eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Panhypopituitarism

Author: Robert P Hoffman, MD, Associate Professor of Pediatrics, Department of Pediatrics, Ohio State University College of Medicine
Contributor Information and Disclosures

Updated: Oct 21, 2009

Introduction

Background

The pituitary gland is called the master endocrine gland of the body because it controls the function of other endocrine organs. The anterior pituitary produces the hormones thyrotropin (thyroid-stimulating hormone [TSH]), corticotropin (adrenocorticotropic hormone [ACTH]), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin (PRL). The anterior pituitary is controlled by specific hypothalamic-releasing hormones. The posterior pituitary produces vasopressin (antidiuretic hormone [ADH]) and oxytocin.

Panhypopituitarism is a condition of inadequate or absent production of the anterior pituitary hormones. It is frequently the result of other problems that affect the pituitary gland and either reduce or destroy its function or interfere with hypothalamic secretion of the varying pituitary-releasing hormones. Panhypopituitarism can be the end result of various clinical scenarios. The signs and symptoms are diverse. Manifestations of congenital anterior hypopituitarism include micropenis, midline defects, optic atrophy, hypoglycemia, and poor growth.

Pathophysiology of panhypopituitarism.

Pathophysiology of panhypopituitarism.

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Pathophysiology of panhypopituitarism.

Pathophysiology of panhypopituitarism.


Pathophysiology

The effects of hypopituitarism in children depend on the affected hormones. GH deficiency can result in hypoglycemia and short stature. Gonadotropin deficiency leads to prenatal micropenis and delayed or interrupted puberty in older children. Corticotropin deficiency interferes with normal carbohydrate, protein, and lipid metabolism and may result in weight loss, hypoglycemia, fatigue, hypotension, and death. Thyrotropin deficiency leads to hypothyroidism.

Frequency

United States

Hypopituitarism is caused by various conditions and is associated with various hormonal deficiencies. Thus, data are limited regarding frequency rates of the various etiologies and components. An Italian study reported GH deficiency prevalence to be approximately 9 cases per 1000 individuals in a pediatric population.1 Data from the Northwest Regional Screening program estimate the frequency of congenital TSH deficiency at 1 case per 29,000 live births.2

Mortality/Morbidity

Morbidity and mortality due to hypopituitarism are caused by the individual hormone deficiencies or the underlying cause of hypopituitarism. Individual hormonal deficiencies are discussed in greater detail in the specific articles, and the underlying causes of death are not discussed here.

Acute mortality due to hormonal deficiencies is rare. When deaths occur due to hormonal deficiencies, they are usually caused by adrenal insufficiency secondary to ACTH deficiency. These deaths are most likely to occur when an accompanying illness prevents appropriate oral glucocorticoid replacement.

Growing, but not completely conclusive, evidence indicates that childhood hypopituitarism may be associated with a shortened adult lifespan, even with adequate hormonal replacement.3 The increased mortality is due to cardiovascular abnormalities that are related to GH deficiency and past practices of not treating a GH deficiency when growth is complete.4,5 Children and adolescents with GH deficiency have been shown to have impaired vascular function.6 In adults, GH treatment restores improves cardiovascular risk factors, but long-term studies that demonstrate reduced cardiovascular disease have not been reported.7,8

Clinical

History

  • Congenital hypopituitarism
    • Suspect hypopituitarism in children with midline defects or optic atrophy (suggestive of septo-optic dysplasia)9,10 and in boys with micropenis (suggestive of gonadotropin deficiency).11,12
    • Evaluate hypopituitarism prior to the development of overt problems due to hormonal deficiencies.
    • Infants with hypopituitarism without such abnormalities present in various ways. For example, children with severe growth hormone (GH) deficiency and adrenocorticotropic hormone (ACTH) deficiency may develop hypoglycemia, which leads to the diagnosis.
    • Another presentation is hypernatremic dehydration due to diabetes insipidus. Accompanying cortisol deficiency may obscure diabetes insipidus because cortisol is necessary to excrete a free water load.13
    • Some infants come to medical attention because of low thyroid hormone concentrations discovered on neonatal thyroid screen. Children with milder defects present with poor growth at varying ages. The symptoms include fatigue, dry skin, and constipation due to thyroid-stimulating hormone (TSH) deficiency and concomitant hypothyroidism and/or nausea, vomiting, and malaise due to ACTH and cortisol deficiency.
  • Acquired hypopituitarism
    • Similar to children with congenital hypopituitarism, many children with acquired hypopituitarism are identified before symptoms are observed.
    • Routinely evaluate pituitary function before and after treatment in children with craniopharyngiomas or other hypothalamic or pituitary tumors. The same is true for children who have received cranial irradiation (eg, before bone marrow transplant or for cranial tumors).
    • Children without a known hypothalamic or pituitary insult with hypopituitarism frequently present with growth failure because of GH deficiency. Some children come to medical attention because of abnormal thyroid function test results suggestive of central hypothyroidism.
    • Older children may present because of absent or interrupted puberty. Girls have primary or secondary amenorrhea.
    • Polyuria and polydipsia due to central diabetes insipidus may also be a presenting symptom.
    • Rarely, patients with ACTH deficiency may present with hyponatremia. This is not due to mineralocorticoid deficiency because aldosterone secretion is not primarily under pituitary control but is likely due to excess vasopressin release because (as mentioned above) cortisol helps the body excrete a free water load and circulating intravascular volume is depleted in cortisol deficiency.13

Physical

  • Neonates
    • Evaluate a newborn with midline defects of the nose, lip, teeth, or mouth.
    • Evaluate the pituitary function in a newborn with nystagmus and optic nerve atrophy on funduscopic examination.
    • Hypogonadotrophism is suggested in the male with a small, normally shaped penis and small testes.
    • Hypopituitarism leading to ambiguous genitalia has been reported.
    • The child with hypoglycemia secondary to hypopituitarism is irritable, jittery, or lethargic. Seizures may be present.
  • Older children
    • The most common presenting feature suggestive of hypopituitarism is growth failure with decreased growth rate for age.
    • Examine optic disks for papilledema and visual fields for bilateral hemianopsia, a sign of optic chiasm compression. These findings quickly suggest the possibility of a craniopharyngioma, other pituitary tumor, or a hypothalamic tumor.
    • Assessing the child's sexual maturation is also important.

Causes

  • Congenital hypopituitarism
    • Congenital midline defects, such as septo-optic dysplasia (de Morsier syndrome), midline facial clefts, or single central incisors, may be accompanied by varying anterior pituitary deficiencies.10 Three fourths of individuals with optic nerve hypoplasia have hormonal abnormalities.14
    • Mutations in various genes have been demonstrated to cause congenital pituitary abnormalities in HESX1, LHX3, LHX4, PROP1, and POU1F1 (formerly known as PIT1) , with varying combinations of one or more hormonal abnormalities with or without anatomic abnormalities. These homeobox genes code various pituitary transcription factors responsible for pituitary development.15,16,17
    • Neonatal hypopituitarism, although not truly congenital, may also result from severe asphyxia either at birth or shortly thereafter.
  • Acquired hypopituitarism: Causes of acquired hypopituitarism are frequently the result of hypothalamic or pituitary tumors and their surgical or radiologic treatment. Craniopharyngiomas, pituitary dysgerminomas, and optic gliomas are particularly common causes of hypopituitarism.18 Other causes include trauma and autoimmune lymphocytic hypophysitis.19,20,21,22 Hormonal abnormalities are noted in 25% of adults with traumatic brain injury.23 The frequency of hormonal abnormalities in children following brain injury is unknown.24

More on Panhypopituitarism

Overview: Panhypopituitarism
Differential Diagnoses & Workup: Panhypopituitarism
Treatment & Medication: Panhypopituitarism
Follow-up: Panhypopituitarism
Multimedia: Panhypopituitarism
References
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References

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  2. Hanna CE, Krainz PL, Skeels MR, Miyahira RS, Sesser DE, LaFranchi SH. Detection of congenital hypopituitary hypothyroidism: ten-year experience in the Northwest Regional Screening Program. J Pediatr. Dec 1986;109(6):959-64. [Medline].

  3. Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. Mar 1996;81(3):1169-72. [Medline].

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  9. Matthai SM, Smith CS. Pituitary hypoplasia associated with a single central maxillary incisor. J Pediatr Endocrinol Metab. Sep-Oct 1996;9(5):543-4. [Medline].

  10. Willnow S, Kiess W, Butenandt O, et al. Endocrine disorders in septo-optic dysplasia (De Morsier syndrome)--evaluation and follow up of 18 patients. Eur J Pediatr. Mar 1996;155(3):179-84. [Medline].

  11. Burgner DP, Kinmond S, Wallace AM, et al. Male pseudohermaphroditism secondary to panhypopituitarism. Arch Dis Child. Aug 1996;75(2):153-5. [Medline].

  12. Setian N, Aquiar CH, Galvao JA. Rathke's cleft cyst as a cause of growth hormone deficiency and micropenis. In: Child's Nervous System. Vol 5. 1999:271-3.

  13. Rajaratnam S, Seshadri MS, Chandy MJ, Rajshekhar V. Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: a prospective randomized controlled study. Br J Neurosurg. Oct 2003;17(5):437-42. [Medline].

  14. Borchert M, Garcia-Filion P. The syndrome of optic nerve hypoplasia. Curr Neurol Neurosci Rep. Sep 2008;8(5):395-403. [Medline].

  15. Rosenbloom AL, Almonte AS, Brown MR, et al. Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. J Clin Endocrinol Metab. Jan 1999;84(1):50-7. [Medline].

  16. Ward L, Chavez M, Huot C, et al. Severe congenital hypopituitarism with low prolactin levels and age- dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation. J Pediatr. Jun 1998;132(6):1036-8. [Medline].

  17. Vieira TC, Boldarine VT, Abucham J. Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arq Bras Endocrinol Metabol. Oct 2007;51(7):1097-103. [Medline].

  18. van Aken MO, Lamberts SW. Diagnosis and treatment of hypopituitarism: an update. Pituitary. 2005;8(3-4):183-91. [Medline].

  19. Bettendorf M, Fehn M, Grulich-Henn J, et al. Lymphocytic hypophysitis with central diabetes insipidus and consequent panhypopituitarism preceding a multifocal, intracranial germinoma in a prepubertal girl. Eur J Pediatr. Apr 1999;158(4):288-92. [Medline].

  20. Maghnie M, Genovese E, Sommaruga MG, et al. Evolution of childhood central diabetes insipidus into panhypopituitarism with a large hypothalamic mass: is 'lymphocytic infundibuloneurohypophysitis' in children a different entity?. Eur J Endocrinol. Dec 1998;139(6):635-40. [Medline].

  21. Mikami-Terao Y, Akiyama M, Yanagisawa T, et al. Lymphocytic hypophysitis with central diabetes insipidus and subsequent hypopituitarism masking a suprasellar germinoma in a 13-year-old girl. Childs Nerv Syst. Mar 25 2006;[Medline].

  22. Tanriverdi F, Senyurek H, Unluhizarci K, et al. High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and at 12-months after the trauma. J Clin Endocrinol Metab. Mar 7 2006;[Medline].

  23. Behan LA, Phillips J, Thompson CJ, Agha A. Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry. Jul 2008;79(7):753-9. [Medline].

  24. Acerini CL, Tasker RC, Bellone S, Bona G, Thompson CJ, Savage MO. Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation. Eur J Endocrinol. Nov 2006;155(5):663-9. [Medline].

  25. Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab. Mar 1999;84(3):838-43. [Medline].

  26. Streeten DH. Shortcomings in the low-dose (1 microg) ACTH test for the diagnosis of ACTH deficiency states. J Clin Endocrinol Metab. Mar 1999;84(3):835-7. [Medline].

  27. Chanoine JP, Rebuffat E, Kahn A, et al. Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5-12 months. J Clin Endocrinol Metab. Oct 1995;80(10):3032-5. [Medline].

  28. Fischli S, Jenni S, Allemann S, et al. Dehydroepiandrosterone sulfate in the assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. Feb 2008;93(2):539-42. [Medline].

  29. Carel JC, Tresca JP, Letrait M, et al. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab. Jul 1997;82(7):2117-21. [Medline].

  30. Marin G, Domene HM, Barnes KM, et al. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. Aug 1994;79(2):537-41. [Medline].

  31. DeVile CJ, Stanhope R. Hydrocortisone replacement therapy in children and adolescents with hypopituitarism. Clin Endocrinol (Oxf). Jul 1997;47(1):37-41. [Medline].

  32. Charmandari E, Lichtarowicz-Krynska EJ, Hindmarsh PC, et al. Congenital adrenal hyperplasia: management during critical illness. Arch Dis Child. Jul 2001;85(1):26-8. [Medline].

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Further Reading

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Keywords

panhypopituitarism, pituitary gland, inadequate anterior pituitary hormone production, absent anterior pituitary hormone production, congenital anterior hypopituitarism, micropenis, hypoglycemia, poor growth, short stature, delayed puberty, interrupted puberty

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Contributor Information and Disclosures

Author

Robert P Hoffman, MD, Associate Professor of Pediatrics, Department of Pediatrics, Ohio State University College of Medicine
Robert P Hoffman, MD is a member of the following medical societies: American Diabetes Association, American Pediatric Society, Christian Medical & Dental Society, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds PI, also occasional consultant

CME Editor

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

 
 
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