Acromegaly Screening & Diagnosis

Acromegaly is a slowly progressing disease, and many of its symptoms are similar to those associated with other conditions. For this reason, acromegaly may remain undetected for 10 years or longer; unfortunately, by this time, ancillary damage may have already occured, owing to years of GH hypersecretion.1 Consequently, it is crucial for endocrinologists to remain alert for the signs and symptoms of acromegaly.

Clinical features of acromegaly1

Most patients with acromegaly present with a variety of clinical features as listed below (not all clinical findings are listed below). These features can vary and may effect:

Local tumor effects1

Potential referring physician: Neurologist

  • Pituitary enlargement:1
    • Visual-field defects1
    • Cranial-nerve palsy1
    • Headache1

Visceromegaly1

Potential referring physician: Primary Care Physician, Internist

  • Tongue1
  • Thyroid gland1
  • Salivary glands1
  • Liver1
  • Spleen1
  • Kidney1
  • Prostate1

Musculoskeletal system1

Potential referring physician: Dentist, Primary Care Physician, Internist

  • Gigantism1
  • Prognathism1
  • Jaw malocclusion1
  • Arthralgia and arthritis1
  • Carpal tunnel syndrome1
  • Acroparesthesia1
  • Proximal myopathy1
  • Hypertrophy of frontal bones1

Dermal system1

Potential referring physicians: Dermatologist, Primary Care Physician

  • Hyperhidrosis1
  • Oily skin1
  • Skin tags1

Gastrointestinal system1

Potential referring physician: Gastroenterologist

  • Colon polyps1

Cardiovascular system1

Potential referring physician: Cardiologist

  • Left ventricular hypertrophy1
  • Asymmetric septal hypertrophy1
  • Cardiomyopathy1
  • Hypertension1
  • Congestive heart failure1

Pulmonary system1

Potential referring physician: Neurologist, Pulmonologist, Primary Care

  • Sleep disturbances1
  • Sleep apnea (central and obstructive)1
  • Narcolepsy1

Reproductive system1

Potential referring physicians: Ob-GYN, Primary Care Physician

  • Menstrual abnormalities1
  • Galactorrhea1
  • Decreased libido, impotence1
  • Low levels of sex hormone-binding globulin1

Endocrine and Metabolic systems1

Potential referring physicians: Primary Care Physician, Internist

  • Impaired carbohydrate tolerance1
    • Insulin resistance and hyperinsulinemia1
    • Diabetes mellitus1
  • Multiple endocrine neoplasia type 11
  • Hypertriglyceridemia1
  • Imbalance of the renin-angiotensin-aldosterone system1
  • Increased urinary mineral excretion1
  • Thyroid1
    • Thyroid-binding globulin deficiency1
    • Goiter1

Diagnosis of acromegaly

Although general practitioners may recognize the signs and symptoms of acromegaly, the diagnosis process generally starts and ends with the endocrinologist, whose involvement is essential.1 A diagnosis is made through an initial clinical assessment and physical examination, followed by a set of biochemical assays and neuroradiological imaging tests9,10,11:

Initial clinical assessment and physical exam

Assess tissue overgrowth and other symptoms of acromegaly and potential comorbidities

Radiological assessment

Pituitary magnetic resonance imaging (MRI)

In 95% of acromegaly cases, there is a tumor in the pituitary, which is located within the sella turcica. The sella turcica in these cases is deformed and increased in volume.

A pituitary MRI is more effective than a computerized tomography (CT) scan in detecting tumor location and tumor size, which is important in determining the patient's prognosis. A CT scan can also be used to confirm the size of the adenoma and its spread.9

Biochemical assays

Measurement of serum IGF-1

Measurement of serum IGF-1 is a reliable indicator of GH status in acromegaly. Acromegaly in the absence of a high IGF-1 is extremely rare. There should be appropriate age- and sex-matched reference intervals. Serum IGF-1 is the best biochemical marker of clinical disease activity. The laboratory should participate in an external quality assurance program and should be able to present individual IGF-1 results as a standard deviation score.10

Normalized levels of IGF-1 are defined by each lab based on patient age and sex.

Measurement of GH value

Measuring GH levels after an oral glucose tolerance test (OGTT) has been the gold standard for 40 years.1 Now, GH measurements using nonisotopic, two-site monoclonal antibody assays are even more sensitive than the polyclonal radioimmunoassays that have been available for the past five decades, allowing for more accurate detection of the lower limits of GH secretion (GH levels as low as 1 ng/mL).10

GH response to an OGTT still offers valuable information when there is a discrepancy between GH and IGF-1 levels. In acromegaly, GH secretion is typically nonsuppressible during an OGTT. The criteria for adequate suppression need to be defined for each specific GH assay.10

Post-diagnosis clinical assessment

Associated comorbidities that should be checked for include: elevated lipoprotein levels, cardiomyopathy, sleep apnea, type 2 diabetes, hypertension, and colon cancer.9

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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