Hyperpituitarism Treatment & Management

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Aug 11, 2010
 

Medical Care

Prolactinoma

Prolactinoma is the only pituitary adenoma for which long-term medical management is fully satisfactory. Unless the patient presents with an acute threat to vision, hydrocephalus, cerebrospinal fluid leak, or other surgical emergency, medical management with dopamine agonists should be attempted before surgical treatment is considered. Dopamine agonists are potent suppressors of PRL secretion and promptly lower serum PRL levels, abolish galactorrhea, and restore normal gonadal function in most patients with hyperprolactinemia of any cause. Dopamine agonists can also inhibit tumor cell replication in 60-80% of prolactinomas. In small tumors, dopamine agonists cause tumor shrinkage, while the results vary in larger tumors. Successful long-term use of these drugs can obviate the need for pituitary surgery.

Corticotropinoma

The treatment of choice for patients with Cushing disease is transsphenoidal microsurgery. Medical therapy for Cushing disease is adjunctive only. The goal is to inhibit the enzymes responsible for cortisol synthesis with adrenal enzyme inhibitors, such as metyrapone, aminoglutethimide, and ketoconazole. Metyrapone and aminoglutethimide have been the standard therapy, and, when the 2 agents are used in combination, adverse effects may be decreased. Ketoconazole, a broad-spectrum antimycotic drug, inhibits adrenal steroid biosynthesis at several sites, including side chain cleavage and 11B-hydroxylation. Occasionally, patients with ACTH-secreting tumors respond to bromocriptine.

Somatotropinoma

Somatostatin analogs are highly effective therapies for patients with GH excess. Octreotide suppresses circulating GH levels to less than 2.5 µg/L in 65% of patients with acromegaly and normalizes IGF-I levels in 70% of patients. Long-term studies of patients older than 14 years confirm that the effects of octreotide remain well sustained over time. Octreotide also shrinks tumors, but the effect is generally modest.

A continuous subcutaneous infusion of octreotide in a pubertal boy with pituitary gigantism consistently suppressed GH production. New long-acting formulations, including long-acting octreotide and lanreotide, have been reported to consistently suppress GH and IGF-I in patients with acromegaly with once monthly or biweekly intramuscular depot injections. The author has had success in using the sustained-release formulation in a female adolescent with MAS-related GH excess and can provide details upon inquiry.

Dopamine agonists bind to pituitary dopamine type 2 (D2) receptors and suppress GH secretion, although the precise mechanism of action remains unclear. PRL levels are often adequately suppressed; however, GH levels and IGF-I levels are rarely normalized with this treatment modality. Fewer than 20% of patients achieve GH levels less than 5 ng/mL and fewer than 10% achieve normalization of circulating IGF-I levels. Tumor shrinkage occurs in a minority of patients. A dopamine agonist is generally used as adjuvant medical treatment for GH excess. Its effectiveness may be additive to that of octreotide. Long-acting formulations are available, but data on long-term control of GH and IGF-I with these agents are not available.

A novel hepatic GH receptor antagonist recently has been approved by the Food and Drug Administration (FDA). Pegvisomant (Sensus Corporation, Austin, Tex) effectively suppresses circulating GH and IGF-I levels in patients with acromegaly due to pituitary tumors, as well as ectopic GHRH hypersecretion. IGF-I levels are normalized in as many as 90% of patients treated daily with this drug for 3 months. Long-term studies must be performed. Pediatric experience, although scant, has been published and agrees with the efficacy and adverse event profile reported with adult patients.

Next

Surgical Care

Transsphenoidal surgery is the treatment of choice for Cushing disease in children. Initial remission rates of 70-98% of patients and long-term success rates of 50-98% have been reported.[1]

The preferred primary treatment for the patient with acromegaly is surgery, with a surgical cure rate at 10 years approaching 83% in the largest reported series.[1] Such surgery should be performed at large centers with documented experience, including published outcome and adverse event profiles.

For prolactinomas, surgery has good outcome with a long-term (10-year) surgical cure rate approaching 82% in the largest reported series with very low morbidity and no mortality.

Irradiation is reserved for the few patients who are intolerant of medication. Irradiation of the pituitary gland in children is not recommended, because it can lead to panhypopituitarism, optic nerve and optic chiasm injury, delayed radiation injury of the brain, increased risk of a second brain tumor, and epilation.

Previous
Next

Consultations

Endocrinologists fill a critical role in the diagnosis, preoperative, perioperative, and postoperative management of all pediatric patients with pituitary adenomas.

The experience of the neurosurgeon is critical for the outcome of transsphenoidal adenomectomy. In addition, the referring physician should obtain the published outcome and adverse event profiles for the surgeon and her or his institution. Such information should be discussed with the patient and patient's family prior to referral to another institution.

Previous
Proceed to Medication
 
 
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 Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor; NovoNordisk SA Grant/research funds Independent contractor; Diamyd Independent contractor

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

Thomas A Wilson, MD  Professor of Clinical Pediatrics, Director of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London)  Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and 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 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: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

References

  1. Devoe DJ, Miller WL, Conte FA, et al. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab. 1997;82:3196-202. [Medline].

  2. Avramides A, Karapiperis A, Triantafyllidou E, et al. TSH-secreting pituitary macroadenoma in an 11-year-old girl. Acta Paediatr. 1992;81:1058-1060. [Medline].

  3. Benveniste RJ, King WA, Walsh J, et al. Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg. 2005;102:1004-1012. [Medline].

  4. Booth GL, Redelmeier DA, Grosman H, et al. Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for localizing pituitary pathology in patients with Cushing's disease. J Clin Endocrinol Metab. Jul 1998;83(7):2291-5. [Medline].

  5. Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8:3-6. [Medline].

  6. Colao A, Loche S, Cappabianca P. Pituitary adenomas in children and adolescents. Clinical presentation, diagnosis, and therapeutic strategies. The Endocrinologist. 2000;10:314-27.

  7. Colao A, Lombardi G. Growth-hormone and prolactin excess. Lancet. Oct 31 1998;352(9138):1455-61. [Medline].

  8. Cozzi R, Attanasio R, Barausse M, et al. Cabergoline in acromegaly: a renewed role for dopamine agonist treatment?. Eur J Endocrinol. Nov 1998;139(5):516-21. [Medline].

  9. [Best Evidence] [Guideline] Cozzi R, Baldelli R, Colao A, Lasio G, Zini M, Attanasio R. AME Position Statement on clinical management of acromegaly. J Endocrinol Invest. 2009;32(6 Suppl):2-25. [Medline].

  10. de Boer L, Hoogerbrugge CM, van Doorn J, et al. Plasma insulin-like growth factors (IGFs), IGF-Binding proteins (IGFBPs), acid-labile subunit (ALS) and IGFBP-3 proteolysis in individuals with clinical characteristics of Sotos syndrome. J Pediatr Endocrinol Metab. 2004;17:615-627. [Medline].

  11. De Menis E, Visentin A, Billeci D, et al. Pituitary adenomas in childhood and adolescence. Clinical analysis of 10 cases. J Endocrinol Invest. 2001;24:92-97. [Medline].

  12. Dhillon KS, Cohan P, Kelly DF, et al. Treatment of hyperthyroidism associated with thyrotropin-secreting pituitary adenomas with iopanoic acid. J Clin Endocrinol Metab. 2004;89:708-711. [Medline]. [Full Text].

  13. Duncan E, Wass JA. Investigation protocol: acromegaly and its investigation. Clin Endocrinol (Oxf). Mar 1999;50(3):285-93. [Medline].

  14. Eugster EA, Pescovitz OH. Gigantism. J Clin Endocrinol Metab. Dec 1999;84(12):4379-84. [Medline].

  15. Gillam MP, Fideleff H, Boquete HR, Molitch ME. Prolactin excess: treatment and toxicity. Pediatr Endocrinol Rev. 2004;2:108-114. [Medline].

  16. Giustina A, Barkan A, Casanueva FF, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab. Feb 2000;85(2):526-9. [Medline].

  17. Gsponer J, De Tribolet N, Deruaz JP, et al. Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients. Medicine (Baltimore). 1999;78:236-269. [Medline].

  18. Herman V, Fagin J, Gonsky R, et al. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab. Dec 1990;71(6):1427-33. [Medline].

  19. Herman-Bonert VS, Zib K, Scarlett JA, Melmed S. Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J Clin Endocrinol Metab. Aug 2000;85(8):2958-61. [Medline]. [Full Text].

  20. Howell DL, Wasilewski K, Mazewski CM, et al. The use of high-dose daily cabergoline in an adolescent patient with macroprolactinoma. J Pediatr Hematol Oncol. 2005;27:326-329. [Medline].

  21. Joshi SM, Hewitt RJ, Storr HL, et al. Cushing's disease in children and adolescents: 20 years of experience in a single neurosurgical center. Neurosurgery. 2005;57:281-285. [Medline].

  22. Kanter AS, Diallo AO, Jane JA Jr, et al. Single-center experience with pediatric Cushing's disease. J Neurosurg. 2005;103:413-420. [Medline].

  23. Kiehna EN, Keil M, Lodish M, Stratakis C, Oldfield EH. Pseudotumor cerebri after surgical remission of Cushing's disease. J Clin Endocrinol Metab. 2010;95:1528-32. [Medline]. [Full Text].

  24. Kunwar S, Wilson CB. Pediatric pituitary adenomas. J Clin Endocrinol Metab. Dec 1999;84(12):4385-9. [Medline].

  25. Lafferty AR, Chrousos GP. Pituitary tumors in children and adolescents. J Clin Endocrinol Metab. Dec 1999;84(12):4317-23. [Medline].

  26. Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab. Aug 1998;83(8):2646-52. [Medline]. [Full Text].

  27. Mindermann T, Wilson CB. Pediatric pituitary adenomas. Neurosurgery. Feb 1995;36(2):259-68; discussion 269. [Medline].

  28. Newman CB. Medical therapy for acromegaly. Endocrinol Metab Clin North Am. Mar 1999;28(1):171-90. [Medline].

  29. Ng LL, Chasalow FI, Escobar O, Blethen SL. Growth hormone isoforms in a girl with gigantism. J Pediatr Endocrinol Metab. 1999;126:99-106. [Medline].

  30. Oliveira Mda C, Abech DD, Barbosa-Coutinho LM, Ferreira NP. Macroprolactinoma at 6 years of age: diagnostic difficulties. [Portuguese]. Arq Neuropsiquiatr. 1992;50:397-401. [Medline].

  31. Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. Aug 1998;83(8):2730-4. [Medline].

  32. Orth DN. Cushing's syndrome. N Engl J Med. Mar 23 1995;332(12):791-803. [Medline].

  33. Pandey P, Ojha BK, Mahapatra AK. Pediatric pituitary adenoma: a series of 42 patients. J Clin Neurosci. 2005;12:124-127. [Medline].

  34. Rix M, Laurberg P, Hoejberg AS, Brock-Jacobsen B. Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl. Eur J Endocrinol. 2005;153:195-201. [Medline].

  35. Saito E, Correll CU, Gallelli K, et al. A prospective study of hyperprolactinemia in children and adolescents treated with atypical antipsychotic agents. J Child Adolesc Psychopharmacol. 2004;14:350-358. [Medline].

  36. Sakazume S, Obata K, Takahashi E, et al. Bromocriptine treatment of prolactinoma restores growth hormone secretion and causes catch-up growth in a prepubertal child. Eur J Pediatr. 2004;163:472-474. [Medline].

  37. Smallridge RC. Thyrotropin-secreting pituitary tumors. Endocrinol Metab Clin North Am. 1987;16:765-792. [Medline].

  38. Sotos JF. Overgrowth. Hormonal Causes. Clin Pediatr (Phila). Nov 1996;35(11):579-90. [Medline].

  39. Stevens JR, Kymissis PI, Baker AJ. Elevated prolactin levels in male youths treated with risperidone and quetiapine. J Child Adolesc Psychopharmacol. 2005;15:893-900. [Medline].

  40. [Guideline] Stewart PM, Petersenn S. Rationale for treatment and therapeutic options in Cushing's disease. Best Pract Res Clin Endocrinol Metab. 2009;23 Suppl 1:S15-22. [Medline].

  41. Storr HL, Afshar F, Matson M, et al. Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing's disease. Eur J Endocrinol. 2005;152:825-833. [Medline].

  42. Tamura T, Tanaka R, Korii K, Okazaki H. Pediatric pituitary adenoma. Endocr J. 2000;47:S95-S99. [Medline].

  43. Thorner MO, Vance ML, Laws ER. The anterior pituitary. In: Wison JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa:. WB Saunders;1998:249-340.

  44. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. Apr 20 2000;342(16):1171-7. [Medline].

  45. van Haelst MM, Hoogeboom JJ, Baujat G, et al. Familial gigantism caused by an NSD1 mutation. Am J Med Genet A. 2005;139:40-44. [Medline].

  46. van Haute FR, Taboada GF, Corrêa LL, Lima GA, Fontes R, Riello AP, et al. Prevalence of sleep apnea and metabolic abnormalities in patients with acromegaly and analysis of cephalometric parameters by magnetic resonance imaging. Eur J Endocrinol. 2008;158:459-65. [Medline].

  47. Yang MH, Chuang H, Jung SM, et al. Pituitary apoplexy due to prolactinoma in a Taiwanese boy: patient report and review of the literature. J Pediatr Endocrinol Metab. 2003;16:1301-1305. [Medline].

  48. Zimmerman D, Lteif AN. Thyrotoxicosis in children. Endocrinol Metab Clin North Am. Mar 1998;27(1):109-26. [Medline].

 
Previous
Next
 
Pituitary macroadenoma.
A 16-year-old boy with Cushing disease.
On the left is an unaffected patient aged 12 years. On the right is the same patient aged 13 years after developing Cushing disease.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.