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].

• Lower Abdominal Pain

  The presentation of delayed menstruation or lower abdominal pain because of menstrual flow obstruction can also occur. Many patients with ambiguous genitalia are eventually assigned to a male phenotype. [lecturio.com]

  abdominal pain associated with endometriosis may occur in individuals with cervical atresia or other forms of müllerian duct anomalies. [emedicine.medscape.com]

• Hirsutism

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

• No Pubic Hair

  CASE REPORT: A 14 years old phenotypic male presented with bilateral significant gynaecomastia which caused serious embarrassment in the school.The patient had pubic hair,right testis measured 8cc,the left 4cc and the penis measured approximately 6 cm.Serum [endocrine-abstracts.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 Mass

  Case report: A rapidly expanding testicular mass due to a ruptured ovarian follicle. Br J Radiol. 1996 Apr. 69(820):366-7. [Medline]. al Jurayyan NA, Patel PJ, al Herbish AS, et al. [emedicine.medscape.com]

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].

Diagnosis and treatment of true hermaphroditism. [ncbi.nlm.nih.gov]

The treatment of patients is therefore becoming more individualized and less standardized. Hermaphroditism is a complex issue and the ideal treatment of the condition is not clear. [news-medical.net]

Plastic surgery is the mainstay after gender is assigned, based on genetic sex, gonadal sex, social sex, psychologic sex and patient request Conservative gonadal surgery with long term followup ( J Urol 2007;177:726 ) Case series on surgical treatment [pathologyoutlines.com]

Prognosis With appropriate corrective surgery, the appearance of external genitalia may appear normal. However, other problems such as virilization may appear later in life. [encyclopedia.com]

The prognosis depends on the specific cause of intersex. With understanding, support, and appropriate treatment, overall outlook is excellent. [medlineplus.gov]

The exact etiology of ODSD is unknown but is largely believed to be genetic based. Sex determining region on the Y chromosome (SRY) is responsible for testicular development in the male fetus. [lecturio.com]

The etiology and pathogenesis of the true hermaphroditism is completely unknown. This disease is not hereditary, as in all cases, brothers and sisters patients developed normally. [medicalency.com]

True hermaphroditism is a rare condition both in North American and Europe, but one of the more common etiologies of male sexual ambiguity. It is, in contrast, common in Africa, especially in South Africa. [humpath.com]

Rosenberg SA (eds): AIDS: Etiology, Diagnosis. Treatment, and Prevention. ‏ الصفحة 190 - Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. ‏ الصفحة 193 - Henson D, Tarone R. [books.google.com]

They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]

The anomalies are organized by anatomical system and presented in a consistent manner, including details of the clinical presentation, epidemiology, embryology, treatment and prevention for each anomaly. [books.google.com]

Definition / general Ovarian and testicular tissue in the same individual (either bilateral or unilateral ovatestes or separate testis and ovary) with or without abnormal genitalia Epidemiology Very rare, with only about 500 cases identified worldwide [pathologyoutlines.com]

Epidemiology of Ovotesticular Disorder of Sexual Development Ovotesticular disorder of sexual development(ODSD) is a rare condition that is responsible for only 10% of the cases of ambiguous genitalia. [lecturio.com]

Epidemiology of hypospadias in Europe: a registry-based study. World J Urol. 2015;33(12):2159-2167. doi: 10.1007/s00345-015-1507-6. [ Links ] 7. [scielo.org.co]

Etiology and Pathophysiology of Ovotesticular Disorder of Sexual Development ODSD is a genetic condition that is characterized by: the presence of an ovotestis gonad, the presence of a normal ovary in one side and an ovotestis gonad on the other, the [lecturio.com]

Pathophysiology People with ovotesticular disorder of sexual development are individuals who have both ovarian and testicular tissue. This diagnostic nomenclature is applied regardless of the peripheral karyotype. [emedicine.medscape.com]

Reproductive endocrinology, physiology, pathophysiology, and clinical management. 4th ed. Philadelphia: W.B. Saunders; 1999. p. 153–190. 20 Larsen WJ. Development of the urogenital system.In: Larsen WJ, editor. Human embryology. 2nd ed. [nature.com]

The anomalies are organized by anatomical system and presented in a consistent manner, including details of the clinical presentation, epidemiology, embryology, treatment and prevention for each anomaly. [books.google.com]

The high testosterone production did not prevent the appearance of a positive oestrogen-LH feedback. The relative peripheral insensitivity to testosterone, is, in some ways, inconsistent with the presence of receptors for androgens. [ncbi.nlm.nih.gov]

Its management involves surgical correction of the external genitalia and treatment with appropriate glucocorticoids to prevent the consequences of its deficiency and arrest rapid virilization. [sonoworld.com]

[…] demonstrated that the derivative X chromosome carries the sex determining region normally seen on the short arm of the Y chromosome.Patient was diagnosed to be an SRY + XX true hermaphrodite.He underwent bilateral orchidectomy with prosthetic replacement to prevent [endocrine-abstracts.org]

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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.