2/4/28 Universiteit Utrecht Outline Use of nti-müllerin hormone () in dignosing ovrin tumors nd cryptorchidism nti-müllerin hormone () Wht, origin, Mrker for equine cryptorchidism Mrker for equine grnulos cell tumors Anthony Cles, DVM, PhD, Diplomte ACT Assistnt Professor in Equine Reproduction Utrecht University.cles@uu.nl Advntges of Anti-Müllerin hormone () Homodimeric glycoprotein Erly in fetl life Sertoli cells Sexul differentition At irth Sexul dimorphic expression is lost Sertoli cells (testis) Grnulos cells (ovry) Equine fetl testis s dignostic mrker for cryptorchidism Equine follicle Equine testis Dignosis of Cryptorchidism Cryptorchidism: Hormone nlysis Endocrine test Bseline testosterone hcg stimultion test Estrone sulphte Inconclusive results* 4 % 6.7 %.3 % One scrotl testis Trnsrectl nd trnscutneous (inguinl or dominl) ultrsonogr. Disdvntges Lrge fluctutions Seril lood smpling: Imprcticl, $$$, time consuming Lrge gry re Age Less relile in horses < 8 months of ge Less relile in horses < 8 months of ge Less relile in horses < 3 yers of ge No scrotl testis/testes Hormone nlysis *Cox et l., Equine Vet J,8:986.
2/4/28 in geldings, cryptorchid stllions nd intct stllions Serum 4 4 3 3 2 2 Intct stllion Cryptorchid stllion c Gelding Cles et l, Theriogenology 23 versus Source Age 9 8 7 6 4 3 2 (pg/ml) Leydig cells (testis) Adrenl glnds Prepuertl colts Postpuertl stllions Sertoli cells (testis) 3 2 2 versus Diurnl fluctutions Sesonl fluctutions 7 6 4 3 2 Lrge 3 3 2 2 Smll Cn we use when testosterone is inconclusive? Jn Fe Mr Apr My Jun Jul Aug Sep Oct Nov Dec Jn Fe Mr Apr My Jun Jul Aug Sep Oct Nov Dec Usefulness of when testosterone is inconclusive? Reference rnges for testosterone* < pg/ml sence of testiculr tissue - pg/ml INCONCLUSIVE (Gry Zone) > pg/ml presence of testiculr tissue Reference rnges for * >. ng/ml presence of testiculr tissue *Clinicl Endocrinology Lortory (UCDvis) Cse : Qurter Horse (7 yo) Month: June Bseline 7. 3 pg/ml 3.4 ng/ml Month: Mrch (following yer) Inconclusive hcg stimultion Time : 8 pg/ml 2.3 ng/ml hr: 88.6 pg/ml 2 hrs: 7.7 pg/ml 24 hrs: 27. pg/ml Testic. tissue Cles et l, J Eq Vet Sc, 24 2
2/4/28 Cse 2: Qurter Horse (3 yo) Disppernce of fter cstrtion Month: Novemer hcg stimultion Time : 26 pg/ml 4. ng/ml Month: My (following yer) hcg stimultion 2 hrs: 4 pg/ml Asence / Inconclusive? Testiculr tissue Time : 26 pg/ml 4 hrs: 39 pg/ml 44. ng/ml Surgery reveled ilterl dominl testes Serum (ng/ml) 2 3 4 6 7 t/2:, dys Dys post cstrtion Grnulos cell tumors (GCT) s dignostic mrker for Grnulos Cells Tumors Most common ovrin tumor Unilterl nd enign Hormonlly ctive A lrge GCT with intr-dominl leeding Endocrinology Dignosis GCT Hormone Inhiin Progesterone Norml Rnge (GCT rnge).-.7 ng/ml (GCT >.7 ng/ml) 2-4 pg/ml (GCT > 4 pg/ml) <. ng/ml (estrus) >. ng/ml (diestrus) Comments Elevted in + 9% of the GCT cses Elevted in + -6% of the GCT cses Typiclly: <. ng/ml in GCT cses 3
2/4/28 Limittions current GCT pnel expression in equine GCTs Inhiin Cyclic chnges Pregnncy Adrenl origin Pregnncy (erly vs lte) Progesterone GCT possile in cyclic mres Solution?? Bll et l, Theriogenology,, 28 Circulting concentrtions Ovriectomized mres (n=) Non-pregnnt mres (n=6) Mres with GCT (n=) Men Undetectle Rnge N/A.96 ±.8.22 2.94 9.4 ± 44.6 4-96 Almeid et l., Theriogenology, 2 Cse Inhiin (pg/ml) Progesterone 96. 4.2.2 2 229..39 83.6. 3 664.2.93 7.8.3 4 49.4. 4.4. 74.2 2. 9.7. 6 44. 8.93 42.9. 7 4..44 23.6. 8 846.. 97..3 9 32.7.4 43.6. 4.3 2. 99.6.4 82.9.33 29.7.2 Sensitivity of, inhiin nd testosterone for dignosis of GCTs Mrker Inhiin Inhiin + Dignostic vlue > 4 pg/ml >.7 ng/ml >.7 ng/ml or > 4 pg/ml Sensitivity 48% 8% 84% > 4 ng/ml 98% Bll et l, EVJ, 23 Repeted lood smples Cse 2 Intervl etween collections Inhiin (pg/ml) d 9..7 34.6 3 d..6 7.7 82 d 4..44 23.6 d.6.9 2.6 3 dys 64.4 2..2 Both GCTs confirmed y histopthology 4
2/4/28 in pregnnt mres Tke home messge in pregnnt mre with GCT Gesttionl dys 73 2. 2 269. 292 296.2 324 39 d p-prtum 342.6 Crtree et l EVE 23 Serum in pregnnt mres without GCT.8.6.4.2.8.6.4.2 2 3 4 6 7 8 9 Month of gesttion Almeid et l., Theriogenology, 2 Cryptorchid > intct stllion > gelding Single lood smple < 8 months of ge +++ over testosterone:. Less diurnl fluctution 2. Incresed sensitivity More sensitive thn inhiin nd/or testosterone GCTs in pregnnt mres Questions