The Identification and Management of Adult Growth hormone INsufficiEncy in Gonadotroph Adenomas study (IMAGINE-GA) — ASN Events
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The Identification and Management of Adult Growth hormone INsufficiEncy in Gonadotroph Adenomas study (IMAGINE-GA) (#308)

Yeung-Ae Park 1 2 3 4 , Elizabeth Azidis-Yates 1 , Angeline Shen 1 3 , Cherie Chiang 1 3 5 , Spiros Fourlanos 1 2 , Yi Zhao 6 , Anna S Trigos 3 7 8 , James King 9 10 , Christopher J Yates 1 2
  1. Department of Diabetes & Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia
  2. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
  3. Peter MacCallum Cancer Centre, Parkville, VIC, Australia
  4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
  5. Department of Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia
  6. Department of Ear, Nose and Throat Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
  7. St. Vincent’s Institute of Medical Research, Fitzroy, VIC, Australia
  8. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  9. Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, Australia
  10. Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia

Background: Adult growth hormone deficiency (AGHD) is caused by structural pituitary disease, pituitary surgery or cranial irradiation.1, 2 Gonadotroph adenomas, the most commonly resected pituitary tumours,3 are an important cause of AGHD.4 AGHD is characterised by insulin resistance, osteoporosis, fatigue, depression, and increased premature cardiovascular mortality.5 We aimed to evaluate current detection and management of AGHD in patients with gonadotroph adenomas.

Methods: In a retrospective cohort study, patients with histologically proven gonadotroph adenomas were identified from the hospital pituitary database (2009-2025). Those without available insulin-like growth factor 1 (IGF1) levels were excluded. Clinical data, including comorbidities, hypopituitarism, malignancy history, growth hormone (GH) replacement, and biochemical and radiological data, were evaluated. Patients with newly identified low IGF1 levels without two other existing hypopituitary axis deficiencies were referred for a glucagon stimulation test.

Results: A total of 128 patients were included; 15.6% had a prior AGHD diagnosis, and low IGF1 was detected in 7.8% (n=10/128) of the remainder. Of these, two resolved spontaneously post-operatively, one normalised on repeat testing, two were lost to follow-up, one was referred for glucagon stimulation testing, and four are followed elsewhere. Among 13 patients on GH therapy, 61.5% reported symptom improvement, adenoma recurrence/progression occurred in two, and no new or recurrent extracranial malignancy was identified. No significant differences in the presence of metabolic, cardiovascular, or bone comorbidities were found between GH-deficient and GH-replete patients, or between GH-deficient patients receiving therapy and those not, in our small cohort.

Conclusion: Systematic IGF1 screening improves detection of AGHD in gonadotroph adenoma patients, and GH replacement appears clinically beneficial and safe, with no new or recurrent extracranial malignancy observed. Adenoma recurrence/progression occurred in a minority, within the ranges reported in the literature for gonadotroph adenomas regardless of GH therapy.6, 7 Nonetheless, experts recommend individualised discussion with patients before commencing GH therapy.8

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  2. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989;70(262):145-60.
  3. Nasi-Kordhishti I, Hladik M, Kandilaris K, Behling F, Honegger J, Schittenhelm J. Transcription factor-based classification of pituitary adenomas / PitNETs: a comparative analysis and clinical implications across WHO 2004, 2017 and 2022 in 921 cases. Acta Neuropathol Commun. 2025;13(1):135.
  4. Gaillard RC, Mattsson AF, Akerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069-77.
  5. Gazzaruso C, Gola M, Karamouzis I, Giubbini R, Giustina A. Cardiovascular Risk in Adult Patients With Growth Hormone (GH) Deficiency and Following Substitution With GH—An Update. The Journal of Clinical Endocrinology & Metabolism. 2014;99(1):18-29.
  6. Hussein Z, Grieve J, Dorward N, et al. Non-functioning pituitary macroadenoma following surgery: long-term outcomes and development of an optimal follow-up strategy. Frontiers in Surgery. 2023;10.
  7. Chen Y, Wang CD, Su ZP, et al. Natural history of postoperative nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Neuroendocrinology. 2012;96(4):333-42.
  8. Boguszewski MCS, Boguszewski CL, 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.