Panhypopituitarism Clinical Presentation

Updated: Apr 29, 2018
  • Author: Robert P Hoffman, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Presentation

History

Congenital hypopituitarism

Suspect hypopituitarism in children with midline defects or optic atrophy (suggestive of septo-optic dysplasia) [6, 7] and in boys with micropenis (suggestive of gonadotropin deficiency). [8, 9]

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. [10]

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.

Pituitary function should be routinely evaluated 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 may 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. [10]

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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.

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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. [7] Three fourths of individuals with optic nerve hypoplasia have hormonal abnormalities. [11]

Mutations in various genes (HESX1, LHX3, LHX4, PROP1, POU1F1 [formerly known as PIT1])have been demonstrated to cause congenital pituitary abnormalities, with varying combinations of one or more hormonal abnormalities occurring with or without anatomic abnormalities. These homeobox genes code various pituitary transcription factors responsible for pituitary development. [12, 13, 14, 15]

Neonatal hypopituitarism, although not truly congenital, may also result from severe asphyxia either at birth or shortly thereafter.

Acquired hypopituitarism

Acquired hypopituitarism frequently occurs as a result of hypothalamic or pituitary tumors and their surgical or radiologic treatment. Craniopharyngiomas, pituitary dysgerminomas, and optic gliomas are particularly common causes of hypopituitarism. [16]  Indeed, a retrospective study by Wijnen et al indicated that compared with adult-onset craniopharyngioma, the childhood-onset form of the disease is more often associated with panhypopituitarism, as well as GH deficiency, diabetes insipidus, morbid obesity, epilepsy, and psychiatric disorders. [17]

Other causes of hypopituitarism include trauma and autoimmune lymphocytic hypophysitis. [18, 19, 20, 21] Hormonal abnormalities are noted in 25% of adults with traumatic brain injury. [22]

In a study of hypopituitarism in 14 children who had survived moderate to severe inflicted traumatic brain injury (iTBI), Auble et al determined that 86% had endocrine dysfunction, with 50% having at least two abnormalities. The most common abnormality was elevated prolactin (64%), with patients also showing abnormal thyroid function (33%), short stature (29%), and reduced growth hormone peak (17%). [23]

A study by Lin et al found that among other complications and comorbidities, transfrontal surgery for pediatric craniopharyngioma leads to a slightly higher frequency of panhypopituitarism than does the transsphenoidal technique (8% vs 5%, respectively). However, a greater incidence of cerebrospinal fluid leak was associated with the transsphenoidal operation. [24]

A study by van Iersel et al indicated that in patients with craniopharyngioma, panhypopituitarism occurs less frequently with partial resection than with gross total resection. [25]

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