[Show abstract][Hide abstract] ABSTRACT: 5α-reductase (5α-R) deficiency is an important cause of ambiguious genitalia in genetic males; however therapeutic experience in literature is limited. In this report authors describe a child with 46 XY Disorder of Sexual Differentiation (DSD), due to 5α-reductase deficiency, who was managed with Dihydrotestosterone (DHT) gel.
The Indian Journal of Pediatrics 09/2013; · 0.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: T is converted to a more potent androgen, DHT by the action of microsomal membrane enzyme 5α reductase 2. Defects in 5α reductase 2 isozyme results in incomplete virilisation of external male genitalia. Mutations in SRD5A2 gene leads to diminished enzyme activity, thus hampering DHT synthesis from T. We describe two unrelated patients from India with 5αRD2 due to novel insertion of nucleotides in the exon 1 of SRD5A2 gene that lead to premature termination of protein. Master S (case 1, III.8) was 3 years old at initial evaluation, had perineoscrotal hypospadias, microphallus and both testes were palpable in the inguinal region. Master P (case 2; III.9) was born as normal full term baby. He had primary complaint of microphallus, penoscrotal hypospadias and gonads in the inguinal region. Diagnosis of 5αRD2 was made, as T/ DHT ratio in the two cases was 41 and 131.2 respectively. Sequence analysis of SRD5A2 gene showed an insertion of nucleotides TA in exon 1 (c.188_189). This resulted in premature termination of the protein due to stop codon at amino acid position 7. The protein formed is drastically truncated and inadequate protein synthesised explains the phenotypic characteristics of our patients.
[Show abstract][Hide abstract] ABSTRACT: Abstract Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23 ± 5.6 years and 25 ± 4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4 ± 5.1 versus 11.3 ± 4.5, p < 0.01) and over-weight PCOS women group (13.4 ± 5.1 versus 9.3 ± 3.2, p < 0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.
[Show abstract][Hide abstract] ABSTRACT: Context:To improve the treatment outcomes in women with PCOS, various drugs like glitazones, OCP's or anti-androgens have been combined with metformin.Objective:To compare the efficacy of combination of low dose spironolactone and metformin with either drug alone in the management of women with PCOS.Design and Setting:The present study was an open labelled, randomized study conducted at tertiary care referral centre.Patients and Intervention:Out of 204 women who qualified Androgen Excess-PCOS (AE-PCOS) 2006 criteria for PCOS, 198 were randomized into 3 equal groups to receive metformin (1000 mg/day), low dose spironolactone (50 mg/day) or combination of the both drugs for a period of six months. One hundred sixty nine (metformin n=56, spironolactone n=51 and combination n=62) subjects completed the study.Main outcome measures:Menstrual cycle pattern, Ferriman-Gallwey (FG) score, body mass index (BMI), waist-hip ratio, blood pressure (BP), LH, FSH, total T, glucose and insulin sensitivity indices were measured at baseline (0 month), at 3 and 6 months after the intervention. Recording of adverse events and drug compliance was assessed at each of the visits.Results:The three groups had comparable mean age and BMI at baseline. By 6 months, menstrual cycles/year increased whereas FG score, serum total T, AUC-glucose and AUC-insulin decreased significantly (P<0.05) in the combination group as compared to either drug alone. There was no significant change in body weight, BMI, WHR, and BP in any of the three groups. The combination group had better compliance than either drug alone and adverse event rate was not higher.Conclusion:Combination of low dose spironolactone with metformin seems superior to either drug alone in terms of clinical benefits and compliance in women with PCOS.
The Journal of Clinical Endocrinology and Metabolism 07/2013; · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Master N had genital malformation at birth and had bilateral gonads in the labial fold. He was reared as a boy and corrective surgery was done at the age of 4 years and was reassessed at the age of 14 years. His testosterone/dihydrotestosterone (DHT) was 11.8 (reference range <=10). Molecular analysis of SRD5A2 gene indicated the presence of a novel heterozygous missense mutation of p.A52T in exon 1, which was also detected in mother. The father, sister and maternal grandfather were found to have normal SRD5A2 gene sequence. We also detected an intronic (1-2) homozygous T>C transition in patient, whereas both parents were found to have the same transition in heterozygous form. Although 5α-steroid reductase 2 deficiency is an autosomal-recessive disorder, in this case, it appears that there may be a dominant inheritance because only one identified mutation was present which was passed from mother to son.
[Show abstract][Hide abstract] ABSTRACT: Congenital adrenal hyperplasia (CAH) is one of the inborn errors of metabolic disorder inherited in an autosomal recessive manner caused by the defects in the steroid 21 hydroxylase CYP21A2 gene. We analyzed the genotype of 62 patients with classic CAH.
To find out the underlying mutations of CYP21A2 gene.
Cohort of CAH patients.
Sixty-two patients with CAH were recruited from the endocrine clinic at AIIMS. Electrochemiluminiscence method was used for estimating the levels of cortisol. Radioimmunoassay kit-based method was used for estimating the 17 OHP levels. Polymerase chain reaction amplification was done using specific primers to amply the CYP21A2 gene.
Statistical analysis was done by using Epi Info Version 126.96.36.1998.
Out of 62 patients, 50 were simple virilizers (SV) and 12 were salt wasters (SW). Fifty-six were females and six were males. Five 46, XX children were reared as males. Age at presentation varied from 8 months to 38 years. Molecular genetic analysis revealed that the highest number of patients harboured (In 2) IVS2-13 A/C > G (48%), followed by p.P30L (46%), p.Q318X (35%), (D 8 bp) deletion 8 bp (26%), p.I172N (26%), and p. R356W (20%) mutations.
This is among the few studies to analyze the mutational spectrum of CYP21A2 gene in a large CAH cohort from India. Molecular diagnosis of CYP21A2 gene should be considered as part of the CAH evaluation to assess the risk of the patients/parents/siblings and to offer genetic counseling.
Indian journal of endocrinology and metabolism. 05/2012; 16(3):384-8.
[Show abstract][Hide abstract] ABSTRACT: This study analysed the relationship of plasma testosterone with β-cell secretion, insulin sensitivity and other pituitary-target gland hormones in normoglycaemic adult men. The sample frame was the 'Offspring of individuals with diabetes study' database. A total of 358 offspring of individuals with type-2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged ≥18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C-peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 ± 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C-peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C-peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and β-cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4.
[Show abstract][Hide abstract] ABSTRACT: The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM) on insulin sensitivity and β-cell function in normoglycemic offspring.
Offspring of T2DM patients (cases) and individuals without family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes.
A total of 271 cases (age 22 ± 10 years; 53% males) and 259 controls (28 ± 10 years, 66% males) were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120) were significantly higher and whole-body insulin sensitivity (WBISI) and disposition index (0-120) [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC) of proinsulin (during OGTT) and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM), maternal DM (MDM), grandparental DM (GPDM), and both parents DM (BPDM). The magnitude of differences varied with relationship (greater when both parents and grandparents were affected). Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender) in the BPDM and GPDM groups respectively compared to controls.
We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and β-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.
Indian journal of endocrinology and metabolism. 01/2012; 16(1):105-11.
[Show abstract][Hide abstract] ABSTRACT: Diabet. Med. 28, 1337–1342 (2011)AbstractAims Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India.Methods Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form.Results Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 ± 7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in 4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied.Conclusions The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.
Diabetic Medicine 10/2011; 28(11):1337 - 1342. · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether subclinical hypothyroidism (SCH) alters the phenotype, insulin resistance, or lipid parameters in young women with polycystic ovary syndrome (PCOS).
Prospective case-control study.
Tertiary care setting.
Sixty-two young women with PCOS and SCH (group I) and 291 euthyroid women with PCOS (group II).
Recording of clinical, biochemical, hormonal profile, and parameters of insulin resistance.
Whether SCH has any association with clinical parameters like hirsutism, menstrual disturbances, lipid profile, and parameters of insulin sensitivity.
Mean (±SD) TSH was 7.13±1.28 IU/L in group I and 2.51±1.21 IU/L in group II, with comparable free triiodothyronine and free thyroxine. The two groups were comparable in age, weight, and body mass index. Parameters like blood pressure, menstrual pattern, and degree and duration of hirsutism did not differ between the two groups. Serum concentrations of triglycerides were significantly higher in the SCH group compared with controls. Plasma glucose concentrations both in fasting and after oral glucose tolerance test were similar between the two groups. Fasting insulin and other parameters of insulin resistance were not altered by SCH.
Mild TSH elevation in the face of normal serum free triiodothyronine and free thyroxine results in a mild increase in serum lipids. Subclinical hypothyroidism is not associated with alteration in phenotypic expression and insulin resistance in young women with PCOS.
Fertility and sterility 02/2011; 95(6):2039-43. · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Offspring of type 2 diabetics have an increased risk of dyslipidemia, glucose intolerance and obesity. The aim of this study was to assess the lipid levels in the offspring of diabetics with normal glucose tolerance and normal body weight.
Normal weight offspring of patients with type 2 diabetes mellitus (DM) who had normal glucose tolerance, and healthy gender matched controls of comparable age without a family history of diabetes mellitus, were the subjects of this study. Lipid profiles were determined in cases and controls.
The study included 114 subjects (64 males and 50 females) in each group, aged (mean ± SD) 24.0 ± 7.9 in cases and 24.1 ± 8.0 years in controls. The body mass index (BMI) was 20.8 ± 3.0 and 20.2 ± 3.1 kg/m2 in cases and controls, respectively. Serum total cholesterol, triglycerides, plasma glucose, fasting insulin, C-peptide and proinsulin levels were comparable in cases and controls. Serum high density lipoprotein (HDL) cholesterol was lower (p <0.001), whilst the serum triglyceride/HDL ratio, low density lipoprotein (LDL) cholesterol and area under the curve for insulin and proinsulin during an oral glucose tolerance test were higher in cases compared to controls. HDL cholesterol showed no significant correlation with plasma glucose, insulin or proinsulin.
Plasma HDL cholesterol is low among normal weight, normoglycemic offspring of subjects with type 2 diabetes mellitus. The implications of this finding are not apparent.
[Show abstract][Hide abstract] ABSTRACT: There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS). This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH) levels with body mass index (BMI) and glucose tolerance.
The sample frame was the "Offspring of individuals with diabetes study" database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM) and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were ≥10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT), and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.
Four hundred and ninety-five participants (305 males [62%] and 190 females [38%]) were included in the analysis. ACTH and cortisol levels were higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and cortisol increased as fasting plasma glucose increased. Cortisol levels were significantly lower in offspring of T2DM subjects with MS than in offspring of T2DM subjects without MS. When adjusted for BMI, the significance was marginal. In males, cortisol levels were negatively correlated with early insulin secretion during OGTT (insulinogenic index [0-30]) and positively with waist circumference and serum high-density lipoprotein cholesterol. In females, fasting glucose and systolic blood pressure were significantly and positively correlated.
Body weight was correlated negatively with morning plasma cortisol and ACTH, whereas fasting glucose was correlated positively.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 01/2011; 4:347-52.
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of type 1 diabetes mellitus (T1DM) requires a genetic predisposition to particular environmental triggers that may activate mechanisms leading to progressive loss of pancreatic beta cells.
We tried to compare the impact of some demographic and environmental factors and breast-feeding on children (aged < 18 years) with recent onset diabetes mellitus (≤1 year) with that on age, sex, and socioeconomic status-matched controls.
A total of 43 consecutive patients (male, 24, mean age ± SD = 12.58 ± 9.6 years) and equal number of controls without diabetes mellitus or dysglycemia were included in this hospital-based case-control study.
A distinct peak in the incidence noted in the early adolescence with segregation in the winter months. Our patients did not differ significantly from the controls with regard to birth order, mode of delivery, parental age, parental education, dietary practices, breast-feeding, and migration in the family. Growth characteristics and nutritional status were also similar. A population study with more power will be better equipped to answer such queries.
Indian journal of endocrinology and metabolism. 01/2011; 15(1):38-42.
[Show abstract][Hide abstract] ABSTRACT: Some recent studies observed that a number of obese children had family members with type 2 diabetes. The aim of the present study was to assess prevalence of obesity and metabolic abnormalities among offspring of subjects with type 2 diabetes mellitus.
Children of patients with type 2 diabetes mellitus were studied. Detailed medical history, physical examination, hemogram, renal and liver function tests, lipid profile, body composition, and oral glucose tolerance tests were done for all subjects. Plasma insulin was also done in addition to glucose at 0, 30, 60, and 120 min after oral glucose.
A total of 355 subjects from 208 families (194 males [55%] and 161 females [45%], mean age 23 +/- 11 years) were studied. Among them, 209 (58.9%) were lean, 91 (25.6%) were overweight, and 55 (15.5%) were obese. Seventeen (4.8%) subjects had impaired fasting glucose, 29 (8.2%) had impaired glucose tolerance, and 10 (2.8) had diabetes mellitus. Twenty (35.7%) of 56 with abnormal glucose tolerance were lean. One hundred six (29.8%) subjects had triglyceride levels greater than 150 mg/dL, 137 (38.6%) had low levels of high-density lipoprotein-cholesterol, and 67 (18.9%) had high total cholesterol levels. Prevalence of obesity, elevated plasma triglyceride, and glucose intolerance was higher among older subjects and subjects both of whose parents had diabetes.
Children from families with type 2 diabetes are at increased risk for obesity. Risk increases by fivefold when both parents have diabetes.
[Show abstract][Hide abstract] ABSTRACT: There is little information on the molecular basis of intrafamilial and inter-familial phenotypic heterogeneity with the same androgen receptor (AR) mutation in patients with partial androgen insensitivity syndrome. A genetic analysis was performed in a large kindred with ambiguous genitalia and the genotype-phenotype correlations were analysed. The index case was brought for sex assignment. Family history revealed four other affected members who had hypospadias and varying degrees of virilisation. All the affected males had hemizygous mutations in the third exon of the AR gene (A596T). One was also found to have a heterozygous mutation in the fourth exon of the 5 alpha reductase type 2 gene (G196S). This affected male with double mutations was better virilised compared with the other affected members with a single mutation. The degree of virilisation correlated with serum testosterone levels. Gynaecomastia was not present in any of these subjects. It is concluded that the subject with dual gene defects also had higher levels of testosterone and pubertal virilsation. Testosterone levels possibly govern the degree of pubertal virilisation in subjects with A596T gene defects. It is not clear whether the better pubertal virilsation and higher testosterone are in any way causally related to the SRD5A2 gene defect.
[Show abstract][Hide abstract] ABSTRACT: Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women.
In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion.
Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM. Glucose/insulin ratio at 0, 1 and 2 h was lower (8.3 +/- 4.2, 2.0 +/- 1.6 and 3.2 +/- 3.5) than that of healthy controls. HOMA-IR was 3.1 +/- 3.0.
Women with PCOS had an exaggerated insulin response to glucose. Thirty-eight percent of PCOS women had some form of abnormal glucose tolerance. Greater insulin response was seen with impairment of glucose tolerance. Obesity had no effect on fasting insulin or insulin response to oral glucose in PCOS women with NGT.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to compare effectiveness and remission rate between gliclazide and insulin as initial treatment in newly diagnosed, drug-naive patients with type 2 diabetes.
Newly diagnosed, drug-naive subjects with type 2 diabetes having mean fasting blood glucose >200 mg/dL were enrolled into either of two groups (gliclazide or insulin). The former received gliclazide modified-release 60 mg daily, while the insulin group received 16 units of premixed insulin as two divided doses along with medical nutrition therapy. Premeal blood glucose was monitored, and the dose was adjusted accordingly. Glycosylated hemoglobin (HbA1c), lipid profile, and postmeal C-peptide were estimated at baseline and 6 months. Remission was defined as euglycemia off drug for a minimum duration of 1 month.
Baseline and 6-month blood glucose, HbA1c, and lipid profile were comparable between groups. Blood glucose levels normalized in 2-6 weeks in both groups. At 6 months, one of 30 (3.33%) in the gliclazide group and 24 of 30 (80%) in the insulin group were in remission. Ten of 16 (62.5%) in the insulin group and one of 20 (.5%) in the gliclazide group continued to maintain euglycemia off all pharmacological treatment at 12 months. At 6 months, C-peptide increased in the insulin group (3.21+/-1.61 ng/mL at baseline vs. 5.82+/-2.23 ng/mL at 6 months), while it remained unchanged in the gliclazide group (3.4+/-1.87 ng/mL at baseline vs. 3.82+/-1.78 ng/mL at 6 months) (P=0.0003).
Comparable glycemic control could be achieved with both insulin and oral hypoglycemic agent in newly diagnosed type 2 diabetes subjects. Insulin treatment exceeded gliclazide in the remission (drug-free) rate.
[Show abstract][Hide abstract] ABSTRACT: To identify the genotype of two Indians with male pseudohermaphroditism.
Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carried out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5alpha-reductase type 2 gene (SRD5A2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus.
We found an SRD5A2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India.
Identification of the R246Q mutation of the SRD5A2 gene from two unrelated Indian families possibly extends the founder gene effect.
Asian Journal of Andrology 10/2008; 10(5):815-8. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Androgen excess is believed to be one of the major factors responsible for poor fertility outcomes in females with congenital adrenal hyperplasia (CAH). Some believe that the adverse effect of androgens on fertility could have its origins as early as the antenatal years. To assess the impact of prolonged androgen exposure on fertility in CAH patients, we compiled the data of females with CAH followed in our clinic during the last 25 years who were sexually active and had not been initiated on steroids until age 9 years.
This was an observational case study on seven patients with classical CAH who fulfilled the inclusion criteria. The age at initiation of therapy in these females ranged from 9 years to 29 years.
All patients had varying degrees of genital ambiguity. The most common presenting complaints were genital ambiguity, non-development of secondary sexual characteristics, hirsutism and primary amenorrhea. Genital surgery was performed in all patients at ages ranging from 12 to 29 years, except for one patient who underwent surgery at age 5 years without a diagnosis of CAH being made. Breast development ensued within 2 to 12 months and periods started in all patients within 2-24 months of steroid initiation. There were 13 pregnancies (seven normal vaginal deliveries, two spontaneous abortions and four pregnancies were medically terminated).
Late initiation of steroid therapy did not affect fertility in our cohort of CAH women. Androgen excess in situations of subnormal cortisol may not adversely affect fertility in females with CAH.
[Show abstract][Hide abstract] ABSTRACT: Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder. Four of our five patients were reared as females. Our assessment of these children reveals that they had male gender identity from childhood. Three of the four reared as females chose to change gender role at adolescence, while the fourth is still prepubertal. We conclude that all these patients had male gender identity from early childhood. The parents took note of this only after the appearance of male secondary sexual characteristics at puberty, thereby giving an impression of change in gender identity and gender role.