Safety profile of growth hormone replacement (GHr) in GH deficient patients during transition period treated for intracranial tumors and malignancy in childhood- Single center expirence

Mirjana Doknic; Mihajlo Curcic; Marko Stojanovic; Tatjana Milenkovic; Vera Zdravkovic; Maja Jesic; Slađana Todorović; Mihailo Milicevic; Aleksandar Stanimirovic; Vuk Scepanovic; Katarina Mitrović; Rade Vukovic; Dragana Miljic; Djurdjevic Sandra Pekic; Ivana Cekic; Ivan Jevtic; Gacic Emilija Manojlovic; Danica Grujicic; Milan Petakov; Ivan Soldatovic

doi:10.1530/endoabs.99.P347

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Endocrine Abstracts (2024) 99 P347 | DOI: 10.1530/endoabs.99.P347

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

Safety profile of growth hormone replacement (GHr) in GH deficient patients during transition period treated for intracranial tumors and malignancy in childhood- Single center expirence

Mirjana Doknic ^1,2 , Mihajlo Curcic ² , Marko Stojanovic ^1,2 , Tatjana Milenkovic ³ , Vera Zdravkovic ^2,4 , Maja Jesic ^2,4 , Slađana Todorović ³ , Mihailo Milicevic ^2,5 , Aleksandar Stanimirovic ^2,5 , Vuk Scepanovic ^2,5 , Katarina Mitrović ^2,3 , Rade Vukovic ^2,3 , Dragana Miljic ^1,2 , Sandra Pekic Djurdjevic ^1,2 , Ivana Cekic ¹ , Ivan Jevtic ¹ , Emilija Manojlovic Gacic ^2,6 , Danica Grujicic ^2,5 , Milan Petakov ^1,2 & Ivan Soldatovic ^2,7

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Author affiliations

¹University Clinical Centre of Serbia - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Neuroendocrine Department, Belgrade, Serbia; ²Faculty of Medicine, University of Belgrade, Belgrade, Serbia; ³Mother and Child Health Care Institute of Serbia‘Dr Vukan Cupic’, Belgrade, Serbia; ⁴University Children’s Clinic ‘Tirsova’, Belgrade, Serbia; ⁵Clinic for Neurosurgery, University Clinical Centre of Serbia, Belgrade, Serbia; ⁶Institute for Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; ⁷Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Introduction: Considering the mitogenic potential of GH and IGF1, the safety profile of growth hormone therapy since the beginning of its use has been debated. From that point of view, adolescents in transition to adulthood who were treated in childhood for endocranial tumors or malignancies require special caution.

Patients and Methods: In a monocentric, observational, retrospective cross-sectional study spanning 18 years, we analyzed 251 childhood onset growth hormone deficiency - COGHD patients (16-25 years old, 181 males) at time-point of pediatric to adult endocrine care transfer and over transition period on GHr. Fifty-three subjects experienced childhood-onset cranial tumor or acute lymphoblastic leukemia-ALL (TUM, 21.1%). Other patients had congenital (CON, 46.2%) or idiopathic COGHD (32.6%). Craniopharyngiomas predominated among TUM group (39.6%), followed by germinoma (15.2%), Langerhans cell histiocytosis (11.3%), medulloblastoma (9.4%), astrocytoma and ALL (each 5.6%), pituitary pseudotumor (TSH hyperplasia-3.8%), PNET, ganglioglioma, hamartoma, thalamic tumor, and malignant triton tumor (1.8% each). We monitored possible tumor recurrence using cranial MRI and hematological evaluation every 12 months in TUM group. Monitoring for recurrent lesions on GHr also extended to 6 of CON patients who underwent non-cranial childhood surgery due to benign tumors of kidney (2), skin (2) adrenals (1) or mediastinum (1).

Results: Median age of patients at time of transfer from pediatrics was 18.1±3.3 years. Patients with persistent GHD (65.8%) continued GHr in daily doses of 0.5±0.2 mg (range 0.3-1.4 mg) with follow-up IGF-I maintained mid-ranged. Duration of GHr during childhood was 5.7±4.9 years (1-16 years), while during the transition period it was 3.6±1.9 years (1-7 years). We detected papillary carcinoma of the thyroid gland in a male patient who had the experience of thalamic germinoma treated by surgery and radiotherapy at the age of 18. He started GHr (0.3 mg daily) at the age of 22 and stopped 3 years later after a malignant thyroid tumor was discovered. His brother was also treated for cranial germinoma and the same mutation on the KRAS gene was proven in both of them. During GHr no benign tumors regrowth was detected in the CON group.

Conclusion: In 53 patients with tumor-related COGHD, we monitored the safety of GH therapy in the transition period. Through follow-up, we detected papillary thyroid carcinoma in a patient previously treated for cranial germinoma. Patients should be carefully monitored on GH treatment due to the possibility of developing not only the recurrence of the tumor causing GHD, but also secondary neoplasms.