Hyperpituitarism 

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

Background

Hyperpituitarism, or primary hypersecretion of pituitary hormones, is rare in children. It typically results from a pituitary microadenoma. The most frequently encountered adenoma in children is the prolactinoma, followed by corticotropinoma and somatotropinoma. Fewer than 20 cases of thyrotropinoma in children have been reported, all with onset after age 11 years. Pediatric gonadotropinoma has not been reported.

Hypersecretion of pituitary hormones secondary to macroadenomas (see the image below) can interfere with other pituitary hormone functions, resulting in target organ hormone deficiencies (hypogonadism, hypoadrenalism, hypothyroidism).

Pituitary macroadenoma. Pituitary macroadenoma.

In some cases, long-standing hormonal hypersecretion is accompanied by sufficient hyperplasia of the pituitary to produce sellar enlargement.

Elevated pituitary hormone levels that result from primary endocrine organ deficiency (eg, high circulating thyroid-stimulating hormone [TSH] levels in primary hypothyroidism due to Hashimoto thyroiditis) quickly suppress to reference range values upon replacement of the active hormone. Most rarely, ectopic tumors can secrete pituitary hormones. This article focuses on the endocrine manifestations of pituitary adenomas in children.

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Pathophysiology

Hypothalamic dysfunction clearly may promote tumor growth, but overwhelming evidence indicates intrinsic pituicyte genetic disruption leads to pituitary tumorigenesis. The monoclonal nature of most pituitary adenomas, confirmed by X-inactivation studies, implies their usual origin from a clonal event in a single cell. Most pituitary adenomas are functional and secrete a hormone that produces a characteristic clinical presentation. Nonfunctioning pituitary adenomas are rare in children, accounting for only 3-6% of all adenomas in 2 large series, whereas they comprise 30% of adenomas in adults. In children, disruption of growth regulation and/or sexual maturation is common, either because of hormone hypersecretion or because of manifestations caused by local compression by the tumor.

Prolactinoma

Overall, prolactinoma is the most common pituitary adenoma encountered in childhood. Most pediatric cases occur in adolescence, more commonly in females than males. Boys tend to have larger tumors and higher serum prolactin (PRL) levels than girls. Females with these tumors present with amenorrhea, and males present with gynecomastia and hypogonadism. Prolactinomas arise from acidophilic cells that are derived from the same lineage as the somatotropes and thyrotropes. Hence, PRL-secreting adenomas may also stain for and secrete growth hormone (GH) and, occasionally, TSH.

Corticotropinoma (Cushing disease)

In children, corticotropinomas are the most common adenomas observed before puberty, although they occur in people of all ages. They increase in frequency in pubescent and postpubescent children, with a female preponderance. First described by Harvey Cushing in the early 1900s, Cushing disease (see the images below) specifically refers to an adrenocorticotropic hormone (ACTH)–producing pituitary adenoma that stimulates excess cortisol secretion.

A 16-year-old boy with Cushing disease. A 16-year-old boy with Cushing disease. On the left is an unaffected patient aged 12 yearsOn the left is an unaffected patient aged 12 years. On the right is the same patient aged 13 years after developing Cushing disease.

Adenomas that cause Cushing disease are significantly smaller than all other types of adenomas at presentation. Children have clinical courses somewhat different from adults. They most commonly present with weight gain (usually not centripetal) and growth failure. As in adults, most patients display an absence of the physiologic diurnal rhythm of plasma cortisol and ACTH with increased urinary excretion of free cortisol and 17-hydroxycorticosteroids (17-OHCS).

Somatotropinoma (gigantism)

GH-secreting adenomas are rare in childhood. Gigantism refers to GH excess in childhood when open epiphysial plates allow for excessive longitudinal growth. Most cases of gigantism result from GH-secreting pituitary adenomas or hyperplasia. Although gigantism typically occurs as an isolated disorder, it occasionally represents one feature of other conditions (eg, multiple endocrine neoplasia [MEN] type 1, McCune-Albright syndrome [MAS], neurofibromatosis, tuberous sclerosis, Carney complex).

Mammosomatotrophs are the most common type of GH-secreting cells in childhood gigantism; hence, GH-secreting adenomas often stain for and secrete PRL (67% in one study). GH-secreting tumors in pediatric patients are more likely to be locally invasive or aggressive than those in adult patients. Activating mutations of the stimulatory Gs alpha (Gsa) protein have been identified in the somatotrophs of pituitary lesions in MAS and in as many as 40% of sporadic GH-secreting pituitary adenomas.

Thyrotropinoma

Very few cases of thyrotropinoma have been reported in children. These adenomas may secrete excess PRL, GH, and alpha subunit in addition to TSH. They are usually large because of their aggressive features and because their diagnosis is often delayed. The clinical presentation consists of signs and symptoms of hyperthyroidism, visual symptoms, and headaches. Biochemical features include the elevation of circulating free thyroxine (T4) and total triiodothyronine (T3) levels but inappropriately unsuppressed TSH.

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Epidemiology

Frequency

United States

Although less common in children than in adults, pituitary adenomas constitute 2.7% of supratentorial tumors in children and 3.6-6% of all pituitary adenomas that are surgically treated. The average annual incidence of pituitary adenomas presenting before age 20 years is estimated to be less than 0.1 per million children.

Mortality/Morbidity

Transsphenoidal pituitary surgery has emerged as the treatment of choice for ACTH-secreting and GH-secreting adenomas. Transsphenoidal surgery is indicated for prolactinomas that do not respond to medical therapy. Transsphenoidal surgery is associated with remarkably little morbidity and near zero mortality. A permanent loss of pituitary function occurs infrequently. The incidence of postoperative hypopituitarism is about 3% in patients with microadenomas and slightly increases with the invasiveness of the tumor.

Race

Race and ethnicity have not been reported as significant contributing factors to hyperpituitarism.

Sex

In prolactinoma, the female-to-male ratio is 4.5:1. In ACTH-releasing adenoma, the female-to-male ratio is 2:1. In GH-releasing adenoma, the female-to-male ratio is 1:2.

Age

In children, ACTH-releasing adenomas are most prevalent in the youngest group and decrease in frequency with advancing age.

The incidence of prolactinomas increases with age; 93% occur in children older than 12 years.

GH-releasing tumors have a fairly even distribution among the various age groups.

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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 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].

 
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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.
 
 
 
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