Preview

MD-Onco

Advanced search

The impact of chemotherapy on pituitary hormonal function in pubertal children with Hodgkin’s lymphoma

https://doi.org/10.17650/2782-3202-2025-5-3-80-88

Abstract

Background. Endocrine disorders are a significant long-term complication in children who have undergone anti-cancer treatment. Despite the relevance of this issue, the effects of chemotherapy (CT) on pituitary hormonal function in pubertal children with Hodgkin’s lymphoma (HL) remain poorly understood.
Aim. To evaluate the levels of pituitary hormones (somatotropic (growth) hormone (GH), thyroid-stimulating (TSH), adrenocorticotropic (ACTH), luteinizing (LH), follicle-stimulating (FSH) hormones, prolactin) in pubertal children with HL before and after chemotherapy. Materials and methods. The study included 40 pubertal children (11–17 years old, median 13.65 years) diagnosed with HL (20 (50 %) boys and 20 (50 %) girls) – main group. The control group comprised 40 conditionally healthy children of the same age range (median age 15.25 years) with equal gender distribution. Blood samples from the HL group were collected before chemotherapy and after its completion (prior to radiotherapy). Hormone levels (GH, TSH, ACTH, LH, FSH, prolactin) were measured using standard radioimmunoassay and enzyme-linked immunosorbent assay kits. Reference values were based on hormone levels in the control group. Statistical analysis was performed using Statistica 10.
Results. In girls with HL, pre-treatment levels of LH, FSH, and the LH/FSH ratio were elevated by 1.8-, 1.4-, and 1.3-fold, respectively, compared to the norm (p <0.05). GH and ACTH levels were 1.6and 3.1-fold below normal, respectively (p <0.05). After CT, LH levels decreased by 2.8-fold from baseline and by 1.5-fold relative to the norm, while FSH levels remained elevated at 1.6-fold above the norm (p <0.05). The LH/FSH ratio dropped by 2.6-fold relative to the norm and by 3.2-fold compared to baseline. Prolactin levels post-CT were 1.7-fold above the norm and 1.5-fold above baseline (p <0.05). GH levels were 7.8-fold lower than normal and 4.8-fold below baseline, whereas ACTH levels increased by 6.7-fold over baseline and were twice the normal level.
In boys with HL, pre-treatment LH levels and LH/FSH ratio were 1.5and 1.4-fold below normal, respectively (p <0.05). Prolactin was 1.8-fold higher than normal (p <0.05), and GH was 3.6-fold below normal. After CT, LH increased by 1.4-fold compared to baseline, reaching reference values (p <0.05).
Based on FSH levels, patients were divided into two subgroups: in 50 %, FSH remained within the normal range, while in the other 50 %, it increased ten-fold. The LH/FSH ratio remained normal in the first subgroup but was 11-fold below normal and 7.8-fold below baseline in the second. Post-treatment prolactin levels were 3.6-fold above normal and twice the baseline level. GH increased threefold from baseline and normalized. ACTH exceeded both normal and baseline levels two-fold. TSH levels decreased by 1.8-fold compared to both the norm and baseline (p <0.05).
Conclusion. The development of HL in pubertal children is associated with suppression of adenohypophyseal function and an imbalance in the synthesis of tropic hormones. Antitumor therapy does not generally restore normal hormone levels, which may be due to dysregulation of the central endocrine axes or the presence of extrapituitary sources of hormone production.

About the Authors

D. A. Dzhavadov
National Medical Research Centre for Oncology, Ministry of Health of Russia; Rostov State Medical University, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037

29 Nakhichevansky Ave., Rostov-on-Don 344022



E. M. Frantsiyants
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



V. A. Bandovkina
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



Yu. Yu. Kozel
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



V. V. Dmitrieva
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



O. V. Kozyuk
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



S. N. Dimitriadi
National Medical Research Centre for Oncology, Ministry of Health of Russia; Rostov State Medical University, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037

29 Nakhichevansky Ave., Rostov-on-Don 344022



G. A. Mkrtchyan
National Medical Research Centre for Oncology, Ministry of Health of Russia
Russian Federation

63 14th Line St., Rostov-on-Don 344037



K. S. Aslanyan
Regional Children’s Clinical Hospital
Russian Federation

14 339th Strelkovoy Divizii St., Rostov-on-Don 344015



References

1. Arega G., Adam H., Girma A. et al. Pediatric T-cell/histiocyte-rich large B-cell lymphoma (THRLBC) in an 8-year-old male child: a case report. Case Rep Oncol Med 2025;2025:8869045. DOI: 10.1155/crom/8869045

2. National Cancer Institute: NCCR. An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available at: https://nccrexplorer.ccdi.cancer.gov (Date of access: 05.01.2025).

3. Malignant neoplasms in Russia in 2016 (incidence and mortality). Ed. by A.D. Kaprin, V.V. Starinskiy, G.V. Petrova, Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2018. 38 p. (In Russ.).

4. Che Y., Ding X., Xu L. et al. Advances in the treatment of Hodgkinʼs lymphoma (Review). Int J Oncol 2023;62(5):61. DOI: 10.3892/ijo.2023.5509

5. Valiev T.T., Morozova O.V., Kovrigina A.M. et al. Diagnosis and treatment of anaplastic large-cell lymphomas in children.

6. Gematologiya i transfuziologiya = Russian Journal of Hematology and Transfusiology 2012;57(1):3–9. (In Russ.).

7. Gurieva O.D., Valiev T.T., Pavlovskaya A.I. Histiocytic neoplasms: modern aspects of pathogenesis, classification, diagnosis and treatment. Onkogematologiya = Oncohematology 2022;17(1):10–25. (In Russ.). DOI: 10.17650/1818-8346-2022-17-1-10-25

8. Kulichkina N.S., Belyaeva E.S., Popa A.V. et al. The predictive role of interim pet-ct in the treatment of Hodgkinʼs lymphoma in children. Sovremennaya onkologiya = Journal of Modern Oncology 2017;19(3):52–6. (In Russ.).

9. Tsaplina N.S., Kozlov A.V., Valiev T.T. et al. Treatment of children with relapsed and refractory classical Hodgkinʼs lymphoma: the experience of two centers. Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology 2024;11(3):22–9. (In Russ.). DOI: 10.21682/2311-1267-2024-11-3-22-29

10. Gurieva O.D., Savelyeva M.I., Valiev T.T. Genetic basis of clinical variants of chemotherapy toxicity in children with acute lymphoblastic leukemia (literature review). Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology 2021;8(4):60–70. (In Russ.). DOI: 10.21682/2311-1267-2021-8-4-60-70

11. Casano-Sancho P., Izurieta-Pacheco A.C. Endocrine late effects in childhood cancer survivors. Cancers (Basel) 2022;14(11):2630. DOI: 10.3390/cancers14112630

12. Zaeva G.E., Valiev T.T., Gavrilenko T.F. et al. Long-term effects of pediatric cancer therapy: 35-year clinical experience. Sovremennaya onkologiya = Journal of Modern Oncology 2015;18(1):55–60. (In Russ.).

13. Pavlova T.Yu., Valiev T.T. Second malignant tumors in pediatric cancer survivors. Pediatriya. Consilium Medicum = Pediatrics. Consilium Medicum 2020;2:12–6. (In Russ.). DOI: 10.26442/26586630.2020.2.200234

14. Chemaitilly W., Li Z., Brinkman T.M. et al. Primary hypothyroidism in childhood cancer survivors: prevalence, risk factors, and long-term consequences. Cancer 2022;128(3):606–14. DOI: 10.1002/cncr.33969

15. Sklar C.A., Antal Z., Chemaitilly W. et al. Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2018;103(8):2761–84. DOI: 10.1210/jc.2018-01175

16. Friedman D.N., Tonorezos E.S., Cohen P. Diabetes and metabolic syndrome in survivors of childhood cancer. Horm Res Paediatr 2019;91(2):118–27. DOI: 10.1159/000495698

17. Pollock N.I., Cohen L.E. Growth hormone deficiency and treatment in childhood cancer survivors. Front Endocrinol (Lausanne) 2021;12:745932. DOI: 10.3389/fendo.2021.745932

18. National Institute for Health and Care Excellence (NICE). NICE Clinical Guidelines, No. 243. Adrenal insufficiency: identification and management. 2024.

19. Wei C., Crowne E.C. The hypothalamic-pituitary-adrenal axis in childhood cancer survivors. Endocr Relat Cancer 2018;25(10):R479–R96. DOI: 10.1530/ERC-18-0217

20. Lewis A., Thant A.A., Aslam A. et al. Diagnosis and management of adrenal insufficiency. Clin Med (Lond) 2024;23(2):115–8. DOI: 10.7861/clinmed.2023-0067

21. Bandovkina V.A., Frantsiyants E.M., Salatova A.M. et al. Thyroid status in patients with early stages of cancer of various localization. Issledovaniya i praktika v meditsine = Researchʼn Practical Medicine Journal 2024;11(2):46–56. (In Russ.). DOI: 10.17709/2410-1893-2024-11-2-4

22. Kit O.I., Frantsiyants E.M., Bandovkina V.A. et al. The content of steroid hormones, their precursors and ACTH in the blood of patients with pathology of pancreas. Onkologiya. Zhurnal im. P.A. Hertzena = P.A. Herzen Journal of Oncology 2020;9(3):29–33. (In Russ.). DOI: 10.17116/onkolog202090312

23. Bandovkina V.A., Frantsiyants E.M., Cheryarina N.D. et al. The response to chemotherapy in patients with breast cancer may depend not only on the biological subtype of the tumor, but also on the hormonal status of the patient. Sovremenniye problemy nauky i obrazivaniya = Modern problems of science and education 2020;5. (In Russ.). DOI: 10.17513/spno.30177

24. Manosroi W., Chirayucharoensak J., Chai-Adisaksopha C., Phinyo P. Hormonal changes after R-CHOP chemotherapy in patients with diffuse large B-cell lymphoma: a prospective study. Medicina (Kaunas) 2022;58(6):710. DOI: 10.3390/medicina58060710

25. Lebbink C.A., van den Bos C., Dierselhuis M.P. et al. Thyroid Profile in the First Three Months after Starting Treatment in Children with Newly Diagnosed Cancer. Cancers (Basel). 2023 Feb 27;15(5):1500. DOI: 10.3390/cancers15051500.

26. Thabit J.A., Almzaiel A.J., Kadhim M.I., Alrufaie M.A. The impact of reproductive hormone changes on the immune response of patients with leukemia. Anaesth Pain Intensive Care 2023;27(5):585−91. DOI: 10.35975/apic.v27i5.2317

27. Frantsiyants E. M., Bandovkina V. A., Dzhavadov D. A. et al. Thyroid status in adolescent patients with Hodgkin’s lymphoma before and after antitumor treatment. Sovremenniye problemy nauky i obrazivaniya = Modern problems of science and education. 2024;5. (In Russ.). DOI: 10.17513/spno.33598

28. Drechsel K.C.E., Broer S.L., van Breda H.M.K. et al. Semen analysis and reproductive hormones in boys with classical Hodgkin lymphoma treated according to the EuroNet-PHL-C2 protocol. Hum Reprod 2024;39(11):2411–22. DOI: 10.1093/humrep/deae204

29. Crowne E., Gleeson H., Benghiat H. et al. Effect of cancer treatment on hypothalamic-pituitary function. Lancet Diabetes Endocrinol 2015;3(7):568–76. DOI: 10.1016/S2213-8587(15)00008-X

30. Link-Rachner C.S., Gobel A., Jaschke N.P., Rachner T.D. Endocrine health in survivors of adult-onset cancer. Lancet Diabetes Endocrinol 2024;12(5):350–64. DOI: 10.1016/S2213-8587(24)00088-3

31. Werner H., Laron Z. Role of the GH-IGF1 system in progression of cancer. Mol Cell Endocrinol 2020;518:111003. DOI: 10.1016/j.mce.2020.111003

32. Boguszewski M.C.S., Boguszewski C.L., Chemaitilly W. et al. Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement. Eur J Endocrinol 2022;186(6):P35–P52. DOI: 10.1530/EJE-21-1186

33. Kazmi S.R.H., Can A.S. Luteinizing hormone deficiency. Treasure Island (FL): StatPearls Publishing, 2024.

34. Hsueh A.J., He J. Gonadotropins and their receptors: coevolution, genetic variants, receptor imaging, and functional antagonists. Biol Reprod 2018;99(1):3–12. DOI: 10.1093/biolre/ioy012

35. Chu Y.L., Xu Y.R., Yang W.X., Sun Y. The role of FSH and TGF-β superfamily in follicle atresia. Aging (Albany NY) 2018;10(3):305–21. DOI: 10.18632/aging.101391

36. Haldar S., Agrawal H., Saha S. et al. Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells. Int J Biol Sci 2022;18(2):675–92. DOI: 10.7150/ijbs.63721

37. Sun Y., Qiu F., Hu C. et al. Hemangioma endothelial cells and hemangioma stem cells in infantile hemangioma. Ann Plast Surg 2022;88(2):244–9. DOI: 10.1097/SAP.0000000000002835

38. Hong Z., Kuang J., Guo Y. et al. Effects of follicle-stimulating hormone on the proliferation and apoptosis of infantile hemangioma stem cells. Biochem Biophys Rep 2023;35:101551. DOI: 10.1016/j.bbrep.2023.101551

39. Ben-Jonathan N., Hugo E. Prolactin (PRL) in adipose tissue: regulation and functions. Adv Exp Med Biol 2015;846:1–35. DOI: 10.1007/978-3-319-12114-7_1

40. Borba V.V., Zandman-Goddard G., Shoenfeld Y. Prolactin and autoimmunity. Front Immunol 2018;9:73. DOI: 10.3389/fimmu.2018.00073

41. Makotela Y., Triebel J., Clapp K. Time for a new look at the role of prolactin in metabolism. Trends Endocrinol Metab 2020;31(4):276–86. DOI: 10.1016/j.tem.2020.01.004

42. Devesa J., Caicedo D. The role of growth hormone on ovarian functioning and ovarian angiogenesis. Front Endocrinol (Lausanne) 2019;10:450. DOI: 10.3389/fendo.2019.00450

43. Huang Z., Huang L., Waters M.J., Chen C. Insulin and growth hormone balance: Implications for obesity. Trends Endocrinol Metab 2020;31(9):642–54. DOI: 10.1016/j.tem.2020.04.005

44. Roelfsema F., Yang R.J., Bowers C.Y., Veldhuis J.D. Modulating effects of progesterone on spontaneous nocturnal and ghrelin-induced GH secretion in postmenopausal women. J Clin Endocrinol Metab 2019;104(6):2385–94. DOI: 10.1210/jc.2018-02639

45. Cuny T., Graillon T., Defilles C. et al. Characterization of the ability of a second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells. Pituitary 2021;24(3):351–8. DOI: 10.1007/s11102-020-01113-4

46. Bando H., Yamamoto M., Urai S. et al. Fluctuations in plasma adrenocorticotropic hormone concentration may predict the onset of immune checkpoint inhibitor-related hypophysitis. J Immunother Cancer 2024;12(2):e008634. DOI: 10.1136/jitc-2023-00863


Review

For citations:


Dzhavadov D.A., Frantsiyants E.M., Bandovkina V.A., Kozel Yu.Yu., Dmitrieva V.V., Kozyuk O.V., Dimitriadi S.N., Mkrtchyan G.A., Aslanyan K.S. The impact of chemotherapy on pituitary hormonal function in pubertal children with Hodgkin’s lymphoma. MD-Onco. 2025;5(3):80-88. (In Russ.) https://doi.org/10.17650/2782-3202-2025-5-3-80-88

Views: 80


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2782-3202 (Print)
ISSN 2782-6171 (Online)