What are the causes of virilization?

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Uzroci virilizacije

Virilizacija kod žena nastaje zbog prekomjerne proizvodnje androgena iz jajnika ili nadbubrežnih žlijezda, pri čemu su najčešći uzroci kongenitalna adrenalna hiperplazija (CAH), sindrom policističnih jajnika (PCOS), androgen-producirajući tumori, i rjeđe poremećaji razvoja spola (DSD).1, 2

Glavni patološki izvori androgena

1. Nadbubrežni uzroci

  • Kongenitalna adrenalna hiperplazija (CAH) - najčešći uzrok virilizacije u djetinjstvu i adolescenciji

    • Deficit 21-hidroksilaze čini ~95% slučajeva CAH 1
    • Blokada sinteze kortizola dovodi do ACTH stimulacije i preusmjeravanja prekursora prema sintezi spolnih hormona 1
    • Neklasični CAH (NCCAH) se javlja kod 0.1-0.2% opće populacije, ali do 1-2% kod određenih etničkih grupa 1
    • Adolescenti s NCCAH i očitom virilizacijom zahtijevaju liječenje 1

  • Androgen-producirajući tumori nadbubrežne žlijezde

    • Proizvode širok spektar C19 androgena 3
    • Karakterizira ih brza progresija simptoma 4, 2

2. Ovarijalni uzroci

  • Sindrom policističnih jajnika (PCOS) - najčešći uzrok kod odraslih žena

    • Povezan s povećanom pulzatilnom i toničkom sekrecijom LH s ovarijalnom hiperstimulacijom 3
    • Javlja se kod 2-4% nehirsutnih žena u klinikama za fertilitet 1

  • Ovarijalni tumori koji proizvode androgene

    • Luče uži raspon androgena od adrenalnih tumora 3
    • Prezentacija može biti prikrivena 3

  • Ovarijalna hipertekoza i hiperplazija stromalne teke 5

    • Često povezana s metaboličkim poremećajima (dijabetes tip 2, hipertenzija) 5

3. Poremećaji razvoja spola (DSD)

  • Mogu ostati nedijagnosticirani do puberteta kada se aktivira disgenična gonada 2
  • Virilizacija u pubertetu može biti prva manifestacija DSD 2
  • Zahtijevaju kompleksnu genetsku obradu uključujući testiranje na varijacije Y-kromosoma 2

4. Egzogeni androgeni

  • Anabolički steroidi, danazol, valproična kiselina 4
  • Transdermalna apsorpcija od partnera koji koristi topikalni testosteron 6
  • Ključno je uzeti detaljnu anamnezu o korištenju lijekova 4

Klinički pristup prema težini

Blaga virilizacija (Ferriman-Gallwey skor 8-15)

  • Približno 50% slučajeva nije povezano s hiperandrogenemijom 4
  • Ne preporučuje se testiranje razina androgena kod izolirane blage virilizacije 4

Umjerena do teška virilizacija (skor >15)

  • Obavezno testiranje razina androgena 4
  • Testosteron, slobodni testosteron, DHEAS 4, 5

Znakovi upozorenja za tumor:

  • Nagli početak i brza progresija 4, 2
  • Klitoromegalija 2, 3
  • Produbljivanje glasa 2
  • Povećana muskularna masa 2
  • Teška akne 2
  • Abdominalna ili pelvična masa 4

Važne kliničke zamke

Neklasični CAH može uzrokovati neočekivanu tešku virilizaciju: Čak 24% pacijenata s V281L mutacijom (obično povezanom s NCCAH) razvija tešku virilizaciju, a 66% onih s P30L mutacijom pokazuje neočekivanu virilizaciju 7. Ovo ima implikacije za prenatalno savjetovanje.

Postmenopauza: Razvoj frank virilizacije u menopauzi uvijek zahtijeva isključivanje tumora koji luče androgene na razini jajnika i nadbubrežnih žlijezda 5. Blagi znakovi hiperandrogenizma mogu biti dio normalnog starenja, ali progresivna virilizacija nije 5.

Interdisciplinarni pristup: Kompleksni slučajevi virilizacije u pubertetu, posebno oni koji uključuju DSD, zahtijevaju timski pristup s ponovljenim i proširenim biokemijskim i genetskim testovima 2.

References

2
Research

Approach to the Virilizing Girl at Puberty.

The Journal of clinical endocrinology and metabolism, 2021

3
Research

Hirsutism and virilism in women.

Special topics in endocrinology and metabolism, 1984

5
Research

[Virilization and metabolic disease in postmenopausal women related to ovarian hyperplasia and hypertecosis].

Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina), 2021

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