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Recovery rate of adrenal function after surgery in patients with acromegaly is higher than in those with non-functioning pituitary tumors: a large single center study

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Abstract

Purpose

To compare hypothalamus–pituitary–adrenal (HPA) axis integrity at diagnosis and recovery after transsphenoidal surgery (TSS), in acromegaly patients, compared with tumor size matched non-functioning adenoma (NFA) patients.

Methods

A retrospective 7-year evaluation of acromegaly patients, who underwent TSS with 52 weeks follow-up at a single institution, was undertaken. 50 acromegaly with complete follow-up data at all points and 50 NFA patients were matched for tumor size; HPA axis was similarly assessed pre-operatively and at 6, 12 and 52 weeks post-operatively. Recovery of HPA axis and gender specific prevalence of adrenal insufficiency (AI), were analyzed in both groups. We also studied AI in acromegaly patients requiring medical therapy post-operatively vs those in remission after surgery.

Results

AI remained less prevalent in acromegaly vs NFA (acromegaly, p = 0.01; NFA, p = 0.15) at 52 weeks after surgery, although the prevalence of AI decreased in both groups from baseline by 52 weeks. Additionally, recovery from baseline AI was significantly greater by 52 weeks in acromegaly patients over NFA patients (p = 0.001). Recovery of HPA axis in acromegaly patients remained significant (p = 0.03) despite the need for medical therapy. AI at baseline was proportionately more prevalent in acromegalic males at baseline (p = 0.002) but no gender difference was apparent at 52 weeks (p = 0.35). Conversely, in NFA patients, no gender difference was apparent pre-operatively (p = 0.49), but AI was more prevalent in males at 52 weeks (p = 0.001).

Conclusion

In the longest comparative study to date using a standard assessment modality, HPA axis recovery was more frequent in acromegaly compared to NFA patients, independent of tumor size, cavernous sinus invasion (CSI), and body mass index (BMI). HPA axis integrity must be carefully and periodically monitored in acromegaly patients during short- and long-term follow-up to prevent overtreatment with glucocorticoids.

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References

  1. Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Investig 119(11):3189–3202

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Nachtigall L, Delgado A, Swearingen B, Lee H, Zerikly R, Klibanski A (2008) Changing patterns in diagnosis and therapy of acromegaly over two decades. J Clin Endocrinol Metab 93(6):2035–2041

    Article  CAS  PubMed  Google Scholar 

  3. Arafah BM (1986) Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 62(6):1173–1179

    Article  CAS  PubMed  Google Scholar 

  4. Greenman Y, Tordjman K, Kisch E, Razon N, Ouaknine G, Stern N (1995) Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas. J Clin Endocrinol Metab 80(5):1577–1583

    CAS  PubMed  Google Scholar 

  5. Tominaga A, Uozumi T, Arita K, Kurisu K, Yano T, Hirohata T (1995) Anterior pituitary function in patients with nonfunctioning pituitary adenoma: results of longitudinal follow-up. Endocr J 42(3):421–427

    Article  CAS  PubMed  Google Scholar 

  6. Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F (1999) Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metabolism 84(10):3696–3700

    Article  CAS  Google Scholar 

  7. Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243–248

    Article  CAS  PubMed  Google Scholar 

  8. Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, Marshall JC, Laws ER Jr, Vance ML (2011) Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96(9):2732–2740

    Article  CAS  PubMed  Google Scholar 

  9. 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(3):294–302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA Jr (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(8):3190–3198

    Article  CAS  PubMed  Google Scholar 

  11. Burgers AM, Kokshoorn NE, Pereira AM, Roelfsema F, Smit JW, Biermasz NR, Romijn JA (2011) Low incidence of adrenal insufficiency after transsphenoidal surgery in patients with acromegaly: a long-term follow-up study. J Clin Endocrinol Metab 96(7):E1163–E1170

    Article  PubMed  Google Scholar 

  12. Ronchi CL, Ferrante E, Rizzo E, Giavoli C, Verrua E, Bergamaschi S, Lania AG, Beck-Peccoz P, Spada A (2008) Long-term basal and dynamic evaluation of hypothalamic-pituitary-adrenal (HPA) axis in acromegalic patients. Clin Endocrinol 69(4):608–612

    Article  CAS  Google Scholar 

  13. Fleseriu M (2013) The role of combination medical therapy in acromegaly: hope for the nonresponsive patient. Curr Opin Endocrinol Diabetes Obes 20(4):321–329

    CAS  PubMed  Google Scholar 

  14. Fleseriu M, Delashaw JB Jr, Cook DM (2010) Acromegaly: a review of current medical therapy and new drugs on the horizon. Neurosurg Focus 29(4):E15

    Article  PubMed  Google Scholar 

  15. Fleseriu M (2014) Advances in the pharmacotherapy of patients with acromegaly. Discov Med 18(96):329–338

    Google Scholar 

  16. Mestron A, Webb SM, Astorga R, Benito P, Catala M, Gaztambide S, Gomez JM, Halperin I, Lucas-Morante T, Moreno B, Obiols G, de Pablos P, Paramo C, Pico A, Torres E, Varela C, Vazquez JA, Zamora J, Albareda M, Gilabert M (2004) Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol 151(4):439–446

    Article  CAS  PubMed  Google Scholar 

  17. Sherlock M, Reulen RC, Alonso AA, Ayuk J, Clayton RN, Sheppard MC, Hawkins MM, Bates AS, Stewart PM (2009) ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab 94(11):4216–4223

    Article  CAS  PubMed  Google Scholar 

  18. Sherlock M, Reulen RC, Aragon-Alonso A, Ayuk J, Clayton RN, Sheppard MC, Hawkins MM, Bates AS, Stewart PM (2014) A paradigm shift in the monitoring of patients with acromegaly: last available growth hormone may overestimate risk. J Clin Endocrinol Metab 99(2):478–485

    Article  CAS  PubMed  Google Scholar 

  19. Ben-Shlomo A (2010) Pituitary gland: predictors of acromegaly-associated mortality. Nat Rev Endocrinol 6(2):67–69

    Article  PubMed  Google Scholar 

  20. Sherlock M, Stewart PM (2013) Updates in growth hormone treatment and mortality. Curr Opin Endocrinol Diabetes Obes 20(4):314–320

    CAS  PubMed  Google Scholar 

  21. Zueger T, Kirchner P, Herren C, Fischli S, Zwahlen M, Christ E, Stettler C (2012) Glucocorticoid replacement and mortality in patients with nonfunctioning pituitary adenoma. J Clin Endocrinol Metab 97(10):E1938–E1942

    Article  CAS  PubMed  Google Scholar 

  22. Fleseriu M, Gassner M, Yedinak C, Chicea L, Delashaw JB Jr, Loriaux DL (2010) Normal hypothalamic-pituitary-adrenal axis by high-dose cosyntropin testing in patients with abnormal response to low-dose cosyntropin stimulation: a retrospective review. Endocr Pract 16(1):64–70

    Article  PubMed  Google Scholar 

  23. Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, Maghnie M, Rose SR, Soule SG, Tordjman K (2008) Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 93(11):4245–4253

    Article  CAS  PubMed  Google Scholar 

  24. Beauregard C, Truong U, Hardy J, Serri O (2003) Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol 58(1):86–91

    Article  Google Scholar 

  25. Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT (1998) Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83(10):3419–3426

    CAS  PubMed  Google Scholar 

  26. Arafah BM, Prunty D, Ybarra J, Hlavin ML, Selman WR (2000) The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab 85(5):1789–1793

    CAS  PubMed  Google Scholar 

  27. Berg C, Meinel T, Lahner H, Mann K, Petersenn S (2010) Recovery of pituitary function in the late-postoperative phase after pituitary surgery: results of dynamic testing in patients with pituitary disease by insulin tolerance test 3 and 12 months after surgery. Eur J Endocrinol 162(5):853–859

    Article  CAS  PubMed  Google Scholar 

  28. Marazuela M, Astigarraga B, Vicente A, Estrada J, Cuerda C, Garcia-Uria J, Lucas T (1994) Recovery of visual and endocrine function following transsphenoidal surgery of large nonfunctioning pituitary adenomas. J Endocrinol Investig 17(9):703–707

    Article  CAS  Google Scholar 

  29. Wass JA, Reddy R, Karavitaki N (2011) The postoperative monitoring of nonfunctioning pituitary adenomas. Nat Rev Endocrinol 7(7):431–434

    Article  PubMed  Google Scholar 

  30. Caputo C, Sutherland T, Farish S, McNeill P, Ng KW, Inder WJ (2013) Gender differences in presentation and outcome of nonfunctioning pituitary macroadenomas. Clin Endocrinol 78(4):564–570

    Article  Google Scholar 

  31. Ahmed S, Elsheikh M, Stratton IM, Page RC, Adams CB, Wass JA (1999) Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience. Clin Endocrinol 50(5):561–567

    Article  CAS  Google Scholar 

  32. Buchfelder M, Schlaffer S (2009) Surgical treatment of pituitary tumours. Best Pract Res Clin Endocrinol Metab 23(5):677–692

    Article  PubMed  Google Scholar 

  33. Gittoes NJ, Sheppard MC, Johnson AP, Stewart PM (1999) Outcome of surgery for acromegaly–the experience of a dedicated pituitary surgeon. QJM 92(12):741–745

    Article  CAS  PubMed  Google Scholar 

  34. Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD (1996) Thyrotropin-secreting pituitary tumors. Endocr Rev 17(6):610–638

    CAS  PubMed  Google Scholar 

  35. Luini A, Lewis D, Guild S, Schofield G, Weight F (1986) Somatostatin, an inhibitor of ACTH secretion, decreases cytosolic free calcium and voltage-dependent calcium current in a pituitary cell line. J Neurosci 6(11):3128–3132

    CAS  PubMed  Google Scholar 

  36. Shimon I (2003) Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogs. Endocrine 20(3):265–269

    Article  CAS  PubMed  Google Scholar 

  37. Mazziotti G, Giustina A (2013) Glucocorticoids and the regulation of growth hormone secretion. Nat Rev Endocrinol 9(5):265–276

    Article  CAS  PubMed  Google Scholar 

  38. Giustina A, Veldhuis JD (1998) Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19(6):717–797

    CAS  PubMed  Google Scholar 

  39. Agha A, Monson JP (2007) Modulation of glucocorticoid metabolism by the growth hormone–IGF-1 axis. Clin Endocrinol 66(4):459–465

    CAS  Google Scholar 

  40. Moore JS, Monson JP, Kaltsas G, Putignano P, Wood PJ, Sheppard MC, Besser GM, Taylor NF, Stewart PM (1999) Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by growth hormone and insulin-like growth factor: in vivo and in vitro studies. J Clin Endocrinol Metab 84(11):4172–4177

    CAS  PubMed  Google Scholar 

  41. Stewart PM, Toogood AA, Tomlinson JW (2001) Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle. Horm Res 56(Suppl.):11–16

    Google Scholar 

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Correspondence to Maria Fleseriu.

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Yedinak, C., Hameed, N., Gassner, M. et al. Recovery rate of adrenal function after surgery in patients with acromegaly is higher than in those with non-functioning pituitary tumors: a large single center study. Pituitary 18, 701–709 (2015). https://doi.org/10.1007/s11102-015-0643-8

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  • DOI: https://doi.org/10.1007/s11102-015-0643-8

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