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SCOPE

DISEASE/CONDITION(S)

Insufficiency of the adrenal cortex in the neonate.

GUIDELINE OBJECTIVE(S)

Identification, management, and monitoring of adrenocortical insufficiency in the neonate.

BRIEF BACKGROUND

Normal Physiology: The Hypothalamic−Pituitary−Adrenal Axis

The cortex of the adrenal gland produces the hormone cortisol, which helps maintain blood pressure, electrolyte balance, and vascular permeability and helps mature the lungs, cardiovascular system, GI tract, and several metabolic pathways. It also facilitates renal free-water excretion, modulates central nervous system processing and behavior, and most importantly, during periods of stress, suppresses the body’s inflammatory responses. Cortisol production is regulated by adrenocorticotrophin (ACTH) produced by the anterior pituitary, which is in turn regulated by corticotrophin-releasing hormone (CRH) secreted from the hypothalamus. Activation of this hypothalamic–pituitary–adrenal (HPA) axis and release of cortisol are critical in mounting a response to stress. Factors influencing the release of CRH and ACTH include neurological inputs from the normal diurnal rhythm, and acute physiological stressors, as well as negative feedback from circulating cortisol.

Fetal and Postnatal Physiology

The adrenal gland develops from the mesoderm and undergoes a remarkable transformation during fetal life to mature into a functioning gland to sustain extrauterine survival. The fetal adrenal cortex consists of a fetal zone (80%) and smaller definitive and transitional zones (20%). The fetal zone gradually involutes and gets replaced by the definitive and transitional zones near term and shortly after birth. The fetal zone expresses high levels of sulfotransferases and very low levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) which leads to production of inactive glucocorticoids and low levels of cortisol exposure to the growing fetus while at the same time providing substrate to placenta for estrogen production. During fetal life, maternal cortisol, while crossing the placenta, is converted to its inactive form cortisone by the enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Maternal stress leading to production of high levels of cortisol can escape inactivation by 11β-HSD2 and lead to fetal growth restriction and inhibition of fetal HPA axis. Human fetal cortisol levels tend to be as low as <5 µg/dL until about near-term gestation (Figure 48.1). Extremely preterm infants born during this phase of adrenal development are therefore likely to suffer from RAI and unable to mount a stress response.

FIGURE 48.1

Maternal–placental–fetal steroid interactions.

As gestation progresses to near term, there is an increase in cortisol production by the fetal adrenal gland mediated by maternal stress of labor and increasing activity of the adrenal 3β-HSD leading to maturation of fetal organs like the lungs, cardiovascular system, and liver enzymes. Caesarean section without labor is associated with lack of the “cortisol surge” leading to higher incidence of respiratory distress and delayed lung fluid clearance in these infants. Infants born at extremely low birth weight are more likely to suffer from ...

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