Skip to main content
  • Meeting abstract
  • Open access
  • Published:

Adrenal insufficiency in the preterm infant

Cortisol production by the human fetal adrenal cortex has been shown to be not adequate at early gestation. This is due to an inefficient expression of 3β-hydroxysteroid dehydrogenase, the enzyme that catalyzes the synthesis of progesterone from pregnenolone, before about 23 weeks of gestation. Whereas, the fetal adrenal cortex it is able to produce dehydroepiandrosterone sulphate for placental estrogen synthesis and to convert placental progesterone to cortisol [1, 2].

During the last trimester of pregnancy the fetal adrenal gland undergoes significant anatomical and functional maturation for adaptation to extra-uterine life and cortisol production increases greatly in the last two months of gestation. Cortisol increases synthesis of surfactant, enhances the reabsorption of lung fluid, promotes the conversion of T4 to T3, favors the closure of the ductus arteriosus and maturation of liver and intestinal enzymes [2].

Adrenal insufficiency can be caused by rare conditions such as adrenocortical hypoplasia or congenital enzymatic deficiencies of steroidogenesis, with clinical variables depending on the hormone involved.

In preterm infants, the developmental immaturity, combined with increased demands in critical illness, may result in insufficient cortisol production to maintain homeostasis in the face of acute stress or illness, despite apparently normal cortisol levels. This condition is known as “transient or relative adrenal insufficiency” (TAI) [3, 4].

TAI usually appears in the first week of life and normalizes in the second week. Infants with TAI can exhibit refractory hypotension (hypotension not responsive to volume expanders and inotropic drugs, but responsive to corticosteroids), respiratory distress, patent ductus arteriosus and bronchopulmonary dysplasia (BPD) [2, 3]. Diagnosis of TAI is not easy because many other conditions can cause hypotension in VLBW infants: hypovolemia, myocardial dysfunction, deficient vascular tone, hyaline membrane disease, infection or a combinations of these factors. In addition, normal basal cortisol levels are extremely variable in preterms and to date there is no consensus on the diagnosis of adrenal insufficiency based on tests with adrenocorticotropic hormone (ACTH) [58]. Appropriate dose and duration of steroid therapy have not been established yet. On the other hand refractory and persistent hypotension is associated with intraventricular hemorrhage, periventricular leukomalacia, increased mortality and neurological disability [9]. Poor adrenal response has been shown to be associated with later development of BPD and with death [10, 11].

For these reasons further studies are needed to evaluate the efficacy and safety of glucocorticoids in the treatment of cardiovascular failure due to TAI in ill preterm and term infants [12, 13].


  1. Watterberg KL: Adrenocortical function and dysfunction in the fetus and neonate. Semin Neonatol. 2004, 9: 13-21. 10.1016/j.siny.2003.08.003.

    Article  PubMed  Google Scholar 

  2. Chung HR: Adrenal and thyroid function in the fetus and preterm infant. Korean J Pediatr. 2014, 57: 425-33. 10.3345/kjp.2014.57.10.425.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Fernandez EF, Watterberg KL: Relative adrenal insufficiency in the preterm and term infant. J Perinatol. 2009, 29 (Suppl 2): S 44-9.

    Article  Google Scholar 

  4. Ng PC, Lee CH, Lam CW, Ma KC, Fok TF, Chan IH, Wong E: Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2004, 89: F 119-26. 10.1136/adc.2002.021972.

    Article  CAS  Google Scholar 

  5. Hochwald O, Holsti L, Osiovich H: The use of an early ACTH test to identify hypoadrenalism-related hypotension in low birth weight infants. J Perinatol. 2012, 32: 412-7. 10.1038/jp.2012.16.

    Article  CAS  PubMed  Google Scholar 

  6. Greaves RF, Zacharin MR, Donath SM, Inder TE, Doyle LW, Hunt RW: Establishment of hormone reference intervals for infants born < 30 weeks'gestation. Clin Biochem. 2014, 47: 101-8. 10.1016/j.clinbiochem.2014.06.002.

    Article  CAS  PubMed  Google Scholar 

  7. Nykänen P, Heinonen K, Riepe FG, Sippell WG, Voutilainen R: Serum concentrations of adrenal steroids and their precursors as a measure of maturity of adrenocortical function in very premature newborns. Horm Res Paediatr. 2010, 74: 358-64. 10.1159/000314970.

    Article  PubMed  Google Scholar 

  8. Fernandez EF, Montman R, Watterberg KL: ACTH and cortisol response to critical illness in term and late preterm newborns. J Perinatol. 2008, 28: 797-802. 10.1038/jp.2008.190.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Dasgupta SJ, Gill AB: Hypotension in the very low birthweight infant: the old, the new, and the uncertain. Arch Dis Child Fetal Neonatal Ed. 2003, 88: F 450-4. 10.1136/fn.88.6.F450.

    Article  CAS  Google Scholar 

  10. Watterberg KL, Gerdes JS, Cook KL: Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatric Res. 2001, 50: 190-5. 10.1203/00006450-200108000-00005.

    Article  CAS  Google Scholar 

  11. Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC, Couser RJ, Garland JS, Rozycki HJ, Leach CL, Backstrom C, Shaffer ML: Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics. 2004, 114: 1649-57. 10.1542/peds.2004-1159.

    Article  PubMed  Google Scholar 

  12. Ng PC, Lee CH, Bnur FL, Chan IH, Lee AW, Wong E, Chan HB, Lam CW, Lee BS, Fok TF: A double-blind, randomized, controlled study of a stress dose of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics. 2006, 117: 367-75. 10.1542/peds.2005-0869.

    Article  PubMed  Google Scholar 

  13. Bonsante F, Latorre G, Iacobelli S, Forziati V, Laforgia N, Esposito L, Mautone A: Early low dose hydrocostisone in very preterm infants: a randomized, placebo-controlled trial. Neonatology. 2007, 91: 217-21. 10.1159/000098168.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Simonetta Picone.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Picone, S., Aufieri, R. & Paolillo, P. Adrenal insufficiency in the preterm infant. Ital J Pediatr 41 (Suppl 1), A30 (2015).

Download citation

  • Published:

  • DOI: