Comparison of Serum Cortisol Concentrations in Preterm Infants With or Without Late-Onset Circulatory Collapse due to Adrenal Insufficiency of Prematurity

Abstract

A recent survey found that approximately 4% of very low birth weight infants in Japan were treated with glucocorticoids postnatally for circulatory collapse thought to be caused by late-onset adrenal insufficiency. We identified 11 preterm infants with clinical signs compatible with this diagnosis (hypotension, oliguria, hyponatremia, lung edema, and increased demand for oxygen treatment) and matched them for gestational age with 11 infants without such signs. Blood samples were obtained for cortisol and its precursors from the patient group before the administration of hydrocortisone, and from the control group during the same postnatal week. All samples were analyzed using a gas chromatography-mass spectrometry system. Cortisol concentrations did not differ between the two groups (6.6 Ϯ 4.5 vs 3.4 Ϯ 2.7 g/dL); however, the total concentration of precursors in the pathway to cortisol production was significantly higher in the patient group (72.2 Ϯ 50.3 vs 25.0 Ϯ 28.5 g/dL; p Ͻ 0.05). We conclude that the clinical picture of late-onset adrenal insufficiency in preterm infants is not a result of an absolute deficiency of cortisol production, but may be a result of a limited ability to synthesize sufficient cortisol for the degree of clinical stress. A ccording to a recent nationwide survey in Japan, about 4% of very low birth weight (VLBW) infants are treated with postnatal steroids because of adrenal insufficiency of prematurity (AOP). This condition was defined in the survey as postnatal steroid usage during a hospital stay for treatment of late-onset circulatory collapse in premature infants (1). Reports on glucocorticoid-responsive hypotension among VLBW infants in the early postnatal period suggest that the hypothalamus-pituitary-adrenal system does not function sufficiently in the immediate postnatal period (2-7), and, as a result, the serum cortisol level is relatively low during the first week of life (8 -13). However, it has been suggested that this adrenal insufficiency in preterm infants is transient and that adrenal function tends to return to normal by the end of the second week of life (14). Two randomized control trials have demonstrated the benefit of glucocorticoids for preventing and treating refractory hypotension during the first week of life in VLBW infants (15,16). Therefore, glucocorticoid-responsive hypotension was not considered a common phenomenon beyond the first week of life in this population. However, VLBW infants sometimes develop late-onset glucocorticoid-responsive circulatory collapse.The purpose of the current study differs from previous reports on the above pathophysiological etiologies, because we focused specifically on late-onset circulatory instability, which is usually prominent after the first week of life in preterm infants. AOP was defined as postnatal steroid treatment for late-onset (after the first week of life) adrenal insufficiency in premature infants. To elucidate the pathogenesis of this disorder, a comparison of steroid hormone concentrations between ...

Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone

“…Identifying infants with relative adrenal insufficiency is difficult; measuring cortisol levels may be useful, however, studies have shown that low cortisol levels are not helpful in defining a population who would benefit from HC therapy. 10,15,16 In our case, information regarding cortisol levels before treatment was not available. Interestingly, those infants who were not pretreated with prophylactic stress HC but subsequently required HC for pressor-resistant hypotension were not clinically different from others in the non-treated group, indicating the challenge of identifying these infants prospectively.…”

Late-Onset Glucocorticoid-Responsive Circulatory Collapse in Preterm Infants: Clinical Characteristics of 14 Patients

“…The pathophysiological mechanism underlying LCC is thought to be relative adrenal insufficiency, because the circulatory failure responds to glucocorticoid therapy but not to volume loading or vasopressors (Masumoto et al 2008). LCC may result from the suppression of fetal cortisol production until late in the gestational period by interaction between the fetal hypothalamic-pituitary-adrenal axis and the placenta (Mesiano and Jaffe 1997;Kapoor et al 2006).…”

“…The pathophysiological mechanism underlying LCC is thought to be relative adrenal insufficiency (Masumoto et al 2008). Levothyroxine replacement has been implicated as one of the factors that provoke LCC (Takizawa et al 2010;Yagasaki et al 2010;Kawai et al 2012).…”

Improved Outcome of Infants Born at less than 24 Weeks of Gestation in Japan

“…Before cutting umbilical cord, promoting placental-fetal transfusion by cautious cord milking is helpful to maintain adequate blood volume of the infant [12]. Often postnatal steroid administration is essential to stabilize blood pressure to encounter adrenal cortical insufficiency due to extreme prematurity and stress [13]. Use of umbilical venous catheter as an infusion route for the first 5 to 7 days is inevitable to avoid excess handling to keep peripheral lines [9].…”