ESPEYB19 9. Oncology and Chronic Disease Cancer treatment and growth hormone therapy: a consensus (1 abstracts)
9.1. Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement
Boguszewski MCS , Boguszewski CL , Chemaitilly W , Cohen LE , Gebauer J , Higham C , Hoffman AR , Polak M , Yuen KCJ , Alos N , Antal Z , Bidlingmaier M , Biller BMK , Brabant G , Choong CSY , Cianfarani S , Clayton PE , Coutant R , Cardoso-Demartini AA , Fernandez A , Grimberg A , Guðmundsson K , Guevara-Aguirre J , Ho KKY , Horikawa R , Isidori AM , Jørgensen JOL , Kamenicky P , Karavitaki N , Kopchick JJ , Lodish M , Luo X , McCormack AI , Meacham L , Melmed S , Mostoufi Moab S , Müller HL , Neggers SJCMM , Aguiar Oliveira MH , Ozono K , Pennisi PA , Popovic V , Radovick S , Savendahl L , Touraine P , van Santen HM & Johannsson G
n.karavitaki@bham.ac.uk Eur J Endocrinol. 2022; 186: P35-P52. PMID: 35319491.
Brief Summary: An international panel of experts produced this consensus statement after critical review of the existing evidence on the safety of GH replacement in cancer and intracranial tumour survivors and in patients with increased cancer risk.
Current evidence does not support an association between GH replacement and primary tumour or cancer recurrence, with more robust data for adults with benign pituitary adenoma and craniopharyngioma. GH replacement should be discontinued when disease relapse or clinically significant tumour progression is confirmed. Resumption of GH replacement could be considered after discussion between clinicians, patient and caregivers one year after further remission. A shorter waiting time may be acceptable for non-malignant tumours and craniopharyngioma. The risk of secondary neoplasia, mainly meningiomas, is less related to GH replacement than to cancer treatments (e.g. radiotherapy), and the suggested timing of GH discontinuation is similar to cancer relapse. Current evidence does not support an association between GH treatment and increased mortality from cancer among childhood cancer survivors with GHD. IGF-I has limited reliability as a marker of GHD in cancer survivors. Furthermore, dynamic testing with GHRH should be avoided in patients who received cranial irradiation, due to possible false negative results, despite the complex disruption of the hypothalamic-pituitary axis. The timing of initiation of GH therapy following completion of cancer treatment should be individualized, as a decision shared by treating physicians, patient, and caregivers. This period may be as early as 3 months in children with radiologically-proven stable craniopharyngiomas who have significant growth failure and metabolic disturbances, and at least 1 year for other types of tumours. A low starting GH dose is suggested, with IGF-1 measurements every 3 months during dose titration and annually thereafter. Increased intracranial pressure, slipped capital femoral epiphysis, and worsening of scoliosis are GH-related side effects that are more common in cancer survivors. In children with cancer predisposition syndromes (including RASopathies such as Noonan syndrome), GH treatment is generally contraindicated, but it may be considered cautiously in cases with proven GHD.
The cautious statements of this extensive and updated consensus represent a useful tool to support physicians, patients and their families in decision-making on GH replacement, in particular in the areas of uncertainly due to lack of data. The position of the consensus concerning GH therapy for patients with RASopathies is noteworthy. While GH treatment has recently been approved in several countries for treatment of children with Noonan syndrome and short stature, regardless of the presence or absence of GHD (1), these experts suggest cautiously considering GH treatment in patients with RASopathies, only in the presence of a proven GHD.
Reference: 1. Jorge AAL, et al. Outcomes in growth hormone-treated Noonan syndrome children: impact of PTPN11 mutation status. Endocr Connect. 2022. PMID: 35245205.
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ESPE Yearbook of Paediatric Endocrinology
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