J. Endocrinol. Invest. 16.345-349 , 1993

CASE REPORT

Thrombocythemia and thrombosis of the adrenal vessels B. Barillari*, B. Shapiro**, D. Gasparini***, M. Rocco****, A. Barillari *****, S. Buzzolo******, and E. Moratti****** *IV Divisione Medica, Ospedale Civile di Udine, **Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor, Michigan , USA, ***11 Istituto di Radiologia Ospedale Civile di Udine, ****Istituto di Anatomia Patologica Ospedale Civile di Udine , *****1 Clinica Medica Universita degli Studi di Bologna, ******General Practitoner, Udine, Italy ABSTRACT. The authors describe a case of primary thrombocythemia and thrombosis of the adrenal vessels which they were able to examine by arteriography of the renal and adrenal arteries, by adrenal CT and at autopsy following the patient's death. The available research data and hypotheses concerning the pathogenesis of thrombosis and

hemorrhage in thrombocythemia are reviewed, but the relationship between platelet number and function and the incidence of thrombotic and hemorrhagic complications has not yet been clearly established. Pathogenesis of thrombosis and hemorrhage in suprarenal vessels is not clear and the majority of authors postulate early venous damage.

INTRODUCTION

ocytes; normal range of WBC, RBC and lymphocytes) was incidental, and he underwent cyclical treatment with oncocarbide and thrombocytic antiaggregants (indobufene). A week before admission (May 17, 1986), while at home, where he was continuing the oncocarbide cycles, the patient had developed diarrhea with vomiting, initially of food and then bile. He was in a state of confusion and extreme prostration and agitation . The electrolyte analysis carried out on this occasion showed a marked hyponatremia (126 mEq/l) and severe hyperkalemia (7.8 mEq/I). He was treated with intravenous 0.9% saline solution only. He was again admitted on May 23, 1986, this time to our division: on admission the patient was in severe shock, with unrecordable blood pressure , and in a state of considerable confusion with mental and motor agitation; his skin was cold and sweaty, his lips , extremities and lower limbs cyanosed ; there was a tracheal rattle , and clinical signs of dehydration . The biochemical test carried out immediately after admission showed the following : serum sodium 97 mEq/l , serum potassium 9.6 mEq/l, creatinine 2.7 mg%, osmolarity 294 mOsm/kg, uric acid 9.6 mg%, extremely low serum cortisol (28 ng/ml) and severe metabolic acidosis (pH 7.11 ; pC0 2 51.3 , Bic .St. 15.4; B.E. -11.5 ; P0 2 73 ; HC0 2 18.5) . The ECG showed signs of severe hyperkalemia (Fig .1). The platelet count was 850 ,000/mm3; blood sugar 70 mg/dl. The patient was treated with iv glucocorticoids (methylprednisolone 1 g), 0.9% saline and 10% glu-

Hemorrhage and thrombosis are the frequent complications encountered in patients suffering from myeloproliferative disorders, although there is disagreement among the various authors as to their exact incidence (1-5). Thrombosis is prevalent in polycythemia vera, while in essential thrombocythemia, idiopathic myelofibrosis and myeloid metaplasia , hemorrhage is more common (6 , 7) . It has also been noted that some patients, during the course of their illness, experience periods of both bleeding and thrombosis (8). Published experience furthermore suggests that older patients are more likely to suffer from these complications and that the risk of thrombosis increases markedly after 70 yr of age. CASE REPORT The patient (71-year-old male) was twice hospitalized for heart failure in another division during 1985; the diagnosis of thrombocytemia (WBC 7.7x103; RBC 5.8x10 6 , Platelets 1,140,000/mm3; Hb 15.8 gr./dl; PCV 48%; MCV 82113; MCH 32 pg; MCHC 26 ,5%. Bone marrow aspiration: absence of the Philadelphia chromosome, increase of megakary-

Key-words. Adrenal vessels , thrombocytemia, thrombosis Correspondence: B. Barillari MD .. Via Aonez 1. 33100 Udine, Italy. Received September 13. 1990; accepted March 1. 1993 .

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B. Barillari, B. Shapiro, 0. Gasparini, et al.

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cose solution and recovered rapidly with normalization of the blood pressure in few h; normalization of the serum sodium was observed within three days and that of the hyperkalemia within ten. The ECG also returned to normal after few days. The urinalysis and chest X ray were negative and the patient was non-febrile for the entire period of hospitalization. He was subsequently managed by means of glucocorticoid and mineralcorticoid therapy, with the

resulting stabilization of the blood pressure in the normal range (120/60 - 140/60) and of the platelets at around 350,000/mm3 Subsequently, because of the clinical suspicion of adrenal infarction, in addition to his routine followup, the patient underwent selective arteriography of the renal and adrenal arteries, which showed, on the left, the complete absence of opacification and vascularization of the adrenal arteries, and on the right, two avascular areas (Fig. 2): with the reser-

Fig. 2 - Combined renal and adrenal arteriography showing normal renal vasculature and total absence of adrenal vascular opacification on the left and defects on the right.

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Thrombocythemia and thrombosis of adrenal vessels

vations due to the limited sensitivity of the technique, the radiologist formulated a diagnosis of bilateral adrenal infarction (9-13). The adrenal CT Scan (Fig . 3) showed both adrenal glands to be enlarged and inhomogeneous, with a nonspecific appearance, nevertheless compatible with significant vascular damage. The platelet count, which had remained within normal levels for about two months , rose to 750,000/mm3 at the time of discharge from hospital. Some months later, the patient was readmitted to hospital with left ventricular insufficiency, and febrile right basal Pseudomonas aeruginosa pneumonia which led to death within few days. Autopsy con-

firmed the clinical diagnoses; the adrenal glands were slightly enlarged and revealed, when incised, multiple small soft whitish nodules. Upon histological examination the nodules were found to be composed of fibrinoid necrosis surrounded by a lymphocytic valium. The adrenal parenchyma was compressed. The above-mentioned histological features of the adrenal glands were indicative of ischemic areas (Fig. 4); the histological and immunhistochemical examination ruled out tubercular disease of the adrenal glands. The diagnosis of ischemia is thus based on criteria of exclusion in analogy with other cases already described in the literature (14). Autopsy also demonstrated a small right cerebellar ischemic infarction, although the patient had never reported any episodes of transient ischemic attacks. DISCUSSION

Thrombosis of the adrenal vessels is rarely observed in the course of myeloproliferative disorders, but when it is, polycytemia vera and essential thrombocytemia are those most commonly involved . Acute adrenal insufficiency may be secondary to infectious or viral diseases, surgery, acute gastroduodenitis, profuse sweating, hematological disorders, anticoagulant therapy, septicemia, widespread burns, trauma, ACTH treatment, dystocia, diabetes, shock and cardiovascular disease. Berte (15) has suggested a classification of adrenal hemorrhage in four groups according to their different etiologies (16). The role of adrenal vein thrombosis, due to considerations of adrenal vascular anatomy, is described as the most frequent cause by Fox et al. (14, 17): in these reports no thrombosis of the adrenal capsular arteries in the studied cases was seen, but only vascular fibrosis and fibrin deposits on the endothelial wall of the capsular an intercapsular arterial vessels; venous thrombosis was postulated to be; the principal cause of adrenal hemorrhage and necrosis. Others (15,18-20) have hypothesized that venous thrombosis is not the only cause of adrenal infarction, that might be secondary to a severe, prolonged reduction of blood flow due to arterial spasms or shock, with parenchymal damage followed by thrombosis of the adrenal arteries and veins; arterial spasm might be secondary to venous thrombosis . According to Greendjke (21), venous thrombosis is secondary to parenchymal necrosis, at least in a certain percentage of cases . This author maintains that venous thrombosis is not always

Fig. 3 - Abdominal CT showing an enlarged right and left adrenal gland. The central area of the right gland is hypodense and solid. Note the presence of significant splenomegaly.

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B. Bariiiari, B. Shapiro, D. Gasparini, et al.

Fig. 4 - Histological evidence of adrenal necrosis.

present in adrenal infarction and vice versa (21). In the patient we treated, besides the clinical and laboratory data documenting acute adrenal insufficiency, which regressed after cortisone therapy, it was possibile to document the nonopacification of the adrenal arteries upon arteriography (9-13) and the increase of adrenal volume by CT scan (24), while the post mortem histological examination of the adrenal glands ruled out foci of tubercular disease and confirmed adrenal infarction. The debatable point is whether the primary cause was thrombosis or acute gastroenteritis with subsequent acute adrenal insufficiency, as the vomiting and diarrhea may have been primarily due to Addisonian crisis, or intercurrent vomiting and diarrhea may have led to dehydration and hemoconcentration, thus further increasing the thrombogenic potential of the blood, followed by adrenal vascular thrombosis and subsequent adrenal failure.

3. Murphy S. Thrombocytosis and thrombocythemia. Clin. Haematol. 12:89,1983. 4. Preston F.E., Emmanuel J.G., Winfield DA, Malia R.G. Essential thrombocythemia and peripheral gangrene. Br. Med. J. 3: 548, 1974.

5. Singh AK., Wetherley-Mein G. Microvascular occlusive lesion in primary thrombocythemia. Br. J. Haematol. 36: 553,1977. 6. Randi M.L., Fabris F., Girolami A. Thrombocytosis in young people: evaluation of 57 cases diagnosed before the age of 40. Blut 60: 233, 1990. 7. Randi M.L., Casonato A., Fabris F., Vito C., Girolami

A

The significance of thrombocytosis in old age. Acta Haematol. 78: 41, 1987. 8. Schafer AI. Bleeding and thrombosis in the myeloproliferative disorders. Blood 64: 1, 1984.

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9. De Maria M., Lanconi A, Lagalla R. Diagnostic images of adrenal glands. La Radiologia Medica 75: 219, 1988. 10. Lindvall N., Slezak P. Arteriography of the adrenals. Radiology 99: 999, 1969.

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12. Roversi R., Golfieri R., Rossi C., Gemelli G. Digital subtraction angiography of renal and adrenal vessels. Applications and suggestions. La Radiologia Medica 71: 740, 1985. 13. Ziosi A. Clinical experiences of digital subtraction angiography. Aulo Gaggi Editore, Bologna, Aprile 1990, p. 107. 14. FoxB. Venous infarction of the adrenal glands. Journal Pathoi. 119: 65, 1976. 15. Berte S.J. Spontaneous adrenal hemorrhage in the adult: Literature review and report of two cases. Ann. Int. Med. 38: 28, 1953. 16. Mitchell N., Angrist A. Focal necrosis of the adrenal cortex. Am. J. Med. Sciences 205: 549, 1943. 17. Botteri A., Orell S.R. Adrenal hemorrhage and necrosis in the adult: A clinicopathological study of 23 cases. ActaMed.Scand. 175, 4:409,1964. 18. Hutt M.S.R., Pinniger J.L. Adrenal failure due to bilateral suprarenal infarction associated with systemic nodular panniculi-

tis and endoarteritis. J. Clin. Pathoi. 9: 316, 1956. 19. Sheen han H.L. Infarctus hemorragique du cortex surrenal dans la grossesse. Ann. Endocrinol. (Paris) 16: 687,1955. 20. Thrash A.M., Iri H. Adrenal infarction six cases reports. Arch. Pathoi. 75: 538, 1963. 21. Greendyke R.M. Adrenal hemorrhage. Am. J. Clin. Pathoi. 43: 210, 1965. 22. Ling D., Korobkin M., Silverman P.M., Dunnick N.R. CT demonstration of bilateral adrenal hemorrhage. AJR 141:307,1983. 23. Siu S.C.B., Kitzman OW., Sheedy P.F., Northcutt R.C. Adrenal insufficiency from bilateral adrenal hemorrhage. Mayo Clin. Proc. 65: 664, 1990. 24. Wolverson M.K., Kannegeiser H. CT of bilateral adrenal hemorrhage with acute adrenal insufficiency in the adult. AJR 1542: 311, 1984.

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