Neuroendocrine, Autonomic and Metabolic Challenges in Hypermobile Ehlers-Danlos Syndrome: A Case Study on Hypoglycemia in a patient with Craniocervical Instability.
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Abstract
This report presents a compelling case of hypoglycemia in a 20-year-old female with craniocervical instability receiving chronic total parenteral nutrition (TPN). Noteworthy is her intricate history, including Chiari malformation, Hypermobile Ehlers-Danlos syndrome, and tethered cord, complicating the clinical picture.
Following a complex spinal surgery, the patient received postoperative dexmedetomidine for pain relief. Subsequent hypoglycemic episodes prompted meticulous investigations and endocrinology consultations. Discrepancies in TPN infusion rates, nephrology perspective on glycogen depletion due to chronic TPN, and the patient's unique medical history added layers of complexity to the clinical landscape.
Our exploration delves into the multifactorial nature of hypoglycemia in this patient. Chronic TPN alters glucose dynamics, impacting glycogen stores, while dexmedetomidine, known for α2-adrenoceptor activation induced sympatholysis, may contribute to hypoglycemia. Dysfunction of hypothalamic-pituitary axis in patients with craniocervical instability necessitated enhanced scrutiny for the detection of potential central etiologies of hypoglycemia.
Our findings underscore the importance of a multidisciplinary approach, integrating pharmacological insights, nutritional considerations, and the patient's unique medical history, to provide a comprehensive understanding of adverse events in complex clinical scenarios. The dynamic nature of glycemic control in this context warrants careful consideration in clinical decision-making.
Glossary of Items: Total parenteral nutrition (TPN), dextrose 50% in water (D50), dextrose 20% in water (D20), dextrose 10% in water (D10), Adrenocorticotropic Hormone (ACTH), Cytochrome P450 (CYP).
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References
2. Lohkamp LN, Marathe N, Fehlings MG. Craniocervical Instability in Ehlers-Danlos Syndrome-A Systematic Review of Diagnostic and Surgical Treatment Criteria. Global Spine J. Oct 2022;12(8):1862-1871. doi:10.1177/21 925682211068520
3. Mao G, Kopparapu S, Jin Y, et al. Craniocervical instability in patients with Ehlers-Danlos syndrome: controversies in diagnosis and management. Spine J. Dec 2022;22(12):1944-1952. doi:10.1016/j.spinee.2022.08.008
4. Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue. Journal of Neurosurgery: Spine SPI. 01 Dec. 2007 2007;7(6):601-609. doi:https://doi.org/10.3171/SPI-07/12/601
5. Henderson FC, Sr., Schubart JR, Narayanan MV, et al. Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion. Neurosurg Rev. Jan 2 2024;47(1):27. doi:10.1007/s10143-023-02249-0
6. Henderson FC, Sr., Francomano CA, Koby M, Tuchman K, Adcock J, Patel S. Cervical medullary syndrome secondary to craniocervical instability and ventral brainstem compression in hereditary hypermobility connective tissue disorders: 5-year follow-up after craniocervical reduction, fusion, and stabilization. Neurosurg Rev. Dec 2019;42(4): 915-936. doi:10.1007/s10143-018-01070-4
7. Sayed MA, Rizvi SW, Khan A, et al. Abstract #1002305: A Rare Coexistence of Secondary Hypothyroidism, Stargardt Disease, and Ehlers-Danlos Syndrome (EDS). Endocrine Practice. 2021;27(6):S157-S158. doi:10.1016/ j.eprac.2021.04.801
8. Kurian M, Solomon GD. Can elevated IGF-1 levels among patients with Ehlers-Danlos syndrome cause idiopathic intracranial hypertension? Headache. Nov-Dec 2013;53(1 0):1666-9. doi:10.1111/head.12242
9. Lewitus Z. Ehlers-Danlos syndrome; report of two cases with hypophyseal dysfunction. AMA Arch Derm. Feb 1956;73(2):158-61. doi:10.1001/archderm.1956.01550020058008
10. Henderson FC, Rowe PC, Narayanan M, et al. Refractory Syncope and Presyncope Associated with Atlantoaxial Instability: Preliminary Evidence of Improvement Following Surgical Stabilization. World Neurosurgery. 2021/05/01/ 2021;149:e854-e865. doi:https://doi.org/10.1016/j.wneu.2021.01.084
11. Mathias CJ, Owens A, Iodice V, Hakim A. Dysautonomia in the Ehlers-Danlos syndromes and hypermobility spectrum disorders-With a focus on the postural tachycardia syndrome. Am J Med Genet C Semin Med Genet. Dec 2021;187(4):510-519. doi:10.1002/ajmg.c.31951
12. Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C. Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology. Apr 2003;144(4):13 57-67. doi:10.1210/en.2002-221076
13. Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. Jun 2009;10(6): 397-409. doi:10.1038/nrn2647
14. Herman JP, Figueiredo H, Mueller NK, et al. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol. Jul 2003;24(3):151-80. doi: 10.1016/j.yfrne.2003.07.001
15. Chen SS, Torres-Sanchez CJ, Hosein N, Zhang Y, Lacy DB, McGuinness OP. Time course of the hepatic adaptation to TPN: interaction with glycogen depletion. Am J Physiol Endocrinol Metab. Jan 2005;288(1):E1 63-70. doi:10.1152/ajpendo.00192.2004
16. Beltrand J, Colomb V, Marinier E, et al. Lower insulin secretory response to glucose induced by artificial nutrition in children: prolonged and total parenteral nutrition. Pediatr Res. Nov 2007;62(5):624-9. doi:10.120 3/PDR.0b013e3181559d5c
17. Benzo CA. The hypothalamus and blood glucose regulation. Life Sciences. 1983/05/30 / 1983;32(22):2509-2515. doi:https://doi.org/10.1016/0024-3205(83)90231-X
18. Pozo M, Claret M. Hypothalamic Control of Systemic Glucose Homeostasis: The Pancreas Connection. Trends in Endocrinology & Metabolism. 2018/08/01/ 2018;29(8):581-594. doi:https://doi.org/10.1016/j.tem.2018.05.001
19. Denko CW, Boja B. Growth hormone, insulin, and insulin-like growth factor-1 in hypermobility syndrome. J Rheumatol. Jul 2001;28(7):1666-9.
20. Kim SH, Park MJ. Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab. Sep 2017;22(3):145-152. doi:10.6065/ apem.2017.22.3.145
21. Kopchick JJ, Berryman DE, Puri V, Lee KY, Jorgensen JOL. The effects of growth hormone on adipose tissue: old observations, new mechanisms. Nature Reviews Endocrinology. 2020/03/01 2020;16(3):135-146. doi:10.1038/s41574-019-0280-9
22. Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. Apr 2009;30(2):152-77. doi:10.12 10/er.2008-0027
23. Kuo T, McQueen A, Chen TC, Wang JC. Regulation of Glucose Homeostasis by Glucocorticoids. Adv Exp Med Biol. 2015;872: 99-126. doi:10.1007/978-1-4939-2895-8_5
24. Thau L, Gandhi J, Sharma S. Physiology, Cortisol. StatPearls. StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC.; 2024.
25. Hwang W, Lee J, Park J, Joo J. Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled study. BMC Anesthesiol. 2015;15:21. doi:10.1186/s12871 -015-0004-1
26. Naik BI, Nemergut EC, Kazemi A, et al. The Effect of Dexmedetomidine on Postoperative Opioid Consumption and Pain After Major Spine Surgery. Anesth Analg. May 2016;122(5):1646-53. doi:10.1213/ane.0000000000001226
27. Tsaousi GG, Pourzitaki C, Aloisio S, Bilotta F. Dexmedetomidine as a sedative and analgesic adjuvant in spine surgery: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. Nov 2018;74(11):1377-1389. doi:10.1007/s00228-018-2520-7
28. Angel I, Bidet S, Langer SZ. Pharmacological characterization of the hyperglycemia induced by alpha-2 adrenoceptor agonists. J Pharmacol Exp Ther. Sep 1988;246(3):1098-103.
29. Metz SA, Halter JB, Robertson RP. Induction of defective insulin secretion and impaired glucose tolerance by clonidine. Selective stimulation of metabolic alpha-adrenergic pathways. Diabetes. May 1978;27( 5):554-62. doi:10.2337/diab.27.5.554
30. Giovannitti JA, Jr., Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. Spring 2015;62(1):31-9. doi:10.2344/00 03-3006-62.1.31
31. Fagerholm V, Haaparanta M, Scheinin M. α2-adrenoceptor regulation of blood glucose homeostasis. Basic Clin Pharmacol Toxicol. Jun 2011;108(6):365-70. doi:10.1111/j.1742-7843.2011.00699.x
32. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. Aug 1981;30(2):239-45. doi:10.1038/clpt.1981.154
33. Weerink MAS, Struys M, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. Aug 2017;56(8):893-913. doi:10.1007/s40262-017-0507-7