Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly

PLoS One. 2013 Sep 9;8(9):e73543. doi: 10.1371/journal.pone.0073543. eCollection 2013.

Abstract

Introduction: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres.

Methods: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database.

Results: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7%) presented with a macroadenoma and 18 (6.7%) with a microadenoma. Radiographic invasion was present in 91 cases (33.8%). Mean tumor diameter was 1.86 cm (0.2-4.6). Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA) in 147 patients, prolactin-production by mixed lactotroph (LA) and SA or mammosomatotroph adenoma (MSA) in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001) less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136) to achieve disease remission.

Conclusions: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.

MeSH terms

  • Acromegaly / complications
  • Acromegaly / metabolism*
  • Acromegaly / pathology*
  • Acromegaly / therapy
  • Adenoma / complications
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Adenoma / therapy
  • Female
  • Glucose / metabolism*
  • Growth Hormone / metabolism
  • Growth Hormone-Secreting Pituitary Adenoma / complications
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism*
  • Growth Hormone-Secreting Pituitary Adenoma / pathology
  • Growth Hormone-Secreting Pituitary Adenoma / therapy
  • Human Growth Hormone / analogs & derivatives
  • Human Growth Hormone / metabolism
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Pituitary Gland / metabolism
  • Pituitary Gland / pathology*
  • Pituitary Neoplasms / complications
  • Pituitary Neoplasms / metabolism
  • Pituitary Neoplasms / pathology
  • Pituitary Neoplasms / therapy

Substances

  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Glucose
  • pegvisomant

Grants and funding

The authors have no support or funding to report.