Defective Cortisol Secretion in Response to Spontaneous Hypoglycemia but Normal Cortisol Response to ACTH stimulation in neonates with Hyperinsulinemic Hypoglycemia (HH). Cortisol secretion in neonates with hyperinsulinemic hypoglycemia

Main Article Content

Shayma Ahmed
Ashraf Soliman
Vincenzo De Sanctis
Fawzia Alyafie
Nada Alaaraj
Noor Hamed
Hamdy A Ali
Abdulla Kamal

Keywords

Key words: Cortisol, Adrenocorticotrophic hormone, neonatal hyperinsulinemia, hypoglycemia, growth hormone, ACTH test.

Abstract

Abstract. Introduction: Hyperinsulinemic Hypoglycaemia (HH) is the most common cause of recurrent and persistent hypoglycemia in the neonatal period. Cortisol and GH play an important role as a counterregulatory hormone during hypoglycemia. Both antagonize the peripheral effects of insulin and directly influences glucose metabolism Patients and Methods: We studied cortisol and GH secretion in newborn infants with HH during spontaneous hypoglycemia. In addition, their basal ACTH level and cortisol response to a standard dose ACTH was performed. Results: Nine newborns with HH were studied during the first 2 weeks of life. During HH, their mean glucose concentration was 1.42 ± 0.7 mmol/L, mean beta hydroxybutyrate level was 0.08 ± 0.04 mmol/L, and mean serum insulin level was 17.78 ± 9.7 µU/mL. Their cortisol and GH levels at the time of spontaneous hypoglycemia were 94.7 ± 83.1 nmol/L and 82.4 ± 29


m IU/L respectively. They had relatively low level of ACTH (range: 14 :72 pg/ml, mean: 39.4 ± 20 pg/mL) during hypoglycemia. All infants had GH concentration > 20 mIU/L at the time of hypoglycemia. All infants underwent ACTH test. Their basal serum cortisol levels did not differ compared to cortisol levels during hypoglycemia, and all had a normal peak cortisol response (> 500 nmol/L) in response to i.v. ACTH stimulation test. Conclusion: Infants with HH have low cortisol response to spontaneous hypoglycemia with normal response to exogenous standard-dose ACTH. Checking hypothalamic-pituitary axis (HPA) axis later in infancy using low dose ACTH may be useful to diagnose persistent HPA abnormalities in these infants. All HH infants had appropriate elevation of GH during hypoglycemia.

Downloads

Download data is not yet available.
Abstract 11 | PDF Downloads 7

References

1. Nold JL,Georgieff MK. Infants of diabetic mothers. Pediatr Clin North Am. 2004;51,619-637.

2. Stanley CA, Baker L. The causes of neonatal hypoglycemia. N Engl J Med. 1999;340:1200–1201.

3. Artavia-Loria E, Chaussain JL, Bougneres PF, et al. Frequency of hypoglycemia in children with adrenal insufficiency. Acta Endocrinol Suppl (Copenh). 1986;279:275–278.

4 . LaFranchi S. Hypoglycemia of infancy and childhood. Pediatr Clin North Am. 1987;34:961–982.

5. Barnes-Powell LL. Infants of diabetic mothers: the effects of hyperglycemia on the fetus and neonate. Neonatal Netw. 2007; 26:283-290.
6. Ward Platt M, Deshpande S. Metabolic adaptation at birth. Semin Fetal Neonatal Med. 2005;10:341-350
7. Hussain K, Hindmarsh P, Aynsley-Green A. Neonates with symptomatic hyperinsulinemic hypoglycemia generate inappropriately low serum cortisol counterregulatory hormonal responses. J Clin Endocrinol Metab. 2003;88:4342-4347.

8. Hussain K, Bryan J, Christesen HT, Brusgaard K, Aguilar-Bryan L. Serum glucagon counterregulatory hormonal response to hypoglycemia is blunted in congenital hyperinsulinism. Diabetes. 2005;54:2946-2951.

9. Mitrakou A, Ryan C, Veneman T, et al . Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol. 1991;260:E67–E74.

10. Kenny FM, Preeyasombat C, Spaulding JS, Migeon CJ. Cortisol production rate. IV. Infants born of steroid-treated mothers and of diabetic mothers. Infants with trisomy syndrome and with anencephaly. Pediatrics. 1966;37:960-966.

11. Senniappan S, Hussain K. An Evaluation of Growth Hormone and IGF-1 Responses in Neonates with Hyperinsulinaemic Hypoglycaemia. Int J Endocrinol. 2013; 2013: 638257 doi: 10.1155/2013/638257.
12. Soliman AT, Eldabbagh M, Saleem W, Zahredin K, Shatla E, Adel A. Placental weight: relation to maternal weight and growth parameters of full-term babies at birth and during childhood. J Trop Pediatr. 2013;59:358-364.
13. Hussain K, Aynsley-Green. Management of hyperinsulinism in infancy and childhood . Ann Med. 2000; 32:544–551.



14. Stevens JF.Plasma cortisol levels in the neonatal period. Arch Dis Child.1970;45: 592–592

15. Weiner DJ, Smith J, Dahlan S, Berg G, Moshang T 1987 Serum adrenal steroid levels in healthy full-term 3 day old infants. J Pediat.1987; 110:122–124.

16. De Feo P, Perriello G, Torlone E, et al. Contribution of cortisol to glucose counterregulation in humans. Am J Physiol. 1989;257:E35-E42

17. Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 1987; 79: 777-781.
18. Plagemann A, Harder T, Rake A, et al. Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome x-like alterations in adulthood of neonatally overfed rats. Brain Res.1999; 836:146–155.

19. Mitanchez D, Yzydorczyk C, Siddeek B, Boubred F, Benahmed M, Simeoni U. The offspring of the diabetic mother--short- and long-term implications. Best Pract Res Clin Obstet Gynaecol. 2015;29:256-269.

20. Howland MA, Sandman CA, Glynn LM. Developmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab. 2017;12:321-339.

21. Tollenaar MS, Beijers R, Jansen J, Riksen-Walraven JM, de Weerth C. et al. Maternal prenatal stress and cortisol reactivity to stressors in human infants. Stress. 2011;14:53–65.

22. Durga KD, Adhisivam B, Vidya G, Vishnu Bhat B, Bobby Z, Chand P. Oxidative stress and DNA damage in newborns born to mothers with hyperglycemia - a prospective cohort study. J Matern Fetal Neonatal Med. 2018;31:2396-2401.

23. Evans ML, McCrimmon RJ, Flanagan DE, et al. Hypothalamic ATP-sensitive K + channels play a key role in sensing hypoglycemia and triggering counterregulatory epinephrine and glucagon responses. Diabetes. 2004;53:2542-2551.

24. Nye EJ, Grice JE, Hockings GI, Strakosch CR, Crosbie GV, Walters MM, Jackson RV. Comparison of adrenocorticotropin (ACTH) stimulation tests and insulin hypoglycemia in normal humans: low dose, standard high dose, and 8-hour ACTH-(1-24) infusion tests. J Clin Endocrinol Metab. 1999;84:3648-3655.

25. Crofton PM, Midgley PC. Cortisol and growth hormone responses to spontaneous hypoglycaemia in infants and children. Arch Dis Child. 2004;89:472-478.
26.Van Dam JM, Garrett AJ, Schneider LA, et al. Reduced Cortical Excitability, Neuroplasticity, and Salivary Cortisol in 11-13-Year-Old Children Born to Women with Gestational Diabetes Mellitus. EBioMedicine. 2018; 31:143-149.

27.Van Dam JM, Goldsworthy MR, HagueWM, et al . Lower Morning Cortisol Secretion in Adolescents Born to Women with Gestational Diabetes Mellitus. Lancet. 2020 (pre-print) https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3516135

28. Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, Kelestimur F. A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol (Oxf). 2015;82:45-52.
29. Crofton PM, Midgley PC. Cortisol and growth hormone responses to spontaneous hypoglycaemia in infants and children. Arch Dis Child. 2004;89:472-478.

30. Kelly A, Tang R, Becker S, Stanley CA. Poor specificity of low growth hormone and cortisol levels during fasting hypoglycemia for the diagnoses of growth hormone deficiency and adrenal insufficiency. Pediatrics. 2008;122: e522-528.

31. Sweet CB, Grayson S, Polak M. Management strategies for neonatal hypoglycemia. J Pediatr Pharmacol Ther. 2013;18:199-208.
32. Jane E. McGowan. Neonatal Hypoglycemia. Pediatr Rev. 1999;20: e6-e15.
33. Mehta A. Prevention and management of neonatal hypoglcaemia. Arch Dis Child. 1994;70:F54–F65.
34.Sweet CB, Grayson S, Polak M. Management strategies for neonatal hypoglycemia. J Pediatr Pharmacol Ther. 2013; 18:199-208.
35. Watterburg KL, Gerdes JS, Cole CH. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics. 2004;114:1649–1657.

36. American Academy of Pediatrics, Committee on Fetus and Newborn and Canadian Paediatric Society, Fetus and Newborn Committee. Post-natal corticosteroids to treat or prevent chronic lung disease in pre-term infants. Pediatrics. 2002;109:330–338.

Most read articles by the same author(s)

1 2 3 4 5 6 7 > >>