Acromegaly: Review of Current Medical Therapy and New Drugs on the Horizon
Acromegaly: Review of Current Medical Therapy and New Drugs on the Horizon
Acromegaly is a disease that results from a growth hormone (GH)–secreting pituitary tumor. Clinically, the disease is characterized by excessive skeletal growth, soft tissue enlargement with disfigurement, and increased risk of cardiovascular death. The goals of treatment are the removal or reduction of the tumor mass via surgery and normalization of GH secretion. Another treatment goal is the preservation of normal pituitary function if possible.
Transsphenoidal surgery by an experienced neurosurgeon is usually the first line of therapy, especially for small tumors. Surgeon expertise is crucial for outcome, with dedicated pituitary surgeons having better results. However, overall cure rates remain low because patients with these tumors usually present at an incurable stage. Therefore, medical therapy to control excess GH secretion plays a significant role in a large proportion of patients with acromegaly who are not cured by surgery or other forms of therapy, such as radiotherapy, and/or are awaiting the effects of radiotherapy. If surgery is not curative, lifelong monitoring and the control of excess GH is usually necessary by a care team experienced in handling this chronic disease.
In the past decade major progress has occurred in the development of highly specific and selective pharmacological agents that have greatly facilitated more aggressive management of active acromegaly. Treatment approach should be individualized and take into consideration a patient's tumor size and location, symptoms, comorbid conditions, and preferences. Because a surgical cure can be difficult to achieve, all patients, even those with what seems to be a clinically and biochemically inactive disease, should undergo long-term biochemical testing and pituitary MR imaging.
Acromegaly was previously considered a rare disease, with a prevalence of 40–70 cases per million persons and an annual incidence of 3–4 new cases per million persons. However, recent European studies suggest that clinically significant pituitary adenomas occur in 1 case per 1064 people. With GH-secreting tumors constituting at least 10% of benign pituitary tumors, the calculated incidence could be 77.6 cases per million inhabitants. Furthermore, a provocative German cross-sectional epidemiological study in almost 7000 unselected primary care patients documented a prevalence of biochemical acromegaly of 1043 per million persons. Acromegaly screening in that study was performed by measuring IGF-I, and most cases were further confirmed by additional testing. Thus, acromegalic patients are theoretically more prevalent than previously thought, and in our opinion, this is clearly conceivable. Nonetheless, more studies are needed to establish an accurate incidence.
The nonspecific and protean symptomatology of acromegaly often results in late diagnosis, that is, 4 to > 10 years after initial symptom onset. Besides the local mass effect of the pituitary tumor, acromegaly results in multiple metabolic and "structural" dysfunctions.
Surgery, medical therapy, and radiation have specific advantages and disadvantages that should be weighed and tailored very carefully for each patient. Surgery is considered the mainstay of therapy for most, whereas medication is reserved for patients with persistent excess GH secretion uncontrolled by surgery. In selected cases, primary medical therapy is also an option, and radiotherapy remains a third line of treatment. Blood tests using serum GH and IGF-I remain the backbone of determining cure or control of the disease. Recently, consensus guidelines regarding the diagnosis and treatment of acromegaly were published.
In this review we focus on the medical treatment of acromegaly, including novel concepts and experimental therapies, and we emphasize our personal experience.
Abstract and Introduction
Abstract
Acromegaly is a disease that results from a growth hormone (GH)–secreting pituitary tumor. Clinically, the disease is characterized by excessive skeletal growth, soft tissue enlargement with disfigurement, and increased risk of cardiovascular death. The goals of treatment are the removal or reduction of the tumor mass via surgery and normalization of GH secretion. Another treatment goal is the preservation of normal pituitary function if possible.
Transsphenoidal surgery by an experienced neurosurgeon is usually the first line of therapy, especially for small tumors. Surgeon expertise is crucial for outcome, with dedicated pituitary surgeons having better results. However, overall cure rates remain low because patients with these tumors usually present at an incurable stage. Therefore, medical therapy to control excess GH secretion plays a significant role in a large proportion of patients with acromegaly who are not cured by surgery or other forms of therapy, such as radiotherapy, and/or are awaiting the effects of radiotherapy. If surgery is not curative, lifelong monitoring and the control of excess GH is usually necessary by a care team experienced in handling this chronic disease.
In the past decade major progress has occurred in the development of highly specific and selective pharmacological agents that have greatly facilitated more aggressive management of active acromegaly. Treatment approach should be individualized and take into consideration a patient's tumor size and location, symptoms, comorbid conditions, and preferences. Because a surgical cure can be difficult to achieve, all patients, even those with what seems to be a clinically and biochemically inactive disease, should undergo long-term biochemical testing and pituitary MR imaging.
Introduction
Acromegaly was previously considered a rare disease, with a prevalence of 40–70 cases per million persons and an annual incidence of 3–4 new cases per million persons. However, recent European studies suggest that clinically significant pituitary adenomas occur in 1 case per 1064 people. With GH-secreting tumors constituting at least 10% of benign pituitary tumors, the calculated incidence could be 77.6 cases per million inhabitants. Furthermore, a provocative German cross-sectional epidemiological study in almost 7000 unselected primary care patients documented a prevalence of biochemical acromegaly of 1043 per million persons. Acromegaly screening in that study was performed by measuring IGF-I, and most cases were further confirmed by additional testing. Thus, acromegalic patients are theoretically more prevalent than previously thought, and in our opinion, this is clearly conceivable. Nonetheless, more studies are needed to establish an accurate incidence.
The nonspecific and protean symptomatology of acromegaly often results in late diagnosis, that is, 4 to > 10 years after initial symptom onset. Besides the local mass effect of the pituitary tumor, acromegaly results in multiple metabolic and "structural" dysfunctions.
Surgery, medical therapy, and radiation have specific advantages and disadvantages that should be weighed and tailored very carefully for each patient. Surgery is considered the mainstay of therapy for most, whereas medication is reserved for patients with persistent excess GH secretion uncontrolled by surgery. In selected cases, primary medical therapy is also an option, and radiotherapy remains a third line of treatment. Blood tests using serum GH and IGF-I remain the backbone of determining cure or control of the disease. Recently, consensus guidelines regarding the diagnosis and treatment of acromegaly were published.
In this review we focus on the medical treatment of acromegaly, including novel concepts and experimental therapies, and we emphasize our personal experience.
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