The Endocrine System

Endocrine emergencies in the newborn period are uncommon, but prompt identification and proper treatment are vital to reduce morbidity and mortality.

Pituitary dwarfism (growth hormone deficiency) is not usually apparent at birth, although male infants with panhypopituitarism may have neonatal hypoglycemia, hyperbilirubinemia, and micropenis. Conversely, primordial dwarfism manifests as in utero growth failure that continues postnatally, with length and weight suggestive of prematurity when born after a normal gestational period; otherwise, physical appearance is normal.

Congenital hypothyroidism is one of the most common preventable causes of developmental disability. Congenital screening followed by thyroid hormone replacement treatment started within 30 days after birth can normalize cognitive development in children with congenital hypothyroidism. Congenital hypothyroidism occurs in approximately 1/2,000 infants worldwide (see Chapter 581 ). Because most infants with congenital hypothyroidism are asymptomatic at birth, all states screen for it. Even though screening is standard in many countries, millions of infants born throughout the world are not screened for congenital hypothyroidism. Thyroid deficiency may also be apparent at birth in genetically determined cretinism and infants of mothers with hyperthyroidism during pregnancy treated with antithyroid medications (PTU). Infants with trisomy 21 have a higher incidence of congenital hypothyroidism and should be screened in the newborn period. Constipation, prolonged jaundice, goiter, lethargy, umbilical hernia, macroglossia, hypotonia with delayed reflexes, mottled skin, or cold extremities should suggest severe chronic hypothyroidism. Levothyroxine is the treatment of choice, with the goal of rapid normalization of thyroid-stimulating hormone (TSH, thyrotropin) and free thyroxine (T ₄ ) to achieve the best outcome. Thyroid hormone treatment is aimed to maintain total thyroxine or free thyroxine in the upper half of the normal range during the 1st 3 yr after birth. Early diagnosis and treatment of congenital thyroid hormone deficiency improve intellectual outcome and are facilitated by screening of all newborn infants for this deficiency. Newborn screening, with early referral to a pediatric endocrinologist for abnormal results, has improved early diagnosis and treatment of congenital hypothyroidism and improved intellectual outcome.

Transient hypothyroxinemia of prematurity is most common in ill and very premature infants. These infants have low thyroxine levels but normal levels of serum thyrotropin and other tests of the pituitary-hypothalamic axis indicating that they are probably chemically euthyroid. Trials of thyroid hormone replacement have reported no difference in developmental outcomes or other morbidities. Current practice is to follow thyroxine until levels normalize. Transient hyperthyroidism may occur at birth in infants of mothers with established or cured hyperthyroidism (e.g., Graves disease with positive TSH receptor–stimulating antibodies). See Chapter 584 for details on diagnosis and treatment.

Transient hypoparathyroidism may manifest as tetany or seizure of the newborn due to hypocalcemia and is associated with low levels of parathyroid hormone and hyperphosphatemia. Testing for DiGeorge syndrome should be considered. (see Chapter 589 ).

Subcutaneous fat necrosis can cause hypercalcemia and can occur after a traumatic birth. On examination, firm purple nodules can be appreciated on the trunk or extremities. An infant with hypercalcemia presents with irritability, vomiting, increased tone, poor weight gain, and constipation. Other causes of hypercalcemia in the newborn period are iatrogenic (excess calcium or vitamin D), maternal hypoparathyroidism, Williams syndrome, parathyroid hyperplasia, and idiopathic.

The adrenal glands are subject to numerous disturbances, which may become apparent and require lifesaving treatment during the neonatal period. Acute adrenal hemorrhage and adrenal failure are uncommon in the neonatal period. Risk factors include vaginal delivery, macrosomia, and fetal acidemia. The clinical presentation is often mild, with spontaneous regression. In neonates with bilateral adrenal hemorrhage, an evaluation of cortisol production is required (high-dose ACTH stimulation test), and, if insufficient, treatment with glucocorticoids and mineralocorticoids is indicated. Differentiation of unilateral adrenal hemorrhage from neuroblastoma is important. All patients should have sonographic and clinical follow-up to ensure resolution.

Congenital adrenal hyperplasia (CAH) is suggested by vomiting, diarrhea, dehydration, hyperkalemia, hyponatremia, shock, ambiguous genitalia, or clitoral enlargement. Some infants have ambiguous genitalia and hypertension. In an infant with ambiguous genitalia, both pelvic and adrenal ultrasound can be performed to aid in diagnosis. An adrenal ultrasound showing bilateral, enlarged, coiled or cerebriform pattern is specific for CAH. Diagnosis is confirmed with an elevated 17-hydroxyprogesterone level for gestational age. Because the condition is genetically determined, newborn siblings of patients with the salt-losing variety of adrenocortical hyperplasia should be closely observed for manifestations of adrenal insufficiency. Newborn screening and early diagnosis and therapy for this disorder may prevent severe salt wasting and adverse outcomes. Congenitally hypoplastic adrenal glands may also give rise to adrenal insufficiency during the 1st few wk of life ( DAX1 mutation).

Disorders of sexual development can present in the newborn period with ambiguous or atypical genitalia, including bilateral cryptorchidism, hypospadias, micropenis, hypoplastic scrotum, or clitoromegaly. More than 20 genes have been associated with disorders of sexual development. The initial management should involve a multidisciplinary team (endocrinology, urology, genetics, and neonatology) and open communication with the family. Sex assignment and naming of the infant should be delayed until appropriate testing is completed. For more about disorders of sexual development, see Chapter 606 .

Female infants with webbing of the neck, lymphedema, hypoplasia of the nipples, cutis laxa, low hairline at the nape of the neck, low-set ears, high-arched palate, deformities of the nails, cubitus valgus, and other anomalies should be suspected of having Turner syndrome . Lymphedema of the hands or lower extremities can sometimes be the only indication. A karyotype can confirm diagnosis (see Chapter 604.1 ).

Transient neonatal diabetes mellitus (TNDM) is rare and typically presents on day 1 of life (see Chapter 607 ). It usually manifests as polyuria, dehydration, loss of weight, or acidosis in infants who are small for gestational age. The most common cause (70%) is a disruption of the imprinted locus at chromosome 6q24. A select group of patients with TNDM are at risk for recurrence of diabetes later in life.