Common Endocrinopathies in the Intensive Care Unit

Transcription

1 Common Endocrinopathies in the Intensive Care Unit Tejal S. Brahmbhatt, MD* Fellow of Trauma Surgery, Surgical Critical Care & Emergency Surgery Hospital of the University of Pennsylvania Philadelphia, Pennsylvania, USA Carrie A. Sims, MD, MS, FACS** Assistant Professor and Director of Research Division of Traumatology, Surgical Critical Care and Emergency Surgery University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania, USA Endocrinopathies in critical illness are not uncommon and require special attention due to their systemic and sometimes nonspecific presentation. Importantly, they may mimic signs and symptoms of the primary cause of the patient s critical illness. The following review includes common endocrinopathies seen in the intensive care unit. Thyroid Storm Thyroid storm, or thyrotoxic crisis, is an acute, potentially life-threatening state that can occur with undertreated or partially treated hyperthyroidism. While the overall incidence of hyperthyroidism is low (0.05% to 1.3%), an even smaller subset of hyperthyroid patients will manifest a crisis (1% to 2%).(1,2) Any acute stress (e.g., surgery, sepsis or myocardial infarction) may precipitate a thyroid storm.(3) Physiologically, a thyroid storm is characterized by an exaggerated response to elevated levels of thyroid hormone, and classic features include fever (>38.5 C) and tachycardia. More severe cardiac derangements may include arrhythmias, heart failure and shock.(4) Gastrointestinal symptoms may include nausea, vomiting, diarrhea, and diffuse abdominal pain.(5) Symptoms in the central nervous system can range from psychosis to coma.(6) Diagnosis is made on clinical grounds in the setting of an elevated T4 (thyroxine) and decreased thyrotropin (thyroid-stimulating hormone, or TSH). Therapeutic goals of treating thyroid storm are to: 1) decrease hormone production and secretion by using thioamides, propylthiouracil and iodinated solutions; 2) decrease the conversion of T4 to its active triiodothyronine (T3) form by utilizing glucocorticoids; and 3) blunt the adrenergic effects thyroid hormone by treating with beta-antagonists (see Table 1). Myxedema Coma Myxedema coma results from decompensated hypothyroidism and is classically characterized by mental status changes and hypothermia (reported as low as 90 F).(7,8) Other symptoms include bradycardia, hypotension, hypoventilation, anorexia, nausea, abdominal pain, and decreased gastrointestinal motility.(9) Underlying infection is common and should be investigated and treated aggressively with antibiotics and surgical intervention if applicable. Although an elevated serum TSH and low free T4 value suppor t the diagnosis, treatment should be initiated on clinical suspicion and not when

2 laboratory data become available. Adrenal insufficiency may exist concurrently and treating hypothyroidism may precipitate an adrenal crisis. As such, a cortisol level should be measured and treatment should include hydrocortisone until adrenal insufficiency is excluded.(7) Due to its rarity, no prospective randomized clinical trials comparing treatment strategies are available. Administration of intravenous T3, T4, or a combination of these, have been employed (see Table 1). Cardiac monitoring is essential during initial treatment as tachyarrhythmias have been described.(9) Supportive care is critical in the reversal of this process, including passive rewarming, hemodynamic support with isotonic fluids and vasopressors, mechanical ventilation, and empiric antibiotics.

3 Electrolyte abnormalities, especially hyponatremia, are common and should be treated and monitored aggressively. Nonthyroidal Illness Syndrome Nonthyroidal illness syndrome (NTIS), formerly known as sick euthyroid syndrome, remains a clinical entity in need of further study. Diagnosis is based on clinical suspicion of thyroid dysfunction, with critically ill patients routinely demonstrating low serum T3 concentrations. As the severity of illness progresses, T4 production also becomes suppressed. TSH levels are typically normal to low.(10) Medications frequently used in the critically ill such as dopamine, glucocorticoids, amiodarone, and propranolol may also contribute to depressed thyroid levels. As a result, controversy remains regarding the treatment of NTIS. Acute NTIS can be viewed as an adaptive response to critical illness, but this may become deranged when critical illness enters a chronic phase.(11,12) Although most patients with NTIS have a return of normal thyroid function and survive, critically ill patients with very low T4 concentrations are at increased risk of death.(13) Convincing proof of efficacy and safety with thyroid supplementation requires further study.(14) Vasopressin Deficiency Vasopressin, a hormone secreted by the posterior pituitary in response to increased osmolarity and hypotension, plays a key role in critical illness. Although vasopressin concentrations are elevated in early septic shock, levels are significantly lower than anticipated in vasopressor-dependent shock, suggesting a relative vasopressin deficiency in severe sepsis.(15) In such circumstances, the use of vasopressin at a physiologic dose of 0.03 U/min significantly improves blood pressure (see Table 1). These findings were confirmed in the Vasopressin in Septic Shock Trial (VASST) where the addition of vasopressin to norepinephrine also resulted in a reduction in the need for norepinephrine. Although no overall difference in 28-day survival was seen between patients randomized to receive vasopressin versus norepinephrine, subgroup analysis revealed a potential survival benefit in patients with less severe septic shock (5 μg/min to 14 μg/min norepinephrine) who were treated with vasopressin.(16,17) Vasopressin is also emerging as an important hormone for maintaining vasomotor tone during hemorrhagic shock. With prolonged hemorrhage and aggressive resuscitation, vasopressin levels decline and vasopressors are frequently required. Clinical evidence has been limited, and has not been able to delineate the efficacy and safety of exogenous vasopressin use in hemorrhagic shock.(18,19) Cohn and colleagues recently reported the first randomized trial to investigate the impact of vasopressin in acute traumatic injury; findings suggest that infusion of lowdose vasopressin decreased resuscitative fluid requirements after injury.(20) Adrenal Insufficiency Depletion of adrenocortical reserve has been linked to the pathogenesis of shock in critically ill patients. Adrenal insufficiency can be caused by derangements at any level of

4 the hypothalamic-pituitary-adrenal axis. Although primary adrenal insufficiency in the critically ill is rare, secondary insufficiency can be caused by any disease process or medication that interferes with adrenocorticotropic hormone secretion.(21) Not surprisingly, therapeutic glucocorticoid use is the most common cause of drug-induced secondary adrenal insufficiency, becoming clinically apparent when the physiologic stress exceeds the anticipated glucocorticoid requirement. These patients may present with lifethreatening hypotension, but more commonly with nonspecific symptoms such as diffuse abdominal pain, nausea, vomiting, fever, lethargy, and mental status changes. Due to its rapid progression to shock and death, treatment of acute adrenal crisis should be based on clinical suspicion. Current recommendations include administration of 100 mg of intravenous hydrocortisone followed by a daily schedule of 200 mg in divided doses. After the underlying illness has been treated and the patient is hemodynamically stable, glucocorticoids may be tapered to baseline dosing regimens. Because surgery and anesthesia can elicit major physiologic stress, patients chronically treated with steroids may not be able to respond accordingly. It is recommended that perioperative steroid supplementation be given to patients who have been treated within the last year (>5 mg/day of prednisone or an equivalent).(22) Dosing should be tailored to the degree of anticipated surgical stress based on the type of procedure. Minor stress procedures (e.g., inguinal herniorrhaphy) should receive 25 mg/day for one day of hydrocortisone equivalent. Moderate stress procedures (e.g., joint replacement, cholecystectomy) should receive 50 mg/day to 75 mg/day (25 mg every 8 to 12 hours) for 1 or 2 days. Major stress procedures (e.g., pancreatoduodenectomy, esophagogastrectomy and cardiac surgery) should receive 100 mg/day to 150 mg/day (50 mg every 8 to 12 hours) for 2 or 3 days.(23) The use of corticosteroids in sepsis may be beneficial but remains controversial. Critically ill patients may develop a state of relative adrenal insufficiency or acquired glucocorticoid resistance. Annane and colleagues demonstrated improved survival with corticosteroid replacement therapy in vasopressor-unresponsive shock.(24) However, in the recent Corticosteroid Therapy of Septic Shock (CORTICUS) study, corticosteroid supplementation did not improve overall survival but was associated with improved hemodynamics.(25) The discrepancy in survival benefit may reflect differences in patient acuity and timing of enrollment. According to the Surviving Sepsis Guidelines intravenous hydrocortisone should be given only to adult septic shock patients after it has been confirmed that their blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy (see Table 1).(26) Mineralocorticoid secretion is generally preserved in adrenal insufficiency due to its dependence on the reninangiotensin system rather than on adrenocorticotropic hormone stimulation.(27) Some critically ill patients can have depressed aldosterone secretion in spite of appropriate cortisol levels, leading to profound electrolyte disturbances.(28) Hydrocortisone does have some mineralocorticoid activity; however, in cases of severely decreased mineralocorticoid secretion, the addition of fludrocortisone needs further study.(24)

5 Conclusion Endocrinopathies may often be underappreciated in the setting of critical illness. Ongoing research has demonstrated the potential morbidity and mortality of these diseases. Thyroid storm, myxedema coma, NTIS, vasopressin deficiency, and adrenal crisis can all have nonspecific signs and symptoms that can be misleading. It is important to maintain a high index of suspicion in the critically ill when disease is recalcitrant to the prescribed therapy. References: 1. Klubo-Gwiezdzinska J, Wartofsky L. Thyrotoxic storm. In: Oxford Textbook of Endocrinology and Diabetes. 2nd ed. Oxford, United Kingdom: Oxford University. Press; 2011: Goldberg PA, Inzucchi SE. Critical issues in endocrinology. Clin Chest Med. 2003;24: Sims C. How do I diagnose and manage acute endocrine emergencies in the intensive care unit? In: Deutschman CS, Neligan PJ, eds. Evidence-Based Practice of Critical Care. Philadelphia, PA: Elsevier; 2010: Dabon-Almirante CL, Surks M. Clinical and laboratory diagnosis of thyrotoxicosis. Endocrinol Metab Clin North Am. 1998;27: Choudhary AM, Ingram R. Thyroid storm presenting with liver failure. J Clin Gastroenterol. 1999;29: Nayuk B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006; Nicoloff JT, LoPresti JS. Myxedema coma: A form of decompensated hypothyroidism. Endocrinol Metab Clin North Am. 1993;22: Wartofsky L. Myxedma coma. Endocrinol Metab Clin North Am. 2006;35: Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician. 2000;62: DeGroot LJ. Non-thyroidal illness syndrome is a manifestation of hypothalamicpituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22: Boelen A, Kwakkel J, Fliers E. Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev. 2011;32: Wartofsky L, Burman KD. Alterations in thyroid function in patients with systemic illnesses: the euthyroid sick syndrome. Endocr Rev. 1982;3:

6 13. Maldonado LS, Murata GH, Hershman JM, Braunstein GD. Do thyroid function tests independently predict survival in the critically ill? Thyroid. 1992;2: DeGroot LJ. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab. 1999;84: Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95: Russell JA. Bench-to-bedside review: vasopressin in the management of septic shock. Crit Care. 2011;15: Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358: Shelly MP, Greatorex R, Calne RY, Park GR. The physiological effects of vasopressin when used to control intra-abdominal bleeding. Intensive Care Med. 1988;14: Tsuneyoshi I, Onomoto M, Yonetani A, Kanmura Y. Low-dose vasopressin infusion in patients with severe vasodilatory hypotension after prolonged hemorrhage during general anesthesia. J Anesth. 2005;19: Cohn SM, McCarthy J, Stewart RM, Jonas RB, Dent DL, Michalek JE. Impact of low-dose vasopressin on trauma outcome: prospective randomized study. World J Surg. 2011;35: Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361: Shaw M. When is perioperative steroid coverage necessary? Cleve Clin J Med. 2002;69: Salem M, Tanish RE Jr., Bromberg J, Loriaux DL, Chernow B. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg. 1994;219: Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288: Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004;329:480.

7 26. Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C. Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med. 2004;141: Lipiner-Fiedman D, Sprung CL, Laterre PF, et al. Adrenal function in sepsis: the retrospective CORTICUS cohort study. Crit Care Med. 2007;35: Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: Crit Care Med. 2008;36: Burke CE. Adrenocortical insufficiency. Clin Endocrinol Metab. 1985;15: Raff H, Findling JW. Aldosterone control in critically ill patients: ACTH metoclopramide, and atrial natriuretic peptide. Crit Care Med. 1990;18: Disclosures: * Author has no disclosures to report. ** Author has no disclosures to report.