560
Journal of the Royal Society of Medicine Volume 84 September 1991
and short chain fatty acids and this may in turn affect corneocyte adhesiveness3. This patient's excellent response to therapy underscores the importance of careful dietetic and plasma exchange intervention.
2 Dykes PJ, Marks R, Davies MG, Reynolds DJ. Epidermal metabolism in heredopathia atactica polyneuritiformis (Refsum's disease). J Invest Dermatol 1978;70:126-9 3 Davies MG, Marks R, Dykes PJ, Reynolds D. Epidermal abnormalities in Refsum's disease. Br J Dermatol 1977;97:401-6
References 1 Gibberd FB, Billimoria JD, Goldman JM, et aL Heredopathia atactica polyneuritiformis: Refsum's disease. Acta Neurol Scand 1985;72:1-17
(Accepted 9 April 1991)
Antiphospholipid syndrome and acute adrenal insufficiency -
antibodywas detected in the absence of antibody against ds -DNA -onfirming the diagnosis of the 'primary' APL
A Dorling MRCP G K Knoles MD fUOP Department of Respiratory Medicine-. Kingston Hospital, Galsworthy Road, Cingstqn Upon Thames, Surrey KT2 7QB Keywords: antiphospholipid syndrome; adrenal insuficiency; veneus thrombosis
The anticardiolipin or antiphospholipid (APL) syndrome was first reported in 1985 to describe the association of venous and/or arterial thromboses with antiphospholipid antibody'. The syndrome is mostly encountered in patients with systemic lupus erythematosus but has also been documented as a 'primary' disorder'. Affected patients frequently have a past history of recurrent deep venous thrombosis36. Recent reports suggest that adrenal impairment may be a manifestation of this syndrome4-7. We describe a patient with the 'primary' APL syndrome who developed acute adrenal insufficiency in association with his first episode of venous thrombosis. Case report A previously fit 33-year-old man presented with fever, productive cough, pleuritic pain, vomiting and diarrhoea. He had no past history of venous thrombosis or tuberculosis and had never received corticosteroid therapy. His chest X-ray showed a small left pleural effusion and shadowing at the right lung base. He was treated with- erythromycin for presumed pneumonia. Two days later he developed an extensive deep venous thrombosis, confirmed on venography, followed by breathlessness and haemoptysis suggesting pulmonary embolism. Treatment with heparin was started. His haemoglobin and platelet count was normal at 14.9 g/dl and 292x109/l respectively. His serum sodium concentration subsequently fell from 128 mmolfl to 118 mmol/l and hyperkalaemia developed (potassium 6.5 mmol/l). A short synacthen test confirmed adrenocortical insufficiency (baseline plasma cortisol 30 nmol/l, 45 min after tetracosactrin, 32 nmol/l). Clotting studies prior to starting heparin showed a prolonged PTT at 68 s and PT at 22 s consistent with the presence of antiphospholipid antibody. The ELISA anticardiolipin IgG antibody test was strongly positive. His anti-adrenal antibody test was negative. ANF titre was 1/40 but ds DNA antibody test was negative. He was treated with intravenous hydrocortisone and has since remained well on warfarin and replacement therapy with hydrocortisone 20 mg in the morning aid 10 mg at night.
Discussion Our patient developed acute adrenal insufficiency at the time of his first deep venous thrombosis. Antiphospholipid
. yndrm.
It has- been suggested that the adrenal failure in such patients may be caused by adrenal haemorrhage and/or infarction secondary to vascular occlusion of adrenal vessels (arterial or venous) or perhaps to anticoagulant therapy7. oweve, antigulant control has been rep6rted as generally satisfactory, without evidence of bleeding elsewhere, in atents developing acute adrenal haemorrhage while taking anticoagulants5. Nevertheless recent or previous adrenal haemorrhage of whatever cause has been reported in instances where computerized tomography has been performed in patients with the 'primary' APL syndrome69. In one patient bilateral haemorrhagic adrenal infarction was found in assciation with thrombosis ofthe adrenal capsular veins6. The latter has been postulated as a cause of adrenal haemorrhage/infarction and for anatomical reasons the adrenal veins would appear to be, susweptible to thrombosisl. Anti-adrenal antibody assays when performed have proved negative, as in our patient4'6'11, which has been taken as evidence against an autoimmune cause for the adrenal. impairment4. Our experience suggests that adrenal insufficiency should be consideved in all patients with thromboembolic disease, whether or not there is a past history of recurrent venous thrombosis, particularly if tests for APL antibody are positive. Such tests should always be included in the assessment ofpatients with adrenal insufficiency of unknown cause7. The association of adrenal impairment with the APL yndrome may be.commoner than hitherto appreciated and deserves recognition in standard textbooks of medicine and endocrinology. References 1 Hughes GRV. The anticardiolipin syndrome. Clin Exp Rheum 1985;3:285-6 2 Asherson RA, Khamashta MA, Ordi-Ros J, et al. The 'primary' antiphc6pholipid syndrome: maor clinical and serological features. Medicine 1989;68:366-74 3 Asherson RA, Harris EN. Anticardiolipin antibodies - clinical associations. Postgrad Med J 1986;62:1081-7 4 Asherson RA, Hughes GRV. Recurrent deep vein thrombosis and Addison's disease in 'primary' antiphospholipid syndrome. J Rheumatol 1989;16:378-80 5 Carette S, Jobin F. Acute adrenal insufficiency as a manifestation of the apticardiolipin syndrome? Ann Rheum Dis 1989;48:430-1 6 Yap AS. Lupus anticoagulant. Ann-Intern Med 1989;111:262-3 7 Asherson RA, Hughes GRV. Addison's disease and prinmary antiphospholipid syndrome. Lancet 1989;ii:874 in 8 O'Connell TX, Aston SJ. Acute adrenal anticoagulant therapy. Surg Gynaecol Obstet 1974;139355-7 9 Rao RH, Vagnucci AH, Amico JA. Bilateral massive adrenal haemorrhage: early recognition and treatment. Ann Intern Med 1989-,110:227-35 10 Fox B. Venous infarction of the adrenal glands. J Pathol
1476;119*65-89
11 Pelkonen P, Simell 0, Rasi V, Vaarala 0. Venous thrombosis associated with lupus anticoagulant and anticardiolipin
antibodies. Acta Paediatr Scand 1988;77:767-72
(Accepted 29 April 1991)
Case presented to Clinical Section, 8 June 1990
0141-0768/91/ 090560-01/$02.00/0 © 1991 The Royal Society of Medicine
Journal of the Royal Society of Medicine Volume 84 September 1991
and short chain fatty acids and this may in turn affect corneocyte adhesiveness3. This patient's excellent response to therapy underscores the importance of careful dietetic and plasma exchange intervention.
2 Dykes PJ, Marks R, Davies MG, Reynolds DJ. Epidermal metabolism in heredopathia atactica polyneuritiformis (Refsum's disease). J Invest Dermatol 1978;70:126-9 3 Davies MG, Marks R, Dykes PJ, Reynolds D. Epidermal abnormalities in Refsum's disease. Br J Dermatol 1977;97:401-6
References 1 Gibberd FB, Billimoria JD, Goldman JM, et aL Heredopathia atactica polyneuritiformis: Refsum's disease. Acta Neurol Scand 1985;72:1-17
(Accepted 9 April 1991)
Antiphospholipid syndrome and acute adrenal insufficiency -
antibodywas detected in the absence of antibody against ds -DNA -onfirming the diagnosis of the 'primary' APL
A Dorling MRCP G K Knoles MD fUOP Department of Respiratory Medicine-. Kingston Hospital, Galsworthy Road, Cingstqn Upon Thames, Surrey KT2 7QB Keywords: antiphospholipid syndrome; adrenal insuficiency; veneus thrombosis
The anticardiolipin or antiphospholipid (APL) syndrome was first reported in 1985 to describe the association of venous and/or arterial thromboses with antiphospholipid antibody'. The syndrome is mostly encountered in patients with systemic lupus erythematosus but has also been documented as a 'primary' disorder'. Affected patients frequently have a past history of recurrent deep venous thrombosis36. Recent reports suggest that adrenal impairment may be a manifestation of this syndrome4-7. We describe a patient with the 'primary' APL syndrome who developed acute adrenal insufficiency in association with his first episode of venous thrombosis. Case report A previously fit 33-year-old man presented with fever, productive cough, pleuritic pain, vomiting and diarrhoea. He had no past history of venous thrombosis or tuberculosis and had never received corticosteroid therapy. His chest X-ray showed a small left pleural effusion and shadowing at the right lung base. He was treated with- erythromycin for presumed pneumonia. Two days later he developed an extensive deep venous thrombosis, confirmed on venography, followed by breathlessness and haemoptysis suggesting pulmonary embolism. Treatment with heparin was started. His haemoglobin and platelet count was normal at 14.9 g/dl and 292x109/l respectively. His serum sodium concentration subsequently fell from 128 mmolfl to 118 mmol/l and hyperkalaemia developed (potassium 6.5 mmol/l). A short synacthen test confirmed adrenocortical insufficiency (baseline plasma cortisol 30 nmol/l, 45 min after tetracosactrin, 32 nmol/l). Clotting studies prior to starting heparin showed a prolonged PTT at 68 s and PT at 22 s consistent with the presence of antiphospholipid antibody. The ELISA anticardiolipin IgG antibody test was strongly positive. His anti-adrenal antibody test was negative. ANF titre was 1/40 but ds DNA antibody test was negative. He was treated with intravenous hydrocortisone and has since remained well on warfarin and replacement therapy with hydrocortisone 20 mg in the morning aid 10 mg at night.
Discussion Our patient developed acute adrenal insufficiency at the time of his first deep venous thrombosis. Antiphospholipid
. yndrm.
It has- been suggested that the adrenal failure in such patients may be caused by adrenal haemorrhage and/or infarction secondary to vascular occlusion of adrenal vessels (arterial or venous) or perhaps to anticoagulant therapy7. oweve, antigulant control has been rep6rted as generally satisfactory, without evidence of bleeding elsewhere, in atents developing acute adrenal haemorrhage while taking anticoagulants5. Nevertheless recent or previous adrenal haemorrhage of whatever cause has been reported in instances where computerized tomography has been performed in patients with the 'primary' APL syndrome69. In one patient bilateral haemorrhagic adrenal infarction was found in assciation with thrombosis ofthe adrenal capsular veins6. The latter has been postulated as a cause of adrenal haemorrhage/infarction and for anatomical reasons the adrenal veins would appear to be, susweptible to thrombosisl. Anti-adrenal antibody assays when performed have proved negative, as in our patient4'6'11, which has been taken as evidence against an autoimmune cause for the adrenal. impairment4. Our experience suggests that adrenal insufficiency should be consideved in all patients with thromboembolic disease, whether or not there is a past history of recurrent venous thrombosis, particularly if tests for APL antibody are positive. Such tests should always be included in the assessment ofpatients with adrenal insufficiency of unknown cause7. The association of adrenal impairment with the APL yndrome may be.commoner than hitherto appreciated and deserves recognition in standard textbooks of medicine and endocrinology. References 1 Hughes GRV. The anticardiolipin syndrome. Clin Exp Rheum 1985;3:285-6 2 Asherson RA, Khamashta MA, Ordi-Ros J, et al. The 'primary' antiphc6pholipid syndrome: maor clinical and serological features. Medicine 1989;68:366-74 3 Asherson RA, Harris EN. Anticardiolipin antibodies - clinical associations. Postgrad Med J 1986;62:1081-7 4 Asherson RA, Hughes GRV. Recurrent deep vein thrombosis and Addison's disease in 'primary' antiphospholipid syndrome. J Rheumatol 1989;16:378-80 5 Carette S, Jobin F. Acute adrenal insufficiency as a manifestation of the apticardiolipin syndrome? Ann Rheum Dis 1989;48:430-1 6 Yap AS. Lupus anticoagulant. Ann-Intern Med 1989;111:262-3 7 Asherson RA, Hughes GRV. Addison's disease and prinmary antiphospholipid syndrome. Lancet 1989;ii:874 in 8 O'Connell TX, Aston SJ. Acute adrenal anticoagulant therapy. Surg Gynaecol Obstet 1974;139355-7 9 Rao RH, Vagnucci AH, Amico JA. Bilateral massive adrenal haemorrhage: early recognition and treatment. Ann Intern Med 1989-,110:227-35 10 Fox B. Venous infarction of the adrenal glands. J Pathol
1476;119*65-89
11 Pelkonen P, Simell 0, Rasi V, Vaarala 0. Venous thrombosis associated with lupus anticoagulant and anticardiolipin
antibodies. Acta Paediatr Scand 1988;77:767-72
(Accepted 29 April 1991)
Case presented to Clinical Section, 8 June 1990
0141-0768/91/ 090560-01/$02.00/0 © 1991 The Royal Society of Medicine
