AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

The pituitary gland is called the master endocrine gland of the body because it controls function over other endocrine organs. The anterior pituitary produces the hormones thyrotropin (thyroid-stimulating hormone [TSH]), corticotropin (adrenocorticotropin [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 a variety of clinical scenarios. The signs and symptoms are diverse. Manifestations of congenital anterior hypopituitarism include micropenis, midline defects, optic atrophy, hypoglycemia, and poor growth.

Pathophysiology

The effects of hypopituitarism in children are dependent on the hormones affected. 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

Few data are available for each of the varied hormone deficiencies individually or combined. Data from the Northwest Regional Screening program estimate the frequency of congenital TSH deficiency at 1 in 135,000 live births.

Mortality/Morbidity

Morbidity and mortality from hypopituitarism are due to 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 are not discussed here.

Acute mortality from hormonal deficiencies is rare. When deaths occur from hormonal deficiencies, they are usually due to 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 life span, even with adequate hormonal replacement. The increased mortality is due to cardiovascular abnormalities that may be related to GH deficiency and past practices of not treating a GH deficiency when growth is complete. This practice is changing as more evidence becomes available.

CLINICAL

Section 3 of 11  

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• Clinical
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History

• Congenital hypopituitarism
• • Suspect hypopituitarism in children with midline defects or optic atrophy (suggestive of septo-optic dysplasia) and in boys with micropenis (suggestive of gonadotropin deficiency).
  • Evaluate hypopituitarism prior to the development of overt problems from hormonal deficiencies.
  • Hypopituitary infants without such abnormalities present in a variety of ways. Children with severe GH deficiency and ACTH deficiency, for example, 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.
  • 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 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 earlier) cortisol helps the body excrete a free water load and circulating intravascular volume is depleted in cortisol deficiency.

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.
  • One case report of hypopituitarism leading to ambiguous genitalia exists.
  • 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.
  • Specific gene defects have been identified as causes of congenital hypopituitarism. These include autosomal dominant and recessive defects in the gene for pituitary transcription factor (POU1F1, formerly known as PIT1) and the gene for a homeodomain protein necessary for POU1F1 expression known as PROP1.
  • 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. Other causes are trauma and autoimmune lymphocytic hypophysitis.

DIFFERENTIALS

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Other Problems to be Considered

Septo-optic dysplasia

WORKUP

Section 5 of 11  

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Lab Studies

• The diagnostic evaluation of a child with hypopituitarism is divided into 2 portions: recognition of the hormonal deficiencies and determination of the cause.
• TSH deficiency
• • Hypothyroidism secondary to hypothyroidism is the easiest of hormonal abnormalities to diagnose. Children have decreased free thyroxine (T4) levels and reference range or low TSH levels. Occasionally, a child with hypothalamic hypopituitarism has a mildly elevated TSH level.
  • Test any child with TSH deficiency for adrenal function prior to T4 replacement. Correction of hypothyroidism without appropriate cortisol replacement can precipitate an adrenal crisis. This is most likely because of accelerated cortisol metabolism upon thyroid hormone treatment.
• ACTH deficiency
• • Testing for ACTH deficiency is more complex. The key element is not the basal cortisol level present but the response to stress.
  • In the past, the most frequently used test was the IV ACTH stimulation test. For this test, 250 mcg of ACTH 1-24 (Cortrosyn) is administered as an IV bolus with measurements of cortisol at 0, 30, and 60 min. This test has a high specificity. A peak cortisol level below 18 mcg/dL is suggestive of cortisol deficiency either because of ACTH deficiency or because of primary adrenal disease. The test has low sensitivity. Many patients with proven ACTH deficiency by insulin tolerance test have responses over 18 mcg/dL. Because of its ease of performance, it may be a reasonable first test but a result within the reference range should never be accepted as an indication of ACTH sufficiency.
  • A low-dose 1-mcg ACTH stimulation test can be used to increase the specificity of the high-dose test. Results of the 1-mcg test correspond well with results from insulin-induced hypoglycemia. The low dose of ACTH does not stimulate cortisol production in an unprimed adrenal gland. However, care must be taken in diluting the ACTH to obtain the 1 mcg dose.
  • The insulin tolerance test is much more sensitive and equally specific for ACTH deficiency, but it entails significant risks. Draw a baseline cortisol level and administer insulin (0.075-0.1 U/kg IV). Blood is drawn every 15 minutes for 1 hour to measure cortisol and glucose levels. For the test to be adequate, the plasma glucose level should decrease to less than 45 mg/dL. This usually happens at the 15-minute sample. The plasma cortisol level should increase to more than 18 mcg/dL, or at least double, in response to hypoglycemia.
  • Obviously, this test involves significant risk to the patient. Therefore, intravenous access must be assured and trained personnel must be present to immediately treat a serious hypoglycemic reaction with intravenous dextrose if needed. Such treatment does not negate the results of the test, and blood sampling should continue until the completion of the study.
  • The glucagon stimulation test is one last convenient test that may be used. Glucagon, 0.1 mg/kg (maximum 1 mg), is administered IV or IM and blood is drawn every 30 minutes for 3 hours for glucose and cortisol levels. An increase in the plasma cortisol level should occur during the fall in plasma glucose levels over the last 1-2 hours of the test.
  • This test is useful in neonates, in whom the adequacy of venous access is a concern, if dextrose must be administered during insulin-induced hypoglycemia. As in the insulin tolerance test, the cortisol response that occurs in the glucagon stimulation test depends on an increase in the patient's own ACTH secretion and therefore is useful to assess the entire hypothalamic-pituitary-adrenal axis.
  • Recently, single measurement of plasma dehydroepiandrosterone sulfate levels has been shown to be at least a reasonable screening test for ACTH deficiency with good sensitivity and sensitivity when compared to the insulin tolerance test. The disadvantage to this test is that normal levels are age dependent and, thus, it is important that the laboratory has age-matched control normal levels available.
• Gonadotropin deficiency
• • Gonadotropin deficiency is difficult to assess in girls prior to puberty or in boys after age 3-6 months and before puberty.
  • Infant males aged 20-60 days have peak testosterone levels of 60-400 ng/dL. At this age, a level below this range with low LH and FSH levels suggests gonadotropin deficiency.
  • At puberty, testosterone levels and LH levels in boys should increase, but the reference range testosterone level is dependent on pubertal stage. A circadian variation exists, with higher levels during the night. Suspect hypogonadotropism if a boy has not started puberty by age 16 years, starts puberty but does not progress to completion, or has completed puberty but has a testosterone level less than 300 ng/dL with low LH and FSH levels.
  • Girls have minimal estradiol secretion during infancy, thus making the diagnosis of gonadotropin deficiency difficult at this age.
  • Estradiol levels are variable and change throughout the menstrual cycle. Suspect gonadotropin deficiency in girls with no breast development by age 14 years, no periods by age 16 years, or secondary amenorrhea and low LH and FSH levels.
  • Testing with any one of a number of short-acting GnRH analogues may also be helpful. For leuprolide acetate, the dose is 20 mcg/kg, and samples are drawn to measure LH and FSH levels at baseline and at 2, 4, 6, and 24 hours after the leuprolide. For males, baseline and 24-hour testosterone levels may also be helpful.
  • In healthy pubertal children, the LH response exceeds the FSH response. In prepubertal children, the FSH response exceeds the LH response. In patients with complete gonadotropin deficiency, little to no response of either LH or FSH occurs. An intermediate response does not distinguish the prepubertal child with gonadotropin deficiency from the child with simple delayed puberty. Hence, this test is of limited value. An increase in testosterone levels in males after 24 hours suggests an intact hypothalamic-pituitary-gonadal axis.
• Growth hormone deficiency
• • The best method to diagnose a GH deficiency is controversial.
  • In the poorly growing child, low baseline measurements of insulinlike growth factor 1, insulinlike growth factor 2, and insulinlike growth factor–binding protein 3 suggest GH deficiency. GH levels less than 5 ng/dL at the time of spontaneous hypoglycemia also suggest GH deficiency. Beyond this, other stimulatory tests are used.
  • Most physicians perform a combination of 2 tests on children with suspected GH deficiency. Again, the criterion standard is insulin-induced hypoglycemia, as described for cortisol deficiency. Arginine infusion with 0.5 mg/kg over 30 minutes is probably equally efficacious. Beyond these 2 tests, other drugs used are glucagon, clonidine, and propranolol.
  • Probably the biggest controversy is establishing the cutoff point for diagnosis of GH deficiency. Over the past 15 years, a peak level less than 10 ng/dL measured by routine radioimmunoassay was considered diagnostic. Before that, a level of 7 ng/dL was used. Differences in radioimmunoassay techniques may alter reported GH levels. Recent studies question the reliability of any testing. A study of children without deficiencies demonstrates a lower 95% confidence interval of 1.9 ng/mL in sex steroid–primed prepubertal individuals.

Imaging Studies

• Head magnetic resonance imaging
• • Perform this test in all children with panhypopituitarism. Look for either underlying structural abnormalities or tumors that may be the cause of the hypopituitarism.
  • The value of such imaging in children with an isolated pituitary hormonal deficiency is not clear. Undertake imaging in such cases based on the clinical judgment of the physician.
  • Perform imaging in all patients with central diabetes insipidus because diabetes insipidus is frequently associated with an organic mass lesion.
• Left hand and wrist radiography for bone age
• This radiograph must be read by an experienced individual. The result can provide guidance regarding the patient's growth potential and sex hormone exposure.
• Bone ages are frequently delayed in patients with hypopituitarism. The diagnostic sensitivity and specificity are low.

TREATMENT

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Medical Care

• ACTH deficiency
• • Cortisol deficiency requires prompt recognition and treatment. This is particularly true for the child who may be facing surgery or experiencing other significant stresses related to the cause of hypopituitarism.
  • Oral replacement is usually with hydrocortisone, usually administered twice daily but can be administered 3 times daily. Prednisone may be considered advantageous because of twice-daily dosing (at about 20-25% of the dose for hydrocortisone). However, growth suppression is a more common problem with prednisone, which should generally be avoided.
• TSH deficiency
• • The dose of L-thyroxine replacement is age dependent. Monitor free T4 levels and adjust the dose of T4 to maintain reference range levels.
  • Evaluate and treat cortisol deficiency before starting T4 replacement to avoid precipitating an adrenal crisis.
• Gonadotropin deficiency: Begin sex steroid replacement at puberty.
• Growth hormone deficiency: Administer GH replacement in doses of 0.18-0.30 mg/kg/wk in 6-7 subcutaneous doses. Higher doses up to 0.7 mg/kg/wk may be beneficial in puberty.

Surgical Care

• Use surgical treatment for operable pituitary and hypothalamic tumors. If the patient has panhypopituitarism prior to surgery, pituitary function is unlikely to recover.

Consultations

• In all incidents of suspected pituitary dysfunction, a pediatric endocrinologist should be involved in the evaluation and treatment of the child.
• Determine additional consultations based on the cause of the hypopituitarism.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Hormones

These medications are used for replacement of deficient hormones.

Drug Name	Levothyroxine (Levothroid, Levoxyl, Synthroid)
Description	This drug is a hormone replacement used in the TSH-deficient patient. Rapidly inhibits the release of thyroid hormones via a direct effect on the thyroid gland and inhibits the synthesis of thyroid hormones. Iodide also appears to attenuate the cAMP-mediated effects of thyrotropin. In active form, influences growth and maturation of tissues. Involved in normal growth, metabolism, and development. The dose of L-thyroxine replacement is age dependent.
Adult Dose	12.5-50 mcg/d PO; may increase by 25-50 mcg/d q2-4wk, not to exceed 100-200 mcg/d
Pediatric Dose	<6 months: 8-12 mcg/kg/d PO 6-12 months: 6-8 mcg/kg/d PO 1-5 years: 4-6 mcg/kg/d PO 5-10 years: 3-4 mcg/kg/d PO >10 years: 2-3 mcg/kg/d PO
Contraindications	Documented hypersensitivity; uncorrected adrenal insufficiency
Interactions	Cholestyramine and iron may decrease liothyronine absorption (Cytomel); estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; effect of anticoagulants are increased when administered with liothyronine; activity of some beta-blockers may decrease when hypothyroid patient is converted to a euthyroid state; soy-based formulas can significantly reduce thyroid hormone absorption in the intestine
Pregnancy	A - Safe in pregnancy
Precautions	Caution in angina pectoris or cardiovascular disease; monitor thyroid status periodically

Drug Name	Somatropin (Genotropin, Humatrope, Nordotropin, Nutropin, Saizen, TevTropin)
Description	Primary use of GH is as a hormone replacement in short poorly growing children. Stimulates growth of linear bone, skeletal muscle, and organs. Stimulates erythropoietin, which increases red blood cell mass. Currently widely available in subcutaneous injection form. Adjust dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum IGF-1, IGFBP-3, serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry. In children, assess response based on height and growth velocity. Continue treatment until final height or epiphysial closure or both have been recorded. Increasing evidence indicates that GH replacement is also beneficial in deficient adults.
Pediatric Dose	0.18-0.3 mg/kg/wk SC; divide in equal doses to be given 6-7 times/wk
Contraindications	Documented hypersensitivity
Interactions	Decreased response to GH may occur with long-term therapeutic use of corticotropin or with daily PO corticosteroid
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Debate exists about when to start GH replacement in those patients who are deficient because of CNS tumors treated with surgery, radiation, or chemotherapy; although no data suggest that GH increases tumor size or recurrence risk, most pediatric endocrinologists wait until the tumor situation has stabilized for at least 1 y before starting therapy; caution in diabetes; reconstitute with sterile water for injection if administering to newborns

Drug Name	Testosterone (Androderm, AndroGel, Andro-LA, Delatest, Depo-Testosterone)
Description	This is used for induction of puberty in hypopituitary males. In the fully developed male, testosterone patches at 5 mg/d provide the advantage of more even control, although some adolescents are uncomfortable wearing them. Administer low-dose testosterone over 1-2 mo to the prepubertal male with gonadotropin deficiency and microphallus who is embarrassed by the small size or the inability to urinate in a standing position.
Adult Dose	75-150 mg IM q7-10d or 100-200 mg IM q2wk
Pediatric Dose	Starting dose: 25-50 mg IM every am, then increase over the next 2-3 y to typical adult doses of 200 mg q2wk; fully developed adolescents can also use testosterone patches 5 mg qd
Contraindications	Documented hypersensitivity; severe cardiac or renal disease; benign prostatic hypertrophy with obstruction; males with carcinoma of the breast, undiagnosed genital bleeding
Interactions	May increase effects of anticoagulants
Pregnancy	X - Contraindicated in pregnancy
Precautions	Anabolic effects may enhance hypoglycemia; monitor hand and wrist every 6 mo to determine rate of bone maturation

Drug Name	Conjugated estrogens (Premarin)
Description	This drug is used for initiation of puberty in girls with hypogonadotropism. Continue everyday treatment until breakthrough menstrual bleeding occurs and then initiate cyclical therapy. This can be achieved with any of a variety of PO contraceptives or the addition of medroxyprogesterone 5 mg to an estradiol regimen during the third wk of every mo with no treatment the last wk. PO contraceptive treatment is easier for patient to follow. Instead of Premarin, ethinyl estradiol (Estrace) can be used.
Pediatric Dose	Premarin: 0.3 mg PO qod starting dose, increase to 0.3 mg qd; switch patients to cyclic therapy when breakthrough bleeding occurs Estrace: 0.5-1 mg PO qd starting dose, increase to 1 mg PO qd
Contraindications	Documented hypersensitivity; thrombophlebitis; undiagnosed vaginal bleeding
Interactions	Caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease
Pregnancy	X - Contraindicated in pregnancy
Precautions	Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; estrogens may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia

FOLLOW-UP

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Further Outpatient Care

• Patients with hypopituitarism need close, ongoing, and regular follow-up by a pediatric endocrinologist.
• Closely monitor growth and measure free T4 levels on a regular basis to assess the adequacy of T4 replacement.
• Body size and symptoms and signs of cortisol deficiency (eg, anorexia, recurrent abdominal pain, malaise) or cortisol excess (eg, excess weight gain, Cushingoid features, hypertension) determine the adequacy of cortisol replacement.
• Close monitoring of pubertal status is also appropriate.

Complications

• Adrenal crisis, as mentioned, is the most acute complication that can arise in the treatment of patients with hypopituitarism, occurring when glucocorticoid replacement is not administered appropriately or more likely when the child develops a concurrent illness or medical treatment that increases the requirement for glucocorticoid and prevents oral replacement.
• GH therapy is reported to cause some rare adverse effects. These include benign intracranial hypertension and slipped capital femoral epiphyses. Treatment also increases insulin resistance and, therefore, possibly increases the risk of diabetes. Although questions have been raised about malignancy, most data show little or no risk.
• Appropriate monitoring should minimize any risks from thyroid or sex steroid treatment.

Patient Education

• Educate parents about the dangers of adrenal insufficiency when the child is unable to take oral medication. Instruct parents to seek medical care rapidly. Many families can administer IM hydrocortisone at home if the child is unable to take oral medications. The home dose is generally 25 mg in children younger than 2 years, 50 mg in children younger than 5 years, and 100 mg in all other children. If children require IM medication, they should be brought to the emergency department. If the family is unable to administer the IM injection, they can take the parenteral hydrocortisone with them to the emergency department to avoid delays in administering appropriate treatment.
• Parents also need to be taught home stress coverage with doubling the dose of glucocorticoid for less serious illnesses, such as fever greater than 38°C.
• For excellent patient education resources, visit eMedicine's Endocrine System Center and Growth Hormone Deficiency Center. Also, see eMedicine's patient education articles Hypopituitarism in Children, Growth Hormone Deficiency in Children, Growth Failure in Children, and Understanding Growth Hormone Deficiency Medications.

MISCELLANEOUS

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Medical/Legal Pitfalls

• The major error that can be made is the failure to adequately evaluate all parts of anterior pituitary function. Of primary importance in this area is the failure to establish adequacy of cortisol function in a child with secondary hypothyroidism prior to T4 replacement. T4 replacement increases cortisol degradation and leads to adrenal crisis in a child with limited ACTH reserve.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Pathophysiology of panhypopituitarism.
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REFERENCES

Section 11 of 11

• Authors and Editors
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• DeVile CJ, Stanhope R. Hydrocortisone replacement therapy in children and adolescents with hypopituitarism. Clin Endocrinol (Oxf). Jul 1997;47(1):37-41. [Medline].
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• 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].
• 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].
• 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].
• 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].
• 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].
• 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. 1999:271-73.
• 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].
• 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].
• 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].
• 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].
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Article Last Updated: Aug 14, 2006