ABOUT ACROMEGALY
ACROMEGALY: A COMPLEX HORMONAL DISORDER
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).1
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).2 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.1
In addition, as acromegaly is associated with a number of comorbidities, diagnosis and early treatment are important.3,4
Signs of acromegaly: Recognizing it can be difficult
The outward effects of acromegaly can happen so slowly even family members may not notice.1,5
Common signs of acromegaly may include1:
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)
Signs of acromegaly: Recognizing it can be difficult
The outward effects of acromegaly can happen so slowly even family members may not notice.1,5
Common signs of acromegaly may include1:
Enlarged tongue, lips, or nose
Coarse, oily, thickened skin
Numerous
skin tags
Enlarged hands and/or feet
Excessive sweating and body odor
Aching
joints
Prognathism (enlarged lower jaw)
Abnormal bone growth in the face
Fatigue
Headaches
Sleep apnea
(severe snoring)
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.3,4
An accurate diagnosis of acromegaly should include3,4:
- 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 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.4,6,7
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.3,4,7
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.8,9
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.6
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.3,4,6
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 acromegaly3,4:
- Somatostatin analog (SSA)
- Growth hormone receptor antagonist (GHRA)
- Dopamine agonist (DA)
REFERENCES:
- Melmed S. Medical progress: acromegaly. N Engl J Med. 2006;355(24):2558-2573. No abstract available. Erratum in: N Engl J Med. 2007;356(8):879.
- Burton T, Le Nestour E, Neary M, et al. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016;19:262-267.
- Katznelson L, Atkinson JL, Cook DM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly-2011 update. Endocr Pract. 2011;17 Suppl 4:1-44.
- Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:3933-3951.
- Zarool-Hassan R, Conaglen HM, Conaglen JV, et al. Symptoms and signs of acromegaly: an ongoing need to raise awareness among healthcare practitioners. J Prim Health Care. 2016;8(2):157-163.
- 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.
- Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561.
- Jane JA Jr, Starke RM, Elzoghby MA, et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab. 2011;96(9):2732-2740.
- Starke RM, Raper DM, Payne SC, et al. Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab. 2013;98(8):3190-3198.