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ICU TopicsEndocrine & metabolic emergencies

ICU · Endocrine & metabolic emergencies

Endocrine & Metabolic Derangements of Critical Illness

Also known as Metabolic response to critical illness · Stress hyperglycaemia · Sick euthyroid syndrome · Low T3 syndrome · Critical illness-related corticosteroid insufficiency · CIRCI · Anabolic failure · ICU-acquired weakness

endocrine metabolic response to the critical the illness — the the biphasic (acute adaptive stress response → chronic maladaptive persistent). The acute: the counter-regulatory the hormones (the cortisol, the catecholamines, the glucagon, the GH), the insulin the resistance (the stress the hyperglycaemia), the hypercatabolism. The chronic: the suppressed the axes (the sick the euthyroid / the low-T3, the hypogonadism, the CIRCI), the anabolic the failure, the muscle the wasting. moderate glycaemic control (the NICE-SUGAR); the hydrocortisone for refractory septic shock; sick euthyroid no replacement. rarer ICU endocrinopathies — the insulinoma (the spontaneous the hypoglycaemia), the VIPoma (the secretory the diarrhoea, the hypokalaemia), the carcinoid / the carcinoid the crisis, the calcitonin in the thyroid the C-cell (the medullary the carcinoma). The hyperglycaemic the emergencies (the DKA / the HHS) the summarised — the detail in the sibling.

medium23 referencesUpdated 19 Aug 202612 min readVerification in progress

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The one-line answer

Critical illness triggers a biphasic endocrine-metabolic response. The acute phase (hours to days) is adaptive — a counter-regulatory surge of cortisol, catecholamines, glucagon and growth hormone, with insulin resistance producing stress hyperglycaemia to feed the brain, wound and immune system. The chronic phase (days to weeks) is maladaptive — suppressed axes (sick euthyroid, hypogonadism, CIRCI), anabolic failure and ICU-acquired weakness. The three decisions that earn marks: moderate glycaemic control (the NICE-SUGAR conventional target of at or below 10 mmol/L — never tight), hydrocortisone for septic shock refractory to fluids and vasopressors (200 mg/day in ADRENAL, under 400 mg/day suggested by the 2017 CIRCI consensus), and no thyroid replacement for sick euthyroid — non-thyroidal illness may be adaptive.[1][2][4][17][19][6]

Meet the patient

A 68-year-old man is on ICU day 2 after a three-vessel CABG on cardiopulmonary bypass. He is in new atrial fibrillation, has had amiodarone and iodinated contrast, and his routine bloods are unremarkable except the thyroid function tests the registrar sent: TSH 0.4, free T3 2.1, free T4 14. The registrar documents possible hypothyroidism and asks whether to start levothyroxine.[1]

The answer is no. This is sick euthyroid — the adaptive down-regulation of the thyroid axis in critical illness — and replacing thyroid hormone here does not help and may harm. The same patient will develop stress hyperglycaemia and may need hydrocortisone if his shock becomes refractory. The whole topic turns on knowing which derangements to treat and which to leave alone.[6]

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References23ShowHide
  1. [1]Preiser JC, Ichai C, Orban JC, et al. Metabolic response to the stress of critical illness Br J Anaesth, 2014.PMID 24970271
  2. [2]Mottale R, Dupuis C, Szklarzewska S, et al. The metabolic response to stress in critical illness: updated review on the pathophysiological mechanisms, consequences, and therapeutic implications Ann Intensive Care, 2025.PMID 41139771
  3. [3]Fowler C, Raoof N, Pastores SM Sepsis and Adrenal Insufficiency J Intensive Care Med, 2023.PMID 37365820
  4. [4]Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients N Engl J Med, 2009.PMID 19318384
  5. [5]van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients N Engl J Med, 2001.PMID 11794168
  6. [6]Fliers E, Bianco AC, Langouche L, et al. Thyroid function in critically ill patients Lancet Diabetes Endocrinol, 2015.PMID 26071885
  7. [7]Korytkowski MT, Muniyappa R, Antinori-Lent K, et al. Management of Hyperglycemia in Hospitalized Adult Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab, 2022.PMID 35690958
  8. [8]Li XH, et al. Predicting 28-day all-cause mortality in patients admitted to intensive care units with pre-existing chronic heart failure using the stress hyperglycemia ratio: a machine learning-driven retrospective cohort analysis Cardiovasc Diabetol, 2025.PMID 39780223
  9. [9]Okabayashi T, Shima Y, Sumiyoshi S, et al. Diagnosis and management of insulinoma World J Gastroenterol, 2013.PMID 23430217
  10. [10]Una Cidon E Vasoactive intestinal peptide secreting tumour: An overview World J Gastrointest Oncol, 2022.PMID 35582098
  11. [11]Ito T, Jensen RT Perspectives on the current pharmacotherapeutic strategies for management of functional neuroendocrine tumor syndromes Expert Opin Pharmacother, 2021.PMID 33131345
  12. [12]Sultana Q, Kar J, Verma A, et al. A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management J Clin Med, 2023.PMID 37568540
  13. [13]Pelizzo MR, et al. Medullary thyroid carcinoma Expert Rev Anticancer Ther, 2023.PMID 37646181
  14. [14]Trimboli P, et al. Diagnostic tests for medullary thyroid carcinoma: an umbrella review Endocrine, 2023.PMID 36877452
  15. [15]Annane D, Sébille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock JAMA, 2002.PMID 12186604
  16. [16]Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock N Engl J Med, 2018.PMID 29490185
  17. [17]Venkatesh B, Finfer S, Cohen J, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock N Engl J Med, 2018.PMID 29347874
  18. [18]Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock N Engl J Med, 2008.PMID 18184957
  19. [19]Annane D, Pastores SM, Rochwerg B, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017 Intensive Care Med, 2017.PMID 28940011
  20. [20]Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU N Engl J Med, 2006.PMID 16452557
  21. [21]Albert SG, Ariyan S, Rather A, et al. The effect of etomidate on adrenal function in critical illness: a systematic review Intensive Care Med, 2011.PMID 21373823
  22. [22]Daghmouri MA, et al. Etomidate versus ketamine for in-hospital rapid sequence intubation: a systematic review and meta-analysis Eur J Emerg Med, 2025.PMID 40239104
  23. [23]Bogazzi F, Bartalena L, Gasperi M, et al. The various effects of amiodarone on thyroid function Thyroid, 2001.PMID 11396710

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