Patients with true hermaphroditism may be diagnosed during infancy or adolescence, depending on the extent of the deviation from the normal male or female phenotype that they exhibit. The spectrum of clinical presentation, focusing on the genital areas, varies greatly. Some individuals may manifest as normally female or male, but the vast majority display aberrantly shaped genitalia that cannot be easily categorized under one of the two sex categories [1] [2].

Newborns affected by true hermaphroditism have labioscrotal folds, which may contain a palpable mass, either testis or ovotestis; such a clinical finding is relevant to the disorder. An ovotestis is present in more than 60% of the cases and constitutes a combination of ovarian and testicular tissue, with the latter situated centrally and the former in a polar location [3].

True hermaphroditism is primarily diagnosed during adolescence, as the physical development process renders genital irregularities more prominent. Specifically, a male adolescent is expected to evince feminization, such as a feminine sexual hair pattern. Female patients manifest with virilization during puberty, including excessive facial hair, small-sized breasts, loss of female fat distribution and abnormal genitalia [4]; a vagina exists in a small number of patients and has a common urogenital sinus with the urethra. In female patients, if a uterus exists (a possibility that cannot be accurately defined), it is usually accompanied by complications, such as uterine hypoplasia, cervical atresia or hemiuterus. The patient may menstruate or have symptoms related to an outflow blockage. In the case of male victims, hypospadias with bifid scrotal folds is a frequent finding; chordee can also be encountered. Individuals who have undergone a male sex assignment surgery during infancy may manifest with abnormally large breasts during adolescence [5].

• Weight Loss

  A 31-year-old 46,XX hermaphrodite presented with a history of vague abdominal symptoms and weight loss. Surgery was performed, and pathology revealed invasive squamous cell cancer arising in an epithelial-lined tissue consistent with vagina. [ncbi.nlm.nih.gov]

• Abdominal Mass

  Clinical presentation was wide-ranging, with age at presentation varying from 2 months to 41 years and symptoms ranging from ambiguous genitalia to a lower abdominal mass. [ncbi.nlm.nih.gov]

• Short Arm

  Since H-Y antigen is thought to be the gene product of the short arm of the Y, then the short arm must be present somewhere in the karyotype. Products of the short arm loci are thought to initiate testicular differentiation and male determination. [ncbi.nlm.nih.gov]

• Corneal Opacity

  We report mutational analysis of the RSPO1 gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma, congenital bilateral corneal opacities, onychodystrophy, and hearing impairment. [ncbi.nlm.nih.gov]

• Hearing Impairment

  We report mutational analysis of the RSPO1 gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma, congenital bilateral corneal opacities, onychodystrophy, and hearing impairment. [ncbi.nlm.nih.gov]

• Hirsutism

  An unusual feature of this patient was the absence of hirsutism in spite of increased serum testosterone level and clitoromegaly. [ijem.in]

• Hypopigmented Skin

  A sharp line separated hypopigmented skin on the left side of the abdomen from normally pigmented skin on the right side. A pendulous, wrinkled labioscrotal fold contained a gonad on the right side. [nejm.org]

• Large Breast

  Individuals who have undergone a male sex assignment surgery during infancy may manifest with abnormally large breasts during adolescence. [symptoma.com]

• Chordee

  Bilateral mammoplasties, repair of a penile chordee, placement of a left testicular prosthesis, and excision of the left hemiuterus and ovary resulted in return to testicular function in this true hermaphrodite. [ncbi.nlm.nih.gov]

  The phallus was 3 cm in length, with perineal hypospadias (inset) and 30-degree chordee. Testing revealed 46,XX/46,XY mosaicism and normal levels of male hormones. [nejm.org]

  In the case of male victims, hypospadias with bifid scrotal folds is a frequent finding; chordee can also be encountered. [symptoma.com]

• Primary Amenorrhea

  We documented a new case of 46,XY true hermaphroditism in an 18-year-old patient, reared as a female at birth, with ambiguous genitalia and primary amenorrhea. At laparotomy, bilateral dysgenetic ovotestis containing gonadoblastoma were found. [ncbi.nlm.nih.gov]

  True hermaphrodite presenting as primary amenorrhea. Indian J Endocr Metab 2012;16:640-2 How to cite this URL: Palo LB, Daniel M, Padma A, Sahoo JP. True hermaphrodite presenting as primary amenorrhea. [ijem.in]

  Primary amenorrhea and virilization in a true hermaphrodite with a rare dicentric Y chromosome. Obstet Gynecol. 1984 Sep. 64(3 Suppl):64S-67S. [Medline]. Sugimoto S, Igarashi T, Tada M, et al. [emedicine.medscape.com]

  Sloan MS, Rosenberg SM, Brown JA (1984) Primary amenorrhea and virilization in a true hermaphrodite with a rare dicentric Y chromosome. Obstet Gynecol 64:64S-67S PubMed Google Scholar 116. [link.springer.com]

• Vaginal Bleeding

  A 23-year-old karyotype 46XX parous female was admitted to hospital because of amenorrhea, irregular vaginal bleeding, an adnexal mass, and an increased beta-hCG serum level. [ncbi.nlm.nih.gov]

• Adnexal Mass

  A 23-year-old karyotype 46XX parous female was admitted to hospital because of amenorrhea, irregular vaginal bleeding, an adnexal mass, and an increased beta-hCG serum level. [ncbi.nlm.nih.gov]

• Testicular Pain

  Four months later he had testicular pain and swelling. US revealed bilateral multiseptate cystic masses. After repeat surgery, he is now free of symptoms. [ncbi.nlm.nih.gov]

The complete workup involved in diagnosing true hermaphroditism entails cytogenetic studies, hormonal laboratory evaluation, imaging studies and laparotomy or laparoscopy.

Cytogenetics

The karyotype most commonly associated with true hermaphroditism is 46 XX, followed by 46 XY. Other, rarely occurring karyotypes include a 46 XY/46 XY mosaicism. Cytogenetic studies are further completed by fluorescent in situ hybridization for occult Y-DNA. The 46 XX karyotype is the predominant one in up to 9 out of 10 patients [6].

Laboratory studies

Patients with true hermaphroditism exhibit normal values of serum 17-hydroxyprogesterone; abnormal concentrations can direct the diagnosis towards congenital adrenal hyperplasia (CAH). Basal levels of testosterone, androstenedione, dehydroepiandrosterone sulfate and dihydrotestosterone (DHT) are also measured in order to reveal occult testicular tissue. After a 5-day administration of human chorionic gonadotropin, the aforementioned hormones are again measured; elevated testosterone levels indicate that testicular tissue is present. An equivalent test is carried out in order to discover ovarian tissue, in which elevated levels of estradiol following the administration of clomiphene citrate or gonadotrophin reveals the presence of female reproductive tissue. A genital skin biopsy can illustrate a potential androgen insensitivity.

The presence of gonads which cannot be decided from the clinical examination can be detected with the use of genital ultrasonography (US). A genitogram will help to define the margins of a potential uterus (should it exist). Presently, the abdominal US, a computerized tomography scan (CT) and magnetic resonance imaging (MRI) are powerful tools to discover internal reproductive organs.

True hermaphroditism can be diagnosed before birth, with the help of amniocentesis, if the fetus features a 46 XX/46 XY or 46 XX/47 XXY or a 46 XX karyotype [7]. Any patient affected by the disorder is considered male or female, depending on penile length [8].

• Ovarian Mass

  Ectopic pregnancy was suspected three times and exploratory laparoscopy done each time removing the right ovarian mass and local pelvic and omental spread. [ncbi.nlm.nih.gov]

1. Sultan C, Paris F, Jeandel C, Lumbroso S, Galifer RB. Ambiguous genitalia in the newborn. Semin Reprod Med. 2002;20:181–8. doi:10.1055/s-2002-35382.
2. Mao Y, Chen S, Wang R, Wang X, Qin D, Tang Y. Evaluation and treatment for ovotesticular disorder of sex development (OT-DSD) - experience based on a Chinese series. BMC Urol. 2017;17: 21.
3. Nihoul-Feketc C, Lortat-Jacob S, Cachin O, Josso N. Preservation of gonadal functions in true hermaphroditism. J Pediatr Surg. 1984;19: 50– 5
4. Selver Eklioglu B, Atabek ME, Akyurek N, Ari Yuca S, Piskin M. The 46XX Ovotesticular Disorders of Sexual Development with Dismorphic Features. J Pediatr Adolesc Gynecol. 2015 Dec;28 (6):e157-9.
5. Ouhilal S, Turco J, Nangia A, et al. True hermaphroditism presenting as bilateral gynecomastia in an adolescent phenotypic male. Fertil Steril. 2005 Apr;83(4):1041.
6. Krob G, Braun A, Kunhle U. True hermaphroditism: geographical distribution clinical findings, chromosomes and gonadal histology. Eur J Pediatr. 1994;153: 2– 7.
7. Chen CP, Chern SR, Sheu JC, et al. Prenatal diagnosis, sonographic findings and molecular genetic analysis of a 46,XX/46,XY true hermaphrodite chimera. Prenat Diagn. 2005 Jun;25(6):502-6.
8. Grumbach MM, Conte FA. Disorders of sex differentiation, Textbook of Endocrinology. Ed 6. Philadelphia: WB Saunders, Co. Chap. 9; pp.198– 473.