Download PDF
Exp Clin Endocrinol Diabetes 2021; 129(09): 644-650
DOI: 10.1055/a-1274-1276
Article

Effectiveness of Cabergoline Treatment in Patients with Acromegaly Uncontrolled with SSAs: Experience of a Single Tertiary Center

Serdar Sahin‡
1   Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul
,
Mehmet Cem Fidan‡
2   Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University- Cerrahpasa, Istanbul
,
Ozge Polat Korkmaz
1   Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul
,
Emre Durcan
1   Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul
,
Hande Mefkure Ozkaya
1   Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul
,
Pinar Kadioglu 
1   Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Purpose To evaluate the effectiveness of cabergoline and the parameters affecting cabergoline response as add-on treatment to somatostatin analaogues (SSA) in patients with acromegaly uncontrolled with SSAs.

Material and Method One hundred and twenty-nine acromegalic patients uncontrolled with SSA who had cabergoline added to their treatment were included in this retrospective study. Patients were divided into the SSAs + cabergoline-responsive (group 1) and non-responsive groups (group 2), and biochemical, pathologic, and radiologic parameters were assessed.

Results IGF-1 normalization was achieved in 75 of 129 patients (58%) when cabergoline was added to the SSA treatment. Female patients were significantly higher in group 1 compared to group 2 (p=0.006). Group 1 had significantly smaller pre- and post-cabergoline tumor size (p=0.011, p=0.007 respectively), lower levels of IGF-1 in pre-and post-operative period (p=0.040, p=0.001), and lower levels of IGF-1 in pre- and post-cabergoline treatment (p<0.001). Cavernous invasion on sellar magnetic resonance imaging, dural invasion in pathologic examination were not significantly different between the groups. Sellar invasion in pathologic examination was significantly higher in group 1 (p=0.011). No significant difference was found in proliferation indices between two groups. The presence of fibrous bodies was significantly lower in group 1 (p=0.010).

Conclusion Cabergoline can be added to the treatment of acromegalic patients uncontrolled with SSAs due to its ease of use and low economic cost, especially in patients with acromegaly who have small adenomas and no fibrous bodies.

Key words

Acromegaly - cabergoline - combined therapy - somatostatin analogue

Supplementary Material



Publication History

Received: 28 April 2020
Received: 24 September 2020

Accepted: 29 September 2020

Article published online:
23 October 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Chanson P, Salenave S, Kamenicky P. et al. Pituitary tumours: acromegaly. Best Pract Res Clin Endocrinol Metab 2009; 23: 555-574
    CrossrefPubMedGoogle Scholar
  • 2 Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest 2009; 119: 3189-3202
    CrossrefPubMedGoogle Scholar
  • 3 Melmed S, Katznelson L, Treatment of acromegaly. UpToDate. Jul 2019 (Accessed December 15, 2019)
    PubMed
  • 4 Webster J, Piscitelli G, Polli A. et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 1994; 331: 904-909
    CrossrefPubMedGoogle Scholar
  • 5 Nutt JG, Wooten GF. Diagnosis and initial management of Parkinson’s disease. N Engl J Med 2005; 353: 1021-1027
    CrossrefPubMedGoogle Scholar
  • 6 Gillam MP, Molitch ME, Lombardi G. et al. Advances in the treatment of prolactinomas. Endocr Rev 2006; 27: 485-534
    CrossrefPubMedGoogle Scholar
  • 7 Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: A meta-analysis. J Clin Endocrinol Metab 2011; 96: 1327-1335
    CrossrefPubMedGoogle Scholar
  • 8 Colao A, Ferone D, Marzullo P. et al. Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab 1997; 82: 518-523
    CrossrefPubMedGoogle Scholar
  • 9 Jackson SN, Fowler J, Howlett TA. Cabergoline treatment of acromegaly: A preliminary dose finding study. Clin Endocrinol (Oxf) 1997; 46: 745-749
    CrossrefPubMedGoogle Scholar
  • 10 Cozzi R, Attanasio R, Lodrini S. et al. Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: Efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf) 2004; 61: 209-215
    CrossrefPubMedGoogle Scholar
  • 11 Gatta B, Hau DH, Catargi B. et al. Re-evaluation of the efficacy of the association of cabergoline to somatostatin analogues in acromegalic patients. Clin Endocrinol (Oxf) 2005; 63: 477-478
    CrossrefPubMedGoogle Scholar
  • 12 Rocheville M, Lange DC, Kumar U. et al. Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity. Science 2000; 288: 154-157
    CrossrefPubMedGoogle Scholar
  • 13 Katznelson L, Laws ER, Melmed S. et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3933-3951
    CrossrefPubMedGoogle Scholar
  • 14 Gola M, Bonadonna S, Mazziotti G. et al. Resistance to somatostatin analogs in acromegaly: An evolving concept?. J Endocrinol Invest 2006; 29: 86-93
    CrossrefPubMedGoogle Scholar
  • 15 Fleseriu M. Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: A literature review. Pituitary 2011; 14: 184-193
    CrossrefPubMedGoogle Scholar
  • 16 Jallad RS, Bronstein MD. Optimizing medical therapy of acromegaly: Beneficial effects of cabergoline in patients uncontrolled with long-acting release octreotide. Neuroendocrinology 2009; 90: 82-92
    CrossrefPubMedGoogle Scholar
  • 17 Vilar L, Azevedo MF, Naves LA. et al. Role of the addition of cabergoline to the management of acromegalic patients resistant to longterm treatment with octreotide LAR. Pituitary 2011; 14: 148-156
    CrossrefPubMedGoogle Scholar
  • 18 Van der Lely AJ, Harris AG, Lamberts SW. The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex. Clin Endocrinol (Oxf) 1992; 37: 181-185
    CrossrefPubMedGoogle Scholar
  • 19 Kiseljak-Vassiliades K, Carlson NE, Borges MT. et al. Growth hormone tumor histological subtypes predict response to surgical and medical therapy. Endocrine 2015; 49: 231-241
    CrossrefPubMedGoogle Scholar
  • 20 Colao A, Amato G, Pedroncelli AM. et al. Gender- and age-related differences in the endocrine parameters of acromegaly. J Endocrinol Invest 2002; 25: 532-538
    CrossrefPubMedGoogle Scholar
  • 21 Sherlock M, Fernandez-Rodriguez E, Alonso AA. et al. Medical therapy in patients with acromegaly: Predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab 2009; 94: 1255-1263
    CrossrefPubMedGoogle Scholar
  • 22 Abs R, Verhelst J, Maiter D. et al. Cabergoline in the treatment of acromegaly: A study in 64 patients. J Clin Endocrinol Metab 1998; 83: 374-378
    CrossrefPubMedGoogle Scholar
  • 23 Bevan JS, Atkin SL, Atkinson AB. et al. Primary medical therapy for acromegaly: An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. J Clin Endocrinol Metab 2002; 87: 4554-4563
    CrossrefPubMedGoogle Scholar
  • 24 Colao A, Pivonello R, Auriemma RS. et al. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: A prospective study in 99 patients. J Clin Endocrinol Metab 2006; 91: 2112-2118
    CrossrefPubMedGoogle Scholar
  • 25 Besser GM, Burman P, Daly AF. Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol 2005; 153: 187-193
    CrossrefPubMedGoogle Scholar
  • 26 Ezzat S, Kontogeorgos G, Redelmeier DA. et al. In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. Eur J Endocrinol 1995; 133: 686-690
    CrossrefPubMedGoogle Scholar
  • 27 Osamura RY, Kajiya H, Takei M. et al. Pathology of the human pituitary adenomas. Histochem Cell Biol 2008; 130: 495-507
    CrossrefPubMedGoogle Scholar
  • 28 Fusco A, Zatelli MC, Bianchi A. et al. Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab 2008; 93: 2746-2750
    CrossrefPubMedGoogle Scholar
  • 29 Amirjmshidi A, Alimohamadi M, Ownagh V. et al. The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: A cohort study. Asian J Neurosurg 2014; 9: 130-136
    Article in Thieme ConnectPubMedGoogle Scholar