Gigantism and Acromegaly Treatment & Management

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Jul 8, 2010
 

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.
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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.
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Contributor Information and Disclosures
Author

Robert J Ferry Jr, MD  Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Hospital; Professor, Department of Pediatrics, University of Tennessee Health Science Center at Memphis; St. Jude Children's Research Hospital, Memphis, TN; Brigade Surgeon, 36th Sustainment Brigade, U.S. Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Riyadh, Saudi Arabia

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Investigator; MacroGenics, Inc. Grant/research funds Investigator; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Investigator

Coauthor(s)

Melanie Shim, MD  Clinical Instructor, Department of Pediatrics, Division of Pediatric Endocrinology, University of California at Los Angeles School of Medicine

Melanie Shim, MD is a member of the following medical societies: American Diabetes Association and Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, The Children's Hospital, North Shore LIJ Health System; Professor of Pediatrics, New York University School of Medicine

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD  Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Lawson-Wilkins Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas College of Medicine and Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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Image shows the coauthor with a statue of Robert Wadlow, who was called the Alton giant. He was the tallest person ever recorded and was 8 feet 11 inches tall at the time of his death.
Photograph shows a 12-year-old boy with McCune-Albright syndrome. His growth-hormone excess manifested as tall stature, coarse facial features, and macrocephaly.
 
 
 
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