A Case of Testicular Regression Syndrome

Abstract Background: Testicular regression syndrome (TRS), also known as vanishing testes syndrome, is a condition of 46, XY males presenting with male phenotypic genitalia and testicular absence. Normal testes are thought to have once existed in fetal life and subsequently atrophied following a catastrophic event. It may present as partial or complete absence of testicular tissue. Fibrotic remnants are commonly found upon surgical exploration. Case: This is the case of a 20-year-old male with a birth-diagnosis of primary hypogonadism. The patient was born prematurely at 5 months following a motor vehicle accident that resulted in his mother’s death. Neonatal evaluation for cryptorchidism revealed no radiological evidence of intra-abdominal testicular mass. Referral to a pediatric-endocrinologist was done at early childhood. Testosterone replacement was started at 12 years of age and pubarche was adequate. After surgical exploration, a testicular remnant was surgically removed. Pathology report revealed fibrotic tissue, yet no histological testicular tissue was found. Due to lack of testes in the scrotum, testicular prosthesis was implanted at age 14, but the etiology of the hypogonadism was never elucidated. The patient was initially seen in our adult-endocrinology clinics at age 21. Upon evaluation, secondary sex characteristics were adequate for age. Penile length was of 3.5 inches. Bilateral testicular prostheses were palpable, and no gynecomastia was present. Despite testosterone replacement, total testosterone was 3.38 ng/ml (n; 2.41-8.27 ng/ml), FSH was 106 mIU/ml (n; 1.4-18.1 mIU/ml) and LH was 34.7 mIU/ml ml (n; 1.5-9.3 miu/ml). Based on history, laboratory workup and surgical pathology, TRS was presumed as the etiology of this patient’s hypogonadism. Testosterone therapy was adjusted to reach physiological expected levels. Conclusion: TRS is an underdiagnosed cause of hypergonadotropic hypogonadism. It is supposed that the initial embryologic development was normal, followed by a vascular accident. There is no clear recommended approach for evaluating a patient once the diagnosis of TRS is suspected. Diagnostic methods may include hormonal and karyotype testing, imaging, and surgical exploration. Furthermore, although clinical recommendations have been published for other disorders of sex development, TRS management has been understudied. Testosterone replacement therapy at the typical time of puberty ensures the development of secondary sexual characteristics, bone health and pubertal growth. Unlike Klinefelter syndrome and cryptorchidism, TRS has not been associated with increased risk of cancer. Thus, it is important to establish the etiology to avoid invasive and unnecessary workup, which will result in psychological distress and excessive healthcare costs.

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HISTOPATHOLOGICAL FEATURES OF TESTICULAR REGRESSION SYNDROME: RELATION TO PATIENT AGE AND IMPLICATIONS FOR MANAGEMENT

Fetal and Pediatric Pathology ◽

10.1080/15513810600788806 ◽

2006 ◽

Vol 25 (2) ◽

pp. 119-129 ◽

Cited By ~ 21

Author(s):

H. Law ◽

I. Mushtaq ◽

K. Wingrove ◽

M. Malone ◽

N. J. Sebire

Keyword(s):

Patient Age ◽

Histopathological Features ◽

Patient Âgé ◽

Testicular Regression ◽

Testicular Regression Syndrome

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Testicular regression syndrome ? a pathological study of 77 cases

Histopathology ◽

10.1111/j.1365-2559.1991.tb00033.x ◽

1991 ◽

Vol 19 (3) ◽

pp. 269-272 ◽

Cited By ~ 41

Author(s):

N.M. SMITH ◽

R.W. BYARD ◽

A.J. BOURNE

Keyword(s):

Pathological Study ◽

Testicular Regression ◽

Testicular Regression Syndrome

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DEAH-box helicase 37 (DHX37) defects are a novel molecular etiology of 46,XY gonadal dysgenesis spectrum

10.1101/477992 ◽

2018 ◽

Author(s):

Thatiana E. da Silva ◽

Nathalia L. Gomes ◽

Antonio M. Lerario ◽

Catherine E. Keegan ◽

Mirian Y. Nishi ◽

...

Keyword(s):

Gonadal Dysgenesis ◽

Autosomal Dominant ◽

Genetic Diagnosis ◽

Gonadal Development ◽

Incomplete Penetrance ◽

Coding Region ◽

Xy Gonadal Dysgenesis ◽

Testicular Regression ◽

Molecular Etiology ◽

Testicular Regression Syndrome

ABSTRACT46,XY gonadal dysgenesis is a heterogeneous disorder of sex development (DSD) that features abnormal gonadal development and varying degrees of undervirilization of the external genitalia, ranging from micropenis to female-like genitalia. Embryonic testicular regression syndrome (ETRS; MIM: 273250) is considered part of the clinical spectrum of 46,XY gonadal dysgenesis. Most ETRS patients present micropenis or atypical genitalia associated with a complete absence of gonadal tissue in one or both sides. In most patients with gonadal dysgenesis, the genetic diagnosis is unclear. We performed whole exome sequencing in ETRS patients and identified a rare variant, the p.Arg308Gln, in DEAH (Asp-Glu-Ala-His) box polypeptide 37 (DHX37) in 5 affected individuals from three unrelated families. We expanded the analysis of DHX37 coding region to additional 71 patients with 46,XY gonadal dysgenesis and identified the p.Arg308Gln and three other DHX37 missense variants (p.Arg151Trp, p.Thr304Met and p.Arg674Trp) in 11 affected members from eight distinct families (8 patients with ETRS, two with partial gonadal dysgenesis and one 46,XY DSD female patient previously gonadectomized). The p.Arg308Gln and p.Arg674Trp recurrent variants were identified in six and three families, respectively. Segregation analysis revealed sex-limited autosomal dominant inheritance in 4 families, autosomal dominant with incomplete penetrance in one family and autosomal recessive in another family. Immunohistochemical analysis of normal testes revealed that DHX37 is expressed in germ cells at different stages of maturation.This study demonstrates an expressive frequency of rare predicted to be deleterious DHX37 variants in 46,XY gonadal dysgenesis group, particularly those individuals exhibiting the ETRS phenotype (25% and 50%, respectively).Our findings indicate that DHX37 is a new player in the complex cascade of male gonadal differentiation and maintenance, thus establishing a novel and frequent molecular etiology for 46,XY gonadal dysgenesis spectrum, mainly for embryonic testicular regression syndrome.

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