Intersex Research Articles

Intramural and Adapted-Germ Cell Neoplasia In situ

Germ cell neoplasia in situ emerges as a precursor lesion configuring type II germ cell tumours as testicular seminoma or post-pubertal non-seminomatous testicular germ cell tumours. Lesion is comprised of neoplastic gonocyte-like cells, latent totipotent or naive germ cells with developmental potential situated within ‘spermatogonial niche’ of seminiferous tubules. Germ cell neoplasia in situ delineates an increased incidence with conditions as uncorrected cryptorchidism, ambiguous genitalia, infertility or preceding history of post-pubertal germ cell tumour within contralateral testis. Neoplasm demonstrates aneuploidy or polypoid genotype with additional chromosomal gains as is chromosome 12p upon commencement of neoplastic invasion. Neoplastic cells appear enlarged, atypical, gonocyte-like and are incorporated with abundant, clear cytoplasm, enlarged, hyper chromatic nuclei, coarse nuclear chromatin, angulated cellular margins and prominent nucleoli.

Dilemmas in Antenatal Reporting of Ambiguous Genitalia on Ultrasound, under Preconception and Prenatal Diagnostic Techniques Act, 1994

Dilemmas in Antenatal Reporting of Ambiguous Genitalia on Ultrasound, under Preconception and Prenatal Diagnostic Techniques Act, 1994

Congenital Adrenal Hyperplasia with Concomitant Mullerian Agenesis: A Rare Occurrence in 46 Xx Disorders of Sexual Development

The most common cause of 46 XX DSD is due to congenital adrenal hyperplasia with varying degrees of virilization. Females with CAH do not produce an anti-mullerian hormone (AMH), therefore the internal genitalia, which are Mullerian derivatives, develop normally. We report a unique case of CAH with aplasia of the uterus and upper vagina. The clinical, laboratory, and imaging findings of the patient are presented with a review of the literature. We report an ongoing case of a 20-year-old patient with ambiguous genitalia and primary amenorrhea. On physical examination, we found that she had an underdeveloped breast and clitoral virilization with separate urethral and vaginal openings. We performed a G-banded chromosome analysis, with 46 XX results. Laboratory test showed her 17-hydroxyprogesterone level was immensely elevated, while her FSH, LH, and estradiol level was below normal. Ultrasound imaging revealed the absence of uterus and cervix. Nevertheless, we found a diminutive uterine remnant during diagnostic laparoscopy with normal ovaries and fallopian tubes. On vaginoscopy examination, we found her vagina to be 5 cm long with blind end. In the presence of primary amenorrhea in patients with CAH, it is important to investigate for possible associated mullerian anomalies.

Karyotypic Analysis of Individuals with Unassigned Sex: First Report from Jammu and Kashmir, India

Every minute of every day, a baby is born. Most babies are easily seen to be a girl or a boy. Imagine how confusing it must be when we don’t know the sex of a newborn? This is rare and it can be very upsetting for parents. During the present study, a total of 47 individuals with unassigned sex were enrolled for chromosome study. These 47 individuals in different age group were categorized into three groups namely ambiguous genitalia, Intersex and Hypospadias. In Ambiguous genitalia group, a total of seventeen individuals were enrolled for chromosome study. Of these, thirteen individuals reared as males were found to have 46, XY karyotype. In the remaining four cases reared as female sex, three were found to have 46, XX karyotype and one which was phenotypically a female was found to have 46, XY karyotype. In Intersex group, a total of fourteen individuals were enrolled for chromosome study. Of these fourteen cases of Intersex reared as male sex by their parents, thirteen were found to possess 46, XY karyotype where as one cases was found possessing 46, XX. In Hypospadias group, a total of sixteen individuals were enrolled for chromosome study and were found to have 46, XY karyotype. The purpose of the present study was to find out the chromosomal sex in these individuals. The study is first of its kind from Jammu region of Jammu and Kashmir, India.

Correlation of consanguinity with prevalence of chromosomal anomalies in patients of ambiguous genitalia: A cytogenetic study

Introduction: The condition when the sex of the baby can’t be determined and there is variation of genitalia from normal is known as ambiguous genitalia. Consanguinity can be defined as blood relationship that exists among individuals that descend from a common ancestor. If two individuals who are in close blood relation get married there is high chance that any single copy of gene which is present in common ancestor gets doubled in the subsequent generation. A recessive gene may thus come to light for the first time in subsequent generation. The aim of the present study was to see the correlation of consanguinity with prevalence of chromosomal anomalies in patients of ambiguous genitalia. Materials and Methods: Study was conducted in the cytogenetic laboratory of the Department of Anatomy, King George’s Medical University UP, Lucknow. The patients were screened in the Department of Paediatrics and Paediatric Surgery and blood samples were taken. Cytogenetic analysis was done. Results: Consanguinity was traced in 4 (18.2%) cases, of whom 3 (75%) had chromosomal anomalies. Out of remaining 18 (81.2%) cases, chromosomal anomalies were seen in 4 (22.2%) cases. Conclusions: The proportion of cases with anomalies was higher in those positive for consanguinity as compared to those without consanguinity. Keywords : Consanguinity, Ambiguous genitalia, Chromosomal anomalies

#382 : Congenital Adrenal Hyperplasia with Concomitant Mullerian Agenesis: A Rare Occurance in 46 XX Disorders of Sexual Development (DSD)

Background and Aims: The most common cause of 46 XX DSD is due to congenital adrenal hyperplasia with varying degree of virilization. Females with CAH do not produce anti mullerian hormone (AMH), therefore the internal genitalia, which are mullerian derivatives, are develop normally. We report a unique case of CAH with absent uterus, cervix, and fallopian tube. Method: The clinical, laboratory, and imaging findings of the patient are presented with literature review. Results: We report an ongoing case of a 20-year-old patient with ambiguous genitalia and primary amenorrhea. She was born from a healthy mother and raised as a female. There was no family history of the same disorder. On physical examination we found that she had normal height, normal blood pressure, palatoschizis, undeveloped breast (Tanner stage 1), and clitoral virilization with single urovaginal opening (Prader stage 3). We performed a G-Banded chromosome analysis, with 46 XX results. Laboratory test showed her 17-hidroxyprogesterone level was 176,93 ng/ml, FSH level was 3,06 mIU/ml, LH level was 2,21 mIU/ml, and estradiol level was 18,0 pg/mL. Ultrasound imaging revealed the absence of uterus, cervix, and vagina, as well as abnormal appearance of ovarium. We have planned to perform a complete MRI study for other anomalies as we suspected this patient had Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome type II. Conclusion: In the presence of external genitalia and urinary tract malformations in patients with CAH, it is important to investigate for possible associated mullerian anomalies. A comprehensive approach in diagnosis could lead to a better outcome in a patient’s treatment and wellbeing.

Birth defect: Findings from Obstetrics & Gynae Department of a tertiary Hospital

Objectives: To determine the frequency and types of birth defect among newborn in Sir Salimullah Medical College Hospital Study Design: Cross-sectional study. Methods: The study was conducted in Sir Salimullah Medical College Hospital from January- December 2018. Birth defect identified previously during pregnancy on USG or defect detected at birth at Obstetrics department were included in the study. The study was conducted at Obstetrics department of SSMC MH. All births with gross congenital malformations were noted. All malformations were classified as per ICD 10 classification. The mother of the newborn with congenital malformations was interviewed consecutively using predesigned, pretested questionnaire. The variables included parents age, antenatal registration, antenatal history of drug intake, consanguinity and previous history of malformations. Statistical analysis was done using chi square test. Results: Out of 8912 live births, congenital malformations were observed in 50 cases. The frequency of congenital malformation was 0.56%. There were 25 males and 23 females and two newborns had ambiguous genitalia. The highest congenital abnormality reported in this study was in the age group between 20-29 years, which was 31(62%), The central nervous system was the most common system involved. Among 50 neonates, 8 neonate had multiple congenital anomalies and 42 babies had isolated malformations. Bangladesh J Obstet Gynaecol, 2022; Vol. 37(2): 127-131

''Should the child be raised as male or female?'' The evaluation and management of different causes of ambiguous genital appearance in children

Diagnosing, managing and assigning gender for different causes of ambiguous genitalia in children can be challenging. This article will discuss about the types, diagnosis and treatment of disorders of sex development including congenital adrenal hyperplasia, 46 XY mixed gonadal dysgenesis and 46XY ovotesticular disorder of sex development. This article reports about 3 cases of disorders of sex development. The first case is about a three-year-old girl who was diagnosed with congenital adrenal hyperplasia, genital examination revealed clitoromegaly and a single urogenital sinus; she was managed medically and surgically. The second case is about a one-month-old child with 46XY karyotype, genital examination revealed penoscrotal hypospadias with right palpable and left impalpable gonads. Patient underwent diagnostic laparoscopy in which both female and male internal organs were found; based on these results a diagnosis of 46XY ovotesticular disorder of sex development was made. The third case is about a 3-month-old child with 46XY karyotype, genital examination revealed hypospadias with bilateral impalpable gonads. Diagnostic laparoscopy showed a uterus with a bilateral ovary-looking gonad; histopathology of the bilateral ovary-looking gonads was consistent with testicular tissue. Based on the above, a diagnosis of 46XY mixed gonadal dysgenesis was made. Disorders of sex development are classified into three main categories based on the karyotype, XX, XY and sex chromosome other than XX and XY. Laboratory investigations, karyotype, genetic analysis, imaging, surgery and tissue biopsy, all aid in diagnosing, deciding gender identity and managing different types of disorders of sex development.

Salt-Wasting Congenital Adrenal Hyperplasia in A 2-Year-Old Patient

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder due to deficiencies of enzymes involved in steroidogenesis in the adrenal cortex. It is known that 90% of CAH are due to 21-hydroxylase enzyme deficiency caused by mutation of the CYP21A2 gene. A female patient aged two years and one month old was reported with a diagnosis of salt-wasting CAH. The diagnosis was based on complaints of genital enlargement since birth. The patient had developed repeated vomiting and severe dehydration since newborn. The patient was diagnosed with CAH and under treatment with glucocorticoid replacement therapy by a pediatrician since the age of 5 months. Body height/age < -3 Standard Deviation (SD) of the Z-score chart (very short stature) and ambiguous genitalia were reported. Laboratory tests indicated thrombocytosis (795x103/uL), mild hyperkalemia (5.4 mmol/L), and increased testosterone (110.1 ng/dL). Bone age study affirmed an advanced bone age. History of increased 17-hydroxyprogesterone (109.19 ng/mL) and decreased morning serum cortisol levels (1.7 ug/dL). History of gynecological ultrasonography (USG) showed uterus, no bilateral testicular structure, hyperplasia of the left adrenal gland, and suggestive of genital ambiguity. The 21-hydroxylase deficiency causes a decrease in aldosterone and cortisol and an increase in androgens. Hypoaldosteronism causes hypovolemia, hyponatremia and hyperkalemia. Hypocortisolime causes hypoglycemia, decreased response to infection, and stress. Hyperandrogenism causes virilization of the genitalia and short stature in patients. A female patient aged two years and one month old was reported with a salt-wasting congenital adrenal hyperplasia diagnosis. Chromosome analysis was the recommended test in this case.

Navigating complexity: Long-term follow-up of an 18-year-old patient from Pakistan with 45 X0 and SRY activating mutation: Ambiguous genitalia, rearing challenges, and pubertal induction

Navigating complexity: Long-term follow-up of an 18-year-old patient from Pakistan with 45 X0 and SRY activating mutation: Ambiguous genitalia, rearing challenges, and pubertal induction

Primary Amenorrhea Due to Ovotesticular Disorder of Sexual Development

Primary amenorrhea with ambiguous genitalia is a diagnostic challenge to physicians. Ovotesticular disorder of sexual development is a one cause for that which need gonadectomy followed by histological assessment to confirm the diagnosis. This is a case of ovotesticular disorder of sexual development which presented with primary amenorrhea with ambiguous genitalia.

Intersexuality: What Primary and Specialized Healthcare Providers Should Know and Do to End Cosmetic and Harmful Medical Practices on Infants and Children Born with Intersex Variations in Tanzania

The Public Statement by the African Intersex Movement, 2017 extends demands to end discrimination against persons born with intersex variations in Africa through legislative and other means. Comestic, irreversible and harmful medical and clinical procedures infants and children born with intersex variations have been subject to include unconsented and medically unnecessary surgeries, mutilation and sterilization that cause irreversible physical and psychological harm. I demonstrate, Tanzania a signatory to The Human Rights Charter is mandated to follow the same route to ensure persons born with intersex variations live and enjoy the right to quality and equitable health and healthcare available without discrimination. To date, however, it is unclear what measures Tanzanian government has taken to prohibit medically unnecessary surgeries and procedures on infants and children born with intersex variations. Similarly, no enacted law banning harmful medical and clinical variations on infants and children born with intersex variations in this country; suggesting violation of intersex rights is ongoing. Data presented in this paper come from desk research I conducted on intersexuality in Tanzania and beyond. I conclude awareness of intersex conditions is increasing among researchers, persons born with intersex variations, parents/guardians, activists and the media. This increase would come with increasing horror, which may stimulate legal reform. I recommend primary and specialized care providers, and the Tanzania government in particular, ought not to wait for this dishonor to surface — rather should act now to end cosmetic and harmful surgeries and protect vulnerable infants and children born with intersex variations in this country.

THU185 Molecular Etiologic Spectrum Of Patients With 46,XY And 46,XX Disorders Of Sex Development

Abstract Disclosure: J. Kim: None. S. Park: None. S. Hwang: None. J. Yoon: None. G. Kim: None. H. Yoo: None. J. Choi: None. Background: Disorders of sexual development (DSDs) is a group of congenital conditions associated with discordant development of chromosomal, gonadal, and anatomical sex. Sex development is a complex process with a precise synergistic temporal-spatial transcriptional regulation of multiple genes. Advances in next-generation sequencing (NGS) techniques have achieved genetic diagnosis for up to 40 % of 46,XY DSDs. This study investigated the etiological distribution of DSDs identified by NGS. Methods: This study included 70 patients with DSDs (56 patients with 46,XY DSD and 14 patients with 46,XX DSD). Molecular genetic analysis was performed using targeted gene panel sequencing (n = 43) and whole-exome sequencing (WES, n = 26), including 25 patients for the first-line test and one without sequence variants by targeted gene panel sequencing. Whole-genome sequencing (WGS) was performed on 7 patients, including two patients for the first-line test and five patients without sequence variants by targeted gene panel sequencing or WES. Results: Patients with DSDs presented in infancy with ambiguous genitalia and at older children with aberrant pubertal development or discordance between karyotype and external genitalia. Twenty-four of 56 patients (42.9%) with 46,XY DSD were reared female, and 5 of 14 patients (35.7%) with 46,XX DSD were raised as a male. Pathogenic or likely pathogenic variants were identified in 21 of 56 patients with 46,XY DSD (37.5%); however, no rare sequence variants were found in patients with 46,XX DSD. The AR variants were the most common (8/70, 11.4%), followed by CYP17A1 (4/70, 5.7%), SRD5A2 (4/70, 5.7%), NR5A1 (2/70, 2.8%), GATA4 (1/70, 1.4%), MYRF (1/70, 1.4%), and deletion of DMRT1/2 (1/70, 1.4%). Mutation-positive patients with 46, XY DSD were assigned as female more frequently than mutation-negative patients (19/21 vs. 6/35, P-value <0.001). The lower diagnostic yield was observed in patients with a less severe phenotype, such as hypospadias or micropenis. Conclusions: This study demonstrated that genetic etiologies could be identified in 37.5% of patients with 46,XY DSD, whereas there were no genetic variants in patients with 46,XX DSD. Patients with a more severe phenotype were more likely to have a conclusive genetic diagnosis. NGS is a helpful technique to improve diagnostic efficiency in patients with DSD because of phenotypic and genetic heterogeneity. Presentation: Thursday, June 15, 2023

FRI446 A Case Of 46 XX Testicular Disorder Of Sex Development Presenting As Hypogonadism And Infertility

Abstract Disclosure: N. Balachandar: None. S. Agarwal: None. K.K. Soe: None. Introduction: Hypergonadotropic hypogonadism in males can be due to genetic, acquired or developmental causes. Common etiologies of testicular failure include trauma, systemic illnesses, radiotherapy, gonadotoxic drugs, and viral orchitis; in addition, genetic causes should be considered. Here, we present a case of primary hypogonadism and infertility due to 46 XX testicular disorder of sex development (DSD). Case Report: A male in his early fifties with history of obesity presented with fatigue to his PCP. A total testosterone level was 1.8 ng/mL (normal: 1.7 - 7.6 ng/mL) with a repeat value confirming the finding. Bioavailable testosterone was low at 85.1 ng/dL (normal: 110-575 ng/dL). FSH was elevated at 39.9 mIU/mL (normal: 1.3 - 19.3 mIU/mL), and LH was elevated at 16.6 mIU/mL (normal: 1.2 - 8.6 mIU/mL). In endocrinology clinic, he reported a year of fatigue, erectile dysfunction despite normal libido, and an inability to conceive despite three years of regular unprotected intercourse. He noted loss of muscle mass, bilateral breast tissue development, and reduction in testicular size. Physical exam revealed normal phallus, diffusely sparse body hair with atypical male distribution, bilateral gynecomastia, and bilateral reduction in testicular volume (right: 5 mL; left: 8 mL). Chromosomal analysis showed a mosaic pattern of 45 XO in 6% of cells and 46 XX in 94% of cells. Fluorescence in situ hybridization (FISH) analysis confirmed the presence of the sex-determining region (SRY) gene in 96% of cells. Metaphase FISH showed cryptic insertion of the SRY gene into the p arm of the X chromosome. Semen analysis showed azoospermia. He was diagnosed with 46 XX testicular DSD with abnormal mosaicism. He was prescribed testosterone gel and counseled on fertility options resulting in improvement of testosterone levels, sexual function, and subjective well-being. Discussion: The SRY gene, normally located on the p arm of the Y Chromosome, is responsible for development of primitive gonads into testicles during embryogenesis. Homologous recombination occurs between chromosomes during gametogenesis. It is hypothesized that in patients with 46 XX DSD, the SRY gene is translocated to the X chromosome, as demonstrated in this case. Its expression helps with selection of male sex in a growing fetus. Thus, in a 46 XX SRY positive male, the phenotypic presentation is male. Since the AZF gene on the q arm of the Y chromosome which is essential for spermatogenesis is not translocated, 46 XX males are infertile and undiagnosed until adulthood when azoospermia is noted during infertility workup. 46 XX SRY negative males develop ambiguous genitalia leading to earlier diagnosis. Eighty-percent of 46 XX males are SRY positive and twenty-percent are SRY negative. Thus, in adult males presenting with infertility and hypogonadism, genetic causes such as 46 XX DSD with SRY translocation should be considered. Presentation: Friday, June 16, 2023

THU189 Complex Treatment Of Recurrent Gynecomastia In An Affirmed Male With 46XX Ovotesticular Difference Of Sexual Differentiation (DSD).

Abstract Disclosure: S. Jumani: None. K. Shimy: None. D. Casella: None. J. Long: None. V. Gomez-Lobo: None. Introduction: Identifying gonads with ovarian and testicular components (ovotestis) can be difficult, despite multimodal imaging, biopsy, and surgical visualization. Here, we describe an unexpected identification of an ovotestis following the initiation of tamoxifen in a patient with 46XX Ovotesticular Difference of Sexual Differentiation (DSD). Case: A 14YO affirmed male with 46XX Ovotesticular DSD presented to our clinic for management of recurrent gynecomastia. At birth, he had ambiguous genitalia consistent with a under-virilized phallus, dorsally hooded foreskin, bifid scrotum, proximal hypospadias, palpable left gonad and non-palpable right gonad. He had a “normal” testosterone (i.e. presumably in male range for mini-puberty, though specific values predate available records). Limited genetic testing showed a karyotype of 46XX and negative SRY. He underwent a laparoscopy during which a right ovary, Müllerian tissue, and a small amount of vaginal tissue were identified and removed. A biopsy of the left gonad showed Sertoli cells without germinal epithelium. In adolescence, he developed progressive gynecomastia, with tanner 3 breasts by 12y6m. Treatment with anastrozole was unsuccessful, and he underwent a reduction mammaplasty at 13y6m. Unfortunately, the gynecomastia recurred shortly thereafter, and he was referred to our institution. At 14y7m bloodwork revealed a robust testosterone (543ng/dL), elevated estradiol (106 pg/mL, ref: 10-36), and estrone (71pg/mL, ref: 15-45). A trial of 20 mg tamoxifen daily was initiated. After 1 month, he developed scrotal pain suspicious for torsion and was taken to the operating room. Scrotal exploration revealed a hemorrhagic cyst at the superior pole of the gonad and an external appearance consistent with an ovo-testis. The hemorrhagic cyst was drained, and the remainder of the gonad left in situ. His pain resolved post-operatively however he returned 3 weeks later with scrotal pain and a recurrent hemorrhagic cyst on ultrasound. Tamoxifen was discontinued, and treatment with a Gonadotropin Releasing Hormone agonist (GnRHa) and concomitant testosterone replacement was initiated. This medication change led to resolution of the gonadal cysts. Conclusion: Initiation of tamoxifen as treatment for gynecomastia resulted in recurrent hemorrhagic cysts and the identification of ovarian tissue in a descended gonad which was presumed to be a biopsy proven testis. Recurrent hemorrhagic cysts in the ovotestis were likely due to physiologic stimulation and tamoxifen1 as well as elevated estradiol. Treatment with a GnRHa and testosterone offered a reversible, non-surgical method to suppress endogenous sex hormones contributing to gynecomastia while continuing male pubertal development. 1.PMID: 16254040. Presentation: Thursday, June 15, 2023

A case of bilateral adrenal myelolipoma in congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: A rare and uncommon finding

Abstract Congenital adrenal hyperplasia (CAH) is a common endocrine disorder that can lead to poor quality of life and the development of adrenal and extra-adrenal mass lesions when poorly controlled. Adrenal myelolipomas are rare, benign neoplasms that have been observed in long-standing, uncontrolled CAH cases. In this report, we describe a 31-year-old patient with ambiguous genitalia, hypokalemia, and normotension. The hormonal profile showed elevated 11-deoxy cortisol and 17-hydroxy progesterone. The clinical and biochemical profile was suggestive of CAH due to 11-beta-hydroxylase deficiency. On evaluation for pain abdomen, bilateral large adrenal myelolipomas were found for which surgery was done. Presently the index case is on steroid replacement therapy. This case emphasizes the importance of timely diagnosis adherence to treatment and appropriate follow-up of CAH cases in order to prevent the development of adrenal myelolipomas.

Intersexuality: The Role of Political Elite in Recognizing, Respecting, Protecting and Affirming Persons Born with Intersex Variations’ Human and Citizenship Rights in Tanzania

Intersex’ is an umbrella for persons born with variations of sex characteristics which may not correspond with societal and medical expected ‘male’ or ‘female’ bodies. Persons with intersex variations, therefore, are born with physical or biological characteristics that do not fit the typical definition for ‘male’ or ‘female’. In this paper I establish that there is no vivacious evidence that the Tanzania Government has taken stern measures to end discrimination against persons born with intersex variations in the country, and to ensure the right of bodily integrity, physical autonomy and self-determination as per demands and calls by The UN Human Rights Declarations and Resolutions, The Vienna Declaration and Programme of Action 1993, The Malta Declaration, 2013, the World Intersex Fora (that took place between 2011 and 2017), The Public Statement by the African Intersex Movement, 2017, and The African Commission on Human and Peoples’ Rights, 2023. Incontestably, awareness of intersex conditions and persons born with intersex variations’ human and citizenship rights is increasing among this population group, researchers, parents/guardians, activists and in the media in this country. Increase of awareness is likely to come with increasing revolt, which may provide the impetus for legal reform. The Tanzania government, therefore, ought not to wait for this ignominy to surface — rather should act now to end cosmetic and harmful surgeries and protect vulnerable infants and children born with intersex variations in this country.

Serum steroid metabolite profiling by LC-MS/MS in two phenotypic male patients with HSD17B3 deficiency: Implications for hormonal diagnosis

Although 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency is diagnosed when a testosterone/androstenedione (T/A-dione) ratio after human chorionic gonadotropin (hCG) stimulation is below 0.8, this cut-off value is primarily based on hormonal data measured by conventional immunoassay (IA) in patients with feminized or ambiguous genitalia. We examined two 46,XY Japanese patients with undermasculinized genitalia including hypospadias (patient 1 and patient 2). Endocrine studies by IA showed well increased serum T value after hCG stimulation (2.91 ng/mL) and a high T/A-dione ratio (4.04) in patient 1 at 2 weeks of age and sufficiently elevated basal serum T value (2.60 ng/mL) in patient 2 at 1.5 months of age. Despite such partial androgen insensitivity syndrome-like findings, whole exome sequencing identified biallelic ″pathogenic″ or ″likely pathogenic″ variants in HSD17B3 (c .188 C>T:p.(Ala63Val) and c .194 C>T:p.(Ser65Leu) in patient 1, and c.139 A>G:p.(Met47Val) and c.672 + 1 G>A in patient 2) (NM_000197.2), and functional analysis revealed reduced HSD17B3 activities of the missense variants (∼ 43% for p.Met47Val, ∼ 14% for p.Ala63Val, and ∼ 0% for p.Ser65Leu). Thus, we investigated hCG-stimulated serum steroid metabolite profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patient 1 at 7 months of age and in patient 2 at 11 months of age as well as in five control males with idiopathic micropenis aged 1 – 8 years, and found markedly high T/A-dione ratios (12.3 in patient 1 and 5.4 in patient 2) which were, however, obviously lower than those in the control boys (25.3 – 56.1) and sufficiently increased T values comparable to those of control males. The elevated T/A-dione ratios are considered be due to the residual HSD17B3 function and the measurement by LC-MS/MS. Thus, it is recommended to establish the cut-off value for the T/A-dione ratio according to the phenotypic sex reflecting the residual function and the measurement method.

Intersexuality: What Public Health Personnel Should Know and Do to Protect and Preserve Persons Born with Intersex Variations’ Human Rights and Citizenship Rights in Tanzania

Intersexuality includes a variety of conditions in which individuals are born with, or develop later in life, ambiguous external genitalia and or a combination of chromosomes, gonads, external genitalia, and hormones that do not align as typical male or typical female. Persons born with intersex variations, therefore, are real and exist in all countries around the globe. What is missing in most countries like Tanzania is the comprehensive understanding of who persons born with intersex variations are; their (health) needs; the parents/guardians’, families’, communities’ experiences and governments’ roles in recognizing and protecting human rights and citizenship rights this group is entitled to. Low awareness and understanding of persons born with intersex variations among the general public, policy makers and the (public) health professionals; lack of empirical research on this group and intersex-LGBTQ confusion explain, in part, why there is paucity of data on this population in Tanzania and other countries mainly where LGBTQ is illegal. Data presented in this paper come from desk research I conducted on intersexuality in Tanzania and beyond. I conclude public health experts in this country stand a better chance to bridge gaps identified in existing intersexuality research to enable Tanzania realize demands and calls made by The African Intersex Movement, 2017. I recommend public health intersexuality research to move towards a psycho-social framework which accepts persons born with intersex variations, because the problem is not with this population; it is, rather, with the society expecting them to conform to their socially constructed architypes.

Ambiguous external genitalia in a 5-year-old intact miniature equid.

Ambiguous external genitalia in a 5-year-old intact miniature equid.