eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Gigantism and Acromegaly: Treatment & Medication
Updated: Jul 1, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Surgery clearly fails to cure a notable number of patients with IGF-I excess. Therefore, medical therapy has taken on an important role in treating these patients. The most remarkable recent progress in treating this disorder has been in medical therapy. Well-tolerated, long-acting somatostatin analogs and dopamine agonists improve adherence and efficacy.
- The goals of medical therapy goals are the following:
- Remove or shrink the pituitary mass
- Restore GH secretory patterns to normal
- Restore serum total IGF-I and IGFBP-3 levels to normal
- Retain normal pituitary secretion of other hormones
- Prevent recurrence of disease
- Somatostatin analogs are highly effective in treating patients with GH excess.
- Octreotide suppresses serum GH level to less than 2.5 mcg/L in 65% of patients with acromegaly and normalizes circulating IGF-I levels in 70% of patients.
- Studies of patients with GH excess for longer than 14 years demonstrated that effects of octreotide are well sustained over time.
- Tumor shrinkage, although generally modest, also occurs with octreotide.
- Consistent GH suppression was achieved with a continuous subcutaneous pump infusion of octreotide in a pubertal boy with pituitary gigantism.
- New long-acting formulations, including long-acting octreotide and lanreotide, were recently demonstrated to produce consistent GH and IGF-I suppression in patients with acromegaly with once-monthly or biweekly intramuscular depot injections.
- Sustained-released preparations have not been tested in children.
- Dopamine agonists (eg, bromocriptine, cabergoline) bind to pituitary dopamine type 2 (D2) receptors and suppress GH secretion, although their precise mechanism of action remains unclear.
- PRL levels are often adequately suppressed. However, circulating GH and IGF-I levels rarely normalize with this therapy. Less than 20% of patients achieve GH levels less than 5 ng/mL, and less than 10% achieve normal IGF-I levels.
- Tumor shrinkage occurs in a few patients.
- Dopamine agonists are generally used as adjuvant medical treatments for GH excess, and their effectiveness may be added to that of octreotide.
- Although long-acting formulations are available, no data about the long-term control of GH and IGF-I with these agents are available.
- Tests of a novel hepatic GH-receptor antagonist (pegvisomant [Somavert]) demonstrated effective suppression of GH and IGF-I levels in patients with acromegaly due to pituitary tumors or ectopic GHRH hypersecretion.
- Normalization of IGF-I levels occurs in as many as 90% of patients treated daily with this drug for 3 months.
- Long-term studies are underway, but pegvisomant has not been tested in children.
Surgical Care
- For well-circumscribed pituitary adenomas, transsphenoidal surgery to completely remove the tumor is the treatment of choice, and it may be curative.
- The likelihood of a surgical cure greatly depends on the surgeons' expertise and on the size and extension of the mass.
- Intraoperative GH measurements can improve the results of tumor resection.
- Transsphenoidal surgery to resect tumors is as safe in children as it is in adults.
- A transcranial approach is sometimes necessary.
- The primary goal of treatment is to normalize GH levels.
- As determined by using GH assays available to date, GH levels should be normalized (<1 ng/mL for >50% of the points measured during the day) in all patients.
- Because this change is impractical to test, GH levels (<1 ng/mL within 2 h after a glucose load) and serum IGF-1 levels (within 2 standard deviations of the reference range adjusted for age, sex, and Tanner stage) are the best results for defining a biochemical cure.
- If surgery does not normalize GH secretion, options include pituitary radiation and medical therapy.
- In general, radiation therapy is recommended if GH hypersecretion is not normalized with surgery. Radiation prevents further growth of the tumor in more than 99% of patients after surgical resection.
- The main disadvantage of irradiation is delayed efficacy in decreasing GH levels. Approximately 50% of the efficacy of this therapy is lost by 2 years, 75% is lost by 5 years, and nearly 90% is lost by 15 years.
- Hypopituitarism is a predictable outcome, occurring in 40-50% of patients within 10 years after irradiation.
Medication
Analogs of somatostatin are the most effective medical therapies for GH excess. Dopamine-receptor agonists are best used as adjuvant treatments.
Somatostatin analogs
Like natural somatostatin, octreotide inhibits the secretion of GH, insulin, and glucagon. After an intravenous administration, basal serum GH, insulin, and glucagon levels fall. Octreotide also inhibits PRL release by means of vasoactive intestinal peptide (VIP)-mediated and TRH-mediated secretion of PRL. Octreotide is used to treat acromegaly and several hormone-secreting tumors.
Octreotide (Sandostatin, Sandostatin LAR)
Effectively lowers serum GH and IGF-I concentrations; may shrink tumor. Forty times more potent than native somatostatin to inhibit GH secretion. Available in immediate-release (Sandostatin) or long-acting depot (Sandostatin LAR) form.
Adult
Sandostatin: 100-200 mcg SC tid
Sandostatin LAR: 10-40 mg IM q4wk
Pediatric
Sandostatin: Limited pediatric data; suggested dose 1-40 mcg/kg/d
Sandostatin LAR depot: Not established for pediatric populations; author successfully transitioned 1 pubertal patient with MAS and acromegaly from daily Sandostatin to equivalent depot dose (based on monthly administration of total monthly dose)
May reduce effects of cyclosporine; may need to adjust dosage in patients taking insulin, PO hypoglycemics, beta-blockers, or calcium channel blockers
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; hypoglycemia and hyperglycemia observed due to altered levels of counterregulatory hormones (insulin, glucagon, GH); bradycardia, cardiac conduction abnormalities, and arrhythmias reported; hypothyroidism may occur due to inhibited TSH secretion; exercise caution in renal impairment; cholelithiasis may occur
Dopamine agonists
Dopamine-receptor agonists are other pharmacologic options. However, these drugs are effective in only a few patients. Cabergoline is well tolerated.
Bromocriptine (Parlodel)
Dopamine agonist most often used to treat GH and PRL excess. Safe when administered to a child for extended period.
Adult
10-60 mg/d PO divided qid
Pediatric
Not established
Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, reserpine; may decrease effects
Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects include nausea, vomiting, abdominal pain, arrhythmias, nasal stuffiness, orthostatic hypotension, sleep disturbances, and fatigue; caution in renal or hepatic disease
Cabergoline (Dostinex)
Potent dopamine agonist with prolonged duration of action. Inhibits PRL secretion more than bromocriptine.
Adult
0.25-1 mg PO 1-2 times/wk
Pediatric
Not established
May increase effects of antihypertensives (adjust dosage accordingly); dopamine agonists may reduce effects
Documented hypersensitivity; uncontrolled hypertension
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects similar to those for bromocriptine (eg, nausea, vomiting, abdominal pain, arrhythmias, nasal stuffiness, orthostatic hypotension, sleep disturbances, fatigue), although reported to be better tolerated than bromocriptine; caution in patients taking antihypertensives
GH-receptor antagonist
This novel class of drugs have demonstrated efficacy to suppress GH and IGF-I levels.
Pegvisomant (Somavert, B2036-PEG)
Recombinant DNA analog of human GH structurally altered to act as GH receptor antagonist. Selectively binds to GH receptors on cell surfaces, blocking endogenous GH binding. Thus interferes with GH signal transduction, decreasing levels of IGF-I, IGFBP-3, and acid-labile subunit.
Adult
Loading dose: 40 mg SC
Maintenance dose: 10 mg SC qd initially; may increase or decrease q4-6wk by 5-mg increments according to IGF-I levels; not to exceed 30 mg/d
Pediatric
Not established
May increase insulin or PO hypoglycemic effects (as serum GH levels fall); patients receiving opioid analgesics may require increased doses to suppress IGF-I production to recommended levels
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Vial stopper contains latex; may cause GH-secreting tumors to grow; may increase insulin sensitivity; may induce GH deficiency; may increase liver enzyme levels; reportedly well tolerated; incidence of adverse effects similar to placebo; may cause nausea, vomiting, shoulder pain with higher daily doses; increased GH levels (long-term data needed)
More on Gigantism and Acromegaly |
| Overview: Gigantism and Acromegaly |
| Differential Diagnoses & Workup: Gigantism and Acromegaly |
 Treatment & Medication: Gigantism and Acromegaly |
| Follow-up: Gigantism and Acromegaly |
| Multimedia: Gigantism and Acromegaly |
| References |
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Further Reading
Keywords
gigantism, acromegaly, growth hormone excess, GH excess, giantism, gigantosoma, giant, hypersomia, somatomegaly, acromegalia, endocrine system, giants, pituitary gland, abnormal growth, multiple endocrine neoplasia type I, MEN type I, McCune-Albright syndrome, MAS, neurofibromatosis, tuberous sclerosis, Carney complex, precocious puberty, café au lait spots, fibrous dysplasia, pituitary hyperplasia, adenoma,
