Sandostatin LAR Depot Text

Acromegaly Diagnosis

In this section, you will find information about:

• The Difficulty of Diagnosis
• Tests Used in Diagnosing Acromegaly
• The Importance of Measuring GH Levels
• Confirming a Diagnosis of Acromegaly
• The Role of Imaging in Diagnosis

The Difficulty of Diagnosis

The difficulty of early diagnosis results from several challenges¹:

• Since symptoms develop gradually, time is required for them to be recognized by patients and physicians
• Patients may exhibit a variety of different clinical signs and symptoms since they may have any combination of the common symptoms
• Other conditions can produce the signs and symptoms of acromegaly and must, therefore, be ruled out

Tests Used in Diagnosing Acromegaly²

Several tests are useful in diagnosing and monitoring acromegaly. The most important are laboratory tests that measure the levels of GH and IGF-1 in the blood. IGF-1 levels are gender and age dependent and are relatively stable throughout the day. In contrast, GH levels can fluctuate throughout the day depending on the patient's age, the time of day, and time since the last meal. There are 2 main approaches to measuring GH levels:

• Multiple tests. To compensate for the variation in levels, the values may be averaged from a series of "random" blood tests²
• Oral glucose tolerance test (OGTT). Another way to get an accurate reading in a single measurement is to take the blood sample after an overnight fast, followed by an early morning drink of concentrated glucose solution. Normal patients will experience glucose-suppressed GH levels, while patients with acromegaly will still have elevated GH levels, despite the introduction of glucose^2,3

The Importance of Measuring GH Levels

Since GH is secreted sporadically throughout the day and has a short half-life, a single random GH test is considered to be of little value in diagnosing acromegaly. However, since elevation in GH is a basic abnormality in acromegaly, basal GH levels may be examined during the diagnostic phase, as well as during the ongoing monitoring of acromegalic patients. When acromegaly is suspected, an OGTT is used to evaluate the response of GH to "glucose challenge." In this test, 100 g of glucose are administered in an oral solution to a patient who has fasted overnight. Blood samples are obtained from the patient 30 minutes before ingestion of the glucose, then every 30 minutes afterwards for a total of 2 hours. The following results are observed³:

• In normal individuals, administration of glucose suppresses GH levels to <2 ng/mL for 1 to 2 hours
• In most acromegalic patients, GH levels remain elevated in the presence of glucose

Confirming a Diagnosis of Acromegaly^2,3

On the other hand, IGF-1 is maintained at relatively stable levels in plasma, but normal concentrations vary as a function of gender and age. IGF-1 becomes elevated as a result of excessive GH secretion.

• Normal levels of IGF-1 depend on gender and age
• Elevated IGF-1 generally confirms a diagnosis of acromegaly

The following steps are carried out in reaching a diagnosis of acromegaly³:

• Acromegaly suspected
• Initiate GH and IGF-1 assays
• If GH and IGF-1 assays are normal, then conduct glucose tolerance test
• If GH, IGF-1 assays and glucose tolerance test are normal, this excludes a diagnosis of acromegaly
• If any of these results are abnormal, then perform an MRI of the pituitary
  • If MRI is normal, then conduct tests for other causes
  • If MRI is abnormal and reveals the presence of an adenoma, then a diagnosis of acromegaly is confirmed

The Role of Imaging in Diagnosis²

When it has been established that a patient has elevated GH and IGF-1 levels, MRI or CT imaging is used to examine the pituitary.

• Imaging studies are used to determine the site and the size of the tumor, which aid in the planning of treatment options
• Images may also be obtained to detect potential enlargement of the organs that may be affected by acromegaly
• If no pituitary tumor is detected, scans of other body areas may be performed to identify the source of excessive GH and/or IGF-1

The image above is an example of magnetic resonance imaging (MRI) studies of an acromegalic patient with a macroadenoma, indicated by the arrows. It is a scan taken from the back (coronal view)⁴.

INDICATIONS AND USAGE

Sandostatin^® LAR Depot (octreotide acetate for injectable suspension) is indicated for patients in whom initial treatment with immediate release Sandostatin^® (octreotide acetate) Injection has been shown to be effective and tolerated for:

• Long-term maintenance therapy in acromegalic patients who have had inadequate response to surgery and/or radiotherapy or for whom surgery and/or radiotherapy is not an option (the goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal).
• Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.
• Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors.

In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and Sandostatin LAR Depot on tumor size, rate of growth and development of metastases has not been determined.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions:

• Gallbladder abnormalities may occur: Patients should be monitored periodically.
• Glucose Metabolism: Hypoglycemia or hyperglycemia may occur. Blood glucose levels should be monitored when Sandostatin LAR Depot treatment is initiated or when the dose is altered. Antidiabetic treatment should be adjusted accordingly.
• Thyroid Function: Hypothyroidism may occur. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended.
• Cardiac Function: Bradycardia, arrhythmia, conduction abnormalities, and other EKG changes may occur. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease. Use with caution in at-risk patients.
• Nutrition: Octreotide may alter absorption of dietary fats. Monitoring of vitamin B₁₂ levels is recommended during therapy with Sandostatin LAR Depot. Patients on total parenteral nutrition (TPN) and octreotide should have periodic monitoring of zinc levels.

Drug Interactions: The following drugs require monitoring and possible dose adjustment when used with Sandostatin LAR Depot: cyclosporine, insulin, oral hypoglycemic agents, beta-blockers, bromocriptine. Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Drugs mainly metabolized by CYP3A4 and which have a low therapeutic index should be used with caution.

Adverse Reactions: The most common adverse reactions occurring in patients receiving Sandostatin LAR Depot are:

• Acromegaly: biliary abnormalities (52%), diarrhea (36-48%), cholelithiasis (13-38%), abdominal pain or discomfort (11-29%), flatulence (26%), influenza-like symptoms (20%), constipation (19%), headache (15%), anemia (15%), hyperglycemia (15%), injection site pain (2-14%), hypertension (13%), dizziness (12%), fatigue (11%), nausea (10%), vomiting (7%), hypothyroidism (2%), hypoglycemia (2%), and goiter (2%).
• Carcinoid Tumors and VIPomas: biliary abnormalities (62%), injection site pain (20-50%), nausea (24-41%), abdominal pain (10-35%), fatigue (8-32%), headache (16-30%), hyperglycemia (27%), back pain (8-27%), constipation or vomiting (15-21%), dizziness (18-20%), sinus bradycardia (19%), pruritus (18%), URTI (10-18%), myalgia (4-18%), flatulence (9-16%), arthropathy (8-15%), rash (15%), generalized pain (4-15%), sinusitis (5-12%), conduction abnormalities (9%), hypoglycemia (4%), and arrhythmia (3%).

References