Acromegaly, Diagnosis & Treatment | Somatuline Depot for Acromegaly HCP

The cause and epidemiology of acromegaly

Acromegaly is a rare disorder caused by an adenoma on the pituitary gland that causes the hypersecretion of growth hormone (GH) into the bloodstream. In turn, GH stimulates the production of another hormone in the liver, insulin-like growth factor 1 (IGF-1).⁵

In the US, overall annual incidence rates were estimated to be ~3,500 new cases each year (~11 per 1,000,000) with an overall prevalence of 25,000 patients (~78 cases per 1,000,000) with acromegaly (2008-2012).⁶ Given the rarity of acromegaly, combined with the slow onset of a variety of clinical features—including skeletal and soft tissue growth of the face, hands, and feet; severe sweating; arthritis; headaches; and in some patients, visual field loss—diagnosis may be delayed by 7 to 10 years after the onset of symptoms.⁵

In addition, as acromegaly is associated with a number of comorbidities, diagnosis and early treatment are important.^7,8

Signs of acromegaly: Recognizing it can be difficult

The outward effects of acromegaly can happen so slowly even family members may not notice.

Common signs of acromegaly may include⁵:

Enlarged tongue, lips, or nose
Enlarged hands and/or feet
Prognathism (enlarged lower jaw)
Headaches
Coarse, oily, thickened skin
Excessive sweating and body odor
Abnormal bone growth in the face
Sleep apnea (severe snoring)
Numerous skin tags
Aching joints
Fatigue
Increased chest size (barrel chest)

Diagnosing acromegaly

As stated earlier, due to its slow evolution, seemingly unrelated symptoms, and rarity in the population, recognizing and diagnosing acromegaly may take years. However, while the outward features of acromegaly may appear benign, the severity of its more systemic effects would suggest the need for a more rapid approach to confirming a diagnosis.^7,8

An accurate diagnosis of acromegaly should include^7,8:

Systemic clinical evaluation of symptoms and signs
Biochemical evaluation of hormonal excess
- Measurement of IGF-1, a marker of integrated GH secretion. It is important to have knowledge of the specific assay used and its age-appropriate normal range
- GH should be measured after an oral glucose challenge in patients with elevated or equivocal serum IGF-1 levels. Diagnosis of acromegaly is confirmed following documented hyperglycemia and lack of suppression of GH to <1 ug/L. Random measurements should not be used.
Magnetic resonance imaging (MRI) to confirm the presence, size, location, and invasiveness of a pituitary tumor

Therapies for treating acromegaly

Surgery, medical therapy, and radiotherapy have positives and negatives that should be considered carefully. Surgery is considered the mainstay of therapy for most patients, with medication reserved for patients with persistent excess GH secretion uncontrolled by surgery. However, in patients for whom surgery is not an option, medication may be the primary therapy. Radiotherapy is currently considered a third line of treatment.¹³

The goals are to normalize excessive hormone secretion of GH and IGF-1, to reduce the clinical signs and symptoms of acromegaly, to reduce the size of the tumor itself, and to alleviate symptoms resulting from the tumor mass‌.^7,8,9

Surgical removal or reduction of the tumor

The first line of therapy is usually transsphenoidal surgery (TSS) by an experienced neurosurgeon, especially for small tumors. The expertise of the surgeon is crucial to the outcome, with better results seen from dedicated pituitary surgeons, extending even to lower complications post surgery. However, overall cure rates remain low because patients with these tumors usually present at an incurable stage.^10,11

Radiotherapy (RT)

RT may be used as adjunctive therapy after unsuccessful surgery, and while it can lower GH levels and normalize IGF-1 levels, the effects may take years to achieve. In addition, a common complication of RT is the development of new hypopituitarism.¹³

The success of current medical therapies for acromegaly has led physicians to reserve RT for patients who are resistant to or intolerant of these therapies or for controlling an expanding tumor mass despite surgery.^7,8,13

Managing acromegaly with medication

Many patients with acromegaly—including some who have had surgery—need to take medication in order to achieve disease control. Currently, there are 3 types of medications used to treat acromegaly.^7,8

Somatostatin analog (SSA)
Growth hormone receptor antagonist (GHRA)
Dopamine agonist (DA)

More information about Somatuline Depot, an SSA treatment option

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IMPORTANT SAFETY INFORMATION & INDICATION

Contraindications

SOMATULINE DEPOT is contraindicated in patients with hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide.

Warnings and Precautions

Cholelithiasis and Gallbladder Sludge
- SOMATULINE DEPOT may reduce gallbladder motility and lead to gallstone formation.
- Periodic monitoring may be needed.
- If complications of cholelithiasis are suspected, discontinue SOMATULINE DEPOT and treat appropriately.
Hypoglycemia or Hyperglycemia
- Patients treated with SOMATULINE DEPOT may experience hypoglycemia or hyperglycemia.
- Blood glucose levels should be monitored when SOMATULINE DEPOT treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly.
Cardiovascular Abnormalities
- SOMATULINE DEPOT may decrease heart rate.
- In cardiac studies with acromegalic patients, the most common cardiac adverse reactions were sinus bradycardia, bradycardia, and hypertension.
- 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 treatment, sinus bradycardia may occur. Care should be taken when initiating treatment in patients with bradycardia.
Thyroid Function Abnormalities
- Slight decreases in thyroid function have been seen during treatment with lanreotide in acromegalic patients.
- Thyroid function tests are recommended where clinically appropriate.
Monitoring/Laboratory Tests: In acromegaly, serum GH and IGF-1 levels are useful markers of the disease and effectiveness of treatment.

Most Common Adverse Reactions

Adverse reactions in >5% of patients who received SOMATULINE DEPOT were diarrhea (37%), cholelithiasis (20%), abdominal pain (19%), nausea (11%), injection-site reactions (9%), constipation (8%), flatulence (7%), vomiting (7%), arthralgia (7%), headache (7%), and loose stools (6%).

Drug Interactions

SOMATULINE DEPOT may decrease the absorption of cyclosporine (dosage adjustment may be needed); increase the absorption of bromocriptine; and require dosage adjustment for bradycardia-inducing drugs (e.g., beta-blockers).

Special Populations

Lactation: Advise women not to breastfeed during treatment and for 6 months after the last dose.
Moderate to Severe Renal and Hepatic Impairment: See full prescribing information for dosage adjustment in patients with acromegaly.

To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program.

INDICATIONS

SOMATULINE^® DEPOT (lanreotide) is a somatostatin analog indicated for the long-term treatment of patients with acromegaly who have had an 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 growth hormone (GH) and insulin growth factor-1 (IGF-1) levels to normal.

Please click here for the full Prescribing Information and Patient Information.

References:

1. Somatuline Depot (lanreotide) Injection [Prescribing Information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; June 2019.

2. Melmed S, Cook D, Schopohl J, Goth MI, Lam KSL, Marek J. Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide autogel therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension. Pituitary. 2010;13:18-28.

3. Data on file. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc.

4. Valery C, Paternostre M, Robert B, et al. Biomimetic organization: octapeptide self-assembly into nanotubes of viral capsid-like dimension. PNAS. 2003;100(18):10258-10262.

5. Melmed S. Medical progress: Acromegaly. N Engl J Med. 2006 Dec 14;355(24):2558-73. Review. No abstract available. Erratum in: N Engl J Med. 2007 Feb 22;356(8):879.

6. Burton T, Le Nestour E, Neary M, Ludlam WH. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016;19:262-267.

7. Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly–2011 update. Endocr Pract. 2011 Jul-Aug;17 Suppl 4:1-44.

8. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:3933-3951.

9. Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH, Strasburger CJ, Luger A, Clemmons DR, Giustina A. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018 Sep;14(9):552-561.

10. Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, Marshall JC, Laws ER Jr, Vance ML. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab. 2011 Sep;96(9):2732-40.

11. Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA Jr. Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab. 2013 Aug;98(8):3190-8.

12. Adelman DT, Truong Thahn X-M, Mégret C. Enhancing patient care: co-creation and validation of a new and improved delivery system for lanreotide autogel/depot and its evaluation by US healthcare professionals. Presented at: 101st Annual Meeting and Expo of the Endocrine Society. New Orleans, LA; March 23-26, 2019.

13. Knappe U, Petroff D, Quinkler M, et al. Fractionated radiotherapy and radiosurgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry. Eur. J. Endocrinol. 2020;182(3):275-284.