong>Siklus menstruasi yang tidak teratur, penurunan </strong><strong>level</strong><strong> progesteron dan peningkatan </strong><strong>level</strong><strong> estrogen, stres, usia <em>menarche</em> yang terlalu cepat, dan status gizi</strong><strong> merupakan beberapa faktor penyebab PMS. Penelitian ini bertujuan u</strong><strong>ntuk mengetahui pengetahuan mahasiswi Universitas Al Azhar Indonesia terhadap PMS<em>. </em></strong><strong>Metodologi yang digunakan yaitu studi <em>Cross Sectiona</em></strong><strong><em>l.</em></strong><strong> Populasi sampel penelitian adalah mahasiswi Universitas Al Azhar Indonesia. Variabel independen yang dipilih yaitu pengetahuan, usia <em>menarche</em>, siklus haid, olahraga, nutrisi, produktivitas, dan indeks massa tubuh (IMT). Berdasarkan uji </strong><strong>bivariat dan multivariat regresi logistik tidak ditemukan hubungan yang signifikan antara pengetahuan dengan premenstrual syndrome pada mahasiswi UAI yaitu pengetahuan dengan p value 0,169; OR 0,473; 95% CI 0,163-1,374</strong><strong>. Responden yang memiliki pengetahuan 0,473 kali lebih baik dalam penatalaksanaan <em>premenstrual syndrome</em> daripada responden yang memiliki pengetahuan kurang.</strong><strong></strong></p><p><strong> </strong></p><p><em>Abstract </em><strong>– Adolescent developmental</strong><strong> stage characterized by common physical changes that accompanied the cognitive and social development. Menstruation was known as a natural process of hormonal control in the female reproductive organs. One of menstrual disorders was premenstrual syndrome or syndrome before menstruation or also known as tension before menstruation. Irregular menstrual cycles, decreased levels of progesterone, increased level of estrogen, stress, menarche age, and nutritional status were informed as factors that cause premenstrual syndrome. This study aimed to determine student’s knowledge to premenstrual syndrome. The methodology used was a cross sectional study. The population sample was a student of University Al Azhar Indonesia. The independent variables were selected, namely knowledge, age of menarche, menstrual cycle, exercise, nutrition, productivity, and body mass index (BMI). Based on the test bivariate and multivariate logistic regression found no significant relationship between knowledge with premenstrual syndrome in UAI student that knowledge with p value 0.169; OR 0.473; 95% CI 0.163 to 1.374. Respondents who had knowledge 0.473 times better than others in treatment of premenstrual syndrome.</strong><strong></strong></p><p><strong><em> </em></strong></p><p><strong><em>Keywords</em></strong><em>: Premenstrual Syndrome</em><em>, </em><em>knowlwdge, menstruation, menarche.</em><em></em></p>

Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population

2019 ◽  
Vol 19 (8) ◽  
pp. 1198-1206 ◽  
Author(s):  
Yenny ◽  
Sonar S. Panigoro ◽  
Denni J. Purwanto ◽  
Adi Hidayat ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Threshold Concentration ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Liquid Chromatography Tandem Mass

Background: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Objective: The purpose of the study was to determine the association between CYP2D6*10 (c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration (MTC) in Indonesian women with breast cancer. Methods: A cross-sectional study was performed in 125 ambulatory patients with breast cancer consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10 (c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the results of which were subsequently confirmed by sequencing. The genotypes were categorized into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively. Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86 (0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference in median Z-END concentration between patients with T/T genotype and those with C/C or C/T genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes and attainment of plasma steady-state Z-END MTC (p<0.001). Conclusion: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day.

Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Vichit Supornsilchai ◽  
Chutima Jantarat ◽  
Wichit Nosoognoen ◽  
Sopon Pornkunwilai ◽  
Suttipong Wacharasindhu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Estrogenic Activity ◽  
Age At Onset ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Normal Weight ◽  
Control Groups ◽  
Limit Of Quantification ◽  
Cross Sectional ◽  
Liquid Chromatography Tandem Mass

AbstractReports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty.A cross-sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL.The median adjust-BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 μg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 μg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 μg/g Cr: p=0.09), but not statistically significant.The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls.

Serum diiodotyrosine—a biomarker to differentiate destructive thyroiditis from Graves’ disease

2021 ◽  
Author(s):  
Naoya Fujita ◽  
Yosuke Ono ◽  
Azusa Sano ◽  
Motohiro Kimata ◽  
Seigo Oyama ◽  
...  
Keyword(s):  
Roc Curve ◽  
Operating Characteristic ◽  
Cross Sectional Study ◽  
Curve Analysis ◽  
Diagnostic Methods ◽  
Graves Disease ◽  
Roc Curve Analysis ◽  
Cross Sectional ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Objective: Conventional diagnostic methods are limited in their ability to differentiate destructive thyroiditis from Graves’ disease. We hypothesised that serum diiodotyrosine (DIT) and monoiodotyrosine (MIT) levels could be biomarkers for differentiating destructive thyroiditis from Graves’ disease. Design: Patients with destructive thyroiditis (n = 13) and Graves’ disease (n = 22) were enrolled in this cross-sectional study. Methods: We assayed the serum DIT and MIT levels using liquid chromatography-tandem mass spectrometry. A receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the serum DIT and MIT levels as biomarkers for differentiating destructive thyroiditis from Graves’ disease. Results: The serum DIT and MIT levels were significantly higher in patients with destructive thyroiditis than in those with Graves’ disease. The ROC curve analysis showed that the serum DIT levels (≥ 359.9 pg/mL) differentiated destructive thyroiditis from Graves’ disease, significantly, with 100.0% sensitivity and 95.5% specificity (P < .001). The diagnostic accuracy of the serum MIT levels (≥119.4 pg/mL) was not as high as that of the serum DIT levels (sensitivity, 84.6%; specificity, 77.3%; P = .001). Conclusions: The serum DIT levels may serve as a novel diagnostic biomarker for differentiating destructive thyroiditis from Graves’ disease.

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