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A 62-Year-Old Man With Hypotension, Hyperkalemia, and HyponatremiaAdrenal Hemorrhage in Antiphospholipid Syndrome FREE TO VIEW

Khalid Mohammad, MD; Nutan Bhaskar, MD; Thaddeus Bartter, MD, FCCP; Manish Joshi, MD, FCCP
Author and Funding Information

From the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR.

Correspondence to: Khalid Mohammad, MD, University of Arkansas for the Medical Sciences, 4301 W Markham St, Slot #555, Little Rock, AR 72205; e-mail: kmohammad@uams.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(6):1822-1825. doi:10.1378/chest.12-2576
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Published online

A 62-year-old man with a history of antiphospholipid syndrome (APS) and recurrent lower extremity DVT on long-term warfarin therapy presented to the outpatient endoscopy suite for an esophagogastroduodenoscopy. His warfarin was withheld in anticipation of the procedure. The endoscopy was uneventful; however, he was admitted for further workup of hyponatremia, hyperkalemia, and mild elevation in liver function tests. His therapeutic anticoagulation was further withheld in the inpatient setting because of concerns over a drop in his hematocrit level. He subsequently developed diffuse abdominal pain and malaise followed by refractory hypotension and was transferred to the ICU for further management of his shock.

Physical Examination Findings

At the time of arrival in the ICU the patient was in respiratory distress. His pulse rate was 120/min, mean arterial BP was 40 mm Hg, respiratory rate was 30/min, and oxygen saturation was 95% on 2 L. There was no jugular venous distension. S1 and S2 were distinct without murmurs. Breath sounds were normal bilaterally. The abdomen was mildly tender to palpation, without guarding or rebound. No hepatosplenomegaly was appreciated.

Diagnostic Studies

Serum chemistry measurements were significant for a potassium level of 5.1 mEq/dL and sodium level of 129 mEq/dL. The activated partial thromboplastin time was prolonged at 69 s (normal, 23-36 s) and did not correct when diluted 1:1 with normal platelet-free plasma. The dilute Russell viper venom time was elevated at 199 s (normal, 27-28 s) and, consistent with a lupus anticoagulant, remained elevated at 142 s despite a mixing study. His serum cortisol level was noted to be low at 0.6 μg/dL (normal, 10-20 μg/dL). Relevant studies obtained on admission are shown in Table 1. A chest radiograph and echocardiogram were normal. CT scan of the abdomen revealed bilateral adrenal hemorrhage (Fig 1).

Table Graphic Jump Location
Table 1 —Pertinent Laboratory Tests in the Patient With APS

APS=antiphospholipid syndrome; GPL=IgG phospholipid units; MPL=IgM phospholipid units.

Figure Jump LinkFigure 1. Axial and coronal sections of the CT images demonstrating bilateral adrenal hemorrhage (arrows).Grahic Jump Location
What is the diagnosis?
Diagnosis: Antiphospholipid syndrome causing shock secondary to adrenal insufficiency from bilateral adrenal hemorrhage

This unusual case combines acute onset Addison disease, adrenal hemorrhage, and APS. General languor and debility, feebleness of the heart’s action, irritability of the stomach, and a peculiar change of the color of the skin form part of the original description of Addison disease, primary hypoadrenalism. When it presents nonacutely, Addison disease represents a diagnostic challenge for the clinician; it has a notoriously nonspecific presentation and can be fatal. Addison disease is believed to be rare, but recent epidemiologic studies have reported a rising prevalence in developed countries, 93 to 140 per million, with an incidence of 4.7 to 6.2 per million. Autoimmune adrenalitis is the most common cause of adrenal failure, accounting for approximately 80% of the cases, followed by TB (15%). The remaining 5% of causes (which includes APS) are uncommon. Although APS is a rare cause, the acute onset helped with the diagnostic challenge in this case.

Hemorrhage of the adrenal glands occurs from traumatic and nontraumatic causes. Nontraumatic hemorrhage is uncommon and can occur because of a variety of causes (Table 2). The clinical manifestations are varied and depend on the amount of hemorrhage, its effect on hemodynamics, rate of onset (gradual or sudden), the ability of the surrounding structures to contain the bleeding, rupture into the perinephric space, and the functional status of the patient. The majority of patients do not have obvious clinical signs of adrenal insufficiency, and the diagnosis is usually made incidentally at imaging performed for other reasons. Acute adrenal insufficiency due to adrenal hemorrhage, as occurred in this case, is rare but life-threatening.

Table Graphic Jump Location
Table 2 Risk Factors for Nontraumatic Bilateral Adrenal Hemorrhage

ACTH=adrenocorticotropic hormone; NSAID=nonsteroidal antiinflammatory drug. See Table 1 legend for expansion of other abbreviation.

APS is characterized by the presence of both venous and arterial recurrent thrombotic events associated with the repeated detection of antibodies directed against phospholipid-protein complexes. To fulfill the diagnosis of APS, patients have to meet at least one clinical sign (vascular thrombosis or recurrent spontaneous abortions) and one laboratory criterion (anticardiolipin IgG or IgM antibodies, lupus anticoagulant of IgG or IgM classes detected on two or more occasions at least 6 weeks apart). Lupus anticoagulant antibodies are generally more specific for APS, whereas anticardiolipin antibodies are more sensitive. Overt Addison disease is reported in only 0.4% of patients with established APS. Although APS is more common in women than men (82:18), adrenal involvement, when it does occur, occurs more often in men (55%).

APS probably causes adrenal insufficiency via a sequence of venous thrombosis followed by infarct. The adrenals have a rich arterial supply (consistent with their important endocrine function) but only a single vein. On the arterial side, three main suprarenal arteries pierce the gland surface, divide into several small branches, and form a subcapsular plexus. The rich arterial vascularization cascades through the zona glomerulosa, zona fasciculata, and the zona reticularis and then drains into the medullary sinusoids via relatively few small venules that eventually form one large central vein. This drop in cross-sectional area forms a sort of functional “vascular dam.” In addition, medullary veins show an eccentric musculature, which favors the development of pouches of local stasis when bundles contract, and vein contraction is promoted by high catecholamine concentrations that can occur at this level. The anatomy thus may promote venous thrombosis followed by intraglandular hypertension and hemorrhage. When it does occur, adrenal thrombosis/hemorrhage due to APS by thrombosis/hemorrhage is usually bilateral.

Clinical Course

The patient was emergently intubated for worsening hypotension and shock and empirically given broad-spectrum antibiotics. The combination of refractory hypotension, hyperkalemia, and hyponatremia, and evidence of adrenal hemorrhage on CT scan led us to suspect acute adrenal insufficiency. The diagnosis was substantiated by the low serum cortisol levels and positive cosyntropin stimulation test. Adrenal hormone replacement therapy and therapeutic anticoagulation with low-molecular-weight heparin were immediately initiated with remarkable improvement in hemodynamics. The dose of glucocorticoid was adjusted over the next few days with subsequent transfer out of the ICU. In this patient with APS, discontinuation of anticoagulation for an invasive procedure may have precipitated adrenal vein thrombosis, leading to bilateral adrenal hemorrhage and the subsequent shock from adrenal insufficiency.

  • 1. Acute adrenal insufficiency due to bilateral adrenal hemorrhage is a potential complication of APS.

  • 2. Acute adrenal insufficiency is a cause of shock, the early identification of which can be life-saving.

  • 3. The diagnosis of bilateral adrenal hemorrhage can be rapidly made with a CT scan of the abdomen, which will help in the prompt initiation of appropriate therapy.

  • 4. In patients with APS, discontinuation of anticoagulation, even for a brief period, can precipitate vascular thrombosis with grave consequences.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The authors obtained patient permission to publish this information.

Asherson RA, Hughes GR. Recurrent deep vein thrombosis and Addison’s disease in “primary” antiphospholipid syndrome. J Rheumatol. 1989;16(3):378-380. [PubMed]
 
Asherson RA, Khamashta MA, Ordi-Ros J, et al. The “primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989;68(6):366-374. [PubMed]
 
Inam S, Sidki K, al-Marshedy AR, Judzewitsch R. Addison’s disease, hypertension, renal and hepatic microthrombosis in ‘primary’ antiphospholipid syndrome. Postgrad Med J. 1991;67(786):385-388. [CrossRef] [PubMed]
 
Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum. 1992;21(5):275-286. [CrossRef] [PubMed]
 
Ames DE, Asherson RA, Ayres B, et al. Bilateral adrenal infarction, hypoadrenalism and sphincter hemorrhages in the “primary” antiphospholipid syndrome. Br J Rheumatol. 1992;31(2):117-120. [CrossRef] [PubMed]
 
Kawashima A, Sandler CM, Ernst RD, et al. Imaging of nontraumatic hemorrhage of the adrenal gland. Radiographics. 1999;19(4):949-963. [PubMed]
 
Kovacs KA, Lam YM, Pater JL. Bilateral massive adrenal hemorrhage. Assessment of putative risk factors by the case-control method. Medicine (Baltimore). 2001;80(1):45-53. [CrossRef] [PubMed]
 
Vella A, Nippoldt TB, Morris JC III. Adrenal hemorrhage: a 25-year experience at the Mayo Clinic. Mayo Clin Proc. 2001;76(2):161-168. [PubMed]
 
Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361(9372):1881-1893. [CrossRef] [PubMed]
 
Espinosa G, Santos E, Cervera R, et al. Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. Medicine (Baltimore). 2003;82(2):106-118. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Axial and coronal sections of the CT images demonstrating bilateral adrenal hemorrhage (arrows).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Pertinent Laboratory Tests in the Patient With APS

APS=antiphospholipid syndrome; GPL=IgG phospholipid units; MPL=IgM phospholipid units.

Table Graphic Jump Location
Table 2 Risk Factors for Nontraumatic Bilateral Adrenal Hemorrhage

ACTH=adrenocorticotropic hormone; NSAID=nonsteroidal antiinflammatory drug. See Table 1 legend for expansion of other abbreviation.

Suggested Readings

Asherson RA, Hughes GR. Recurrent deep vein thrombosis and Addison’s disease in “primary” antiphospholipid syndrome. J Rheumatol. 1989;16(3):378-380. [PubMed]
 
Asherson RA, Khamashta MA, Ordi-Ros J, et al. The “primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore). 1989;68(6):366-374. [PubMed]
 
Inam S, Sidki K, al-Marshedy AR, Judzewitsch R. Addison’s disease, hypertension, renal and hepatic microthrombosis in ‘primary’ antiphospholipid syndrome. Postgrad Med J. 1991;67(786):385-388. [CrossRef] [PubMed]
 
Alarcón-Segovia D, Pérez-Vázquez ME, Villa AR, Drenkard C, Cabiedes J. Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. Semin Arthritis Rheum. 1992;21(5):275-286. [CrossRef] [PubMed]
 
Ames DE, Asherson RA, Ayres B, et al. Bilateral adrenal infarction, hypoadrenalism and sphincter hemorrhages in the “primary” antiphospholipid syndrome. Br J Rheumatol. 1992;31(2):117-120. [CrossRef] [PubMed]
 
Kawashima A, Sandler CM, Ernst RD, et al. Imaging of nontraumatic hemorrhage of the adrenal gland. Radiographics. 1999;19(4):949-963. [PubMed]
 
Kovacs KA, Lam YM, Pater JL. Bilateral massive adrenal hemorrhage. Assessment of putative risk factors by the case-control method. Medicine (Baltimore). 2001;80(1):45-53. [CrossRef] [PubMed]
 
Vella A, Nippoldt TB, Morris JC III. Adrenal hemorrhage: a 25-year experience at the Mayo Clinic. Mayo Clin Proc. 2001;76(2):161-168. [PubMed]
 
Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361(9372):1881-1893. [CrossRef] [PubMed]
 
Espinosa G, Santos E, Cervera R, et al. Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. Medicine (Baltimore). 2003;82(2):106-118. [CrossRef] [PubMed]
 
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