Epidemiology & Pathophysiology

Epidemiology of acromegaly

Acromegaly is a rare condition, with an annual estimated incidence of three to four cases per million people.3 Since acromegaly is associated with multisystem comorbidities, prompt diagnosis and treatment are essential to improve patient outcomes.1

Pathophysiology of acromegaly

Acromegaly is caused when the pituitary gland triggers GH hypersecretion, which in turn stimulates production of IGF-1.1 95% of acromegaly cases are due to pituitary somatotroph adenomas, which generally grow over several years, and secrete GH.1

This link in hormone control is known as the GH-IGF-1 axis and is responsible for the growth control of most tissues in the body.

The paracrine and autocrine actions of IGF-1 make it challenging to dissociate the direct physiologic effects of GH from IGF-1.

Evidence suggests that GH effects on growth (independent of IGF-1) may include:14

  • Absence of decreased proteolysis14
  • Inhibition of amino acid oxidation14
  • Stimulation of lipolysis14
  • Increased sodium and water retention14
  • Insulin resistance and decreased glucose uptake
  • Increased cellular retention of nitrogen leading to decreased urea production

As the result of excess GH secretion, IGF-1 is, in turn, oversecreted (primarily by the liver, although most tissues possess GH receptors and secrete some quantity of IGF-1). The combined impact of GH and IGF-1 oversecretion can effect growth-related functions, including:8

  • Stimulation of cellular proliferation8
  • Induction of cellular differentiation8
  • Enhanced cellular metabolism8
  • Suppression of protein degradation8

Indication and Important Safety Information

  • Somatuline® Depot (lanreotide) Injection is a somatostatin analog indicated for the long-term treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy.

CONTRAINDICATIONS

  • None.

WARNINGS & PRECAUTIONS

  • Somatuline Depot may reduce gallbladder motility and lead to gallstone formation; therefore, patients may need to be monitored periodically.
  • Somatuline Depot and other somatostatin analogs can inhibit the secretion of insulin and glucagon. Patients treated with Somatuline Depot may experience hypoglycemia or hyperglycemia.
  • Antidiabetic treatment may need to be adjusted when Somatuline Depot treatment is initiated or when the dose is altered.
  • Slight decreases in thyroid function have been seen during treatment with Somatuline Depot. Thyroid function tests are recommended where clinically indicated.
  • The most common cardiac adverse reactions observed in patients in 3 pooled cardiac studies were sinus bradycardia (5.5%), bradycardia (2.8%), and hypertension (5.6%).
    • In patients without underlying cardiac disease, Somatuline Depot may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia.
    • In patients suffering from cardiac disorders prior to Somatuline Depot treatment, sinus bradycardia may occur. Care should be taken when initiating Somatuline Depot treatment in patients with bradycardia.
  • The pharmacological gastrointestinal effects of Somatuline Depot may reduce the intestinal absorption of concomitant drugs.
  • Somatuline Depot may decrease the relative bioavailability of cyclosporine. Cyclosporine dose may need to be adjusted to maintain levels.

SPECIAL POPULATIONS

  • Patients with moderate and severe renal impairment or moderate and severe hepatic impairment should begin treatment with Somatuline Depot 60 mg. Caution should be exercised when considering these patients for an extended dosing interval of Somatuline Depot 120 mg every 6 or 8 weeks.
  • There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, Somatuline Depot should be used during pregnancy only if the potential benefit justifies potential risk to the fetus.
  • A decision should be made whether to discontinue nursing or discontinue Somatuline Depot taking into account the importance of the drug to the mother.
  • Patients receiving beta-blockers, calcium channel blockers, or other drugs that affect heart rate may need dose adjustments to those drugs. Somatuline Depot may reduce the intestinal absorption of coadministered drugs. Caution should be used.

ADVERSE EVENTS

  • In pooled studies (N = 416), the most common adverse reactions (incidence > 5%) were diarrhea (37%), cholelithiasis (20%), abdominal pain (19%), nausea (11%), injection–site reaction (9%), constipation (8%), flatulence (7%), headaches (7%), arthralgia (7%),vomiting (7%), and loose stools (6%).
  • Gastrointestinal adverse reactions were mild to moderate and typically resolved within 8 to 10 weeks.
    • 1% of patients in the pooled studies with Somatuline Depot discontinued treatment due to gastrointestinal adverse events.
  • Occasional cases of pancreatitis have been reported.
  • Injection-site pain (4.1%) and injection-site mass (1.7%) were the most frequently reported local adverse reactions.
  • Local side effects were more common at the start of treatment and less common as treatment continued.
    • Injection–site reactions were usually mild to moderate but did lead to withdrawal from clinical studies in two patients.
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