Because elevated GH/IGF-I concentration is associated with increased mortality rates, try to decrease/normalize their concentration. Most experts define cure, or adequate control, as a glucose-suppressed GH concentration of less than 2 ng/mL by radioimmunoassay (RIA) (1 mcg/L by IRMA) and normalization of the serum IGF-I concentration.
No single modality of treatment consistently achieves the above levels. A multimodality approach usually requires surgery as the first line of treatment, followed by medical therapy for residual disease. Radiation treatment is generally reserved for refractory cases.
1* Somatostatin and dopamine analogues and GH receptor antagonists are the mainstays of medical treatment and are generally used after failure of primary surgery to induce complete remission.
2* Bromocriptine is a dopamine agonist with limited effectiveness in the treatment of acromegaly. It can reduce the circulating GH level to less than 5 ng/mL in only 20% of patients and can normalize the IGF-I concentration in 10% of patients. Shrinkage in tumor size is also observed in fewer than 20% of patients. Cabergoline, another dopamine agonist, fares somewhat better with response rates of 46%.
3* Tumors that cosecrete prolactin have a better response rate to dopamine agonists. The response to these agents is often detected by a trial of the drug in suitable patients.
4* Somatostatin is a natural inhibitor of GH secretion. Because of its very short half-life, long-acting analogues have been developed. The long-acting analogue can be administered once per month but is extremely expensive (>$12,000/y in 1999).
o Octreotide is the most extensively studied and used somatostatin
analogue.
o It primarily binds to the somatostatin receptor subtypes II and V and
inhibits GH secretion.
o Treatment with octreotide reduces GH concentration to less than 5 ng/mL
in 65% of patients and to less than 2 ng/mL in 40% of patients; it
normalizes concentration IGF-I in 60% of patients.
o Tumor shrinkage is observed in 20-50% of patients.
5* Pegvisomant, a GH receptor antagonist normalizes IGF-I levels in 90-100% of patients. As expected from its mechanism of action, GH levels increase during treatment and no decrease in tumor size is seen. A minority of patients may experience an increase in tumor size; whether this is due to natural history of the disease or an effect of treatment is unclear. Periodic imaging studies are advised in patients on this medication.
6* Radiation treatment takes to reduce/normalize GH/IGF-I levels. About 60% of patients have a GH concentration of less than 5 ng/mL 10 years after radiotherapy. A similar percentage of patients develop panhypopituitarism as a result of treatment. Because of the disappointing results and adverse effects, radiotherapy is used as an adjuvant for large invasive tumors and when surgery is contraindicated. Some studies suggest that radiation is associated with the development of secondary tumors.
Surgical Care:
Even though surgery might not cure a significant number of patients, it is employed as first-line therapy. Patients with residual disease can then be offered adjuvant treatment.
* Transsphenoidal hypophysectomy has the dual advantage of rapidly improving
symptoms caused by mass effect of the tumor and significantly reducing or
normalizing GH/IGF-I concentrations CLICK HERE
* Remission depends on the initial size of the tumor, the GH level, and the
skill of the neurosurgeon.
* A remission rate of 80-85% can be expected for microadenomas and 50-65% for
macroadenomas.
* The postoperative GH concentration may predict remission rates. According to
the results of one study, a postoperative GH concentration of less than 3
ng/dL was associated with a 90% remission rate, which declined to 5% in
patients with postoperative GH concentration greater than 5 ng/dL.
Prognosis:
-Remission depends on the initial size of the tumor, the GH level, and the skill of the neurosurgeon.
* Remission rates of 80-85% and 50-65% can be expected for microadenomas and
macroadenomas, respectively.
* The postoperative GH concentration may predict remission rates. According to
the results of one study, a postoperative GH concentration of less than 3
ng/dL was associated with a 90% remission rate, which declined to 5% in
patients with a postoperative GH concentration greater than 5 ng/dL.