Definition

  • A chronic, slowly developing disease with progressive disfigurement and disability
  • Early diagnosis is difficult as most signs and symptoms are due to long-standing overproduction of growth hormone (GH) and/or insulin-like growth factor 1 (IGF-1) causing metabolic, endocrine and morphological changes

Epidemiology

  • A rare disease with an estimated prevalence of of 30-70 individuals per million in Europe
  • Mean age of diagnosis is early to mid-40s in both males and females, with higher incidence in females
  • Diagnosis is often delayed due to its insidious onset

Pathophysiology

  • >95% of patients with acromegaly have hypersecretion of GH and IGF-1 secondary to GH-secreting pituitary adenoma that arise from somatotroph cells
    • In response to inducing signals including hypothalamic growth hormone-releasing hormone (GHRH), GH is synthesized and stored in the somatotroph cells
    • Production of GH is suppressed by somatostatin signaling primarily through the somatostatin receptor subtype 2
    • Peripheral signals (eg IGF-1, steroid and paracrine growth factors) also regulate production of GH
  • <5% of patients with acromegaly have excess GH secretion from a hypothalamic tumor or a neuroendocrine tumor that leads to somatotroph hyperplasia and acromegaly

Signs and Symptoms

Signs and Symptoms of Excess GH and/or IGF-1

  • Soft tissue swelling and extremity enlargement
  • Hyperhidrosis (excessive sweating)
  • Hypogonadism symptoms
  • Coarsening of facial features
  • Prognathism
  • Macroglossia
  • Arthritis
  • Gigantism
  • Increased incidence of obstructive sleep apnea
  • Increased incidence of diabetes mellitus (DM) (glucose intolerance)
  • Increased incidence of cardiovascular diseases (hypertension, coronary heart disease [CHD])
  • Increased incidence of thyroid disorders (eg multinodular goiter)
  • Metabolic effects: Hyperphosphatemia, hypercalciuria, hypertriglyceridemia and low high-density lipoprotein-C
  • Increased incidence of colonic polyps and adenocarcinoma

Symptoms Caused by Suprasellar Extension of Pituitary Adenoma

  • Visual field defects
  • Diplopia (secondary to cranial nerve palsy)
  • Headache
  • Loss of pituitary function resulting in lethargy, menstrual dysfunction, erectile dysfunction, infertility and loss of libido

Etiology

 Other Causes of Acromegaly

  • Rarely, from ectopic pituitary tumor or ectopic production of GH by other tumors like cancers of pancreas or lung
  • May also be caused by ectopic production of GHRH by a tumor in the hypothalamus or tumors of the pancreas, kidney and lungs