mixed gonadal dysgenesis is a condition of unusual and asymmetrical gonadal development leading to an unassigned sex differentiation .
a number of differences have been reported in the karyotype , most commonly a mosaicism 45,x/ 46 , xy .
a 16-year - old person , reared as female , born out of nonconsanguineous marriage , presented to our clinic with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters .
there was no h / s / o crisis or cyclical abdominal pain in the past .
however , the patient was taking 5 mg of prednisolone after being labeled as a case of congenital adrenal hyperplasia ( cah ) .
other past history , family history , antenatal history , perinatal history , and developmental history were noncontributory . on earlier evaluations , a small uterus was found on ultrasonogrphy ( usg ) studies but no gonads were visualized . on examination ,
genital examination revealed a single perineal opening , phallic length of 5 cm , with a well - formed glans and a well - formed scrotal sac .
there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh- progesterone ( 0.16 ng / ml ) .
basal testosterone level was 588 ng / dl with basal androstenedione level of 1.83 ng / ml ( male : 0.7 - 3.6 , female : 0.3 - 3.5 ) .
pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml .
basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) .
mri pelvis [ figure 1 ] revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . magnetic resonance imaging ( mri ) showing rudimentary uterus and bilateral ovarian - like structures the patient
was managed in collaboration with department of gynecology and obstetrics and discussions with patient party and a decision was taken to remove the gonads and mullerian structures laparoscopically .
however at the time of surgery , only right sided gonads and adjacent tubal structures were visualized and removed .
however , left sided mullerian remnants could not be removed due to adhesion to sigmoid colon .
histopathological examination [ figure 2 ] revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . epididymal tissue and an epididymal cyst are also present . however , no ovarian tissue was seen .
histopathological examination ( hpe ) of resected gonads showing atrophic seminiferous tubules ( 20 ) the patient is still admitted with us as on the day of writing this manuscript and is being managed with oral estrogens .
there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh- progesterone ( 0.16 ng / ml ) .
basal testosterone level was 588 ng / dl with basal androstenedione level of 1.83 ng / ml ( male : 0.7 - 3.6 , female : 0.3 - 3.5 ) .
pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml .
basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) .
mri pelvis [ figure 1 ] revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . magnetic resonance imaging ( mri ) showing rudimentary uterus and bilateral ovarian - like structures
the patient was managed in collaboration with department of gynecology and obstetrics and discussions with patient party and a decision was taken to remove the gonads and mullerian structures laparoscopically .
however at the time of surgery , only right sided gonads and adjacent tubal structures were visualized and removed .
however , left sided mullerian remnants could not be removed due to adhesion to sigmoid colon .
histopathological examination [ figure 2 ] revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . epididymal tissue and an epididymal cyst are also present . however , no ovarian tissue was seen .
histopathological examination ( hpe ) of resected gonads showing atrophic seminiferous tubules ( 20 ) the patient is still admitted with us as on the day of writing this manuscript and is being managed with oral estrogens .
this 16-year - old normotensive person reared as a girl came with a labeled diagnosis of 46xx disorder of sexual differentiation ( dsd ) ( diagnosed to be 46xx on the basis of buccal smear examination done outside ) , thought to be due to cah and started on prednisolone 5 mg once a day , even without a history suggestive of salt losing crisis . before the karyotype report was available , since the patient could not produce documents or investigation reports favoring the diagnosis of cah and thus justifying the use of prednisolone , we thought of reevaluating the patient completely .
we stopped the corticosteroid for 3 days and then reevaluated the adrenal axis , which was normal .
since the basal testosterone level was high , aromatase deficiency and partial androgen insensitivity syndrome ( pais ) were next in the line of diagnostic possibilities .
pais was ruled out due to presence of mullerian structures visualized on mri pelvis , as mullerian - inhibiting substance ( mis ) secretion is not hampered in pais .
the patient had no clinical or hormonal features suggestive of aromatase deficiency in the form of absence of virilization of mother during pregnancy , presence of significant values of serum estradiol levels , low normal levels of serum androstenedione and an absence of a significant rise of serum androstenedione levels even after beta - hcg stimulation .
lastly , we were left with diagnostic considerations of ovotesticular dsd ( ot - dsd ) and mgd .
the syndromic diagnoses associated with abnormal gonadal development were not suspected as patient did not reveal any of the known features of such defects ( e.g. , wild type [ wt]-1 , steroidogenic factor [ sf]-4 , dax-1 , etc . ) .
since patient was reared as female with history of clitoroplasty and vaginoplasty in the past and functionality of the external genital organs was not expected , a combined decision involving the patient party , gynecologist , and our department was taken to remove the gonads and assign a female sex to the patient .
on histopathological examination ( hpe ) of the gonadal tissue , only testicular tissue was seen , which favored the diagnosis of mgd over ot - dsd .
also a 46xx karyotype is more likely to be found in patients with ot - dsd .
although 46xo/46xy is the most common karyotype in patients with mgd , 46xy karyotype has also found in such patients .
the only method of differentiating 46xy mgd from 46xy ot - dsd is by histopathological demonstration of testicular tissue .
another point favoring mgd over ot - dsd is the presence of mullerian structures and testicular tissue on the same side , which is not seen in ot - dsd , as the testicular tissue is functional and secretes adequate amounts of mis .
however , in mgd , since the testicular tissue is dysgenetic , mullerian structures may be preserved on the side of testicular tissue .
the points that do not favor a diagnosis of mgd in our patient include an absence of short stature and turner 's stigmata .
the most common genotype in these patients is 46xo / xx , however 46xy genotype has also been described , which can be difficult to distinguish from 46xy ot - dsd .
the management of these patients can be difficult as phenotypically females may need multiple staged procedures for clitoroplasty , vaginoplasty , and gonadal biopsies / gonadectomies .
phenotypically male patients may need multiple procedures for hypospadias repair with limited gain in corporal tissue .
these patients are at increased risk of cancer , so it is prudent to remove the nonfunctional gonadal tissues .
these patients usually need a multidisciplinary approach for management , but still long - term data on fertility and functional improvement of each approach of treatment is lacking .
 a 16-year - old person , reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters , but without short stature and turner 's stigmata . 
 she was taking steroids after being misdiagnosed as congenital adrenal hyperplasia ( cah ) . 
 karyotype analysis revealed 46xy karyotype . 
 there was no evidence of hypocortisolemia ( cortisol 9.08 g / dl , adrenocorticotropic hormone [ acth ] 82.5 pg / ml ) or elevated level of 17-oh - progesterone ( 0.16 ng / ml ) . 
 pooled luteinizing hormone ( lh ) was 11.79 miu / ml and follicle - stimulating hormone ( fsh ) was 66.37 miu / ml . 
 serum estradiol level was 25 pg / ml ( 21 - 251 ) . 
 basal and 72 h post beta - human chorionic gonadotropin ( hcg ) levels of androstenedione and testosterone levels were done ( basal testosterone of 652 ng / dl and basal androstenedione of 1.17 ng / ml ; 72 h post hcg testosterone of 896 ng / dl and androstenedione of 1.34 ng / ml ) . magnetic resonance imaging ( mri ) 
 pelvis ( with ultrasonogrphy [ usg ] correlation ) revealed uterus didelphys with obstructed right moiety and bilateral ovarian - like structures . right sided gonads and adjacent tubal structures were visualized laparoscopically and removed . 
 left sided gonads were not visualized and mullerian remnants were adhered to sigmoid colon . 
 histopathological examination revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of leydig cells . no ovarian tissue was seen . 
 based on these results a diagnosis of 46xy mixed gonadal dysgenesis ( mgd ) was made , which is rare and is difficult to distinguish from 46xy ovotesticular disorder of sexual differentiation ( ot - dsd ) . 
 the patient was managed with a multidisciplinary approach and fertility issues discussed with the patient 's caregivers . 
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