scholarly journals CYP21 Genotype, Adult Height, and Pubertal Development in 55 Patients Treated for 21-Hydroxylase Deficiency

2003 ◽  
Vol 88 (12) ◽  
pp. 5680-5688 ◽  
Author(s):  
Antonio Balsamo ◽  
Alessandro Cicognani ◽  
Lilia Baldazzi ◽  
Michela Barbaro ◽  
Federico Baronio ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
First Year ◽  
Compound Heterozygous ◽  
Target Height ◽  
Hydroxylase Deficiency ◽  
Genotypic Analysis ◽  
Group A ◽  
Group B ◽  
21 Hydroxylase Deficiency ◽  
First Year Of Life

Abstract In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height (FH), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, ∼2–3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. FH was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an FH within 0.5 sd of target height. Four of the 7 patients diagnosed via neonatal screening achieved an FH equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better FH. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced FH. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.

Low Adrenomedullary Function Predicts Acute Illness in Infants with Classical Congenital Adrenal Hyperplasia

2021 ◽  
Author(s):  
Jonathan Weber ◽  
Veeraya K Tanawattanacharoen ◽  
Amy Seagroves ◽  
Mark C Liang ◽  
Christina M Koppin ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Acute Illness ◽  
First Year ◽  
Plasma Epinephrine ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Young Infants ◽  
Increased Risk ◽  
21 Hydroxylase Deficiency ◽  
First Year Of Life

Abstract Context Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective To study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Design Prospective cohort study. Setting Study participants were recruited from a pediatric tertiary care center. Patients or Other Participants 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main Outcome Measures Plasma epinephrine levels (N=27), CYP21A2 genotype (N=15), and incidence of acute illnesses from birth to 1 year of age (N=28). Results Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β=-0.018, R=-0.45, P=0.02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R=-0.51, P=0.007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P=0.02). CAH patients had lower epinephrine as newborns than controls (P=0.007) and showed decreases in epinephrine from birth to 1 year of age (P=0.04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusions Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height

1997 ◽  
Vol 136 (2) ◽  
pp. 188-195 ◽  
Author(s):  
Naomi Weintrob ◽  
Zvi Dickerman ◽  
Elliot Sprecher ◽  
Avinoam Galatzer ◽  
Atalia Pertzelan
Keyword(s):  
Final Height ◽  
Bone Age ◽  
Peak Height ◽  
Height Velocity ◽  
Peak Height Velocity ◽  
Hydroxylase Deficiency ◽  
Group A ◽  
Parental Height ◽  
Group B ◽  
21 Hydroxylase Deficiency

Abstract Objective: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height. Design: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7·5–15 mg/m2 per 24 h, initiated ≥1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present. Participants: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0·5–10·6 years were followed-up for 9·0 ± 3·8 years (mean±s.d.). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels. Results: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7·9 ± 1·4 years and peak height velocity at 9·2 ± 1·4 years vs 10·2 ± 0·4 years (P = 0·002) and 11·5 ± 0·7 years (P = 0·006) in group A. Menarche, however, occurred only slightly earlier in group B (12·0 ± 1·1 vs 12·8 ±0·5 years, P = 0·068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0·0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0·041). The final height SDS was significantly better for group A (0·05 ± 0·19, mean ± s.e.m.) than group B (−1·63 ± 0·23, P = 0·0007), even when adjusted for a significant effect of the mean parental height SDS (A, −0·63 ± 0·28; B, −0·89 ± 0·31, P = 0·0245, ANCOVA). Conclusion: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height. European Journal of Endocrinology 136 188–195

scholarly journals Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency

2000 ◽  
pp. 397-403 ◽  
Author(s):  
N Weintrob ◽  
C Brautbar ◽  
A Pertzelan ◽  
Z Josefsberg ◽  
Z Dickerman ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Phenotypic Expression ◽  
Ethnic Origin ◽  
Stepwise Logistic Regression ◽  
Compound Heterozygous ◽  
Significant Variable ◽  
Hydroxylase Deficiency ◽  
Severe Mutation ◽  
Group B ◽  
21 Hydroxylase Deficiency

OBJECTIVE: To evaluate whether genotype differences can explain the clinical variability of non-classical steroid 21-hydroxylase deficiency (NC21-OHD) and to determine if genotype is related to ethnic origin. DESIGN: Genotyping for mutations in the steroid 21-hydroxylase (CYP21) gene was performed in 45 unrelated Israeli Jewish patients (nine males) with NC21-OHD (60min 17-hydroxyprogesterone (17-OHP), 45-386nmol/l) who were referred for evaluation of postnatal virilization or true precocious/early puberty. Eleven siblings diagnosed through family screening were genotyped as well. METHODS: Patients were divided by genotype into three groups: (A) homozygous or compound heterozygous for the mild mutations (V281L or P30L) (n=29; eight males); (B) compound heterozygous for one mild and one severe mutation (Q318X, I2 splice, I172N) (n=12; no males); (C) mild mutation detected on one allele only (n=4; one male; peak 17-OHP 58-151nmol/l). We then related the genotype to the ethnic origin, clinical phenotype and hormone level. Since group C was very small, comparisons were made between groups A and B only. RESULTS: At diagnosis, group B tended to be younger (5. 8+/-3.0 vs 8.1+/-4.3 years, P=0.09), had greater height SDS adjusted for mid-parental height SDS (1.6+/-1.1 vs 0.7+/-1.4, P=0.034), tended to have more advanced bone age SDS (2.9+/-1.5 vs 1.7+/-2.1, P=0.10) and had a higher peak 17-OHP level in response to ACTH stimulation (226+/-92 vs 126+/-62nmol/l, P<0.01). Group B also had pubarche and gonadarche at an earlier age (5.1+/-2.4 vs 7.4+/-2.2 years, P<0.01 and 7.4+/-1.8 vs 9.9+/-1.4 years, P<0.001, respectively) and a higher rate of precocious puberty (50 vs 17%, P=0.04). Stepwise logistic regression analysis (excluding males) yielded age at gonadarche as the most significant variable differentiating the two groups, with a positive predictive value of 86% for a cut-off of 7.5 years. CONCLUSIONS: The findings suggest that genotype might explain some of the variability in the phenotypic expression of NC21-OHD. Compound heterozygotes for one mild and one severe mutation have a higher peak 17-OHP associated with pubarche and gonadarche at an earlier age and more frequent precocious puberty. Hence, the severity of the enzymatic defect might determine the timing and pattern of puberty.

Immunity to Diphtheria, Pertussis, Tetanus, and Poliomyelitis in Children with Acute Lymphocytic Leukemia After Cessation of Chemotherapy

PEDIATRICS ◽  
1981 ◽  
Vol 67 (2) ◽  
pp. 222-229 ◽  
Author(s):  
A. van der Does-van den Berg ◽  
J. Hermans ◽  
J. Nagel ◽  
G. van Steenis
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
First Year ◽  
Healthy Children ◽  
Healthy Control ◽  
Antibody Titers ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Antibody Levels

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N= 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

scholarly journals In congenital hypothyroidism bone maturation at birth may be a predictive factor of psychomotor development during the first Year of life irrespective of other variables related to treatment

2003 ◽  
pp. 1-6 ◽  
Author(s):  
M Wasniewska ◽  
F De Luca ◽  
A Cassio ◽  
N Oggiaro ◽  
P Gianino ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Psychomotor Development ◽  
First Year ◽  
X Rays ◽  
Bone Maturation ◽  
Gestation Age ◽  
Group A ◽  
One Year ◽  
First Year Of Life ◽  
Tsh Levels

OBJECTIVE: To evaluate in a cohort of infants with congenital hypothyroidism (CH): (a) the frequency of bone maturation (BM) retardation at birth and (b) whether BM delay at birth may be considered as a tool to make a prognosis of psychomotor status at the age of 1 Year, irrespective of other variables related to treatment. DESIGN: BM at birth, CH severity and developmental quotient (DQ) at the age of 1 Year were retrospectively evaluated in 192 CH infants selected by the following inclusion criteria: (a) gestation age ranging between 38 and 42 weeks; (b) onset of therapy within the first Month of life; (c) initial thyroxine (l-T(4)) dosage ranging from 10 to 12 microg/kg/day; (d) normalization of serum thyrotropin (TSH) levels before the age of 3 Months; (e) Monthly adjustments of l-T(4) dose during the first Year of life with serum TSH levels ranging from 0.5 to 4 mIU/l; (f) no major diseases and/or physical handicaps associated with CH; (g) availability of both thyroid scanning and knee X-rays at the time of treatment initiation; (h) availability of DQ assessment at an average age of 12 Months. METHODS: BM was considered normal if the distal femur bony nucleus diameter exceeded 3 mm (group A) or retarded if either this nucleus was absent (subgroup B1) or its diameter was <3 mm (subgroup B2). DQ was evaluated with the Brunet-Lezine test. RESULTS: In 44.3% of cases BM was either delayed (23.5%) or severely delayed (20.8%). The risk of BM retardation was higher in the patients with athyreosis than in the remaining patients (41/57 vs 44/135, chi(2)=25.13, P<0.005). BM-retarded infants showed a more severe biochemical picture of CH at birth and a lower DQ at the age of one Year compared with the group A patients. If compared with infants of subgroup B2 those of subgroup B1 exhibited significantly lower T(4) levels at birth and a more frequent association with athyreosis (70.0 vs 30.0%; chi(2)=7.49, P<0.01), whereas DQ was superimposable in both subgroups. CONCLUSIONS: (a) BM at birth is delayed in almost half of CH patients and (b) CH severity per se can affect DQ at the age of 1 Year irrespective of other variables related to therapy.

Near-final height in 82 Chinese patients with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency: a single-center study from China

2016 ◽  
Vol 29 (7) ◽  
Author(s):  
Lin Juan ◽  
Ma Huamei ◽  
Su Zhe ◽  
Li Yanhong ◽  
Chen Hongshan ◽  
...  
Keyword(s):  
Treatment Group ◽  
Congenital Adrenal Hyperplasia ◽  
Early Treatment ◽  
Final Height ◽  
Adrenal Hyperplasia ◽  
Target Height ◽  
Hydroxylase Deficiency ◽  
Cox Regression Analysis ◽  
Late Treatment ◽  
21 Hydroxylase Deficiency

AbstractThe objective of this study was to identify variables that might interfere with reaching the near final height (NFH) in Congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD).A cross-sectional study of 82 (24 males and 58 females) classic (23 salt-wasting form [SW] and 59 simple-virilizing form [SV]) CAH 21-OHD patients seen in our institution between 1989 and 2015 with 10.6 (0.5~25.5) years of follow-up who reached their NFH was conducted. The variables related to NFH were explored.NFH (153.35±8.31) cm, (–1.9±1.1) SD was significantly lower than the normal population (p<0.001). The treated patients reached a significantly higher NFH (–1.7±1.1) SD than those untreated (–2.6±1.0) SD (p<0.05). Both of early treatment and late treatment group were taller than untreated group (p<0.001, p=0.013, respectively), and early treatment group had a taller height trend than late treatment group (p=0.089). A better height outcome was observed in patients with advantage in target height, good compliance, and low hydrocortisone dose by multivariate Cox regression analysis in 62 treatment patients. NFH and hydrocortisone dose was negatively correlated (r=–0.23, p=0.078) in treated group. Patients complicated by central precocious puberty (CPP) received gonadotropin-releasing hormone analogue (GnRHa) plus letrozole had increased NFH with height SD for bone age and Ht SD improved after treatment compare to no intervention group (p=0.001, p=0.035).Patients with classic 21-OHD have blunted final height, as compared with their target height and the population norm, not-treated even worse. Careful treatment adjustments have a favorable influence on growth. Alternative treatments, such as the use of puberty inhibitors GnRHa in addition to anti-estrogen therapy letrozole can somewhat improve NFH in children with 21-OHD complicated by CPP.

Experimental Study on Early Diagnosis of Malignant Pleural Mesothelioma with Computed Tomography Combined Serum Soluble Mesothelin-Related Proteins

2021 ◽  
Vol 11 (3) ◽  
pp. 667-671
Author(s):  
Jiang Jie ◽  
Qin Zhanxiong ◽  
Wu Li ◽  
Xie Xiaojie ◽  
Zhao Xunran ◽  
...  
Keyword(s):  
Serum Level ◽  
Early Diagnosis ◽  
Pleural Cavity ◽  
Control Group ◽  
Post Injection ◽  
Pleural Thickening ◽  
Time Period ◽  
Group A ◽  
Group B ◽  
Related Proteins

Objective: To investigate the value on early diagnosis of experimental rat according to computed tomography (CT) combined with the serum level of Serum Soluble Mesothelin-related Proteins (SMRP). Methods: Thirty-two SD rat were divided into three groups, including group A (experimental group) of 20 rats with pleural cavity injection of crocidolite suspension, group B (negative control group) of 6 rats with pleural cavity injection of saline, group C (blank control group) of 6 rats without any processing. Chest and abdominal CT scan and enhancement were performed in the three months and six months after induction and the pleural thickening was analyzed. The serum level of SMRP was measured at the different time period including pre-injection, the postinjection first month, the second month, the third month and the sixth month. The correlation between pleural thickening and serum level of SMRP was analyzed. Results: In group A: 20 cases were performed on CT scan in post-injection third month and we found 13 cases without pleural lesions and 7 cases with pleural lesions including of 4 cases with mild pleural thickening, 1 moderate thickening and 2 severe thickening (2 cases died). Moreover, 18 cases were done by CT in post-injection third month and we found 3 cases without pleural lesions and 15 cases with pleural lesions including of 6 cases with mild pleural thickening, 5 moderate thickening and 4 severe thickening (3 cases died). No pleural lesions were found in group B and group C. SMRP expression level differences in the three groups was statistically significant. However, there was no difference in pre-injection in the three groups and there were no difference in group B and C at the different time period. In group A, there was no difference between post-injection first month and second month, whereas, there had statistically difference in post-injection third and sixth month. In group A, SMRP level gradually increased over time. The high correlation between pleural thickening and serum level of SMRP was seen at the post-injection third and sixth month, which the expression of SMRP gradually increased as the pleural thickening. Conclusion: Serum SMRP expression level has a certain value for early diagnosis and staging of MPM, which can be used as an important biomarker for early screening of high-risk groups exposed to asbestos.

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