Acromegaly—An Update on Clinical Approach and Management
Acromegaly is an uncommon disorder, with an annual incidence of three to four cases per million.1,2 It is characterized by excessive secretion of growth hormone (GH), resulting in exaggerated growth of bone and soft tissues, multisystem involvement with multiple comorbidities, and heightened risk of premature mortality. GH is produced by the somatotroph cells of the pituitary gland in a pulsatile fashion. Circulating GH stimulates hepatic secretion of insulin like growth factor-1 (IGF-1). More than 90% of cases of acromegaly are due to an adenomatous growth of the pituitary somatotroph cells. Both GH and IGF-1 circulate, and are responsible for the exaggerated somatic growth and metabolic derangements characteristic of this disease. Somatotroph adenomas usually occur in a sporadic fashion, but uncommonly can be part of a familial multiple endocrine neoplasia (MEN-1) syndrome associated with parathyroid and pancreatic disease, or as isolated, familial acromegaly. There are several effective treatment modalities to control this disorder and reduce or prevent the associated morbidity and mortality. This article reviews the clinical approach to acromegaly and highlights the therapies currently available.
Men and women are affected equally by this disease and are diagnosed at a mean age of 40 years. Signs and symptoms of acromegaly are attributable either to GH hypersecretion or to localized mass effects of the tumor itself. The classic features of GH excess include frontal bossing, enlarged lips and nose, prognathic jaw, increased spacing of the teeth, enlarged tongue, changes in voice, oily skin or excess acne, and enlarged hands and feet. Other than menstrual irregularities in women, most patients with acromegaly do not present with complaints or symptoms of somatic overgrowth. Rather, acromegaly is most commonly detected incidentally. Due to the fact that acromegaly is an insidious disease, it can go undetected for a decade or more prior to diagnosis. Therefore, GH secreting pituitary adenomas are generally greater than 1cm (macroadenoma) at the time of initial presentation and frequently cause multiple systemic comorbidities resulting from chronic GH excess. GH hypersecretion is associated with carpal tunnel syndrome, type 2 diabetes mellitus, obstructive sleep apnea, headache, and painful joint destruction. Cardiovascular (CV) abnormalities include hypertension, atherosclerosis, GH-mediated-myocardial hypertrophy, and diastolic and—in later stages—systolic dysfunction. Control of GH hypersecretion and normalization of IGF-1 can dramatically improve these medical comorbidities. Signs and symptoms of local tumor invasion include headache, visual compromise due to involvement of the optic chiasm or cavernous sinuses, or hypopituitarism due to compression of the normal gland.
Retrospective studies have suggested an increased incidence of malignancy in patients with acromegaly, particularly of the colon.3 These findings are controversial and have not been clearly demonstrated in other studies. In a recent case-control study, the prevalence of colorectal hyperplastic polyps was significantly higher in patients with acromegaly compared with controls.4 Whether the risk of colon cancer and/or polyps is improved with biochemical control is unknown. A baseline screening colonoscopy to exclude colon cancer may be warranted in patients with acromegaly.
Untreated, acromegaly causes an approximate two- to four-fold increase in mortality, primarily due to CV complications.1 In a recent meta-analysis, acromegaly was associated with a mean standardized mortality ratio of 1.62 compared with a normal population.5 In this study, biochemical cure following surgery was associated with a residual 10% increased mortality risk, though the authors note that this analysis should be interpreted with caution as it is based on a small number of studies and did not take into account treatment modalities in addition to surgery. Other studies have demonstrated that biochemical normalization is associated with a mortality risk similar to that of the general population.6
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