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Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.
The prevalence in Europe is estimated at 1/250,000 -1/100,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected).
Due to its insidious onset and slow progression, acromegaly is often diagnosed from four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened, thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis.
In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth hormone-releasing hormone (GHRH), responsible for pituitary hyperplasia. The gene aryl hydrocarbon receptor interacting protein, AIP (11q13.3), has been identified as a major susceptibility factor, particularly in cases of familial acromegaly or when acromegaly begins in childhood or adolescence. Acromegaly may also be part of multiple endocrine neoplasia syndromes such as MEN1 (gene MEN1, 11q13) or Carney complex (gene PRKAR1A , 17q24.2) (see these terms).
The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly.
Management and treatment
Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with dopamine agonists and/or somatostatin analogs is proposed. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Radiotherapy may be discussed as a third line of treatment in cases of medical treatment failure.
Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.