J Neurol Surg B Skull Base
DOI: 10.1055/a-2319-0344
Original Article

Early Predictors of Remission in Acromegaly Patients after Pure Endoscopic Endonasal Transsphenoidal Surgery

1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
,
Gamze Akkus
2   Division of Endocrinology, Department of Internal Medicine, Cukurova University Faculty of Medicine, Adana, Türkiye
,
Gulsah Seydaoglu
3   Department of Biostatistics, Cukurova University Faculty of Medicine, Adana, Türkiye
,
Kerem Mazhar Ozsoy
1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
,
Mevlana Akbaba
1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
,
Okay Baykara
1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
,
Kadir Oktay
1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
,
Tahsin Erman
1   Department of Neurosurgery, Cukurova University Faculty of Medicine, Balcali, Adana, Türkiye
› Author Affiliations

Abstract

Objective Surgery is the first-line treatment in acromegaly but it takes months to confirm remission. It is crucial to determine remission early in order to inform the patient and plan further treatment options. We aimed to evaluate the predictors of remission at the early phase after endoscopic endonasal pituitary surgery in acromegaly patients.

Methods Fifty-four growth hormone (GH)-adenoma patients operated via pure endoscopic endonasal approach were analyzed in this observational study. We compared the basic clinical, radiological characteristics, and the preoperative and postoperative hormone levels in terms of remission according to current guidelines.

Results The surgical remission rate was 61.1%. When the patients were compared according to surgical remission, the age, gender, and immunohistochemical granulation type were found to be nonsignificant, while diabetes mellitus was more common (55.6 vs. 44.4%). The preoperative tumor volume (1.2 ± 0.9 vs. 4.1 ± 4.2 cm3) and postoperative GH and insulin-like growth factor-1 (IGF-1) levels were higher in the nonremission group (p < 0.05). We defined a number of cut-off values of both GH and IGF-1 levels to predict remission at the postoperative phase. Age standardized regression analyses showed that postoperative day 1 (POD-1) GH levels (odds ratio [OR]: 8.9; 95% confidence interval [CI]: 1.99–40.0, p = 0.004) and tumor volume (OR: 3.14; 95% CI: 1.09–9.0, p = 0.034) were found to be significant independent predictors for remission.

Conclusion We demonstrated that tumor volume and POD-1 GH levels are independent predictors of remission in acromegaly patients operated via the pure endoscopic endonasal technique and may be used as an early marker of remission, and this may lead to taking adjuvant medical therapies early into account to improve prognosis.



Publication History

Received: 04 February 2024

Accepted: 23 April 2024

Accepted Manuscript online:
03 May 2024

Article published online:
23 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 de Herder WW. Acromegaly and gigantism in the medical literature. Case descriptions in the era before and the early years after the initial publication of Pierre Marie (1886). Pituitary 2009; 12 (03) 236-244
  • 2 Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP. Mortality in acromegaly: a metaanalysis. J Clin Endocrinol Metab 2008; 93 (01) 61-67
  • 3 Chiloiro S, Giampietro A, Gagliardi I. et al. Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience. Pituitary 2022; 25 (06) 831-841
  • 4 Beauregard C, Truong U, Hardy J, Serri O. Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol (Oxf) 2003; 58 (01) 86-91
  • 5 Orme SM, McNally RJ, Cartwright RA, Belchetz PE. United Kingdom Acromegaly Study Group. Mortality and cancer incidence in acromegaly: a retrospective cohort study. J Clin Endocrinol Metab 1998; 83 (08) 2730-2734
  • 6 Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: acromegaly. Best Pract Res Clin Endocrinol Metab 2009; 23 (05) 555-574
  • 7 Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary 1999; 2 (01) 29-41
  • 8 Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 2008; 62 (05) 1006-1015 1015–1017
  • 9 Tabaee A, Anand VK, Barrón Y. et al. Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg 2009; 111 (03) 545-554
  • 10 Starnoni D, Daniel RT, Marino L, Pitteloud N, Levivier M, Messerer M. Surgical treatment of acromegaly according to the 2010 remission criteria: systematic review and meta-analysis. Acta Neurochir (Wien) 2016; 158 (11) 2109-2121
  • 11 Giustina A, Chanson P, Bronstein MD. et al; Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 2010; 95 (07) 3141-3148
  • 12 Fleseriu M, Biller BMK, Freda PU. et al. A Pituitary Society update to acromegaly management guidelines. Pituitary 2021; 24 (01) 1-13
  • 13 Jane Jr JA, Starke RM, Elzoghby MA. et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 2011; 96 (09) 2732-2740
  • 14 Sarkar S, Jacob KS, Pratheesh R, Chacko AG. Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays. Acta Neurochir (Wien) 2014; 156 (07) 1379-1387
  • 15 Campbell PG, Kenning E, Andrews DW, Yadla S, Rosen M, Evans JJ. Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus 2010; 29 (04) E5
  • 16 Chen CJ, Ironside N, Pomeraniec IJ. et al. Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications. Acta Neurochir (Wien) 2017; 159 (11) 2193-2207
  • 17 Hazer DB, Işık S, Berker D. et al. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg 2013; 119 (06) 1467-1477
  • 18 Yildirim AE, Sahinoglu M, Divanlioglu D. et al. Endoscopic endonasal transsphenoidal treatment for acromegaly: 2010 consensus criteria for remission and predictors of outcomes. Turk Neurosurg 2014; 24 (06) 906-912
  • 19 Cardinal T, Rutkowski MJ, Micko A. et al. Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly. Neurosurg Focus 2020; 48 (06) E10
  • 20 Coopmans EC, Postma MR, Wolters TLC. et al. Predictors for remission after transsphenoidal surgery in acromegaly: a Dutch Multicenter Study. J Clin Endocrinol Metab 2021; 106 (06) 1783-1792
  • 21 Giustina A, Biermasz N, Casanueva FF. et al; Acromegaly Consensus Group. Consensus on criteria for acromegaly diagnosis and remission. Pituitary 2024; 27 (01) 7-22
  • 22 Esposito D, Ragnarsson O, Johannsson G, Olsson DS. Prolonged diagnostic delay in acromegaly is associated with increased morbidity and mortality. Eur J Endocrinol 2020; 182 (06) 523-531
  • 23 Siegel S, Streetz-van der Werf C, Schott JS, Nolte K, Karges W, Kreitschmann-Andermahr I. Diagnostic delay is associated with psychosocial impairment in acromegaly. Pituitary 2013; 16 (04) 507-514
  • 24 Sibeoni J, Manolios E, Verneuil L, Chanson P, Revah-Levy A. Patients' perspectives on acromegaly diagnostic delay: a qualitative study. Eur J Endocrinol 2019; 180 (06) 339-352
  • 25 Kothari RU, Brott T, Broderick JP. et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996; 27 (08) 1304-1305
  • 26 Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993; 33 (04) 610-617
  • 27 Zhou Q, Yang Z, Wang X. et al. Risk factors and management of intraoperative cerebrospinal fluid leaks in endoscopic treatment of pituitary adenoma: analysis of 492 patients. World Neurosurg 2017; 101: 390-395
  • 28 American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care 2022; 45 (Suppl. 01) S17-S38
  • 29 Baussart B, Declerck A, Gaillard S. Mononostril endoscopic endonasal approach for pituitary surgery. Acta Neurochir (Wien) 2021; 163 (03) 655-659
  • 30 Cappabianca P, Alfieri A, de Divitiis E. Endoscopic endonasal transsphenoidal approach to the sella: towards functional endoscopic pituitary surgery (FEPS). Minim Invasive Neurosurg 1998; 41 (02) 66-73
  • 31 Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 1997; 87 (01) 44-51
  • 32 Anik I, Cabuk B, Gokbel A. et al. Endoscopic transsphenoidal approach for acromegaly with remission rates in 401 patients: 2010 Consensus Criteria. World Neurosurg 2017; 108: 278-290
  • 33 Babu H, Ortega A, Nuno M. et al. Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery 2017; 81 (02) 357-366
  • 34 Taghvaei M, Sadrehosseini SM, Ardakani JB, Nakhjavani M, Zeinalizadeh M. Endoscopic endonasal approach to the growth hormone-secreting pituitary adenomas: endocrinologic outcome in 68 patients. World Neurosurg 2018; 117: e259-e268
  • 35 Haliloglu O, Kuruoglu E, Ozkaya HM. et al. Multidisciplinary approach for acromegaly: a single tertiary center's experience. World Neurosurg 2016; 88: 270-276
  • 36 Claessen KMJA, Kroon HM, Pereira AM. et al. Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study. J Clin Endocrinol Metab 2013; 98 (12) 4808-4815
  • 37 Mazziotti G, Bianchi A, Porcelli T. et al. Vertebral fractures in patients with acromegaly: a 3-year prospective study. J Clin Endocrinol Metab 2013; 98 (08) 3402-3410
  • 38 Mortini P, Barzaghi LR, Albano L, Panni P, Losa M. Microsurgical therapy of pituitary adenomas. Endocrine 2018; 59 (01) 72-81
  • 39 Cardinal T, Collet C, Wedemeyer M. et al. Postoperative GH and degree of reduction in IGF-1 predicts postoperative hormonal remission in acromegaly. Front Endocrinol (Lausanne) 2021; 12: 743052
  • 40 Ludecke DK, Abe T. Transsphenoidal microsurgery for newly diagnosed acromegaly: a personal view after more than 1,000 operations. Neuroendocrinology 2006; 83 (3-4): 230-239
  • 41 Agrawal N, Ioachimescu AG. Prognostic factors of biochemical remission after transsphenoidal surgery for acromegaly: a structured review. Pituitary 2020; 23 (05) 582-594
  • 42 Oldfield EH, Jane Jr JA, Thorner MO, Pledger CL, Sheehan JP, Vance ML. Correlation between GH and IGF-1 during treatment for acromegaly. J Neurosurg 2017; 126 (06) 1959-1966
  • 43 Trepp R, Stettler C, Zwahlen M, Seiler R, Diem P, Christ ER. Treatment outcomes and mortality of 94 patients with acromegaly. Acta Neurochir (Wien) 2005; 147 (03) 243-251
  • 44 Hofstetter CP, Mannaa RH, Mubita L. et al. Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus 2010; 29 (04) E6
  • 45 Shin SS, Tormenti MJ, Paluzzi A. et al. Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary 2013; 16 (04) 435-444
  • 46 Yilmaz M, Vural E, Koc K, Ceylan S. Cavernous sinus invasion and effect of immunohistochemical features on remission in growth hormone secreting pituitary adenomas. Turk Neurosurg 2015; 25 (03) 380-388
  • 47 Hannon AM, Thompson CJ, Sherlock M. Diabetes in patients with acromegaly. Curr Diab Rep 2017; 17 (02) 8
  • 48 Umemura T, Kawamura T, Hotta N. Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: a possible link between cerebral and retinal microvascular abnormalities. J Diabetes Investig 2017; 8 (02) 134-148
  • 49 Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary 2014; 17 (01) 81-89
  • 50 Fieffe S, Morange I, Petrossians P. et al; French Acromegaly Registry. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol 2011; 164 (06) 877-884
  • 51 Petrossians P, Daly AF, Natchev E. et al. Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database. Endocr Relat Cancer 2017; 24 (10) 505-518
  • 52 Rosario PW. Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population. Pituitary 2011; 14 (03) 217-221
  • 53 Suda K, Fukuoka H, Iguchi G. et al. The prevalence of acromegaly in hospitalized patients with type 2 diabetes. Endocr J 2015; 62 (01) 53-59
  • 54 Mercado M, Molitch ME, Baumann G. Low plasma growth hormone binding protein in IDDM. Diabetes 1992; 41 (05) 605-609
  • 55 Wurzburger MI, Sönksen PH. Natural course of growth hormone hypersecretion in insulin-dependent diabetes mellitus. Med Hypotheses 1996; 46 (02) 145-149
  • 56 Wijayaratne DR, Arambewela MH, Dalugama C, Wijesundera D, Somasundaram N, Katulanda P. Acromegaly presenting with low insulin-like growth factor-1 levels and diabetes: a case report. J Med Case Rep 2015; 9: 241
  • 57 Lim DJ, Kwon HS, Cho JH. et al. Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia. Endocr J 2007; 54 (04) 537-541
  • 58 Moustaki M, Paschou SA, Xekouki P. et al. Secondary diabetes mellitus in acromegaly. Endocrine 2023; 81 (01) 1-15
  • 59 Droste M, Domberg J, Buchfelder M. et al. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol 2014; 171 (01) 59-68