- Email: [email protected]
Unusual Cause of Adrenal Insufficiency
Accepted Manuscript An Unusual Cause of Adrenal Insufficiency Cherng Jye Seow, MBBS, MRCPS(Glas), FRCP(Edin), Abel Weiliang Chen, MBBS PII:
S0002-9343(16)30452-1
DOI:
10.1016/j.amjmed.2016.04.014
Reference:
AJM 13501
To appear in:
The American Journal of Medicine
Received Date: 28 March 2016 Revised Date:
14 April 2016
Accepted Date: 14 April 2016
Please cite this article as: Seow CJ, Chen AW, An Unusual Cause of Adrenal Insufficiency, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.04.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page Title:
An Unusual Cause of Adrenal Insufficiency.
1.
RI PT
Authors:
Cherng Jye Seow, MBBS, MRCPS(Glas), FRCP(Edin), Department of Endocrinology, Tan Tock Seng Hospital
Abel Weiliang Chen, MBBS, Department of Endocrinology, Tan Tock Seng Hospital
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2.
M AN U
Corresponding Author:
Cherng Jye Seow, MBBS, MRCPS(Glas), FRCP(Edin)
Department of Endocrinology, Tan Tock Seng Hospital; 11 Jalan Tan Tock Seng Singapore 308433. Email: [email protected]
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Article Type:
Images in Radiology
EP
Funding Sources:
Nil
AC C
Key Words:
Adrenal Hemorrhage, Anti Phospholipid Syndrome, Adrenal Insufficiency
Conflict of Interest Statement
The authors have no multiplicity of interest to disclose.
Declaration
All authors had access to the data and a role in writing the manuscript
ACCEPTED MANUSCRIPT
PRESENTATION Primary adrenal insufficiency is uncommon, with autoimmune adrenalitis accounting for the overwhelming majority of cases in developed countries. We present a patient with primary adrenal insufficiency, with quite
RI PT
an unexpected underlying cause.
A 59-year-old housewife of Chinese ethnicity presented to our Emergency Department with a 2-year history of nausea, bilateral flank pain and weight loss for investigation. The flank pain had no preceding trauma and was non-mechanical in nature. It was not associated with fever, early morning stiffness, urinary symptoms or
SC
radiculopathy. There were no other joint pains, mouth ulcers or rashes. She also complained of poor appetite and a weight loss of 8kg over the past 2 years, as well as generalized fatigue which worsened with minor
nor night sweats, fevers or hemoptysis.
M AN U
ailments such as upper respiratory tract infections. She did not report any other symptoms of thyrotoxicosis,
Of note, her family members had commented that she had been looking more tanned over the past year despite infrequent sun-exposure.
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ASSESSMENT
EP
or supplements.
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She had no other significant medical, surgical or obstetric history of note, and denied taking any medications
Physical examination revealed conjunctival pallor and a tanned appearance with hyperpigmentation over the 2
palmar creases, elbows and buccal mucosa. Her BMI was 17.9kg/m . Postural hypotension was elicited (Supine: 125/65mmHg, Standing: 105/60mmHg).
Initial laboratory tests performed showed anemia, transminitis and a deranged coagulation profile which failed to correct after mixing studies: hemoglobin level 8.8 g/dL (11-15 g/dL), white blood cell count 8.7 X 109/L (3.69.3 x 109/L), platelet count 246 x 109/L (170-420 x 109 /L), erythrocyte sedimentation rate 122 mm/hr (3-15 mm/hr), prothrombin time 14 s (11.7-14 s), aPTT 41.8 s (25-36 s), aPTT after mixing study 36.6 s (25-36 s), alanine aminotransferase 47 U/L (14-54 U/L), aspartate aminotransferase 44 U/L (14-41 U/L), alkaline
ACCEPTED MANUSCRIPT phosphatase 162 U/L (38-126 U/L), gamma-glutamyl transferase 164 U/L (7-50 U/L). Her electrolytes were normal: sodium 136 mmol/l (134-144 mmol/l), potassium 3.8 mmol/L(3.5-5.0 mmol/L), creatinine 42 mmol/L(40-75 mmol/L), urea 4.9 mmol/L (2.9-9.3 mmol/L).
She developed a fever shortly after admission, with no obvious localizing signs or symptoms of infection. In
RI PT
view of her fever, transaminitis and flank pain, an ultrasound of the abdomen was done to evaluate for a hepatobiliary source of sepsis. The ultrasound scan showed no obvious source of sepsis but revealed an
incidental 5.7 x 2.4x 3.5 cm mass in the right adrenal. A subsequent CT scan showed that this was actually an
SC
area of acute adrenal hemorrhage, with the left adrenal gland similarly affected as well. (Fig. 1)
The serendipitous finding of bilateral adrenal hemorrhages, together with her postural hypotension,
M AN U
borderline low blood pressure in the ward (systolic blood pressure averaging 100mmHg) and tanned appearance fitted neatly into the diagnosis of primary adrenal insufficiency. Further tests confirmed decreased glucocorticoid, mineralocorticoid and adrenal androgen levels, with high adrenocorticotropic hormone levels. The results were as follows: adenocorticotrophic hormone 194 pmol/L (<10.2 pmol/L), cortisol (0, 30, 60 minutes after 250mcg Cosyntropin stimulation test) 35 >34>35 nmol/L, aldosterone < 31 pmol/L (28-445
(0.51-5.56 umol/L).
TE D
pmol/L), renin 4.96 ng/ml/hr (0.15-2.33 ng/ml/hr) and dehydroepiandrosterone sulfate (DHEA-S) 0.05 umol/L
Further blood tests were done to find out the cause of the hemorrhages. In view of the coagulation profile and
EP
mixing study suggesting the presence of an inhibitor, as well as radiological evidence of hemorrhage, an autoimmune screen was also performed: anti beta 2 glycoprotein 174 RU/mL (<20 RU/mL); anti-cardiolipin
AC C
IgM 77 (<10U/Ml); anti-cardiolipin IgG 85 (<10 U/ml), lupus anticoagulant: strongly positive. All other autoimmune markers including rheumatoid factor, anti-nuclear antibody, anti-dsDNA, anti-Scl-70, anti-Ro and anti-La returned negative. A screen for common causes of thrombophilia was done: anti-thrombin III 120% (80130%), activated protein C resistance test 0.86 (1-1.3), protein C activity 132% (70-150%), protein S activity 44 (55-130%), factor V Leiden normal (wild type), homocysteine 7 umol/L (4-15 umol/L).
Magnetic Resonance Imaging(MRI) of the adrenal glands (Fig. 2A - Pre-Contrast and 2B – Post-Contrast) was performed after discussion with the radiologist to assess for the presence of adrenal vein thrombosis leading
ACCEPTED MANUSCRIPT 1
to a hemorrhagic infarction , which would strongly suggest an underlying thrombophilia. Unfortunately, this could not be conclusively demonstrated through the images taken.
RI PT
DIAGNOSIS The diagnosis of primary adrenal insufficiency secondary to bilateral adrenal hemorrhage associated with primary antiphospholipid syndrome was made in view of a blunted response to 250mcg of Cosyntropin with
SC
very high levels of adenocorticotrophic hormone, radiological signs of adrenal hemorrhages as well as the presence of associated antibodies without clinical evidence of concomitant rheumatological conditions such as 2
M AN U
systemic lupus erythematosus .
MANAGEMENT
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The patient was promptly started on hydrocortisone and fludrocortisone, with the doses gradually converted to oral form and tapered to replacement levels. Endoscopy proved negative for any gastrointestinal malignancy or hemorrhage. A CT scan of the thorax, abdomen and pelvis was done in view of the thrombotic episode (postulated haemorrhage secondary to adrenal vein thrombosis) as well as long standing weight loss,
EP
but it showed no signs of malignancy. Anticoagulation is the mainstay of therapy to prevent future thrombotic events in antiphospholipid syndrome.
3,4
As such, subcutaneous enoxaparin was commenced in our patient,
AC C
with subsequent conversion to life-long warfarin therapy. Our patient thereafter reported marked improvements in her lethargy and appetite, and continued to follow-up regularly with the Endocrine clinic after her discharge.
Antiphospholipid syndrome is characterized by thrombotic tendencies in the presence of antiphospholipid antibodies which target negatively charged phospholipids and plasma protein complexes such as beta 2 5
glycoprotein. The mechanism of how this results in thrombosis, while not completely elucidated, is hypothesized to involve the inhibition of natural anticoagulants, activation of platelets and endothelial cells,
ACCEPTED MANUSCRIPT 6
with subsequent blocking of the fibrinolytic system and triggering of the complement cascade. These changes, coupled with innate inflammatory responses, is probably necessary to initiate the thrombosis.
7
The adrenal vasculature, on the other hand, is also anatomically predisposed to the development of thrombosis and consequent hemorrhagic infarction. The adrenal glands have a rich arterial supply which drains
RI PT
into the medullary sinusoids by relatively few venules that eventually form a central vein. This results in a functional bottleneck at the level of the zona reticularis due to the abrupt transition from the arterial to
capillary system. Additionally, the eccentrically arranged musculature of adrenal veins may promote the 8,9,10
SC
formation of thrombi in areas of local stasis due to their contraction.
Adrenal hemorrhages seem to be uncommon in antiphospholipid syndrome, with a study showing that 4 out
M AN U
of 228 (1.75%) of patients with elevated levels of lupus anticoagulant or anti-cardiolipin antibodies showed 1
radiological (3 patients) or autopsy evidence (1 patient) of adrenal hemorrhage. The diagnosis of adrenal hemorrhage used to be an exclusively post-mortem diagnosis before the advent of advanced imaging. As CT and MRI imaging become more readily available, it is suggested that more of such events will be picked up at an earlier stage.
11
TE D
As part of the follow-up for this patient, an MRI of the adrenal glands was done 6 months later (Fig. 3) which indicated a significant regression in the size of the adrenal masses (1.5 cm on the right and 0.9cm on the left). An MRI 20 months later (Fig. 4) showed normal-thickness adrenal glands with resolution of hemorrhage.
EP
Despite the improvement seen on radiological imaging, complete adrenal insufficiency persists and the patient continues to require both glucocorticoid and mineralocorticoid replacement 5 years after diagnosis. This is
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consistent with a recent case series showing that the majority of similarly affected patients have irreversible 12
and complete adrenal failure . This case illustrates the index of suspicion needed to diagnose adrenal insufficiency, the importance of considering antiphospholipid syndrome in patients with unexplained adrenal hemorrhage, as well the high likelihood of persistent adrenal insufficiency despite resolution of the hemorrhage.
REFERENCES
ACCEPTED MANUSCRIPT (1) Provenzale, J.M., Ortel T.L., Nelson R.C. Adrenal hemorrhage in patients with primary antiphospholipid syndrome: imaging findings. AJR Am J Roentgenol 1995;165:361 (2) Miyakis S., Lockshin M.D., Atsumi T., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost.
RI PT
2006;4(12)295 (3) Ruiz-Irastorza, G., Cuadrado, M.J., Ruiz-Arruza, I., et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive
patients: report of a task force at the 13th International Congress on antiphospholipid antibodies.
SC
Lupus 2011;20:206
(4) Rao, R.H. Bilateral Massive adrenal hemorrhage. Med Clin North Am 1995;79:107
M AN U
(5) Ruiz-Irastorza, G., Crowther, M., Branch, W., et al. Antiphospholipid syndrome. Lancet 2010;376:1498-509
(6) Palomo, I., Segovia, F., Alarcon, M., et al. An insight into the pathophysiology of thrombosis in antiphospholipid syndrome. Front Biosci 2007;12:3093-103
(7) Meroni, P., Borghi, M., Raschi, E., et al. Pathogenesis of antiphospholipid syndrome: understanding
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the antibodies. Nat Rev Rheumatol 2011;7:330-9 (8) Espinosa, G., Santos, E., Cervera, R., et al. Adrenal involvement in the antiphospholipid syndrome. Clinical and immunologic characteristics of 86 patients. Medicine 2003, 82:106
EP
(9) Berneis K., Buitrago-Tellez C., Muller B., et al. Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis? European Journal of Hematology 2003;71:299-30
AC C
(10) Fox B. Venous infarction of the adrenal glands. J Pathol 1976;119:65-89 (11) Caron, P., Chabannier, M., Cambus, J., et al. Definitive adrenal insufficiency due to bilateral hemorrhage and primary antiphospholpid syndrome. J Clin Endocrinol Metab 1998;83(5):1437-9
(12) Ramon, I., Mathian, A., Bachelot, A., et al. Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab 2013;98(8):3179
ACCEPTED MANUSCRIPT
LEGEND Figure 1: Non-contrast enhanced CT showing bilateral adrenal enlargement and hyperattenuation, consistent with acute haemorrhage. Figure 2A: MRI of adrenal glands at presentation (Pre-Contrast).
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Figure 2B: MRI of adrenal glands at presentation (Post-Contrast). The heterogenous T1 hyperintense masses (2.0 x 3.9 cm on the right and 1.9 x 3.4 cm on the left, shown with arrows) without central enhancement are indicative of haematomas. There is a smooth, thin rim enhancement consistent with a benign etiology. Figure 3: MRI of adrenal glands at 6 months post-diagnosis showing marked reduction in size of adrenal hemorrhages.
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Figure 4: MRI of adrenal glands at 20 months post diagnosis showing complete resolution of adenal hemorrhages.
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S0002-9343(16)30452-1
DOI:
10.1016/j.amjmed.2016.04.014
Reference:
AJM 13501
To appear in:
The American Journal of Medicine
Received Date: 28 March 2016 Revised Date:
14 April 2016
Accepted Date: 14 April 2016
Please cite this article as: Seow CJ, Chen AW, An Unusual Cause of Adrenal Insufficiency, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.04.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title Page Title:
An Unusual Cause of Adrenal Insufficiency.
1.
RI PT
Authors:
Cherng Jye Seow, MBBS, MRCPS(Glas), FRCP(Edin), Department of Endocrinology, Tan Tock Seng Hospital
Abel Weiliang Chen, MBBS, Department of Endocrinology, Tan Tock Seng Hospital
SC
2.
M AN U
Corresponding Author:
Cherng Jye Seow, MBBS, MRCPS(Glas), FRCP(Edin)
Department of Endocrinology, Tan Tock Seng Hospital; 11 Jalan Tan Tock Seng Singapore 308433. Email: [email protected]
TE D
Article Type:
Images in Radiology
EP
Funding Sources:
Nil
AC C
Key Words:
Adrenal Hemorrhage, Anti Phospholipid Syndrome, Adrenal Insufficiency
Conflict of Interest Statement
The authors have no multiplicity of interest to disclose.
Declaration
All authors had access to the data and a role in writing the manuscript
ACCEPTED MANUSCRIPT
PRESENTATION Primary adrenal insufficiency is uncommon, with autoimmune adrenalitis accounting for the overwhelming majority of cases in developed countries. We present a patient with primary adrenal insufficiency, with quite
RI PT
an unexpected underlying cause.
A 59-year-old housewife of Chinese ethnicity presented to our Emergency Department with a 2-year history of nausea, bilateral flank pain and weight loss for investigation. The flank pain had no preceding trauma and was non-mechanical in nature. It was not associated with fever, early morning stiffness, urinary symptoms or
SC
radiculopathy. There were no other joint pains, mouth ulcers or rashes. She also complained of poor appetite and a weight loss of 8kg over the past 2 years, as well as generalized fatigue which worsened with minor
nor night sweats, fevers or hemoptysis.
M AN U
ailments such as upper respiratory tract infections. She did not report any other symptoms of thyrotoxicosis,
Of note, her family members had commented that she had been looking more tanned over the past year despite infrequent sun-exposure.
AC C
ASSESSMENT
EP
or supplements.
TE D
She had no other significant medical, surgical or obstetric history of note, and denied taking any medications
Physical examination revealed conjunctival pallor and a tanned appearance with hyperpigmentation over the 2
palmar creases, elbows and buccal mucosa. Her BMI was 17.9kg/m . Postural hypotension was elicited (Supine: 125/65mmHg, Standing: 105/60mmHg).
Initial laboratory tests performed showed anemia, transminitis and a deranged coagulation profile which failed to correct after mixing studies: hemoglobin level 8.8 g/dL (11-15 g/dL), white blood cell count 8.7 X 109/L (3.69.3 x 109/L), platelet count 246 x 109/L (170-420 x 109 /L), erythrocyte sedimentation rate 122 mm/hr (3-15 mm/hr), prothrombin time 14 s (11.7-14 s), aPTT 41.8 s (25-36 s), aPTT after mixing study 36.6 s (25-36 s), alanine aminotransferase 47 U/L (14-54 U/L), aspartate aminotransferase 44 U/L (14-41 U/L), alkaline
ACCEPTED MANUSCRIPT phosphatase 162 U/L (38-126 U/L), gamma-glutamyl transferase 164 U/L (7-50 U/L). Her electrolytes were normal: sodium 136 mmol/l (134-144 mmol/l), potassium 3.8 mmol/L(3.5-5.0 mmol/L), creatinine 42 mmol/L(40-75 mmol/L), urea 4.9 mmol/L (2.9-9.3 mmol/L).
She developed a fever shortly after admission, with no obvious localizing signs or symptoms of infection. In
RI PT
view of her fever, transaminitis and flank pain, an ultrasound of the abdomen was done to evaluate for a hepatobiliary source of sepsis. The ultrasound scan showed no obvious source of sepsis but revealed an
incidental 5.7 x 2.4x 3.5 cm mass in the right adrenal. A subsequent CT scan showed that this was actually an
SC
area of acute adrenal hemorrhage, with the left adrenal gland similarly affected as well. (Fig. 1)
The serendipitous finding of bilateral adrenal hemorrhages, together with her postural hypotension,
M AN U
borderline low blood pressure in the ward (systolic blood pressure averaging 100mmHg) and tanned appearance fitted neatly into the diagnosis of primary adrenal insufficiency. Further tests confirmed decreased glucocorticoid, mineralocorticoid and adrenal androgen levels, with high adrenocorticotropic hormone levels. The results were as follows: adenocorticotrophic hormone 194 pmol/L (<10.2 pmol/L), cortisol (0, 30, 60 minutes after 250mcg Cosyntropin stimulation test) 35 >34>35 nmol/L, aldosterone < 31 pmol/L (28-445
(0.51-5.56 umol/L).
TE D
pmol/L), renin 4.96 ng/ml/hr (0.15-2.33 ng/ml/hr) and dehydroepiandrosterone sulfate (DHEA-S) 0.05 umol/L
Further blood tests were done to find out the cause of the hemorrhages. In view of the coagulation profile and
EP
mixing study suggesting the presence of an inhibitor, as well as radiological evidence of hemorrhage, an autoimmune screen was also performed: anti beta 2 glycoprotein 174 RU/mL (<20 RU/mL); anti-cardiolipin
AC C
IgM 77 (<10U/Ml); anti-cardiolipin IgG 85 (<10 U/ml), lupus anticoagulant: strongly positive. All other autoimmune markers including rheumatoid factor, anti-nuclear antibody, anti-dsDNA, anti-Scl-70, anti-Ro and anti-La returned negative. A screen for common causes of thrombophilia was done: anti-thrombin III 120% (80130%), activated protein C resistance test 0.86 (1-1.3), protein C activity 132% (70-150%), protein S activity 44 (55-130%), factor V Leiden normal (wild type), homocysteine 7 umol/L (4-15 umol/L).
Magnetic Resonance Imaging(MRI) of the adrenal glands (Fig. 2A - Pre-Contrast and 2B – Post-Contrast) was performed after discussion with the radiologist to assess for the presence of adrenal vein thrombosis leading
ACCEPTED MANUSCRIPT 1
to a hemorrhagic infarction , which would strongly suggest an underlying thrombophilia. Unfortunately, this could not be conclusively demonstrated through the images taken.
RI PT
DIAGNOSIS The diagnosis of primary adrenal insufficiency secondary to bilateral adrenal hemorrhage associated with primary antiphospholipid syndrome was made in view of a blunted response to 250mcg of Cosyntropin with
SC
very high levels of adenocorticotrophic hormone, radiological signs of adrenal hemorrhages as well as the presence of associated antibodies without clinical evidence of concomitant rheumatological conditions such as 2
M AN U
systemic lupus erythematosus .
MANAGEMENT
TE D
The patient was promptly started on hydrocortisone and fludrocortisone, with the doses gradually converted to oral form and tapered to replacement levels. Endoscopy proved negative for any gastrointestinal malignancy or hemorrhage. A CT scan of the thorax, abdomen and pelvis was done in view of the thrombotic episode (postulated haemorrhage secondary to adrenal vein thrombosis) as well as long standing weight loss,
EP
but it showed no signs of malignancy. Anticoagulation is the mainstay of therapy to prevent future thrombotic events in antiphospholipid syndrome.
3,4
As such, subcutaneous enoxaparin was commenced in our patient,
AC C
with subsequent conversion to life-long warfarin therapy. Our patient thereafter reported marked improvements in her lethargy and appetite, and continued to follow-up regularly with the Endocrine clinic after her discharge.
Antiphospholipid syndrome is characterized by thrombotic tendencies in the presence of antiphospholipid antibodies which target negatively charged phospholipids and plasma protein complexes such as beta 2 5
glycoprotein. The mechanism of how this results in thrombosis, while not completely elucidated, is hypothesized to involve the inhibition of natural anticoagulants, activation of platelets and endothelial cells,
ACCEPTED MANUSCRIPT 6
with subsequent blocking of the fibrinolytic system and triggering of the complement cascade. These changes, coupled with innate inflammatory responses, is probably necessary to initiate the thrombosis.
7
The adrenal vasculature, on the other hand, is also anatomically predisposed to the development of thrombosis and consequent hemorrhagic infarction. The adrenal glands have a rich arterial supply which drains
RI PT
into the medullary sinusoids by relatively few venules that eventually form a central vein. This results in a functional bottleneck at the level of the zona reticularis due to the abrupt transition from the arterial to
capillary system. Additionally, the eccentrically arranged musculature of adrenal veins may promote the 8,9,10
SC
formation of thrombi in areas of local stasis due to their contraction.
Adrenal hemorrhages seem to be uncommon in antiphospholipid syndrome, with a study showing that 4 out
M AN U
of 228 (1.75%) of patients with elevated levels of lupus anticoagulant or anti-cardiolipin antibodies showed 1
radiological (3 patients) or autopsy evidence (1 patient) of adrenal hemorrhage. The diagnosis of adrenal hemorrhage used to be an exclusively post-mortem diagnosis before the advent of advanced imaging. As CT and MRI imaging become more readily available, it is suggested that more of such events will be picked up at an earlier stage.
11
TE D
As part of the follow-up for this patient, an MRI of the adrenal glands was done 6 months later (Fig. 3) which indicated a significant regression in the size of the adrenal masses (1.5 cm on the right and 0.9cm on the left). An MRI 20 months later (Fig. 4) showed normal-thickness adrenal glands with resolution of hemorrhage.
EP
Despite the improvement seen on radiological imaging, complete adrenal insufficiency persists and the patient continues to require both glucocorticoid and mineralocorticoid replacement 5 years after diagnosis. This is
AC C
consistent with a recent case series showing that the majority of similarly affected patients have irreversible 12
and complete adrenal failure . This case illustrates the index of suspicion needed to diagnose adrenal insufficiency, the importance of considering antiphospholipid syndrome in patients with unexplained adrenal hemorrhage, as well the high likelihood of persistent adrenal insufficiency despite resolution of the hemorrhage.
REFERENCES
ACCEPTED MANUSCRIPT (1) Provenzale, J.M., Ortel T.L., Nelson R.C. Adrenal hemorrhage in patients with primary antiphospholipid syndrome: imaging findings. AJR Am J Roentgenol 1995;165:361 (2) Miyakis S., Lockshin M.D., Atsumi T., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost.
RI PT
2006;4(12)295 (3) Ruiz-Irastorza, G., Cuadrado, M.J., Ruiz-Arruza, I., et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive
patients: report of a task force at the 13th International Congress on antiphospholipid antibodies.
SC
Lupus 2011;20:206
(4) Rao, R.H. Bilateral Massive adrenal hemorrhage. Med Clin North Am 1995;79:107
M AN U
(5) Ruiz-Irastorza, G., Crowther, M., Branch, W., et al. Antiphospholipid syndrome. Lancet 2010;376:1498-509
(6) Palomo, I., Segovia, F., Alarcon, M., et al. An insight into the pathophysiology of thrombosis in antiphospholipid syndrome. Front Biosci 2007;12:3093-103
(7) Meroni, P., Borghi, M., Raschi, E., et al. Pathogenesis of antiphospholipid syndrome: understanding
TE D
the antibodies. Nat Rev Rheumatol 2011;7:330-9 (8) Espinosa, G., Santos, E., Cervera, R., et al. Adrenal involvement in the antiphospholipid syndrome. Clinical and immunologic characteristics of 86 patients. Medicine 2003, 82:106
EP
(9) Berneis K., Buitrago-Tellez C., Muller B., et al. Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis? European Journal of Hematology 2003;71:299-30
AC C
(10) Fox B. Venous infarction of the adrenal glands. J Pathol 1976;119:65-89 (11) Caron, P., Chabannier, M., Cambus, J., et al. Definitive adrenal insufficiency due to bilateral hemorrhage and primary antiphospholpid syndrome. J Clin Endocrinol Metab 1998;83(5):1437-9
(12) Ramon, I., Mathian, A., Bachelot, A., et al. Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab 2013;98(8):3179
ACCEPTED MANUSCRIPT
LEGEND Figure 1: Non-contrast enhanced CT showing bilateral adrenal enlargement and hyperattenuation, consistent with acute haemorrhage. Figure 2A: MRI of adrenal glands at presentation (Pre-Contrast).
RI PT
Figure 2B: MRI of adrenal glands at presentation (Post-Contrast). The heterogenous T1 hyperintense masses (2.0 x 3.9 cm on the right and 1.9 x 3.4 cm on the left, shown with arrows) without central enhancement are indicative of haematomas. There is a smooth, thin rim enhancement consistent with a benign etiology. Figure 3: MRI of adrenal glands at 6 months post-diagnosis showing marked reduction in size of adrenal hemorrhages.
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Figure 4: MRI of adrenal glands at 20 months post diagnosis showing complete resolution of adenal hemorrhages.
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