Skip to main content
SpringerLink
Log in

Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays

  • Clinical Article - Brain Tumors
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Early detection of residual disease may benefit management strategies in patients undergoing transsphenoidal surgery for acromegaly. This requires establishing objective thresholds for early postoperative growth hormone (GH) assays, and incorporating these parameters into a scale for outcome prediction.

Method

We analyzed a database containing the records of 86 patients who had undergone gross total transsphenoidal resection of GH-secreting pituitary adenomas. Early postoperative biochemical testing included a morning fasting basal GH assay on the first postoperative day (POD1) and a second GH assay following suppression with 100 g of oral glucose on the seventh postoperative day (POD7). Remission was defined as a normal IGF-1 with either a GH nadir <0.4 ng/ml following suppression with oral glucose or a basal fasting GH <1 ng/ml on follow-up dated >3 months after surgery. Receiver operator characteristic (ROC) curves identified optimal thresholds for all biochemical parameters. Logistic regression analysis assessed the statistical significance of factors associated with cure. A point system was developed, employing regression coefficients obtained from the multivariate statistical model to quantify the impact of each predictor on cure.

Results

Remission was achieved in 34.6 % of patients and was associated with smaller, non-invasive tumors with lower preoperative, POD1 and POD7 GH levels. Optimal thresholds obtained from the ROC analysis suggested that lower POD1 and POD7 GH values provided good sensitivity and specificity for cure, despite modest predictive values. The model with the best ability to predict outcome included size, POD1 GH and POD7 GH levels, with a score of ≥95 demonstrating high specificity for prediction of remission.

Conclusion

Early postoperative GH assays are highly sensitivity and specific. The scoring system that we propose provided excellent predictive value and requires further validation in larger cohorts and in different populations. The model may help guide the intensity of follow-up and enable early identification of residual disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Albarel F, Castinetti F, Morange I, Conte–Devolx B, Gaudart J, Dufour H, Brue T (2013) Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients. Clin Endocrinol (Oxf) 78:263–270

    Article  CAS  Google Scholar 

  2. Alexopoulou O, Bex M, Abs R, T’Sjoen G, Velkeniers B, Maiter D (2008) Divergence between growth hormone and insulin-like growth factor-I concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab 93:1324–1330

    Article  CAS  PubMed  Google Scholar 

  3. Berkmann S, Schlaffer S, Buchfelder M (2013) Tumor shrinkage after transsphenoidal surgery for nonfunctioning pituitary adenoma: clinical article. J Neurosurg 119:1447–1452

    Article  PubMed  Google Scholar 

  4. Bianchi A, Giustina A, Cimino V, Pola R, Angelini F, Pontecorvi A, De Marinis L (2009) Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab 94:2015–2022

    Article  CAS  PubMed  Google Scholar 

  5. Bourdelot A, Coste J, Hazebroucq V, Gaillard S, Cazabat L, Bertagna X, Bertherat J (2004) Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly. Eur J Endocrinol 150:763–771

    Article  CAS  PubMed  Google Scholar 

  6. Campbell PG, Kenning E, Andrews DW, Yadla S, Rosen M, Evans JJ (2010) Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus 29:E5

    Article  PubMed  Google Scholar 

  7. Cappabianca P, Cavallo L, Colao A, De Caro MDB, Esposito F, Cirillo S, Lombardi G, De Divitiis E (2002) Endoscopic endonasal transsphenoidal approach: outcome analysis of 100 consecutive procedures. Minim Invasive Neurosurg 45:193–200

    Article  CAS  PubMed  Google Scholar 

  8. Ceylan S, Cabuk B, Koc K, Anik I, Vural C (2013) Endoscopic distinction between capsule and pseudocapsule of pituitary adenomas. Acta Neurochir (Wien) 155:1611–1619

    Article  Google Scholar 

  9. Dehdashti AR, Ganna A, Karabatsou K, Gentili F (2008) Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 62:1006–1017

    Article  PubMed  Google Scholar 

  10. Dina T, Feaster S, Laws E, Davis D (1993) MR of the pituitary gland postsurgery: serial MR studies following transsphenoidal resection. AJNR Am J Neuroradiol 14:763–769

    CAS  PubMed  Google Scholar 

  11. Freda PU, Wardlaw SL, Post KD (1998) Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 89:353–358

    Article  CAS  PubMed  Google Scholar 

  12. Giustina A, Chanson P, Bronstein M, Klibanski A, Lamberts S, Casanueva F, Trainer P, Ghigo E, Ho K, Melmed S (2010) A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95:3141–3148

    Article  CAS  PubMed  Google Scholar 

  13. Giustina A, Mazziotti G, Fontanella M (2013) Commentary: post-surgical monitoring of acromegaly. Neurosurgery 73:E746–E748

    Article  PubMed  Google Scholar 

  14. Gondim JA, Schops M, de Almeida JPC, de Albuquerque LAF, Gomes E, Ferraz T, Barroso FAC (2010) Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center. Pituitary 13:68–77

    Article  PubMed  Google Scholar 

  15. Hazer DB, Işık 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: clinical article. J Neurosurg 119:1467–1477

    Article  PubMed  Google Scholar 

  16. Hofstetter CP, Mannaa RH, Mubita L, Anand VK, Kennedy JW, Dehdashti AR, Schwartz TH (2010) Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus 29:E6

    Article  PubMed  Google Scholar 

  17. Kaltsas G, Isidori A, Florakis D, Trainer P, Camacho-Hubner C, Afshar F, Sabin I, Jenkins J, Chew S, Monson J (2001) Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity. J Clin Endocrinol Metab 86:1645–1652

    Article  CAS  PubMed  Google Scholar 

  18. 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

    Article  PubMed  Google Scholar 

  19. Kitano M, Taneda M, Shimono T, Nakao Y (2008) Extended transsphenoidal approach for surgical management of pituitary adenomas invading the cavernous sinus. J Neurosurg 108:26–36

    Article  PubMed  Google Scholar 

  20. 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 33:610–618

    Article  CAS  PubMed  Google Scholar 

  21. Kremer P, Forsting M, Ranaei G, Wüster C, Hamer J, Sartor K, Kunze S (2002) Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma. Acta Neurochir (Wien) 144:433–443

    Article  CAS  Google Scholar 

  22. Kristof RA, Grote A, Redel L, Neuloh G, Klingmüller D, Schramm J (2011) The common consensus criteria have high predictive values for long-term postoperative acromegaly remission. Acta Neurochir (Wien) 153:19–25

    Article  Google Scholar 

  23. Lüdecke DK, Abe T (2006) Transsphenoidal microsurgery for newly diagnosed acromegaly: a personal view after more than 1,000 operations. Neuroendocrinology 83:230–239

    Article  PubMed  Google Scholar 

  24. Machado EO, Taboada GF, Neto LV, Haute FR, Corrêa LL, Balarini GA, Shrank Y, Goulart M, Gadelha MR (2008) Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR. Growth Horm IGF Res 18:389–393

    Article  CAS  PubMed  Google Scholar 

  25. Meij BP, Lopes M-BS, Ellegala DB, Alden TD, Laws ER Jr (2002) The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg 96:195–208

    Article  PubMed  Google Scholar 

  26. Minniti G, Jaffrain-Rea M, Esposito V, Santoro A, Tamburrano G, Cantore G (2003) Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature. Endocr Relat Cancer 10:611–619

    Article  CAS  PubMed  Google Scholar 

  27. Nomikos P, Buchfelder M, Fahlbusch R (2005) The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol 152:379–387

    Article  CAS  PubMed  Google Scholar 

  28. Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–407

    Article  CAS  PubMed  Google Scholar 

  29. Shin M-S, Yu JH, Choi JH, Jung CH, Hwang JY, Cho YH, Kim CJ, Kim M-S, Kim C-J (2013) Long-term changes in serum IGF-1 levels after successful surgical treatment of growth hormone secreting pituitary adenoma. Neurosurgery 73:473–479

    Article  PubMed  Google Scholar 

  30. Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang Y-F, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA (2012) Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary 16:435–444

    Article  Google Scholar 

  31. Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA (2013) Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:3190–3198

    Article  CAS  PubMed  Google Scholar 

  32. Theodosopoulos PV, Leach J, Kerr RG, Zimmer LA, Denny AM, Guthikonda B, Froelich S, Tew JM Jr (2010) Maximizing the extent of tumor resection during transsphenoidal surgery for pituitary macroadenomas: can endoscopy replace intraoperative magnetic resonance imaging? Clinical article. J Neurosurg 112:736–743

    Article  PubMed  Google Scholar 

  33. van Bunderen CC, van Varsseveld NC, Baayen JC, van Furth WR, Aliaga ES, Hazewinkel MJ, Majoie CB, Freling NJ, Lips P, Fliers E (2013) Predictors of endoscopic transsphenoidal surgery outcome in acromegaly: patient and tumor characteristics evaluated by magnetic resonance imaging. Pituitary 16:158–167

    Article  PubMed Central  PubMed  Google Scholar 

  34. Vieira JO Jr, Cukiert A, Liberman B (2006) Evaluation of magnetic resonance imaging criteria for cavernous sinus invasion in patients with pituitary adenomas: logistic regression analysis and correlation with surgical findings. Surg Neurol 65:130–135

    Article  PubMed  Google Scholar 

  35. Wang YY, Higham C, Kearney T, Davis JR, Trainer P, Gnanalingham KK (2012) Acromegaly surgery in Manchester revisited–the impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission. Clin Endocrinol (Oxf) 76:399–406

    Article  CAS  Google Scholar 

  36. Wilson CB (1979) Neurosurgical management of large and invasive pituitary tumors. Raven, New York

    Google Scholar 

  37. Yang I, Kim W, De Salles A, Bergsneider M (2010) A systematic analysis of disease control in acromegaly treated with radiosurgery. Neurosurg Focus 29:E13

    Article  PubMed  Google Scholar 

  38. Zhao B, Wei Y-K, Li G-L, Li Y-N, Yao Y, Kang J, Ma W-B, Yang Y, Wang R-Z (2010) Extended transsphenoidal approach for pituitary adenomas invading the anterior cranial base, cavernous sinus, and clivus: a single-center experience with 126 consecutive cases: clinical article. J Neurosurg 112:108–117

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Section of Neurosurgery, Department of Neurological Sciences, Christian Medical College, Vellore, India

    Sauradeep Sarkar, Ravindran Pratheesh & Ari George Chacko

  2. Section of Neurosurgery, Department of Psychiatry, Christian Medical College, Vellore, India

    K. S. Jacob

Authors
  1. Sauradeep Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. S. Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ravindran Pratheesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ari George Chacko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ari George Chacko.

Additional information

Comment

This large series of trans-sphenoidal surgery results for acromegaly presents a ‘warts and all’ approach, now that remission has recently been redefined by an International Consensus Group. Many historic series presenting surgical cure rates would need redefining in the light of the new definition.

The authors set themselves a difficult target defining total removal according to the surgeons views, including patients in whom, realistically, it was unlikely ever to have been achieved. However, it does show that if we are truthful, our results are not always as good as we would wish.

We certainly used early (Day 2/3) GH GTT nadir to plan our own acromegalic management in the last two decades. IgF1 may take more than six months to drift down to acceptable levels for our endocrinologists. It also is important to note that many patients ‘almost’ cured by the new definition will ‘feel’ cured and will need little or anything further doing for some time, until GH and IgF1 starts to drift up - which may take more than a decade.

Michael Powell

London, UK

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sarkar, S., Jacob, K.S., Pratheesh, R. et al. Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays. Acta Neurochir 156, 1379–1387 (2014). https://doi.org/10.1007/s00701-014-2098-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-014-2098-5

Keywords

Search

Navigation