Pediatric Hypopituitarism Clinical Presentation

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

Neonates

Most neonates with hypopituitarism have normal or even high birth weights and lengths and no history of intrauterine growth retardation. However, they often have histories of breech presentation (particularly neonates with MPHD), although the explanation for this is unclear. Microgenitalia, mainly in males, may result from a gonadotropin deficiency or from GH deficiency.

The hypoglycemia risk is higher in neonates with hypopituitarism, with various manifesting symptoms, such as lethargy, jitteriness, pallor, cyanosis, apnea, or convulsions. Jaundice may be secondary to indirect hyperbilirubinemia (as occurs in TSH axis deficiency) or to direct hyperbilirubinemia (as occurs in GH or 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.

Electrolyte disturbances can also occur in neonates with hypopituitarism. Hyponatremia unassociated with hypovolemia and unresponsive to fluid restriction can develop. 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.^[18] Hypernatremia secondary to excess free-water loss associated with uncontrolled diabetes insipidus may also occur.

Depending on the etiology of the hypopituitarism, associated findings in the neonate, infant, or child may include developmental delay, various visual and neurologic symptoms, seizure disorder, and a number of congenital malformation syndromes.

Older infants and children

Common presenting features include growth failure, disorders of pubertal development, and diabetes insipidus. Growth failure may be the most common presenting symptom in this age group, possibly with an associated delay in tooth development. Hypoglycemia, although less frequent, can also be a presenting sign of hypopituitarism in older infants and children. 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 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, seizure disorder, and a number of congenital malformation syndromes. Optic nerve hypoplasia has been associated with a spectrum of endocrine abnormalities, from isolated GHD to MPHD. Patients with acquired hypopituitarism, caused by a suprasellar tumor, often present with headaches, visual disturbances, and other neurologic symptoms.

Anencephaly is associated with variable pituitary hypoplasia and complete absence of the hypothalamus. Various forms of holoprosencephaly particular associated with HESX1 mutations may be associated with hypopituitarism.

Neonates

Birth weights and lengths are typically within the reference range in neonates with hypopituitarism. 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).^[19]

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.^[20] Cryptorchidism is often associated with micropenis.

Optic nerve hypoplasia is associated with hypopituitarism; the presence of small, pale optic disks or nystagmus should prompt consideration of hypopituitarism.^{[21, 22]}

Older infants and children

Growth failure (see the image below) 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).

During the physical examination, pay particular attention to pubertal development, because patients with hypopituitarism may present with microgenitalia in infancy or with delayed or absent puberty. Anosmia, particularly in a patient with delayed or absent puberty, should prompt consideration of Kallmann syndrome (KS).

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 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.

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.