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I. Endocrinopathies of the high-risk infant

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  1. Endocrine adaptation to extrauterine life

    The endocrine system plays a vital role in fetal development and the transition from intrauterine to extrauterine life. The endocrine pathways are not static, but rather complex and constantly adapting to regulation by hormones, nutrients, cytokines, and growth factors.

    1. Growth hormone (GH), prolactin, and the insulin-like growth factors (IGFs)

      1. Random GH levels in the fetus are high (~30 to 35 ng/mL) at midgestation. Values decline toward term but generally exceed 10 ng/mL within the first week of life (Figure 20-1). Thus random GH levels are useful for the diagnosis of GH deficiency before a week of age.

      2. The decline of GH is associated with a rise in serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF BP-3) levels, reflecting an increase in hepatic sensitivity to GH. Nevertheless, IGF-1 levels are low in the first year of life, making them unreliable for assessment of GH production or action. IGF BP-3 levels are more useful for diagnosis of GH deficiency in early life. Still, both IGF BP-3 and in particular IGF-I are modulated by nutritional status and systemic health. Consequently, the levels of IGF-1 and (to a lesser degree) IGF BP-3 are often low in malnourished, ill infants even if their ability to produce GH is normal.

      3. Prolactin levels can be as high as 400 ng/mL within the first few weeks of life in normal infants. Levels are higher in patients with hypothalamic disease and lower in infants with primary pituitary disease or those treated with dopamine.

    2. Thyroid function

      1. In the fetus, T4 and TSH levels rise progressively after midgestation; T3 levels increase later after 30 weeks (Figure 20-2).

      2. In full-term infants, the rapid shift in ambient temperature (from 37°C to 23°C) stimulates a striking rise in TSH, which peaks at ~70 μU/mL within 45 to 60 minutes after birth. This is followed by increases in both T4 and T3, which attain levels (T4, 13 to 22 μg/dL; T3, 250 to 400 ng/dL) seen in hyperthyroidism in older children and adults. T4 and T3 decline progressively after the first week of life but remain slightly higher than those in older children throughout the first 6 to 8 months. TSH levels decline after the first week but can be as high as 7.5 μU/mL before 6 months of age.

      3. In preterm infants, the basal T4, T3, and TSH levels are low; this reflects immaturity of the hypothalamic-pituitary-thyroid axis. Differentiation of this hypothyroxinemia of prematurity from central hypothyroidism or the sick euthyroid syndrome can be difficult.

      4. Findings that suggest true central (hypopituitary) hypothyroidism include midfacial hypoplasia, midline cleft lip or palate, nystagmus (seen with optic nerve hypoplasia), midline defects in CNS development such as holoprosencephaly, third ventricular hemorrhage, microphallus, and abnormalities in the levels of other pituitary hormones (eg, low GH, cortisol, ...

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