Cryptorchidism

undescending testis

1. Cryptorchidism Amir Saad Aljboory Urological resident Iraqi board urology Arabic board urology

2. DEFINITIONS • Normal scrotal position : positioning of midpoint of the testis at or below midscrotum . • Undescended testis : absence of one or both testes in normal scrotal position. • Vanishing testes : present initially in development but are lost owing to vascular accident or torsion unilaterally ( monorchia ) or, very rarely, bilaterally ( anorchia ). Agenesis: testis that was never present and therefore associated with ipsilateral müllerian duct persistence. • Congenital cryptorchidism: testes that are extrascrotal at birth.

3. • Recurrent cryptorchidism is when testes descend spontaneously postnatally but subsequently return to a nonscrotal position . Testicular ascent or acquired cryptorchidism : Testes are intrascrotal at birth but subsequently identified in an extrascrotal position • Secondary cryptorchidism- testes that are suprascrotal after inguinal hernia repair; testicular retraction- as a complication of orchidopexy . • Retractile testes are scrotal testes that retract easily out of scrotum but can be manually replaced in a stable scrotal position and remain there at least temporarily.

4. Introduction: Development of the Testis Initial differentiation of male and female gonad development is dependent on: Presence of Y chromosome SRY gene ( protein product of the Y chromosome ) steroidogenic factor 1 (SF1/ Nr5a1 ) Sox9 (SRY box-containing 9 ) Within the developing testis the three main differentiating cell types are: - spermatogonia ( gamete forming cells) – Sertoli cells (support cells) and - Leydig or interstitial cells (hormone secreting cells)

5. Phases of testicular descent • Phase 1: 5 weeks - The caudal mesonephros contacts the future gubernaculum at the internal inguinal ring. • Phase 2: 7 weeks -The genitofemoral nerve accompanies the newly formed gubernaculum and processus vaginalis . • Phase 3: 10 to 12 weeks - Gubernaculum remains a thin cord in both sexes . Phase 3a: 12 to 14 weeks - The testis overrides the genital ducts and contacts the gubernaculum. • Phase 4: 14 to 20 weeks swelling of the gubernaculum , further development of the cremaster muscle, and migration of the processus vaginalis produce widening of the inguinal canal • Phase 5: 20 to 28 weeks - Release of the distal subcutaneous attachment of the gubernaculum and transinguinal passage of the testis. Phase 5a : after 7th month – Caudal movement of the testis, regression of the gubernaculum

6. Regulation of testicular descent • Mechanical factors Intra-abdominal Pressure Gubernaculum tension Processus vaginalis patency • Growth factors Insulin-like 3 (INSL3) growth factor ( Abdominal phase ) Calcitonin gene related peptide ( Inguinoscrotal Phase ) Epidermal growth factor (EGF) may promote by activating the androgen responsive systems • Hormonal factors Testosterone ( Inguinoscrotal Phase)

7. Undescended testis • One of the most common pediatric disorders of male endocrine glands & Most common genital disorder identified at birth. Cryptorchidism : A greek word which means ‘ hidden testis ’ • Retractile- 60 % • Undescended- 35% • Ectopic- 3 % • Ascending- <2%

8. Epidemiology & Risk factors Incidence of Undescended testis 1–9% of full-term infants , by 1 year incidence is 0.8% 30 % of premature infants Occurs on the right-50 %, left-35% , bilateral-10-15% Prevalence reported to be (possibly) increasing • Risk factors • Maternal & Gestational Factors – Maternal Obesity – Low birth weight – Prematurity Maternal smoking- small-to-moderate increased risk for cryptorchidism is present in offspring

9. Genetic Factors • 14% of cryptorchid boys – have positive family history. • Multifactorial pattern transmission • Father affected – 4% • Sibiling affected – 6-10 % • Gene mutation have identified -cryptorchidism – INSL3 – LGR8 – Androgen receptor polymorphism – HOXA10 – HOXD13 Environmental Prenatal exposure - endocrine disrupters – DES – Pesticide (DDT) – Nonylphenol – Natural phytoestrogens – Phthalates etc.

10. Associated conditions • Abdominal wall defects ( eg , prune belly) • Neural tube defects (eg, myelomeningocele) • Cerebral palsy ~50% • Disorders of sexual development • Genetic disorders • Diminished testosterone secretion ( eg , Klinefelter ) • Diminished testosterone action ( eg , Androgen insens .) • Primary hypogonadism ( eg , Noonan) • Chromosomal disorders ( eg , trisomy 18, trisomy 13)

11. Classification A . Based on palpation (Kaplan-1993) Impalpable: Accounts for 20% -30 % of UDT . High canalicular Deep inguinal ring Intra-abdominal Palpable: Accounts for 70% - 80 % of UDT Neck of scrotum Superficial inguinal ring Low canalicular

12. Classification contd B . Based on exploration findin gs: intra-abdominal intracanalicular extracanalicular (suprapubic or infrapubic ), or ectopic.

13. Pathological changes often macroscopically normal in early childhood but by puberty some degree of atrophy occur.. Microscopic evidence of tubular atrophy is evident by 5-6years of age, & hyalinization is present by the time of puberty . loss of volume and progressive germ cell depletion starting at 6 months of age

14. histologic changes include : decreased tubular diameter, and decreased numbers of Leydig cells, atrophy of Leydig cells degeneration of Sertoli cells Abnormal germ cell development o Delayed disappearance of Gonocytes o Delayed appearance of Adult dark spermatogonia o failure of primary spermatocytes to develop, and o reduced total germ cell counts

15. Clinical features Most patients presents in infancy and around school age . few present after puberty. Absence of one or both testes swelling in the groin (may be the testis or a hernia) May present with attacks of pain in the groin due either to recurrent torsion of the testis or strangulation of an associated hernia gestational age at birth- usually preterm Determining if the testis was palpable in the scrotum at any time is important past history of inguinal surgery should be noted family history of cryptorchidism and other associated conditions.

16. Examination • Patient should be warm and relaxed for the examination Observation should precede the examination. • Supine and, if possible, upright cross-legged and standing positions . • Abduction of the thighs contributes to inhibition of the cremaster reflex. • Document testicular palpability, position, mobility, size, and possible associated findings such as hernia, hydrocele, penile size, and urethral position.   Palpable Testes • Undescended testes may be located along the line of normal descent between the abdomen and scrotum or in an ectopic position. • Ectopic:  Superficial inguinal pouch( m.c. )  Perirenal  Prepubic  Femoral  Peripenile  Perineal  Contralateral scrotal

17.   Nonpalpable testes Examination under anaesthesia is done for impalpable testis before exploration • When a testis is nonpalpable , possible clinical findings at surgery include : 1. abdominal or transinguinal “peeping” location (25% to 50 %), 2. complete atrophy (“vanishing” testis, 15% to 40%), and 3 . extra-abdominal location but nonpalpable due to body habitus, testicular size, and/or limited pts.’cooperation (10-30%).

18. Investigation Imaging Abdominal USS CT Scan MRI Because imaging has not been proved to be reliable in demonstrating whether the testis is present or absent, its routine use is discouraged

19. Laboratory Investigations Karyotyping ↑ FSH- likely represent bilateral anorchia HCG Stimulation tests- has clinical use where gonadothrophins are normal FBC, Urinalysis, Serum electrolytes Diagnostic Laparoscopy

20. Management of undescended testis • Cryptorchid testis should be treated – between 6 month to 1 year of age. • 12-18 months – histological deterioration of the testis noted. • Testis rarely descends – after 6 months. • Surgical advantage to Orchiopexy - within 6 months specially in high undescended testis.

21. Hormonal therapy hCG (human Chorionic Gonadotropin) Stimulate endogenous secretion of testosterone. Therapeutic dose – 1500 U/ m 2 body surface area twice in a week for 4 weeks (FDA approved). • Total dose should not exceed 15,000 units. • Testicualar descent rate – 25% with hCG – 18 % with GnRH LHRH- 1.2 mg/ day in divided doses intranasal for 4 weeks . • Testicular descent rate –about 20%. • Not FDA approved • Boserelin – superanalogue of LHRH – Small dose- 10μg every other day for 6 months. – Descent rate – 17%

22. Surgical Management • Palpable testes one stage orchidopexy Non- palpable testes • Laparoscopy / open • High incidence of congenital inguinal hernia ( hernia repair) Retractile or ectopic testes Cremasterotomy

23. Inguinal Orchidopexy Principles of orchidopexy • Adequate exposure • Herniotomy • Mobilization of cord • Fixation of testis • Most commonaly performed – creation of subdartos pouch and placing the testis. • General anesthesia; useful to re-examine the child- previously nonpalpable testis may become palpable . • Groin crease incision is made Careful dissection to expose the external oblique aponeurosis and the external ring