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 include7,8:
- 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)