- Email: [email protected]
Bilateral adrenal hemorrhage: An overlooked cause of hypotension
The Journal of Emergency Medicine, Vol. 32, No. 2, pp. 167–169, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/07 $–see front matter
doi:10.1016/j.jemermed.2006.05.046
Clinical Communications
BILATERAL ADRENAL HEMORRHAGE: AN OVERLOOKED CAUSE OF HYPOTENSION Michalis K. Picolos,
MD,*†
Ajay Nooka, MD, MPH,† Anu Bhalla Davis, and Philip R. Orlander, MD*
MD,*
Bharat Raval,
MD,‡
*Division of Endocrinology, Diabetes and Metabolism, The University of Texas – Houston Medical School, Houston, Texas, †Department of Endocrine Neoplasia and Hormonal Disorders, and ‡Department of Radiology, The University of Texas – M.D. Anderson Cancer Center, Houston, Texas Reprint Address: Michalis K. Picolos, MD, The University of Texas – Houston Medical School, 6431 Fannin Street, MSB 6.100, Houston, TX 77030; [email protected]
e Abstract—Bilateral adrenal hemorrhage resulting in acute adrenal insufficiency is a rare complication of anticoagulant therapy. We present the case of a patient who came to the Emergency Department with unsuspected adrenal insufficiency, followed by a second visit within 1 month with shock, to demonstrate the importance of early detection and treatment. © 2007 Elsevier Inc.
brillation presented to the Emergency Department (ED) with weakness, dizziness, shortness of breath, low back pain, and hypotension (blood pressure 50/30 mm Hg). Treatment included intravenous fluids and discontinuation of antihypertensive medications. The patient recovered quickly and was discharged 12 h later with a blood pressure of 110/70 mm Hg. One month later, he presented to the ED with similar complaints. The blood pressure was 56/32 mm Hg, heart rate 82 beats/min, respirations 20 breaths/min, SaO2 98% on room air. He was afebrile, awake, oriented but diaphoretic. The hypotension was refractory to hydration, and after 3 liters of normal saline, intravenous dopamine infusion was initiated. Medications included digoxin, terazosin and warfarin 7.5 mg daily. The initial studies are shown in Table 1. The patient received antibiotics, fresh frozen plasma, and 250 mg of methylprednisolone intravenously and was transferred to our hospital. The blood pressure stabilized and the dopamine infusion was discontinued. A cosyntropin stimulation test was performed after the patient was begun on dexamethasone. Thirty and 60 min after intravenous administration of 250 g of cosyntropin, serum cortisol was 10.9 g/dL and 12.7 g/dL, respectively. Findings on magnetic resonance imaging (MRI) of the adrenal glands were consistent with bilateral adrenal hemorrhage (Figure 1). The patient was
e Keywords—adrenal insufficiency; adrenal hemorrhage; anticoagulation; warfarin; hypotension
INTRODUCTION Bilateral adrenal hemorrhage is a rare condition that is life threatening due to adrenal insufficiency (1). Due to the absence of specific signs and symptoms, it may only be found postmortem (2). We present the case of a man with adrenal insufficiency due to bilateral adrenal hemorrhage who presented for emergency care twice in a period of 1 month. The diagnosis was only established during the second hospital visit. CASE REPORT A 68-year-old man with congestive heart failure due to systolic dysfunction, hypertension, and chronic atrial fi-
Clinical Communications (Adults) is coordinated by Thomas O. Stair, Massachusetts
RECEIVED: 18 July 2005; ACCEPTED: 23 May 2006 167
MD,
of Harvard Medical School, Boston,
168
M. K. Picolos et al.
Table 1. Pertinent Initial Studies during the Patient’s Second Hospital Visit Test Hemoglobin White blood cells Eosinophils Platelets Glucose Blood urea nitrogen Creatinine Sodium Potassium Chloride Bicarbonate AST ALT Albumin INR (International normalized ratio) TSH CPK Troponin Digoxin Random cortisol Blood cultures Urine culture Sputum culture Electocardiogram 2-D Echocardiogram
Computed Tomography of Chest and Abdomen
Result (normal range) 12.6 (14–18 g/dL) 7.8 (4.5–11 K/uL) 5.8 (0–3%) 167 (130–440 K/L) 95 (70–99 mg/dL) 20 (10–20 mg/dL) 1.9 (0.5–1.4 mg/dL) 138 (135–145 mmol/L) 4.0 (3.5–5.1 mmol/L) 108 (95–109 mmol/L) 24 (24–32 mmol/L) 54 (10–34 U/L) 56 (10–44 U/L) 3.9 (3.5–5.0 g/dL) 4.71 (Therapeutic range 2.5–3.5) 0.89 (0.34–5.60 uIU/mL) 29.2 (24–204 U/L) 0.00 (0–0.5) 1.35 (Therapeutic range 0.8–2.0 ng/mL) 5.9 g/dL Negative Negative Normal respiratory flora Atrial fibrillation No acute ischemic changes Systolic dysfunction Ejection fraction of 30 –35% Absence of significant pericardial effusion Bilateral 3.5– 4.7 cm adrenal masses Left lower lobe lung infiltrate
discharged on hospital day 6. Discharge medications included maintenance doses of hydrocortisone, digoxin, aspirin, diltiazem and terazosin. The blood pressure at discharge was 132/84 mm Hg. Adrenal insufficiency due to bilateral adrenal hemorrhage can be caused by blunt abdominal trauma, antiphospholipid syndrome, thermal injuries, sepsis, anticoagulation (mostly associated with recent heparin use), adrenocorticotrophic hormone (ACTH) treatment, or can be idiopathic (3–9). Anticoagulation was the most likely cause in the current patient. The exact mechanism of adrenal hemorrhage is not clear. It is believed that diminished capillary resistance due to aging plays an important role (10). Another proposed mechanism consists of platelet aggregation leading to venous thrombosis, vasoconstriction, and regional hypotension. Bleeding occurs as reperfusion occurs, especially within the distal corticomedullary junction capillaries (4,11). These changes can be induced by stress leading to elevated ACTH and catecholamines, which produce platelet aggregation and vasoconstriction.
Symptoms of acute adrenal insufficiency are relatively non-specific and include weakness and fatigue, anorexia, nausea, vomiting, myalgias, and postural dizziness. Findings on physical examination may include hypotension, tachycardia or fever. Increased skin pigmentation is consistent with chronic primary adrenal insufficiency. Laboratory findings can include hyponatremia, hyperkalemia, hypoglycemia, and eosinophilia. In adrenal hemorrhage a drop in hemoglobin may be seen. Adrenal insufficiency can be established in critically ill patients with a random serum cortisol level (12). This condition can be excluded if the serum cortisol is ⬎34 g/dL. Conversely, the diagnosis is likely if the serum cortisol is ⬍15g/dL. After intravenous administration of 250 g of cosyntopin, a serum cortisol value at 30 or 60 min later of ⬍14.9g/dL also points towards adrenal insufficiency (13). Before testing, dexamethasone can be used as corticosteroid replacement because it is not measured by the cortisol assay.
Figure 1. Magnetic resonance images of the adrenal glands (arrows) in coronal (A) and axial (B) views demonstrate bilateral adrenal hemorrhage characterized by asymmetrical adrenal enlargement, and inhomogeneous appearance with areas of high and low signal intensity.
Bilateral Adrenal Hemorrhage
Computed tomography or MRI can exhibit radiological features highly suggestive of adrenal hemorrhage, with rounded enlargement of the adrenal glands, and variable density depending on the age of the hematoma (9). Other causes of bilateral adrenal enlargement leading to adrenal insufficiency include granulomatous infections, amyloidosis, and infiltrative disorders. Metastatic tumor deposits are the most common cause of bilateral adrenal enlargement, but adrenal insufficiency is uncommon in these situations (14). The treatment of adrenal insufficiency consists of prompt administration of parenteral hydrocortisone, tapered to maintenance oral hydrocortisone once the acute illness resolves (12). In primary adrenal insufficiency, mineralocorticoids can be added once the dose of hydrocortisone is ⬍50 mg daily. Prolonged mineralocorticoid replacement is usually not required in patients with adrenal insufficiency due to bilateral adrenal hemorrhage (15). Our patient did not require mineralocorticoids. The electrolytes remained normal, and the blood pressure was actually mildly elevated on maintenance dose of hydrocortisone alone, indicating residual function of the zona glomerulosa.
CONCLUSION Adrenal hemorrhage leading to adrenal insufficiency is a rare complication of anticoagulation. Random serum cortisol, cosyntropin stimulation test, computed tomography and magnetic resonance imaging are valuable tools in establishing the diagnosis of adrenal hemorrhage, and corticosteroid replacement can be life saving.
169
REFERENCES 1. Rao RH, Vagnucci AH, Amico JA. Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern Med 1989;110:227–35. 2. Xarli VP, Steele AA, Davis PJ, Buescher ES, Rios CN, GarciaBunuel R. Adrenal hemorrhage in the adult. Medicine (Baltimore) 1978;57:211–21. 3. Francque SM, Schwagten VM, Ysebaert DK, Van Marck EA, Beaucourt LA. Bilateral adrenal haemorrhage and acute adrenal insufficiency in a blunt abdominal trauma: a case-report and literature review. Eur J Emerg Med 2004;11:164 –7. 4. Caron P, Chabannier MH, Cambus JP, Fortenfant F, Otal P, Suc JM. Definitive adrenal insufficiency due to bilateral adrenal hemorrhage and primary antiphospholipid syndrome. J Clin Endocrinol Metab 1998;83:1437–9. 5. Deeb SA, Rosenberg RB, Wilkerson RJ, Griswold JA. Adrenal hemorrhage in a pediatric burn patient. Burns 2001;27:658 – 61. 6. Zaloga GP. Sepsis-induced adrenal deficiency syndrome. Crit Care Med 2001;29:688 –90. 7. Ries MD, Guiney W Jr, Lynch F. Fatal massive adrenal hemorrhage after bilateral total knee arthroplasty. J Arthroplasty 1994; 9:559 – 62. 8. Kornbluth AA, Salomon P, Sachar DB, et al. ACTH-induced adrenal hemorrhage: a complication of therapy masquerading as an acute abdomen. J Clin Gastroenterol 1990;12:371–7. 9. Tan PL, Moore NR. Spontaneous idiopathic bilateral adrenal haemorrhage in adults. Clin Radiol 2003;58:890 –2. 10. McDonald FD, Myers AR, Pardo R. Adrenal hemorrhage during anticoagulant therapy. JAMA 1966;198:1052– 6. 11. LaBan MM, Whitmore CE, Taylor RS. Bilateral adrenal hemorrhage after anticoagulation prophylaxis for bilateral knee arthroplasty. Am J Phys Med Rehabil 2003;82:418 –20. 12. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727–34. 13. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003;139:194 –204. 14. Lam KY, Lo CY. Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 2002;56:95–101. 15. Jahangir-Hekmat M, Taylor HC, Levin H, Wilbur M, Llerena LA. Adrenal insufficiency attributable to adrenal hemorrhage: longterm follow-up with reference to glucocorticoid and mineralocorticoid function and replacement. Endocr Pract 2004;10:55– 61.
doi:10.1016/j.jemermed.2006.05.046
Clinical Communications
BILATERAL ADRENAL HEMORRHAGE: AN OVERLOOKED CAUSE OF HYPOTENSION Michalis K. Picolos,
MD,*†
Ajay Nooka, MD, MPH,† Anu Bhalla Davis, and Philip R. Orlander, MD*
MD,*
Bharat Raval,
MD,‡
*Division of Endocrinology, Diabetes and Metabolism, The University of Texas – Houston Medical School, Houston, Texas, †Department of Endocrine Neoplasia and Hormonal Disorders, and ‡Department of Radiology, The University of Texas – M.D. Anderson Cancer Center, Houston, Texas Reprint Address: Michalis K. Picolos, MD, The University of Texas – Houston Medical School, 6431 Fannin Street, MSB 6.100, Houston, TX 77030; [email protected]
e Abstract—Bilateral adrenal hemorrhage resulting in acute adrenal insufficiency is a rare complication of anticoagulant therapy. We present the case of a patient who came to the Emergency Department with unsuspected adrenal insufficiency, followed by a second visit within 1 month with shock, to demonstrate the importance of early detection and treatment. © 2007 Elsevier Inc.
brillation presented to the Emergency Department (ED) with weakness, dizziness, shortness of breath, low back pain, and hypotension (blood pressure 50/30 mm Hg). Treatment included intravenous fluids and discontinuation of antihypertensive medications. The patient recovered quickly and was discharged 12 h later with a blood pressure of 110/70 mm Hg. One month later, he presented to the ED with similar complaints. The blood pressure was 56/32 mm Hg, heart rate 82 beats/min, respirations 20 breaths/min, SaO2 98% on room air. He was afebrile, awake, oriented but diaphoretic. The hypotension was refractory to hydration, and after 3 liters of normal saline, intravenous dopamine infusion was initiated. Medications included digoxin, terazosin and warfarin 7.5 mg daily. The initial studies are shown in Table 1. The patient received antibiotics, fresh frozen plasma, and 250 mg of methylprednisolone intravenously and was transferred to our hospital. The blood pressure stabilized and the dopamine infusion was discontinued. A cosyntropin stimulation test was performed after the patient was begun on dexamethasone. Thirty and 60 min after intravenous administration of 250 g of cosyntropin, serum cortisol was 10.9 g/dL and 12.7 g/dL, respectively. Findings on magnetic resonance imaging (MRI) of the adrenal glands were consistent with bilateral adrenal hemorrhage (Figure 1). The patient was
e Keywords—adrenal insufficiency; adrenal hemorrhage; anticoagulation; warfarin; hypotension
INTRODUCTION Bilateral adrenal hemorrhage is a rare condition that is life threatening due to adrenal insufficiency (1). Due to the absence of specific signs and symptoms, it may only be found postmortem (2). We present the case of a man with adrenal insufficiency due to bilateral adrenal hemorrhage who presented for emergency care twice in a period of 1 month. The diagnosis was only established during the second hospital visit. CASE REPORT A 68-year-old man with congestive heart failure due to systolic dysfunction, hypertension, and chronic atrial fi-
Clinical Communications (Adults) is coordinated by Thomas O. Stair, Massachusetts
RECEIVED: 18 July 2005; ACCEPTED: 23 May 2006 167
MD,
of Harvard Medical School, Boston,
168
M. K. Picolos et al.
Table 1. Pertinent Initial Studies during the Patient’s Second Hospital Visit Test Hemoglobin White blood cells Eosinophils Platelets Glucose Blood urea nitrogen Creatinine Sodium Potassium Chloride Bicarbonate AST ALT Albumin INR (International normalized ratio) TSH CPK Troponin Digoxin Random cortisol Blood cultures Urine culture Sputum culture Electocardiogram 2-D Echocardiogram
Computed Tomography of Chest and Abdomen
Result (normal range) 12.6 (14–18 g/dL) 7.8 (4.5–11 K/uL) 5.8 (0–3%) 167 (130–440 K/L) 95 (70–99 mg/dL) 20 (10–20 mg/dL) 1.9 (0.5–1.4 mg/dL) 138 (135–145 mmol/L) 4.0 (3.5–5.1 mmol/L) 108 (95–109 mmol/L) 24 (24–32 mmol/L) 54 (10–34 U/L) 56 (10–44 U/L) 3.9 (3.5–5.0 g/dL) 4.71 (Therapeutic range 2.5–3.5) 0.89 (0.34–5.60 uIU/mL) 29.2 (24–204 U/L) 0.00 (0–0.5) 1.35 (Therapeutic range 0.8–2.0 ng/mL) 5.9 g/dL Negative Negative Normal respiratory flora Atrial fibrillation No acute ischemic changes Systolic dysfunction Ejection fraction of 30 –35% Absence of significant pericardial effusion Bilateral 3.5– 4.7 cm adrenal masses Left lower lobe lung infiltrate
discharged on hospital day 6. Discharge medications included maintenance doses of hydrocortisone, digoxin, aspirin, diltiazem and terazosin. The blood pressure at discharge was 132/84 mm Hg. Adrenal insufficiency due to bilateral adrenal hemorrhage can be caused by blunt abdominal trauma, antiphospholipid syndrome, thermal injuries, sepsis, anticoagulation (mostly associated with recent heparin use), adrenocorticotrophic hormone (ACTH) treatment, or can be idiopathic (3–9). Anticoagulation was the most likely cause in the current patient. The exact mechanism of adrenal hemorrhage is not clear. It is believed that diminished capillary resistance due to aging plays an important role (10). Another proposed mechanism consists of platelet aggregation leading to venous thrombosis, vasoconstriction, and regional hypotension. Bleeding occurs as reperfusion occurs, especially within the distal corticomedullary junction capillaries (4,11). These changes can be induced by stress leading to elevated ACTH and catecholamines, which produce platelet aggregation and vasoconstriction.
Symptoms of acute adrenal insufficiency are relatively non-specific and include weakness and fatigue, anorexia, nausea, vomiting, myalgias, and postural dizziness. Findings on physical examination may include hypotension, tachycardia or fever. Increased skin pigmentation is consistent with chronic primary adrenal insufficiency. Laboratory findings can include hyponatremia, hyperkalemia, hypoglycemia, and eosinophilia. In adrenal hemorrhage a drop in hemoglobin may be seen. Adrenal insufficiency can be established in critically ill patients with a random serum cortisol level (12). This condition can be excluded if the serum cortisol is ⬎34 g/dL. Conversely, the diagnosis is likely if the serum cortisol is ⬍15g/dL. After intravenous administration of 250 g of cosyntopin, a serum cortisol value at 30 or 60 min later of ⬍14.9g/dL also points towards adrenal insufficiency (13). Before testing, dexamethasone can be used as corticosteroid replacement because it is not measured by the cortisol assay.
Figure 1. Magnetic resonance images of the adrenal glands (arrows) in coronal (A) and axial (B) views demonstrate bilateral adrenal hemorrhage characterized by asymmetrical adrenal enlargement, and inhomogeneous appearance with areas of high and low signal intensity.
Bilateral Adrenal Hemorrhage
Computed tomography or MRI can exhibit radiological features highly suggestive of adrenal hemorrhage, with rounded enlargement of the adrenal glands, and variable density depending on the age of the hematoma (9). Other causes of bilateral adrenal enlargement leading to adrenal insufficiency include granulomatous infections, amyloidosis, and infiltrative disorders. Metastatic tumor deposits are the most common cause of bilateral adrenal enlargement, but adrenal insufficiency is uncommon in these situations (14). The treatment of adrenal insufficiency consists of prompt administration of parenteral hydrocortisone, tapered to maintenance oral hydrocortisone once the acute illness resolves (12). In primary adrenal insufficiency, mineralocorticoids can be added once the dose of hydrocortisone is ⬍50 mg daily. Prolonged mineralocorticoid replacement is usually not required in patients with adrenal insufficiency due to bilateral adrenal hemorrhage (15). Our patient did not require mineralocorticoids. The electrolytes remained normal, and the blood pressure was actually mildly elevated on maintenance dose of hydrocortisone alone, indicating residual function of the zona glomerulosa.
CONCLUSION Adrenal hemorrhage leading to adrenal insufficiency is a rare complication of anticoagulation. Random serum cortisol, cosyntropin stimulation test, computed tomography and magnetic resonance imaging are valuable tools in establishing the diagnosis of adrenal hemorrhage, and corticosteroid replacement can be life saving.
169
REFERENCES 1. Rao RH, Vagnucci AH, Amico JA. Bilateral massive adrenal hemorrhage: early recognition and treatment. Ann Intern Med 1989;110:227–35. 2. Xarli VP, Steele AA, Davis PJ, Buescher ES, Rios CN, GarciaBunuel R. Adrenal hemorrhage in the adult. Medicine (Baltimore) 1978;57:211–21. 3. Francque SM, Schwagten VM, Ysebaert DK, Van Marck EA, Beaucourt LA. Bilateral adrenal haemorrhage and acute adrenal insufficiency in a blunt abdominal trauma: a case-report and literature review. Eur J Emerg Med 2004;11:164 –7. 4. Caron P, Chabannier MH, Cambus JP, Fortenfant F, Otal P, Suc JM. Definitive adrenal insufficiency due to bilateral adrenal hemorrhage and primary antiphospholipid syndrome. J Clin Endocrinol Metab 1998;83:1437–9. 5. Deeb SA, Rosenberg RB, Wilkerson RJ, Griswold JA. Adrenal hemorrhage in a pediatric burn patient. Burns 2001;27:658 – 61. 6. Zaloga GP. Sepsis-induced adrenal deficiency syndrome. Crit Care Med 2001;29:688 –90. 7. Ries MD, Guiney W Jr, Lynch F. Fatal massive adrenal hemorrhage after bilateral total knee arthroplasty. J Arthroplasty 1994; 9:559 – 62. 8. Kornbluth AA, Salomon P, Sachar DB, et al. ACTH-induced adrenal hemorrhage: a complication of therapy masquerading as an acute abdomen. J Clin Gastroenterol 1990;12:371–7. 9. Tan PL, Moore NR. Spontaneous idiopathic bilateral adrenal haemorrhage in adults. Clin Radiol 2003;58:890 –2. 10. McDonald FD, Myers AR, Pardo R. Adrenal hemorrhage during anticoagulant therapy. JAMA 1966;198:1052– 6. 11. LaBan MM, Whitmore CE, Taylor RS. Bilateral adrenal hemorrhage after anticoagulation prophylaxis for bilateral knee arthroplasty. Am J Phys Med Rehabil 2003;82:418 –20. 12. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727–34. 13. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003;139:194 –204. 14. Lam KY, Lo CY. Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. Clin Endocrinol (Oxf) 2002;56:95–101. 15. Jahangir-Hekmat M, Taylor HC, Levin H, Wilbur M, Llerena LA. Adrenal insufficiency attributable to adrenal hemorrhage: longterm follow-up with reference to glucocorticoid and mineralocorticoid function and replacement. Endocr Pract 2004;10:55– 61.