TEK DOZ VE ÇOĞUL DOZ hCG UYARI TESTLERİNİN KARŞILAŞTIRILMASI

Öz

Amaç: hCG uyarı testi, testis steroidogenezini değerlendirmek için yaygın olarak kullanılmaktadır. Bu test hipogonadizm, 46,XY cinsel gelişim bozukluğu veya mikropenisi olan hastalarda Leydig hücre fonksiyonunu, testise bağlı enzim kusurlarını değerlendirmektedir. Bu çalışmada tek doz 5000 IU/m2 ve 3 gün 1500 IU/ m2 hCG testlerine testosteron yanıtlarının karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya mikropenis, hipospadyas veya inmemiş testisi (Grup 1) olan 18 hasta ile moleküler olarak tanılı androjen reseptör kusuru (%56) ve 5α redüktaz eksikliği (%44) olan 18 hasta (Grup 2) dahil edildi. Hastaların median (çeyrekler aralığı) yaşı Grup 1 için 1,4 (0,8-4,2) yıl, Grup 2 için 0.7 (0,3-0,8) yıl idi. Bazal testosteron düzeyi ölçüldükten sonra ilk gruba tek doz 5000 IU/m2 hCG uygulanarak testosteron düzeyleri 1. ve 4. gün ölçüldü. İkinci gruba ise 3 gün 1500 IU/m2 hCG uygulanarak testosteron düzeyleri 4. gün ölçüldü. Bulgular: Grup 1 ve Grup 2 arasında boy, kilo, vücut kitle indeksi SDS ve bazal testosteron seviyeleri arasında anlamlı bir fark yoktu. hCG uyarısı sonrasında testosteron yanıtlarında da anlamlı fark saptanmadı. Testosteron seviyeleri bazale göre kıyaslandığında 4. günde Grup 1’de 40 kat ve Grup 2’de 40.1 kat artış gösterdi. Grup 1 hastalarında testosteron yanıtı 1. gün ile karşılaştırıldığında 4. günde anlamlı olarak daha yüksek idi (p=0,001). Sonuç: Tek doz ve çoğul doz ile gerçekleştirilen hCG uyarı testlerinin sonucunda testosteron yanıtları benzer çıkmış olup bu sonuç her iki testin de uygulanabilir olduğunu göstermiştir. 5000 IU/m2 testi daha az enjeksiyon gerektirdiği ve uygulaması kolay olduğu için Leydig hücre fonksiyonunu değerlendirmede bu test tercih edilebilir. Yeterli testosteron yanıtı için tek doz 5000 IU/m2 hCG uygulandıktan sonra 4. gün testosteron düzeylerini ölçmeyi önermekteyiz.

Anahtar Kelimeler

• Cinsiyet gelişim bozukluğu
• hCG uyarı testi
• testosteron
• 46
• XY

COMPARISON OF SINGLE DOSE AND MULTI-DOSE hCG STIMULATION TESTS

Öz

Objective: The human chorionic gonadotropin (hCG) stimulation test is widely used to assess testicular steroidogenesis. This test evaluates Leydig cell function and helps to evaluate testosterone synthesis in testicular enzyme defects, hypogonadism, 46,XY sexual development disorders (DSD), and micropenis. This study will compare testosterone responses to a single dose of 5000 IU/m2 and three consecutive days of 1500 IU/m2 hCG regimens. Materials and Methods: The study evaluated 18 patients who were admitted with micropenis, hypospadias, or undescended testis (Group 1) and 18 patients with a molecular diagnosis of androgen receptor insensitivity (56%) or 5α reductase deficiency (44%) (Group 2). The median (interquartile range; IQR) age of the patients were 1.4 (0.8-4.2) years for Group 1 and 0.7 (0.3-0.8) years for Group 2. Baseline testosterone levels were checked and after a single dose of hCG 5000 IU/m2 injection into the first group, testosterone levels were observed on day one and day four. In the second group, after the injection of hCG 1500 IU/m2 for three days, testosterone levels were checked on the fourth day. Results: There was no significant difference in height, weight, BMI SDS, and baseline testosterone levels between groups. After hCG, stimulation testosterone responses did not vary among the groups. Testosterone levels were increased 40-fold and 40.1- fold on day four compared to the baseline in Group 1 and Group 2. In Group 1, testosterone response was significantly higher on day four compared to day one (p=0.001). Conclusions: The hCG tests performed with a single dose or multidoses showed that there was no difference between testosterone responses and these two tests were applicable the 5000 IU/m2 hCG test requires fewer injections and is easy to administer, this test may be preferred to an evaluation of the Leydig cell function. For an adequate testosterone response, the researchers suggest measuring testosterone levels on the fourth day after the single dose of 5000 IU/m2 .

Anahtar Kelimeler

• Disorders of sex development
• hCG stimulation test
• testosterone
• 46
• XY

Kaynakça

1. 1. Palmert MR, Dunkel L, Witchel SF. Puberty, and its disorders in the male. In: Sperling MA (ed). Pediatric Endocrinology 4th edition. Philadelphia: Elsevier Saunders; 2014:pp 697- 733. [CrossRef]
2. 2. Bertelloni S, Russo G, Baroncelli GI. Human Chorionic Gonadotropin Test: Old Uncertainties, New Perspectives, and Value in 46,XY Disorders of sex development. Sex Dev 2018;12(1-3):41-9. [CrossRef]
3. 3. Oliveira LR, Homma TK, Woloszynek RR, Brito VN, Longui CA. Gonadal response after a single-dose stimulation test with recombinant human chorionic gonadotropin (rhCG) in patients with isolated prepubertal cryptorchidism. Basic Clin Androl 2016;26:13. [CrossRef]
4. 4. Forest MG. How should we perform the human chorionic gonadotrophin (hCG) stimulation test? Int J Androl 1983;6(1):1-4. [CrossRef]
5. 5. Holterhus PM, Honour JW, Savage MO. Endocrine function of the testes. In: Ranke MB, Mullis PE (eds). Diagnostics of Endocrine Function in Children and Adolescents. Basel: Karger AG; 2011:pp.309-30. [CrossRef]
6. 6. Lucas-Herald AK, Kyriakou A, Alimussina M, Guaragna- Filho G, Diver LA, McGowan R, et al. Serum antimullerian hormone in the prediction of response to hCG stimulation in children with DSD. J Clin Endocrinol Metab 2020;105(5):1608-16. [CrossRef]
7. 7. Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F, et al. Reference values for weight, height, head circumference, and body mass index in Turkish children. Journal of clinical research in pediatric endocrinology 2015; 7:280-93. [CrossRef]
8. 8. Valeri C, Schteingart HF, Rey RA. The prepubertal testis: biomarkers and functions. Curr Opin Endocrinol Diabetes Obes 2013;20(3):224-33. [CrossRef]

9. 9. Kogan SJ. Cryptorchidism. In: Kelalis PP, King LR, Belman AB (eds). Clinical Pediatric Urology 3rd edition. Philadelphia: W. B. Saunders;1992:pp. 1063.
10. 10. Casarini L, Santi D, Brigante G, Simoni M. Two hormones for one receptor: evolution, biochemistry, actions, and pathophysiology of LH and hCG. Endocr Rev 2018;39(5):549- 92. [CrossRef]
11. 11. Trinchard-Lugan I, Khan A, Porchet HC, Munfano A. Pharmacokinetics and pharmacodynamics of recombinant human chorionic gonadotrophin in healthy male and female volunteers. Reproductive Biomedicine Online 2002;4:106- 15. [CrossRef]
12. 12. Cailleux-Bounacer A, Reznik Y, Cauliez B, Menard JF, Duparc C, Kuhn JM. Evaluation of endocrine testing of Leydig cell function using extractive and recombinant human chorionic gonadotropin and different doses of recombinant human LH in normal men. Eur J Endocrinol 2008;159(2):171-8. [CrossRef]
13. 13. Tapanainen J, Martikainen H, Dunkel L, Perheentupa J, Vihko R. Steroidogenic response to a single injection of hCG in pre- and early pubertal cryptorchid boys. Clin Endocrinol (Oxf) 1983;18(4):355-62. [CrossRef]
14. 14. Ishii T, Matsuo N, Sato S, Ogata T, Tamai S, Anzo M, et al. Human chorionic gonadotropin stimulation test in prepubertal children with micropenis can accurately predict leydig cell function in pubertal or postpubertal adolescents. Horm Res Paediatr 2015;84(5):305-10. [CrossRef]
15. 15. Okuyama A, Namiki M, Koide T, Itatani H, Mizutani S, Sonoda T, et al. A simple hCG stimulation test for normal and hypogonadal males. Arch Androl 1981;6(1):75-81. [CrossRef]
16. 16. Davenport M, Brain C, Vandenberg C, Zappala S, Duffy P, Ransley PG, et al. The use of the hCG stimulation test in the endocrine evaluation of cryptorchidism. Br J Urol 1995;76(6):790-4. [CrossRef]
17. 17. Kolon TF, Miller OF. Comparison of single versus multiple dose regimens for the human chorionic gonadotropin stimulatory test. J Urol 2001;166(4):1451-4. [CrossRef]
18. 18. Forest MG. Pattern of the response of testosterone and its precursors to human chorionic gonadotropin stimulation in relation to age in infants and children. J Clin Endocrinol Metab 1979;49(1):132-7. [CrossRef]
19. 19. Bang AK, Nordkap L, Almstrup K, Priskorn L, Petersen JH, Rajpert-De Meyts E, et al. Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels. Eur J Endocrinol 2017;176(4):379-91. [CrossRef]
20. 20. Bertelloni S, Federico G, Baroncelli GI, Cavallo L, Corsello G, Liotta A, et al. Biochemical selection of prepubertal patients with androgen insensitivity syndrome by sex hormone-binding globulin response to the human chorionic gonadotropin test. Pediatr Res 1997;41(2):266-71. [CrossRef]