Transsphenoidal surgery (TSS) is the cornerstone of acromegaly treatment. Two biochemical parameters, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, sometimes diverge postoperatively; however, it is important to maintain disease control without further treatment, regardless of whether these parameters converge. This study investigated whether remission and long-term disease control could be predicted using early postoperative GH and IGF-1 levels.
We reviewed 36 consecutive surgically treated patients with acromegaly. IGF-1 levels and minimum GH levels during an oral glucose tolerance test (OGTT) were evaluated at 2 weeks, as well as at 3 months postoperatively. After comparison between the remission and nonremission groups, we analyzed whether early postoperative parameters could predict remission and long-term disease control.
Twenty-five patients (69.4%, Group A) achieved remission within 1 year postoperatively. Of the remaining patients (median follow-up period, 53 months), seven (19.5%, Group B) maintained normal IGF-1 levels without treatment, whereas four (11.1%, Group C) required additional treatment. GH levels <1.5 ng/mL measured on the morning after surgery and nadir GH levels <0.7 ng/mL during the OGTT conducted at 2 weeks postoperatively were predictive of remission, with the latter demonstrating 95.2% sensitivity and 100% specificity. All group C patients had nadir GH levels ≥0.7 ng/mL during the OGTT and IGF-1 levels ≥SD +3 at 2 weeks postoperatively.
Early postoperative nadir GH levels during the OGTT and IGF-1 levels at 2 weeks postoperatively demonstrated excellent predictive value for both endocrinological remission and the necessity for additional treatment.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
The datasets and analyzed data in this current study are available from the corresponding author upon reasonable request.
Alexopoulou O, Bex M, Abs R, T’Sjoen G, Velkeniers B, Maiter D (2008) Divergence between growth hormone and insulin-like growth factor-1 concentrations in the follow-up acromegaly. J Clin Endocrinol Metab 93:1324–1330. https://doi.org/10.1210/jc.2007-2104
Anik I, Cabuk B, Gokbel A, Selek A, Cetinarslan B, Anik Y, Ceylan S (2017) Endoscopic transsphenoidal approach for acromegaly with remission rates in 401 patients: 2010 consensus criteria. World Neurosurg 108:278–290. https://doi.org/10.1016/j.wneu.2017.08.182
Antunes X, Ventura N, Camilo GB, Wildemberg LE, Guasti A, Pereira PJM, Camacho AHS, Chimelli L, Niemeyer P, Gadelha MR, Kasuki L (2018) Predictors of surgical outcome and early criteria remission in acromegaly. Endocrine 60:415–422. https://doi.org/10.1007/s12020-018-1590-8
Asha MJ, Takami H, Velasquez C, Oswari S, Almeida JP, Zadeh G, Gentili F (2019) Long-term outcomes of transsphenoidal surgery for management of growth hormone-secreting adenomas: single-center results. J. Neurosurg Oct 11:1–11. https://doi.org/10.3171/2019.6.JNS191187 [Epub ahead of print]
Babu H, Ortega A, Nuno M, Dehghan A, Schweitzer A, Bonert HV, Carmichael JD, Cooper O, Melmed S, Mamelak A (2017) Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery 81:357–366. https://doi.org/10.1093/neuros/nyx020
Burton T, Nestour EL, Neary M, Ludlam WH (2016) Incidence and prevalence of acromegaly in large US health plan database. Pituitary 19:262–267. https://doi.org/10.1007/s11102-015-071-2
Colao A, Auriemma RS, Pivonello R (2016) The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary 19:210–221. https://doi.org/10.1007/s11102-015-0677-y
Colao A, Pivonello R, Cavallo LM, Gaccione M, Auriemma RS, Esposito F, Cappabianca P, Lombardi G (2006) Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly. Clin Endocrinol (Oxf) 65:250–256. https://doi.org/10.1111/j.1365-2265.2006.02584.x
Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP (2008) Mortality in acromegaly: a metaanalysis. J Clin Endocrinol Metab 93:61–67. https://doi.org/10.1210/jc.2007-1191
Ding D, Mehta GU, Patibandla MR, Lee CC, Liscak R, Kano H, Pai FY, Kosak M, Sisterson ND, Martinez-Alvarez R, Martinez-Moreno N, Mathieu D, Grills IS, Blas K, Lee K, Cifarelli CP, Katsevman GA, Lee JYK, McShane B, Kondziolka D, Lunsford LD, Vance ML, Sheehan JP (2019) Stereotactic radiosurgery for acromegaly: an international multicenter retrospective cohort study. Neurosurgery 84:717–725. https://doi.org/10.1093/neuros/nyy178
Dutta P, Korbonits M, Sachdeva N, Gupta P, Srinivasan A, Devgun JS, Bajaj A, Mukherjee KK (2016) Can immediate postoperative random growth hormone levels predict long-term cure in patients with acromegaly? Neurol India 64:252–258. https://doi.org/10.4103/0028-3886.177622
Faje AT, Barken AL (2010) Basal, but not pulsatile, growth hormone secretion determines the ambient circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab 95:2486–2491. https://doi.org/10.1210/jc.2009-2634
Feelders RA, Bidlingmaier M, Strasburger CJ, Janssen JA, Uitterlinden P, Hofland LJ, Lamberts SW, van der Lely AJ, de Herder WW (2005) Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor-I, acid-labile subunit, and growth hormone-binding protein levels. J Clin Endocrinol Metab 90:6480–6489
Freda PU, Nuruzzaman AT, Reyrs CM, Sundeen RE, Post KD (2004) Significance of “abnormal” nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 89:495–500
Freda PU (2009) Monitoring of acromegaly: What should be performed when GH and IGF-1 levels are discrepant? Clin Endocrinol (Oxf) 71:166–170. https://doi.org/10.1111/j.1365-2265.2009.03556.x
Gheorghiu ML (2017) Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary 20:154–168. https://doi.org/10.1007/s11102-016-0783-5
Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526–529. https://doi.org/10.1210/jc.85.2.526
Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S (2010) Acromegaly Consensus Group. J Clin Endocrinol Metab 95:3141–3148. https://doi.org/10.1210/jc.2009-2670
Hage M, Kamenický P, Chanson P (2019) Growth hormone response to oral glucose load: from normal to pathological conditions. Neuroendocrinology 108:244–255. https://doi.org/10.11159/000497214
Haliloglu O, Kuruoglu E, Ozkaya HM, Keskin FE, Gunaldi O, Gazioglu N, Kadioglu P, Tanriover N (2016) Multidisciplinary approach for acromegaly: a single tertiary center’s experience. World Neurosurg 88:270–276. https://doi.org/10.1016/j.wneu.2015.12.092
Hazer DB, Işik S, Berker D, Güler S, Gürlek A, Yücel T, Berker M (2013) Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg 119:1467–1477. https://doi.org/10.3171/2013.8.JNS13224
Katznelson L, Laws ER, Melmed S, Molitch ME, Utz A, Wass JA (2014) Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocriol Metab 99:3933–3951. https://doi.org/10.1210/jc.2014-2700
Kim EH, Oh MC, Lee EJ, Kim SH (2012) Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly. Neurosurgery 70:1106–1113. https://doi.org/10.1227/NEU.0b013e31823f5c16
Kinoshita Y, Tominaga A, Usui S, Arita K, Sakaguchi T, Sugiyama K, Kuris K (2016) Clinical features and natural course of acromegaly in patients with discordance in the nadir GH level on the oral glucose test and IGF-1 value at 3 months after adenomectomy. Neurosurg Rev 39:313–319. https://doi.org/10.1007/s10143-015-0692-5
Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:610–617; discussion 617–618. https://doi.org/10.1227/00006123-199310000-00008
Leonart LP, Borba HHL, Ferreira VL, Riveros BS, Pontarolo R (2018) Cost-effectiveness of acromegaly treatments: a systematic review. Pituitary 21:642–652. https://doi.org/10.1007/s11102-018-0908-0
Markkanen H, Pekkarinen T, Välimäki MJ, Alfthan H, Kauppinen-Mäkelin R, Sane T, Stenman UH (2006) Effect of sex and assay method on serum concentrations of growth hormone in patients with acromegaly and in healthy controls. Clin Chem 52:468–473. https://doi.org/10.1373/clinchem.2005.060236
Melmed S, Casanueva FF, Klibanski A, Bronstein MD, Chanson P, Lamberts SW, Strasburger CJ, Wass JA, Giustina A (2013) A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16:294–302. https://doi.org/10.1007/s11102-012-0420-x
Nagata Y, Inoshita N, Fukuhara N, Yamaguchi-Okada M, Nishioka H, Iwata T, Yoshimoto K, Yamada S (2018) Growth hormone-producing pituitary adenomas in childhood and young adulthood: clinical features and outcomes. Pituitary 21:1–9. https://doi.org/10.1007/s11102-017-0836-4
Nishioka H, Fukuhara N, Yamaguchi-Okada M, Takeshita A, Takeuchi Y, Yamada S (2017) Pitfalls in early biochemical evaluation after transsphenoidal surgery in patients with acromegaly. Endocrine J 64:1073–1078. https://doi.org/10.1507/endocrj.EJ17-0261
Otani R, Fukuhara N, Ochi T, Oyama K, Yamada S (2012) Rapid growth hormone measurement during transsphenoidal surgery: analysis of 252 acromegalic patients. Neurol Med Chir (Tokyo) 52:558–562. https://doi.org/10.2176/nmc.52.558
Pivonello R, Auriemma RS, Grasso LF, Pivonello C, Simeoli C, Patalano R, Galdiero M, Colao A (2017) Complications of acromegaly: cardiovascular, respiratory8, and metabolic comorbidities. Pituitary 20:46–62. https://doi.org/10.1007/s11102-017-0797-7
Rostomyan L, Daly AF, Petrossians P, Nachev E, Lila AR, Lecoq AL et al (2015) Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer 22:745–757. https://doi.org/10.1530/ERC-15-0320
Rotermund R, Burkhardt T, Rohani Z, Jung R, Aberle J, Flitsch J (2018) Value of early postoperative random growth hormone levels and nadir growth hormone levels after oral glucose tolerance testing in acromegaly. Growth Horm IGF Res 41:64–70. https://doi.org/10.1016/j.ghir.2018.03.002v
Sarkar S, Jacob KS, Pratheesh R, Chacko AG (2014) Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays. Acta Neurochir (Wien) 156:1379–1387. https://doi.org/10.1007/s00701-014-2098-5
Schilbach K, Gar C, Lechner A, Nicolay SS, Schwerdt L, Haenelt M, Dal J, Jørgensen JOL, Störmann S, Schopohl J, Bidlingmaier M (2019) Determinants of the growth hormone nadir during oral glucose tolerance test in adults. Eur J Endocrinol 181:55–67. https://doi.org/10.1530/EJE-19-0139
Shen M, Tang Y, Shou X, Wang M, Zhang Q, Qiao N, Ma Z, Ye Z, He W, Zhang Y, Chen Z, Zhang Z, Ye H, Li Y, Li S, Zhao Y, Zhou Z, Wang Y (2019) Surgical results and predictors and delayed remission for growth hormone-secreting pituitary adenoma using the 2010 consensus criteria in 162 patients from a single center. World Neurosurg 124:e39–e50. https://doi.org/10.1016/j.wneu.2018.11.179
Shin MS, Yu JH, Choi JH, Jung CH, Hwang JY, Cho YH, Kim CJ, Kim MS (2013) Long-term changes in serum IGF-1 levels after successful surgical treatment of growth hormone-secreting pituitary adenoma. Neurosurgery 73:473–479. https://doi.org/10.1227/01.neu.0000431480.87160.84
Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA (2013) Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:3190–3198. https://doi.org/10.1210/jc.2013-1036
Taghvaei M, Sadrehosseini SM, Ardakani JB, Nakhjavani M, Zeinalizadeh M (2018) Endoscopic endonasal approach to the growth hormone-secreting pituitary adenomas: endocrinologic outcome in 68 patients. World Neurosurg 117:e259–e268. https://doi.org/10.1016/j.wneu.2018.06.009
Theodosopoulos PV, Leach J, Kerr RG, Zimmer LA, Denny AM, Guthikonda B, Froelich S, Tew JM (2010) Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging? J Neurosurg 112:736–743. https://doi.org/10.3171/2009.6.JNS08916
Vierhapper H, Heinze G, Gessl A, Exner M, Bieglmayr C (2003) Use of the oral glucose tolerance test to define remission in acromegaly. Metabolism 52:181–185. https://doi.org/10.1053/meta.2003.50036
Vilar L, Vilar CF, Lyra R, Lyra R, Naves LA (2017) Acromegaly: clinical features at diagnosis. Pituitary 20:22–32. https://doi.org/10.1007/s11102-016-0772-8
Wang Z, Guo X, Gao L, Feng C, Lian W, Deng K, Bao X, Feng M, Wang R, Xing B (2019) Delayed remission of growth hormone-secreting pituitary adenoma after transsphenoidal adenectomy. World Neurosurg 122:e1137–e1145. https://doi.org/10.1016/j.wneu.2018.11.004
Xie T, Liu T, Zhang X, Chen L, Luo R, Sun W, Hu F, Yu Y, Gu Y (2016) Time to revive the value of the pseudocapsule in endoscopic endonasal transsphenoidal surgery for growth hormone adenomas. World Neurosurg 89:65–71. https://doi.org/10.1016/j.wneu.2016.01.036
Yano S, Shinojima N, Kawashima J, Kondo T, Hide T (2017) Intraoperative scoring system to predict postoperative remission in endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. World Neurosurg 105:375–385. https://doi.org/10.1016/j.wneu.2017.05.162
Yu M, Bruns DE, Jane JA, Nass RM, Oldfield EH, Vance ML, Thorner MO (2017) Decrease of serum IGF-1 following transsphenoidal pituitary surgery for acromegaly. Clin Chem 63:486–494. https://doi.org/10.1373/clinchem.2016.262592
Zahr R, Fleseriu M (2018) Updates in diagnosis and treatment of acromegaly. Eur Endocrinol 14:57–61. https://doi.org/10.17925/EE.2018.14.2.57
We would like to thank our helpful and efficient nursing, ENT, and anesthesiology teams for perioperative management of the endoscopic endonasal pituitary surgery.
This study was approved by the ethics committee of the Kurume University School of Medicine (approval number: 18019).
Consent to participate
All patients concurred with the proposed treatment plan after all options for the management of acromegaly were clearly explained. Informed consent was obtained from all individual participants included in this study.
Consent for publication
All authors have read and approved the final manuscript.
Conflict of interest
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Sakata, K., Nagata, Y., Takeshige, N. et al. Early postoperative prediction of both disease remission and long-term disease control in acromegaly using the oral glucose tolerance test. Hormones (2021). https://doi.org/10.1007/s42000-021-00281-7
- Growth hormone
- Endoscopic transsphenoidal surgery
- Oral glucose tolerance test
- Insulin-like growth factor-1