eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypopituitarism

Lawrence A Wetterau, MD, Assistant Professor, Section of Endocrinology, Children's Hospital Central California

Updated: May 5, 2009

Introduction

Background

Hypopituitarism is a partial or complete insufficiency of pituitary hormone secretion, which may derive from pituitary or hypothalamic disease. Onset can occur in children or adults; underlying causes and clinical presentation vary considerably with age. The focus of this article is childhood-onset hypopituitarism.

A brief review of pituitary anatomy, development, and physiology facilitates comprehension of childhood-onset hypopituitarism.

The pituitary gland, located at the base of the brain, is comprised of anterior (ie, adenohypophysis) and posterior (ie, neurohypophysis) regions. The anterior pituitary is an ectodermal structure that derives from the pharynx as the Rathke pouch. The anterior pituitary synthesizes and releases the following hormones into systemic circulation:

• Growth hormone (GH)
• Adrenocorticotropic hormone (ACTH)
• Thyroid-stimulating hormone (TSH)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Prolactin (PRL)

The anterior pituitary is primarily regulated by neuropeptide-releasing and release-inhibiting hormones produced in the hypothalamus. These regulatory hormones are transported to the anterior pituitary via the pituitary portal system circulation. The release-stimulating hormones include growth hormone–releasing hormone (GHRH), corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone (GnRH). In some instances, other peptides may also have a regulatory influence as is the case for antidiuretic hormone (ADH), which acts synergistically with CRH to promote ACTH release. PRL secretion is regulated by dopamine, which inhibits its release.

Additionally, a negative feedback loop occurs such that the hormones produced in the target glands inhibit the release of their respective regulatory pituitary and hypothalamic factors. For example, hypothalamic TRH stimulates TSH release, which, in turn, stimulates the thyroid gland resulting in increased serum levels of thyroxine (T4) and triiodothyronine (T3). When they have reached sufficient levels, T3 and T4 suppress further TRH and TSH release.

The posterior pituitary consists of neural tissue that descends from the floor of the third ventricle. In contrast to the anterior pituitary hormones, the posterior pituitary hormones (ie, ADH, oxytocin) are synthesized by cell bodies in the hypothalamus and transported along the neurohypophyseal tract of the pituitary stalk. Release of these hormones occurs in response to neurohypophyseal stimuli.

Intrinsic pituitary disease (or any process that disrupts the pituitary stalk or damages the hypothalamus) may produce pituitary hormone deficiency.

The clinical presentation of hypopituitarism widely varies, depending on patient age and on the specific hormone deficiencies that may occur singly or in various combinations. As a general rule, diagnosis of a single pituitary hormone deficiency requires evaluating the other hormone axes.

Pathophysiology

Hypopituitarism has multiple possible etiologies; the pathophysiology depends on the underlying cause (see Causes). The common endpoint is disrupted synthesis or release of one or more pituitary hormones, resulting in clinical manifestations of hypopituitarism.

Frequency

United States

Multiple pituitary hormone deficiency (MPHD) is rare in childhood, with a possible incidence of fewer than 3 cases per million people per year. The most common pituitary hormone deficiency, growth hormone deficiency (GHD), is much more frequent; a United States study reported a prevalence of 1 case in 3480 children.

International

A Scottish survey of 48,000 school-aged children reported a prevalence of 1 case of GHD in 4000 children.

Mortality/Morbidity

Morbidity and mortality generally relate to the underlying cause of hypopituitarism. Morbidity and mortality are minimal when pituitary insufficiency is recognized properly and appropriate hormone replacement (including stress doses of hydrocortisone, when indicated) is instituted. However, failure to recognize and treat clinical manifestations of hypopituitarism can result in significant sequelae.

• Hypoglycemia can cause convulsions; persistent severe hypoglycemia can cause permanent CNS injury.
• During periods of significant stress, an untreated ACTH deficiency can lead to profound hypotension, severe shock, and death.
• Short stature caused by hypopituitarism can have significant psychosocial consequences.
• Hypopituitarism appears to shorten life expectancy. In 1990, Rosen and Bengtsson reported a series of 333 consecutive cases of hypopituitarism diagnosed from 1956-1987 in patients who received routine hormone replacement.¹ Overall mortality was significantly increased in age-matched and sex-matched populations and was attributed to cardiovascular causes. GHD was believed to be an important contributing factor.

Race

Hypopituitarism exhibits no specific racial predilection.

Sex

Hypopituitarism exhibits no specific predilection for either sex.

Age

Because hypopituitarism has both congenital and acquired forms, the disease can occur in neonates, infants, children, adolescents, or adults.

Clinical

History

Clinical presentation of hypopituitarism, which widely varies, depends on the patient's age, etiology, and the specific hormone deficiencies, which may occur as isolated deficiencies or in various combinations of multiple pituitary hormone deficiency (MPHD). Presenting signs and symptoms may develop insidiously and can be nonspecific, requiring a high index of suspicion.

• Hypopituitarism in neonates
  • Most neonates with hypopituitarism have normal or even high birth weights and lengths and no history of intrauterine growth retardation.
  • Neonates (particularly those with MPHD) often have histories of breech presentation, although the explanation for this is unclear.
  • Presenting features in newborns may include hypoglycemia, prolonged jaundice, history of a complicated neonatal course, hyponatremia, and small genitalia.
  • Signs of hypoglycemia may be nonspecific and include lethargy, jitteriness, pallor, cyanosis, apnea, and convulsions.
  • Jaundice may be secondary to indirect hyperbilirubinemia (as occurs in thyroid stimulating hormone [TSH] axis deficiency) or to direct hyperbilirubinemia (as occurs in growth hormone [GH] or adrenocorticotropic hormone [ACTH] axis deficiencies).
  • Neonates with hypopituitarism may have undergone several evaluations to exclude sepsis or for unexplained apnea, hypotension, or temperature instability. Consider hypopituitarism as a possible diagnosis when these conditions occur in a full-term infant.
  • Hyponatremia unassociated with hypovolemia and unresponsive to fluid restriction occurs in infants with hypopituitarism. In contrast to the hyponatremia that occurs with the salt-losing crisis of 21-hydroxylase deficiency, serum potassium levels are typically low or within the reference range. The hyponatremia resolves with physiologic corticosteroid replacement.²
  • Microgenitalia may result from a gonadotropin deficiency or from GH deficiency.
• Hypopituitarism in older infants and children
  • Common presenting features include growth failure, disorders of pubertal development, and diabetes insipidus.
  • Hypoglycemia, although less frequent, can also be a presenting sign of hypopituitarism in older infants and children.
  • Growth failure may be the most common presenting symptom in this age group, possibly with an associated delay in tooth development.
  • Patients with acquired or milder forms of gonadotropin deficiency who do not present with microgenitalia in infancy may present later with absent or delayed puberty.
  • Central diabetes insipidus secondary to antidiuretic hormone (ADH) deficiency can be difficult to recognize in infancy because patients often present with nonspecific signs (eg, irritability, unexplained fever).
  • Symptoms of polyuria and polydipsia are more readily obvious in older children.
  • Patients with hypothyroidism secondary to a TSH axis deficiency present with signs and symptoms identical to those of primary hypothyroidism, although typically less severe. These include fatigue, cold intolerance, constipation, dry skin, slow growth, and weight gain.
• Depending on the etiology of the hypopituitarism, associated findings in the neonate, infant, or child may include developmental delay, various visual and neurologic symptoms, and a number of congenital malformation syndromes.
  • Optic nerve hypoplasia warrants careful follow-up of linear growth and consideration of pituitary hormone testing.
  • Anencephaly is associated with variable pituitary hypoplasia and complete absence of the hypothalamus.
  • Various forms of holoprosencephaly may be associated with hypopituitarism.
  • Patients with acquired hypopituitarism, caused by a suprasellar tumor, often present with headaches, visual disturbances, and other neurologic symptoms.

Physical

• Neonates
  • Birth weights and lengths are typically within the reference range.
  • Important physical signs in the neonate that may suggest a diagnosis of hypopituitarism include microgenitalia, jaundice, and physical evidence of possible hypoglycemia (ie, jitteriness, pallor).
  • Microgenitalia includes micropenis (which has a well-documented association with hypopituitarism) and an underdeveloped clitoris. Micropenis is defined as stretched penile length less than 2.5 cm (reference range mean length is 4 cm). Data on normal clitoral size, including that for different gestational ages, are also available.
  • Optic nerve hypoplasia is associated with hypopituitarism; the presence of small pale optic disks or nystagmus should prompt consideration of hypopituitarism.
• Older infants and children
  • Growth failure (see Media file 1) is the most important sign to recognize in hypopituitarism. Growth failure may often exist for a considerable period of time before it is recognized. In addition to short stature and abnormal growth rate, the affected child may show evidence of delayed skeletal maturation (eg, delayed dental development).
    
    

    

    The left photograph shows an untreated 21-month-old girl with congenital hypopituitarism. The right panel depicts the same child aged 29 months, following 8 months of growth hormone therapy.

    
    
  • Weight gain typically is out of proportion to growth, resulting in relative obesity. This obesity is truncal in distribution; skull and head circumference growth are typically preserved, producing the impression of a large head.
  • Craniofacial features of pituitary growth hormone deficiency (GHD) include craniofacial disproportion (ie, normal head circumference, small facies, prominent forehead, frontal bossing). The presence of a central incisor is an important finding because it may represent hypopituitarism in a midline CNS abnormality.
  • During physical examination, pay particular attention to pubertal development because patients with hypopituitarism may present with microgenitalia in infancy or with delayed or absent puberty.
  • Visual and neurologic abnormalities may represent important features associated with hypopituitarism. When not recognized in infancy, optic nerve hypoplasia may be noted in childhood as decreased visual acuity. Signs that may indicate the potential presence of a suprasellar mass include decreased visual acuity, visual field defects, papilledema, and/or optic atrophy.
  • Anosmia, particularly in a patient with delayed or absent puberty, should prompt consideration of Kallmann syndrome (KS).

Causes

Mutations in pituitary transcription factors can cause multiple or isolated pituitary hormone deficiency. Mutations in PIT1 and PROP1 (ie, prophet of Pit-1) were the first shown to cause MPHD. Pit-1 is a homeobox transcription factor expressed in the anterior pituitary during early fetal development and throughout life. Mutations in the PIT1 gene produce a phenotype consisting of deficiencies of GH, prolactin (PRL), and TSH. PROP1 is expressed before Pit-1 and is a prerequisite for the expression of Pit-1. Inactivating mutations of PROP1 cause deficiencies of LH, follicle-stimulating hormone (FSH), GH, PRL, and TSH. Clinical phenotypes of MPHD patients with PROP1 defects, determined by the pattern of hormone deficiency, can vary considerably even among patients with the same mutation.

HESX1 and KAL are two additional genes for which mutations have been found to cause pituitary abnormalities. Homozygous inactivating mutations in HSEX1 produce a complex phenotype with pituitary hypoplasia that resembles septo-optic dysplasia (SOD). Most cases of SOD remain sporadic without a known genetic defect and much remains to be learned about the role of HESX1 in other forms of hypopituitarism.

KAL plays a causative role in some forms of KS. KS is a rare syndrome consisting of hypogonadotropic hypogonadism and anosmia. Cases may be sporadic or familial with X-linked, autosomal recessive, and autosomal dominant forms being reported. The X-linked form is caused by a KAL gene defect and is characterized by failure of gonadotropin-releasing hormone (GnRH) secretion caused by the failure of GnRH neurons to migrate normally from the olfactory bulb to the hypothalamus. KAL gene defects are only responsible for a small percentage of other familial cases as well as some sporadic cases. Defects in autosomal genes that have yet to be identified are thought to be likely to account for most familial (and presumably sporadic) cases of KS.

In the past several years, several novel transcription factor gene alterations have been reported as a cause of congenital pituitary hormone deficiencies. In addition to the above, these include mutations in LHX3, LHX4, TPIT, and PTX2.

Congenital etiologies

• Perinatal insults (eg, traumatic delivery, birth asphyxia)
• Genetic disorders
  • Isolated GHD types IA, IB, II, III
  • MPHD (eg, PIT1, PROP1 gene mutations)
  • Septo-optic dysplasia
  • KS
• Developmental CNS defects
  • Anencephaly
  • Holoprosencephaly
• Pituitary aplasia or hypoplasia
  • Interrupted pituitary stalk
  • Absent or ectopic neurohypophysis
  • Pallister-Hall syndrome

Acquired etiologies

• Cranial irradiation
• Infiltrative disorders
  • Histiocytosis X
  • Tuberculosis
  • Sarcoidosis
  • Lymphocytic hypophysitis
• Hemochromatosis
• Tumors (eg, sellar, suprasellar, pineal)
  • Craniopharyngioma (most common)
  • Germinoma
  • Glioma/astrocytoma
  • Pituitary adenoma (rare prior to adulthood)

Differential Diagnoses

Other Problems to Be Considered

Delayed puberty
Psychosocial deprivation

Workup

Laboratory Studies

• To evaluate growth hormone deficiency (GHD), tests for insulinlike growth factor-I (IGF-I) and insulinlike growth factor–binding protein 3 (IGFBP-3) are useful for screening, although their use is limited in very young children or children with brain tumors.⁴ When GHD is strongly suspected, further provocative testing of GH secretion is typically performed under the supervision of a pediatric endocrinologist.
  • Insulin-induced hypoglycemia is the most reliable provocative test for GHD and has the added advantage of accurately assessing the corticotropin-releasing hormone (CRH)–adrenocorticotropic hormone (ACTH)–cortisol axis. However, this test also has the greatest potential for harm; thus, it is not routinely used in most pediatric centers.
  • Alternative GH secretagogues used successfully in combination as 2 serial tests include arginine, levodopa, growth hormone–releasing hormone (GHRH), propranolol with glucagon, exercise, clonidine, and epinephrine. In prepubertal children, consideration should be given to "priming" with sex steroids prior to testing.
  • A random serum GH level is rarely helpful; the exception is during early infancy when GH levels usually are tonically elevated.
• Measurement of morning serum cortisol levels can help exclude a CRH-ACTH-cortisol axis deficiency; a level of 20 mcg/dL virtually excludes this diagnosis.
• Insulin-induced hypoglycemia probably is the criterion standard test but has limitations secondary to its inherent risks.
• As an alternative, metyrapone, which transiently induces adrenal insufficiency by blocking 11-hydroxylase activity, can be used to stimulate cortisol secretion. This test is quite variable and has some inherent risk.
• ACTH stimulation testing is sensitive, reproducible, and extremely safe. Even though it directly examines the state of the adrenal cortices, indirectly it provides information about the hypothalamic-pituitary unit because the cortisol response to exogenous ACTH is blunted in long-standing (>10 d) hypopituitarism.
• CRH stimulation testing can also be considered. It is of equivalent value to the ACTH stimulation test.
• In patients with acute hypoglycemia, a critical sample documenting low serum glucose, while simultaneously measuring GH and cortisol levels, can also be diagnostic.
• To assess central hypothyroidism (ie, thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH) deficiency), low free thyroxine (FT4) levels assayed by dialysis and reference range or low serum TSH levels are diagnostic.⁵
• Laboratory approaches to assess the pituitary-gonadal axis vary based on patient age.
  • Young infants spontaneously secrete follicle-stimulating hormone (FSH) and leuteinizing hormone (LH) in amounts that can be detected by radioimmunoassay; they also produce substantial amounts of testosterone and estradiol. At this age, random measurements of estradiol or testosterone levels and of LH and FSH levels are adequate to assess the gonadal axis.
  • From later infancy until about age 4 years, spontaneous secretion of LH and FSH is reduced, but stimulated responses to gonadotropin-releasing hormone (GnRH) are retained, making GnRH testing an option.
  • No method reliably assesses the axis in preadolescent children older than 4 years. Testing is typically deferred until puberty, when diagnostic findings show low random LH and FSH levels in conjunction with low sex steroid levels (eg, testosterone, estradiol).
• Elevated serum sodium and serum osmolality levels, when combined with low or low-normal urine osmolality, suggest diabetes insipidus. A low serum antidiuretic hormone (ADH) level in this context can be diagnostic for central diabetes insipidus (ie, pituitary vasopressin deficiency). A water deprivation test is definitive; this test is performed under the supervision of a pediatric endocrinologist. In patients with diabetes insipidus, serum sodium and serum osmolality levels rise during water deprivation, while urine fails to concentrate properly. A normal response to administered vasopressin differentiates central diabetes insipidus from nephrogenic diabetes insipidus.

Imaging Studies

• A brain MRI with specific cuts of the pituitary is the preferred imaging study for hypopituitarism. This may be obtained pre–gadolinium contrast and post–gadolinium contrast, which can be helpful in the delineation of the posterior pituitary and some pituitary tumors.

Treatment

Medical Care

Appropriate treatment primarily involves appropriate hormone replacement.

Surgical Care

Tumor location and type dictate the choice of surgical procedures.

Consultations

Consultation with a pediatric hematologist-oncologist is necessary for patients with a pituitary tumor or histiocytosis X.

Diet

Diet is unrestricted.

Activity

Activity is unrestricted.

Medication

Endocrine hormones

These hormones are designed to replace absent hormones in patients with a pituitary deficiency.

Somatropin (Nutropin, Genotropin, Saizen, Humatrope)

Recombinant human growth hormone (rhGH) used to treat growth failure and metabolic abnormalities that accompany GHD. Somatropin is a purified polypeptide hormone of recombinant DNA origin. The amino acid sequence of somatropin is identical to pituitary derived human GH. Growth response of infants and children with severe GHD secondary to congenital hypopituitarism often is remarkable (see Media file 1, which depicts the results achieved with rhGH therapy for 8 mo).

Dosing

Adult

Pediatric

0.025-0.050 mg/kg/d SC hs

Interactions

Glucocorticoids may decrease growth-promoting effects

Contraindications

Documented hypersensitivity; closed epiphyses; actively growing intracranial tumor; critical illness related to respiratory failure

Precautions

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

Regularly monitor growth velocity and assess IGF-I and IGFBP-3 levels at least annually during rhGH therapy; caution in diabetes mellitus; reconstitute with sterile water for injection if administering to newborns

Levothyroxine (Synthroid, Levoxyl)

In active form, influences growth and maturation of tissues. Sufficient thyroid hormone is mandatory for normal growth, metabolism, and neurologic development. For central hypothyroidism, the goal is normal FT4.

Dosing

Adult

Pediatric

Replacement: 100 mcg/m²/d, individualize and titrate according to thyroid function test (TFT) results
Neonates: 25-37.5 mcg PO qd; titrate based on TFT results
6-12 months: 50-75 mcg/d PO
1-5 years: 75-100 mcg/d PO
6-12 years: 100-150 mcg/d PO
>12 years: 150 mcg/d PO

Interactions

Cholestyramine may decrease levothyroxine absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants increases when administered with levothyroxine; activity of some beta-blockers may decrease when hypothyroid patient is converted to a euthyroid state; phenytoin may decrease levels; soy protein ingestion can inhibit absorption of levothyroxine

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in angina pectoris or cardiovascular disease; periodically monitor thyroid status

Hydrocortisone (Cortef, Solu-Cortef)

Used for cortisol replacement therapy; has mineralocorticoid activity and glucocorticoid effects.

Dosing

Adult

Pediatric

Replacement: 8-12 mg/m²/d PO divided bid (usually two thirds in morning and one third in evening to simulate diurnal variation)
Acute adrenal insufficiency: 50-100 mg/m² IV bolus initially; followed by 50-100 mg/m²/d IV divided q6h

Interactions

Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

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

Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes mellitus, and myasthenia gravis; during intercurrent illness, maintenance dose must be increased 2-fold to 3-fold and/or parenterally administrated

Vasopressin (Pitressin)

Used for ADH replacement therapy; dose widely varies and is titrated depending on serum and/or urine sodium osmolality, fluid balance, and urine output; may be administered IM, SC, or as continuous IV infusion.

Dosing

Adult

Pediatric

2.5-10 U IM/SC bid/qid

Interactions

Lithium, epinephrine, demeclocycline, heparin, and alcohol may decrease effects; chlorpropamide, urea, fludrocortisone, and carbamazepine may potentiate effects

Contraindications

Documented hypersensitivity; coronary artery disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with predisposition to thrombus formation and conditions associated with fluid and electrolyte imbalance, cardiovascular disease, seizure disorders, nitrogen retention, asthma, or migraine; excessive doses may result in hyponatremia

Desmopressin (DDAVP)

Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys; used for ADH replacement.

Dosing

Adult

Pediatric

0.05-0.4 mg PO qd or divided bid; 5-40 mcg/d intranasally qd or divided bid

Interactions

Coadministration with demeclocycline and lithium decreases effects; fludrocortisone and chlorpropamide increase effects of desmopressin

Contraindications

Documented hypersensitivity; platelet-type von Willebrand disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with predisposition to thrombus formation and conditions associated with fluid and electrolyte imbalance or cardiovascular disease

Follow-up

Further Outpatient Care

• Routinely monitor growth and development at 3-month intervals in patients with hypopituitarism.
• If a patient is receiving recombinant human growth hormone (rhGH) therapy, monitor for adverse effects and monitor insulinlike growth factor (IGF)-I levels at least annually. Also, consider obtaining periodic hemoglobin A1c (HgbA1c), particularly in the patient with risk factors (eg, family history, obesity) for diabetes mellitus.
• Monitor low free thyroxine (FT4), when appropriate.
• When relevant, monitor blood sugar to ensure euglycemia; the condition may or may not require intravenous dextrose.

Inpatient & Outpatient Medications

• The presence of one or more hormone deficiencies determines medication choice (see Medication).

Deterrence/Prevention

• Genetic counseling with parents and patients about the mode of transmission is important for cases involving heritable forms of hypopituitarism.

Complications

• Sequelae from episodes of severe hypoglycemia, hypernatremia, or adrenal crises are among potential complications. Long-term complications include short stature and infertility.

Prognosis

• With appropriate treatment, overall prognosis is very good. Previous findings of increased cardiovascular morbidity and decreased life expectancy in adults with hypopituitarism were thought to be largely secondary to untreated growth hormone deficiency (GHD).

Patient Education

• When treatment includes rhGH therapy, instruct parents and patients to recognize and report adverse effects.
• Teaching patients when and how to administer appropriate stress doses (oral and parenteral) of hydrocortisone is essential.
• Stress the importance of wearing a medical identification bracelet or necklace.
• For excellent patient education resources, visit eMedicine's Endocrine System Center and Growth Hormone Deficiency Center. Also, see eMedicine's patient education articles Anatomy of the Endocrine System, Hypopituitarism in Children, Growth Hormone Deficiency in Children, Understanding Growth Hormone Deficiency Medications, and Growth Failure in Children.

Miscellaneous

Medicolegal Pitfalls

• Any patient with hypopituitarism must have an MRI examination to exclude a brain tumor.
• Close monitoring is mandatory for patients receiving recombinant human growth hormone (rhGH) therapy to identify possible adverse effects.

Special Concerns

• Conduct appropriate stress dosing of corticosteroid replacement.

Multimedia

Media file 1: The left photograph shows an untreated 21-month-old girl with congenital hypopituitarism. The right panel depicts the same child aged 29 months, following 8 months of growth hormone therapy.

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Keywords

hypopituitarism, growth hormone deficiency, GHD, multiple pituitary hormone deficiency, MPHD, pituitary hypothalamus, hypoglycemia, short stature, jaundice, hyponatremia, sepsis, microgenitalia, growth failure, diabetes insipidus, gonadotropin deficiency, cold intolerance, constipation, micropenis, obesity, craniofacial abnormalities, Kallmann syndrome, KS, septo-optic dysplasia, anencephaly, holoprosencephaly, Pallister-Hall syndrome, histiocytosis, tuberculosis, tuberculosis, sarcoidosis, lymphocytic hypophysitis, hemochromatosis, craniopharyngioma, germinoma, glioma, astrocytoma, pituitary adenoma, treatment, diagnosis

Contributor Information and Disclosures

Author

Lawrence A Wetterau, MD, Assistant Professor, Section of Endocrinology, Children's Hospital Central California
Lawrence A Wetterau, 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.

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; 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.

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

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.

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

• Relevant clinical guidelines include the following:
  • American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly
  • American College of Radiology Appropriateness Criteria for neuroendocrine imaging
  • Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management
• Relevant clinical trials include the following:
  • Effects of Corticotropin Releasing Hormone (CRH) on the Sleep in Patients With Hypopituitarism
  • Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
  • Detection and Treatment of Endocrine Abnormalities in Childhood Cancer Survivors
• Related eMedicine topics include the following:
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  • Growth Hormone Deficiency (Endocrinology)
  • Growth Hormone Deficiency (Pediatrics: General Medicine)

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