Strength of relationship between body mass index and gross motor capacity in youth with intellectual disabilities.

BACKGROUND: Adequate skill levels of gross motor capacity affect activities of daily living, participation in recreational activities and general physical activity levels of youths (7-21 years). Most studies of typically developing youths have reported significant negative relationships between gross motor capacity and body mass index. The latter findings are especially of concern for youths with intellectual disabilities in that it has been estimated that 61% of children and 66% of adolescents were classified as overweight/obese. Therefore, the purpose of this study was to determine the strength of the relationship between body mass index and gross motor capacity among youths with mild to moderate intellectual disability (ID). METHODS: Components of the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) were used for designated aspects of gross motor capacity: six items for upper limb coordination (ULC); seven items for balance (BAL); six items for bilateral coordination (BLC); and one item for agility (A-2). Participants consisted of 654 youths (438 men), ages 8-21 years with ID. Participants were divided into pre-puberty and post-puberty men (post ≥12 years) and women (post ≥10 years of age). Body mass index (BMI, kg/m2) was determined by height and weight measurements on the day of testing. A Kendall's tau correlation coefficient (τ) was used to determine the strength of the relationship between body mass index and gross motor capacity (BOT-2 test scores). RESULTS: The τ values for both pre-puberty and post-puberty for all BAL, BLC, A-2 tests and for three of the six ULC tests were negligible to very weak (τ = 0 to ±0.19). Higher τ values were seen for pre-puberty youths in three of the ULC tests, but they fell within the weak range (τ < 0.24). When combining all pre-puberty and post-puberty participants, τ values were in the negligible to very weak range for all tests. CONCLUSION: The strength of relationship between body mass index and gross motor capacity as measured by the BOT-2 subtest item scores used in this study is very weak and suggests that they are not clinically relevant.

Association of muscular strength with total and central adiposity in adolescents with intellectual disability.

BACKGROUND: It has been established that for youth without disabilities, muscular strength (MS) is negatively associated with total and central adiposity. However, this relationship has not been clearly established for youth with intellectual disability (ID). The purpose of this study was to examine the association of MS with total and central adiposity in adolescents with ID. METHOD: Participants were 59 adolescents (40 males and 19 females: age 16.29 ± 1.66 years) with ID. Total and central adiposity were evaluated with dual-energy x-ray absorptiometry (DXA), body mass index (BMI), BMI z-score, waist circumference (WC), and conicity index (C-index). MS was evaluated with the score on the Bruininks-Oseretsky Test of Motor Proficiency (range, 0 to 42, with higher scores indicating better performance). Sex-specific maturity offset equations were used to evaluate somatic maturity. Spearman's correlation coefficients and sequential multiple regression were used to examine associations between MS and adiposity. RESULTS: Muscular strength score was negatively associated with BMI (sr = -0.32; P < 0.05), percent body fat (%BF; total, trunk, android and gynoid regions) (sr = -0.51 to -0.58; P < 0.01), and android-to-gynoid fat ratio (sr = -0.29; P < 0.05). After control for somatic maturity and sex, regression analysis indicated that MS score explained 10%-17% of the variance in BMI, BMI z-score, %BF (total, trunk, android and gynoid regions), WC, C-index and android-to-gynoid fat ratio. CONCLUSIONS: These findings suggest that MS is associated with DXA- and anthropometric-determined total and central adiposity among adolescents with ID.

Sex dimorphism of weight and length at birth: evidence based on disorders of sex development.

BACKGROUND: Males have higher weight and length at birth than females. AIM: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). SUBJECTS AND METHODS: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. RESULTS: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. CONCLUSIONS: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

Predicting the rate of oxygen uptake from step counts using ActiGraph waist-worn accelerometers in adults with Down syndrome.

BACKGROUND: Step rate predicts ambulatory intensity as reflected in the rate of oxygen uptake (VO2 ) - a measure of energy expenditure. Whether step rate as measured by an accelerometer predicts VO2 in adults with Down syndrome (DS) is unknown. We examined whether step rate predicts VO2 in adults with and without DS. We also developed an equation for predicting VO2 and examined its accuracy. METHOD: Sixteen adults with DS (6 women and 10 men; age 31 ± 15 years) and 19 adults without DS (9 women and 10 men; age 25 ± 6 years) performed standing and walking at their preferred speed, 0.8 and 1.4 m·s-1 . We measured VO2 with a portable spirometer and step rate with a triaxial accelerometer (wGT3X-BT; ActiGraph) on the non-dominant hip, using the low-frequency extension filter. We ran multilevel regression for predicting VO2 from linear and quadratic terms for step rate, group (1 = DS; 0 = non-DS), body mass, height, body mass index (BMI), leg length and sex. We estimated VO2 with the resultant equation and calculated the equation's absolute per cent error, which we compared between groups. RESULTS: VO2 was higher in persons with than without DS only at the fast walking speed (P = 0.018). DS did not predict VO2 . Step rate, step rate squared and BMI were significant predictors of VO2 (P < 0.001; R2  = 0.80). Absolute error across walking speeds was 13.5-18.8% and 11.7-13.4% for adults with and without DS, respectively, and did not differ between groups or speeds. CONCLUSIONS: Step rate, step rate squared and BMI predict VO2 in adults with and without DS. Prediction error does not differ between groups.

Two Novel Mutations in the Thyroid Hormone Receptor ß in Patients with Resistance to Thyroid Hormone (RTH ß): Clinical, Biochemical, and Molecular Data.

The syndrome of resistance to thyroid hormone (RTH ß) is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,30-L-triiodothyronine (T(3)), with persistent elevation of free-circulating T(3) (FT(3)) and free thyroxine (FT(4)) levels in association with nonsuppressed serum thyrotropin (TSH). Clinical presentation is variable and the molecular analysis of THRB gene provides a short cut diagnosis. Here, we describe 2 cases in which RTH ß was suspected on the basis of laboratory findings. The diagnosis was confirmed by direct THRB sequencing that revealed 2 novel mutations: the heterozygous p.Ala317Ser in subject 1 and the heterozygous p.Arg438Pro in subject 2. Both mutations were shown to be deleterious by SIFT, PolyPhen, and Align GV-GD predictive methods.

Secular trends of height, weight and BMI in young adult Brazilian military students in the 20th century.

BACKGROUND: Secular trends of increasing weight and height over past centuries are well documented in developed countries. However, these data are still scarce in developing countries such as Brazil. AIM: To verify the secular trends of height, weight and body mass index (BMI) of military students from Brazilian Army schools who were born between the 1920s and 1990s. SAMPLE AND METHODS: A retrospective study was performed, which included a survey of data from the files of two Army schools. The sample was composed of subjects aged between 18-20 years old. RESULTS: The study analysed 2169 heights and 1741 weights and BMIs. During the evaluation period, height increased 7.3 cm, weight 9.8 kg and BMI 1.8 kg/m(2). The most significant gains were observed in subjects born from the 1920s to the 1940s and the 1960s to the 1970s. CONCLUSION: Secular trends of growth in military students born in the 20th century were positive in Brazil, although increases were not constant decade-by-decade.

Complete XY gonadal dysgenesis due to p.D293N homozygous mutation in the NR5A1 gene: a case study.

The SRY gene (sex-determining region on the Y chromosome; MIM *480000) is responsible for initiating male gonadal development. However, only 15-20% of the cases of XY gonadal dysgenesis are due to mutations in its sequence. Recently, heterozygous mutations in the NR5A1 gene (nuclear receptor subfamily 5, group A, member 1; MIM +184757) have been described in association with ovarian failure and disorders of testis development with or without adrenal failure. Here we describe a case of XY complete gonadal dysgenesis due to a p.D293N homozygous mutation in the NR5A1 gene, with normal SRY and no adrenal failure.

Influence of gender on the EMG signal of the quadriceps femoris muscles and performance in high-intensity short-term exercise.

The aim of this study was to investigate the influence of gender on the EMG signal of the muscles of the quadriceps femoris and the physical performance in high-intensity, short-term exercise. Fourteen volunteers (7 men = 29.1 +/- 2.8 years and 7 women = 22.6 +/- 2.9 years) performed a Wingate Test (WT) with a load of 7.5% of body mass. The variables analyzed during the WT were the Relative Peak Power (W.Kg(-1)) (RPP), Relative Mean Power (W.Kg(-1)) (RMP), Fatigue Index (%) (FI) and Peak Power Instant (s) (PPI). EMG signals of the superficial muscles of the quadriceps femoris (QF) from the right leg: rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) were analyzed through root mean square (RMS) values and the normalized median frequency (MNF) determined using the Fast Fourier Transform (FFT). The RPP and the RMP were significantly higher in men when compared to women (9.99 +/- 0.96 vs. 7.66 +/- 1.00 W.kg(-1); 7.23 +/- 0.49 vs. 5.65 +/- 0.61 W.kg(1), P < 0.05; respectively). No significant difference between genders was found on RMS and NMF during WT (P > 0.05). Although RPP and RMP were influenced by gender, the RMS and the NMF of the superficial muscles of the QF did not show the same behavior, suggesting that other mechanisms, not related to motor unit recruitment and speed of nervous stimuli in the muscle fiber may be associated to the lower performance of women in high-intensity, short-term exercise.

Complement 4 phenotypes and genotypes in Brazilian patients with classical 21-hydroxylase deficiency.

The aim of this work was to analyse C4 genotypes, C4 protein levels, phenotypes and genotypes in patients with the classical form of 21-hydroxylase deficiency. Fifty-four patients from 46 families (36 female, 18 male; mean age 10.8 years) with different clinical manifestations (31 salt-wasting; 23 simple-virilizing) were studied. Taq I Southern blotting was used to perform molecular analysis of the C4/CYP21 gene cluster and the genotypes were defined according to gene organization within RCCX modules. Serum C4 isotypes were assayed by enzyme-linked immunosorbent assay. The results revealed 12 different haplotypes of the C4/CYP21 gene cluster. Total functional activity of the classical pathway (CH50) was reduced in individuals carrying different genotypes because of low C4 concentrations (43% of all patients) to complete or partial C4 allotype deficiency. Thirteen of 54 patients presented recurrent infections affecting the respiratory and/or the urinary tracts, none of them with severe infections. Low C4A or C4B correlated well with RCCX mono-modular gene organization, but no association between C4 haplotypes and recurrent infections or autoimmunity was observed. Considering this redundant gene cluster, C4 seems to be a well-protected gene segment along the evolutionary process.

Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients.

BACKGROUND: Most patients with 21-hydroxylase deficiency carry CYP21A1P-derived mutations, but an increasing number of novel and rare mutations have been reported in disease-causing alleles. OBJECTIVE: Functional effects of three novel (p.G56R, p.L107R, p.L142P) and one recurrent (p.R408C) CYP21A2 mutations were investigated. The degree of enzyme impairment caused by p.H62L alone or combined to p.P453S was also analyzed. DESIGN: The study included 10 Brazilian and two Scandinavian patients. To determine the deleterious role of each mutant protein, in vitro assays were performed in transiently transfected COS-1 cells. For a correct genotype-phenotype correlation, the enzymatic activities were evaluated toward the two natural substrates, 17-hydroxyprogesterone and progesterone. RESULTS: Low levels of residual activities obtained for p.G56R, p.L107R, p.L142P, and p.R408C mutants classified them as classical congenital adrenal hyperplasia mutations, whereas the p.H62L showed an activity within the range of nonclassical mutations. Apparent kinetic constants for p.H62L confirmed the nonclassical classification as the substrate binding capacity was within the same magnitude for mutant and normal enzymes. A synergistic effect was observed for the allele bearing the p.H62L+p.P453S combination because it caused a significant reduction in the enzymatic activity. CONCLUSIONS: We describe the functional analysis of five rare missense mutations identified in Brazilian and Scandinavian patients. The p.G56R, p.L107R, and p.L142P are reported for the first time. Most probably these novel mutations are closer to null than the p.I172N, but for the p.G56R, that might not be the case, and the p.H62L is definitely a nonclassical mutation.

Congenital perineal lipoma presenting as ambiguous genitalia.

BACKGROUND: Congenital perineal lipoma is extremely rare and may lead to a misdiagnosis of ambiguous genitalia. CASE REPORTS: We report on two girls referred to our service for ambiguous genitalia. Patient 1 (17 days old) and patient 2 (2 months old) had unremarkable gestational and perinatal histories. Both had normal female external genitalia and a 46,XX karyotype. Patient 1 had a polypoid, protruding 3.0 x 2.0 x 1.5-cm phallic-like mass arising at the inferior border of the left labium majora, and patient 2 had a similar mass of 1.5 x 1.5 x 1.0 cm at the same site and an imperforate anus. In both cases the mass was removed and found to be a lipoma. DISCUSSION: To our knowledge, perineal lipoma has been reported only in eleven girls, nine of them with associated anorectal malformation. Migration and fusion of the labioscrotal folds and formation of the urorectal septum are simultaneous developmental events occurring in the same region, which may explain the association of perineal lipoma and anorectal malformations.

Association between serotonin 2C receptor gene (HTR2C) polymorphisms and psychopathological symptoms in children and adolescents.

Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory. Eighty-five psychiatric outpatients between 8 and 18 years of age underwent genotyping of the rs6318 SNP. The CBCL/6-18 scale was administered to their caregivers. The chi-squared test was used to assess differences in the frequency of C and G alleles of the rs6318 SNP relative to the grouped CBCL/6-18 scores; significance level was 5%. The presence of the G allele of rs6318 was found to be associated with characteristics of aggressive behavior and social problems, and aggressive behavior was found to be associated with heterozygosis in females. These findings contribute to the identification of mental and behavioral phenotypes associated with gene expression.

The influence of parental origin of X chromosome genes on the stature of patients with 45 X Turner syndrome.

Thirty-seven 45 X Turner syndrome patients with confirmed peripheral blood lymphocyte karyotype were initially selected to determine the origin of the retained X chromosome and to correlate it with their parents' stature. Blood samples were available in 25 families. The parental origin of the X chromosome was determined in 24 informative families through the analysis of the exon 1-CAG repeat variation of the androgen receptor gene. In 70.8% of the cases, the retained X chromosome was maternal in origin and 29.2% was paternal. When we classified the patients according to maternal (Xm) or paternal (Xp) X chromosome, there was a positive correlation between patients' and maternal heights only in the Xm group. There was no correlation with paternal height in either group, and a significant correlation with target height was only observed in the Xm group. In conclusion, maternal height is the best variable correlating with the height of 45 X Turner syndrome patients who retain the maternal X chromosome, suggesting a strong influence of genes located on the maternal X chromosome on stature.

Bone density gain at proximal phalanges in healthy males aged 18-25 years after 16 weeks of upper-arm muscle weight training.

AIM: The aim of this study was to determine the effect of an upper-arm muscle weight training (WT) protocol over 16 weeks on bone density at the proximal phalanges in young healthy men. METHODS: Fifty-one healthy volunteer men were selected, 16 for an experimental group and 35 for a control group. The experimental group was submitted to the prescribed WT protocol to develop the strength of upper arm muscles, during 16 weeks, at a frequency of 3 times per week for approximately 60 min per session. Anthropometric data (weight, height, body mass index, corrected mid upper-arm circumference [cMUAC], and percentage of upper-arm muscle mass [%UAMM]) and bone density by quantitative ultrasound (DBM Sonic BP, IGEA, Italy) at proximal phalanges (amplitude dependent speed of sound [AD-SoS], T-score, %T-score) were evaluated on non-dominant limb before the beginning of the study (T0) and after 16 weeks (T1). RESULTS: There were no significant differences among all variables at T0 and T1 in the control group, nor at T0 between both groups. In the experimental group, cMUAC, %UAMM, AD-SoS, T-score and %T-score were significantly higher at T1 in relation to T0, as well as between T1 of the experimental group and T1 of the control group (all with P<0.0001). The gain of %T-score showed a correlation between cMUAC gain (P=0.005) and %UAMM gain (P=0.002). The experimental group showed 7% of bone mass gain. CONCLUSION: These data suggested that a WT protocol to develop strength of upper arm muscles over 16 weeks was effective for increasing bone density at the proximal phalanges in healthy young men.

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene.

BACKGROUND: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. OBJECTIVE: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis. METHODS: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR. RESULTS: The median ages at presentation and at the time of the study were 1 month (range, 1 day to 16 years) and 22 years (range, 16 to 52 years), respectively. Of the cohort, 29 men (56%) had 20 different AR mutations reported. At diagnosis, the median external masculinization scores were 7 and 6 in cases with and without AR mutation, respectively (P = .9), and median current external masculinization scores were 9 and 10, respectively (P = .28). Thirty-five men (67%) required at least one surgical procedure, and those with a mutation were more likely to require multiple surgeries for hypospadias (P = .004). All cases with an AR mutation had gynecomastia, compared to 9% of those without an AR mutation. Of the six men who had a mastectomy, five (83%) had an AR mutation. CONCLUSIONS: Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation. Routine genetic analysis of AR to confirm PAIS informs long-term prognosis and management.

Inhibin alpha-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers.

The R337H TP53 mutation is a low-penetrance molecular defect that predisposes to adrenocortical tumour (ACT) formation in Brazilian and possibly other populations. Additional genetic defects may be responsible for the variable expression of ACTs in these cases. The inhibin alpha-subunit gene (INHA) on 2q33-qter has been implicated in mouse adrenocortical tumourigenesis. We studied 46 pediatric patients with ACTs from Brazil for INHA genetic alterations; 39 of these patients were heterozygous carriers of the R337H TP53 mutation. We first mapped the INHA gene by radiation hybrid analysis and determined 10 linked microsatellite markers in an area flanked by D2S1371 and D2S206 on 2q33-qter. These markers were then used for loss of heterozygozity (LOH) studies in nine paired germline and tumour DNA samples. Mapping placed the INHA gene in close proximity to D2S2848 (SHGC11864) with a log of odds (LOD) score of 5.84. LOH for at least one marker in the region was identified in 8/9 tumours (89%). Six patients were heterozygous for three INHA mutations: one in exon 1, 127C>G, and two in exon 2, 3998G>A and 4088G>A, all leading to amino acid substitutions (P43A, G227R, and A257T, respectively). A257T is located in a conserved INHA region, highly homologous to transforming growth factor-beta; both G227R and A257T change polarity, and, in addition, G227R changes the pH. We conclude that these sequence alterations and the detected 2q allelic changes suggest that INHA may be one of the contributing factors needed for ACT formation in pediatric patient carriers of the R337H TP53 mutation.

Mutations in SRY and WT1 genes required for gonadal development are not responsible for XY partial gonadal dysgenesis.

The WT1 transcription factor regulates SRY expression during the initial steps of the sex determination process in humans, activating a gene cascade leading to testis differentiation. In addition to causing Wilms' tumor, mutations in WT1 are often responsible for urogenital defects in men, while SRY mutations are mainly related to 46,XY pure gonadal dysgenesis. In order to evaluate their role in abnormal testicular organogenesis, we screened for SRY and WT1 gene mutations in 10 children with XY partial gonadal dysgenesis, 2 of whom with a history of Wilms' tumor. The open reading frame and 360 bp of the 5' flanking sequence of the SRY gene, and the ten exons and intron boundaries of the WT1 gene were amplified by PCR of genomic DNA. Single-strand conformation polymorphism was initially used for WT1 mutation screening. Since shifts in fragment migration were only observed for intron/exon 4, the ten WT1 exons from all patients were sequenced manually. No mutations were detected in the SRY 5' untranslated region or within SRY open-reading frame sequences. WT1 sequencing revealed one missense mutation (D396N) in the ninth exon of a patient who also had Wilms' tumor. In addition, two silent point mutations were found in the first exon including one described here for the first time. Some non-coding sequence variations were detected, representing one new (IVS4+85A>G) and two already described (-7ATG T>G, IVS9-49 T>C) single nucleotide polymorphisms. Therefore, mutations in two major genes required for gonadal development, SRY and WT1, are not responsible for XY partial gonadal dysgenesis.

True agonadism: report of a case analyzed with Y-specific DNA probes.

We report on a 5-year-old girl with a male karyotype (46,XY), severe psychomotor and physical retardation, minor anomalies, and female external genitalia with a blindly ending vagina. She has normal adrenal function, prepubertal serum gonadotropin and testosterone levels, which did not rise after hCG stimulation. On abdominal exploration no gonads were found, and only mesonephric and Müllerian remnants. She was HY positive, and no deletion was detected in the Y chromosome using 5 different probes. Although a genetic defect is not excluded, pregnancy complications suggest an environmental insult to the developing testes.

Evaluation of the tubular and interstitial functions of the testis in 46,XY patients with ambiguous genitalia.

Investigation of the origin of sexual ambiguity is complex. Although testicular function has traditionally been assessed only by examining the steroidogenic capacity of Leydig cells and spermatogenesis, it has recently been shown that the measurement of serum anti-Müllerian hormone (AMH) as a marker of Sertoli cell function may also help clinicians. The aim of this study was to evaluate both Leydig and Sertoli cell functions in 46,XY patients with intersex states in order to establish biochemical patterns that would help to reach an etiologic diagnosis. We measured serum androgens, AMH and gonadotropins in 24 patients with sexual ambiguity and XY karyotype: 8 with gonadal dysgenesis (GD), 3 with 3beta-hydroxysteroid dehydrogenase deficiency (3betaHSD), 5 with androgen insensitivity syndrome (AIS), 4 with 5alpha-reductase 2 (SRD5A2) deficiency, and 4 were of unknown origin or idiopathic. Our results showed that while testosterone was low and gonadotropins elevated in patients with either GD or 3betaHSD, AMH was low in the former and high in the latter. Serum AMH and gonadotropins were normal or high in patients with 3betaHSD or AIS, but these could be distinguished by testosterone levels. Serum testosterone and gonadotropins were normal or high in AIS and SRD5A2 deficiency patients; however, while AMH was elevated in AIS, it was not the case in SRD5A2 deficiency patients, indicating that testosterone is sufficient to inhibit AMH within the testis. In idiopathic cases gonadotropins and testosterone were normal, and AMH was normal or low. We conclude that the combined measurement of androgens, AMH and gonadotropins helps to establish the diagnosis in intersex patients.