Treatment of Endocrine Disorders in the Neuroscience Intensive Care Unit

Part of the following topical collections:
  1. Topical Collection on Critical Care Neurology

Opinion statement

This review discusses concepts and treatments associated with the most clinically relevant areas of acute endocrine dysfunction amongst patients with common diseases in neuroscience intensive care units (Neuro ICUs). We highlight the following points:

• While a thorough work-up for hyponatremia when it is present is always warranted, subarachnoid hemorrhage (SAH) patients who are in a time window concerning for cerebral vasospasm and who are hyponatremic with high urine output are generally thought to have cerebral salt wasting. These patients are typically treated with a combination of continuous hypertonic saline infusion and fludrocortisone.

• Diabetes insipidus (DI) is often seen in patients fulfilling death by neurological criteria, as well as in patients with recent pituitary surgery and less often in SAH and traumatic brain injury patients who are not brain dead. Patients with DI in the Neuro ICU often cannot drink to thirst and may require a combination of desmopression/vasopressin administration, aggressive fluid repletion, and serum sodium monitoring.

• Diagnosing adrenal insufficiency immediately following pituitary injury is complicated by the fact that the expected atrophy of the adrenal glands, due to lack of a stimulus from pituitary adrenocorticotropic hormone, may take up to 6 weeks to develop. Cosyntropin testing can be falsely normal during this period.

• Both hyperglycemia (glucose >200 mg/dL) and hypoglycemia (glucose <50 mg/dL) are strongly associated with neurological morbidity and mortality in ICUs and should be avoided. Glucose concentrations between 120–160 mg/dL can serve as a reasonable target for insulin infusion protocols.

• There is no data to suggest that treatment of abnormal thyroid function tests in nonthyroidal illness syndrome/sick euthyroid leads to benefits in either mortality or morbidity. True myxedema coma is a rare clinical diagnosis that is treated with intravenous levothyroxine accompanied by stress-dose steroids.


Endocrine system Intensive care units Subarachnoid hemorrhage Traumatic brain injury Stroke Pituitary apoplexy Brain death Hyperglycemia Hypoglycemia Diabetes insipidus Hyponatremia Inappropriate ADH syndrome Adrenal insufficiency Thyroid Myxedema coma 

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356:2064–72.PubMedCrossRefGoogle Scholar
  2. 2.••
    Kirkman MA, Albert AF, Ibrahim A, Doberenz D. Hyponatremia and brain injury: historical and contemporary perspectives. Neurocrit Care. 2013;18:406–16. This article is a thorough review of hyponatremia as it relates to neurocritical care management.PubMedCrossRefGoogle Scholar
  3. 3.
    Wright WL. Sodium and fluid management in acute brain injury. Curr Neurol Neurosci Rep. 2012;12:466–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Sviri GE, Feinsod M, Soustiel JF. Brain natriuretic peptide and cerebral vasospasm in subarachnoid hemorrhage. Clinical and TCD correlations. Stroke. 2000;31:118–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Tomida M, Muraki M, Uemura K, Yamasaki K. Plasma concentrations of brain natriuretic peptide in patients with subarachnoid hemorrhage. Stroke. 1998;29:1584–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Qureshi AI, Suri MF, Sung GY, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002;50:749–55. discussion 755–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Seckl J, Dunger D. Postoperative diabetes insipidus. BMJ. 1989;298:2–3.PubMedCrossRefGoogle Scholar
  8. 8.
    McIver B, Connacher A, Whittle I, et al. Adipsic hypothalamic diabetes insipidus after clipping of anterior communicating artery aneurysm. BMJ. 1991;303:1465–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, et al. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429–38.PubMedCrossRefGoogle Scholar
  10. 10.
    Crompton MR. Hypothalamic lesions following the rupture of cerebral berry aneurysms. Brain. 1963;86:301–14.PubMedCrossRefGoogle Scholar
  11. 11.•
    Klose M, Brennum J, Poulsgaard L, et al. Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage. Clin Endocrinol. 2010;73:95–101. These two papers are amongst the few studies available examining acute pituitary function following subarachnoid hemorrhage.Google Scholar
  12. 12.•
    Parenti G, Cecchi PC, Ragghianti B, et al. Evaluation of the anterior pituitary function in the acute phase after spontaneous subarachnoid hemorrhage. J Endocrinol Invest. 2011;34:361–5. These two papers are amongst the few studies available examining acute pituitary function following subarachnoid hemorrhage.PubMedGoogle Scholar
  13. 13.
    Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629–38.PubMedCrossRefGoogle Scholar
  14. 14.
    Gomis P, Graftieaux JP, Sercombe R, et al. Randomized, double-blind, placebo-controlled, pilot trial of high-dose methylprednisolone in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2010;112:681–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Hashi K, Takakura K, Sano K, et al. Intravenous hydrocortisone in large doses in the treatment of delayed ischemic neurological deficits following subarachnoid hemorrhage–results of a multi-center controlled double-blind clinical study. No To Shinkei. 1988;40:373–82.PubMedGoogle Scholar
  16. 16.
    Coronado VG, Xu L, Basavaraju SV, et al. Surveillance for traumatic brain injury-related deaths—United States, 1997-2007. MMWR Surveill Summ. 2011;60:1–32.PubMedGoogle Scholar
  17. 17.
    Agha A, Rogers B, Sherlock M, et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab. 2004;89:4929–36.PubMedCrossRefGoogle Scholar
  18. 18.
    Agha A, Rogers B, Mylotte D, et al. Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol. 2004;60:584–91.CrossRefGoogle Scholar
  19. 19.
    Moro N, Katayama Y, Igarashi T, et al. Hyponatremia in patients with traumatic brain injury: incidence, mechanism, and response to sodium supplementation or retention therapy with hydrocortisone. Surg Neurol. 2007;68:387–93.PubMedCrossRefGoogle Scholar
  20. 20.
    Cohan P, Wang C, McArthur DL, et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med. 2005;33:2358–66.PubMedCrossRefGoogle Scholar
  21. 21.
    Watson NF, Barber JK, Doherty MJ, et al. Does glucocorticoid administration prevent late seizures after head injury? Epilepsia. 2004;45:690–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomized placebo-controlled trial. Lancet. 2004;364:1321–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Edwards P, Arango M, Balica L, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet. 2005;365:1957–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Agha A, Thornton E, O'Kelly P, et al. Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab. 2004;89:5987–92.PubMedCrossRefGoogle Scholar
  25. 25.••
    Glynn N, Agha A. Which patient requires neuroendocrine assessment following traumatic brain injury, when and how? Clin Endocrinol. 2013;78:17–20. This article contains an in-depth review of the evaluation of acute and chronic pituitary injury following traumatic brain injury.CrossRefGoogle Scholar
  26. 26.
    Hensen J, Henig A, Fahlbusch R, et al. Prevalence, predictors and patterns of postoperative polyuria and hyponatraemia in the immediate course after transsphenoidal surgery for pituitary adenomas. Clin Endocrinol. 1999;50:431–9.CrossRefGoogle Scholar
  27. 27.
    Kronenberg H, Williams RH. Williams textbook of endocrinology. 11th ed. Philadelphia, PA: Saunders/Elsevier; 2008.Google Scholar
  28. 28.
    Smith M. Physiologic changes during brain stem death–lessons for management of the organ donor. J Heart Lung Transplant. 2004;23:S217–22.PubMedCrossRefGoogle Scholar
  29. 29.
    Ranasinghe AM, Bonser RS. Endocrine changes in brain death and transplantation. Best Pract Res Clin Endocrinol Metab. 2011;25:799–812.PubMedCrossRefGoogle Scholar
  30. 30.
    Venkateswaran RV, Patchell VB, Wilson IC, et al. Early donor management increases the retrieval rate of lungs for transplantation. Ann Thorac Surg. 2008;85:278–86. discussion 286.PubMedCrossRefGoogle Scholar
  31. 31.
    Nicolas-Robin A, Barouk JD, Amour J, et al. Hydrocortisone supplementation enhances hemodynamic stability in brain-dead patients. Anesthesiology. 2010;112:1204–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Venkateswaran RV, Dronavalli V, Lambert PA, et al. The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy. Transplantation. 2009;88:582–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Guesde R, Barrou B, Leblanc I, et al. Administration of desmopressin in brain-dead donors and renal function in kidney recipients. Lancet. 1998;352:1178–81.PubMedCrossRefGoogle Scholar
  34. 34.
    Howlett TA, Keogh AM, Perry L, et al. Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy. Transplantation. 1989;47:828–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Gramm HJ, Meinhold H, Bickel U, et al. Acute endocrine failure after brain death? Transplantation. 1992;54:851–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Randell TT, Hockerstedt KA. Triiodothyronine treatment in brain-dead multiorgan donors—a controlled study. Transplantation. 1992;54:736–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Goarin JP, Cohen S, Riou B, et al. The effects of triiodothyronine on hemodynamic status and cardiac function in potential heart donors. Anesth Analg. 1996;83:41–7.PubMedGoogle Scholar
  38. 38.•
    Kramer AH, Roberts DJ, Zygun DA. Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis. Crit Care. 2012;16:R203. This review and meta-analysis addresses management of glycemic control specifically with regards to neurocritical care patients.PubMedCrossRefGoogle Scholar
  39. 39.
    Griesdale DE, Tremblay MH, McEwen J, Chittock DR. Glucose control and mortality in patients with severe traumatic brain injury. Neurocrit Care. 2009;11:311–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Dorhout Mees SM, van Dijk GW, Algra A, et al. Glucose levels and outcome after subarachnoid hemorrhage. Neurology. 2003;61:1132–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Badjatia N, Topcuoglu MA, Buonanno FS, et al. Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage. Crit Care Med. 2005;33:1603–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology. 2003;61:1351–6.PubMedCrossRefGoogle Scholar
  43. 43.
    van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.PubMedCrossRefGoogle Scholar
  44. 44.
    Investigators N-SS, Finfer S, Chittock DR, et al. Intensive vs. conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–97.CrossRefGoogle Scholar
  45. 45.
    Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.PubMedCrossRefGoogle Scholar
  46. 46.
    Arabi YM, Dabbagh OC, Tamim HM, et al. Intensive vs. conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36:3190–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008;300:933–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Ajaz F, Kudva YC, Erwin PJ. Residual dysphasia after severe hypoglycemia in a patient with immune-mediated primary adrenal insufficiency and type 1 diabetes mellitus: case report and systematic review of the literature. Endocr Pract. 2007;13:384–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Kurabayashi H, Kubota K, Tamura K, et al. Motor aphasia due to prolonged hypoglycaemic coma in a patient with insulin-dependent diabetes mellitus. J Int Med Res. 1996;24:487–91.PubMedGoogle Scholar
  50. 50.
    Auer RN, Wieloch T, Olsson Y, Siesjo BK. The distribution of hypoglycemic brain damage. Acta Neuropathol. 1984;64:177–91.PubMedCrossRefGoogle Scholar
  51. 51.
    Guettier JM, Gorden P. Hypoglycemia. Endocrinol Metab Clin North Am. 2006;35:753–66, viii–ix.Google Scholar
  52. 52.
    Service FJ. Hypoglycemia. Endocrinol Metab Clin North Am. 1997;26:937–55.PubMedCrossRefGoogle Scholar
  53. 53.
    Arem R, Wiener GJ, Kaplan SG, et al. Reduced tissue thyroid hormone levels in fatal illness. Metabolism. 1993;42:1102–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Attia J, Margetts P, Guyatt G. Diagnosis of thyroid disease in hospitalized patients: a systematic review. Arch Intern Med. 1999;159:658–65.PubMedCrossRefGoogle Scholar
  55. 55.
    Spencer C, Eigen A, Shen D, et al. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem. 1987;33:1391–6.PubMedGoogle Scholar
  56. 56.
    Stathatos N, Levetan C, Burman KD, Wartofsky L. The controversy of the treatment of critically ill patients with thyroid hormone. Best Pract Res Clin Endocrinol Metab. 2001;15:465–78.PubMedCrossRefGoogle Scholar
  57. 57.
    Slag MF, Morley JE, Elson MK, et al. Free thyroxine levels in critically ill patients. A comparison of currently available assays. JAMA. 1981;246:2702–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Slag MF, Morley JE, Elson MK, et al. Hypothyroxinemia in critically ill patients as a predictor of high mortality. JAMA. 1981;245:43–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Chinga-Alayo E, Villena J, Evans AT, Zimic M. Thyroid hormone levels improve the prediction of mortality among patients admitted to the intensive care unit. Intensive Care Med. 2005;31:1356–61.PubMedCrossRefGoogle Scholar
  60. 60.
    Brent GA, Hershman JM. Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J Clin Endocrinol Metab. 1986;63:1–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Becker RA, Vaughan GM, Ziegler MG, et al. Hypermetabolic low triiodothyronine syndrome of burn injury. Crit Care Med. 1982;10:870–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Klemperer JD, Klein I, Gomez M, et al. Thyroid hormone treatment after coronary-artery bypass surgery. N Engl J Med. 1995;333:1522–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am. 2006;35:687–98, vii–viii.Google Scholar
  64. 64.
    Jellinek EH. Fits, faints, coma, and dementia in myxoedema. Lancet. 1962;2:1010–2.PubMedCrossRefGoogle Scholar
  65. 65.
    Edwards GA. Neurologic manifestations of myxedema. Med Times. 1968;96:1125–30.PubMedGoogle Scholar
  66. 66.
    Nieman EA. The electroencephalogram in myxoedema coma: clinical and electroencephalographic study of three cases. BMJ. 1959;1:1204–8.PubMedCrossRefGoogle Scholar
  67. 67.
    River Y, Zelig O. Triphasic waves in myxedema coma. Clin Electroencephalogr. 1993;24:146–50.PubMedGoogle Scholar
  68. 68.
    Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342:1581–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Human T, Onuoha A, Diringer M, Dhar R. Response to a bolus of conivaptan in patients with acute hyponatremia after brain injury. J Crit Care. 2012;27(745):e741–5.Google Scholar
  70. 70.
    Murphy T, Dhar R, Diringer M. Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care. 2009;11:14–9.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Wright WL, Asbury WH, Gilmore JL, Samuels OB. Conivaptan for hyponatremia in the neurocritical care unit. Neurocrit Care. 2009;11:6–13.PubMedCrossRefGoogle Scholar
  72. 72.
    Woo CH, Rao VA, Sheridan W, Flint AC. Performance characteristics of a sliding-scale hypertonic saline infusion protocol for the treatment of acute neurologic hyponatremia. Neurocrit Care. 2009;11:228–34.PubMedCrossRefGoogle Scholar
  73. 73.
    Shetty S, Inzucchi SE, Goldberg PA, et al. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol. Endocr Pract. 2012;18:363–70.PubMedCrossRefGoogle Scholar
  74. 74.
    Kunjan K, Lloyd FP. Automated blood sampling and glucose sensing in critical care settings. J Diabetes Sci Technol. 2008;2:194–200.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Skjaervold NK, Solligard E, Hjelme DR, Aadahl P. Continuous measurement of blood glucose: validation of a new intravascular sensor. Anesthesiology. 2011;114:120–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Holzinger U, Warszawska J, Kitzberger R, et al. Real-time continuous glucose monitoring in critically ill patients: a prospective randomized trial. Diabetes Care. 2010;33:467–72.PubMedCrossRefGoogle Scholar
  77. 77.
    Brunner R, Kitzberger R, Miehsler W, et al. Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients. Crit Care Med. 2011;39:659–64.PubMedCrossRefGoogle Scholar
  78. 78.
    Goldberg PA, Siegel MD, Russell RR, et al. Experience with the continuous glucose monitoring system in a medical intensive care unit. Diabetes Technol Ther. 2004;6:339–47.PubMedCrossRefGoogle Scholar
  79. 79.
    Rabiee A, Andreasik V, Abu-Hamdah R, et al. Numerical and clinical accuracy of a continuous glucose monitoring system during intravenous insulin therapy in the surgical and burn intensive care units. J Diabetes Sci Technol. 2009;3:951–9.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Yamashita K, Okabayashi T, Yokoyama T, et al. Accuracy and reliability of continuous blood glucose monitor in postsurgical patients. Acta Anaesthesiol Scand. 2009;53:66–71.PubMedCrossRefGoogle Scholar
  81. 81.
    Inzucchi SE, Kosiborod M. Continuous glucose monitoring during critical care. Anesthesiology. 2011;114:18–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of EndocrinologyYale School of MedicineNew HavenUSA
  2. 2.Division of Neurocritical Care and Emergency MedicineYale School of MedicineNew HavenUSA

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