Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Acute abdominal pain in a man with Cushing syndrome M. Rahmanian, J. J. Nedooshan, S. Rafat, R. Rafie, M. Rafiei & R. N. Moghadam To cite this article: M. Rahmanian, J. J. Nedooshan, S. Rafat, R. Rafie, M. Rafiei & R. N. Moghadam (2015) Acute abdominal pain in a man with Cushing syndrome, Acta Clinica Belgica, 70:5, 372-374, DOI: 10.1179/2295333715Y.0000000025 To link to this article: http://dx.doi.org/10.1179/2295333715Y.0000000025
Published online: 06 May 2015.
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Article views: 11
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20 Download by: [University of Western Ontario]
Date: 16 March 2016, At: 08:25
Case Report
Acute abdominal pain in a man with Cushing syndrome M. Rahmanian*1, J. J. Nedooshan2, S. Rafat3, R. Rafie4, M. Rafiei 5, R. N. Moghadam1 Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, 2Department of Surgery, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, 3Department of Cardiology, Mortaz Hospital of Yazd, Yazd, Iran, 4Kaiser Permanente Southern California Medical Center, 1526 Edgemont Street, Los Angeles, CA, 5Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
1
Arterial thrombosis or emboli have rarely been reported in Cushing syndrome (CS). Here we describe the first case of mesenteric ischaemia secondary to ventricular emboli in a patient with CS. Laboratory evaluation showed increased fibrinogen and factor VIII. Previous studies showed that venous thromboembolism (VTE) increases in CS. This case for the first time described arterial system thrombosis and emboli in a patient with adrenocorticotropin (ACTH)-dependent CS. Keywords: Cushing syndrome, Mesenteric ischaemia, Thromboembolism
Introduction Thromboembolism is a well-known complication of Cushing syndrome (CS), which is appearing at twice the rate observed in the general population,1 especially after surgical procedures.2 The exact mechanism of the hypercoagulable state in hypercortisolism is not clear; however, some studies have shown increased procoagulant factor production and decreased fibrinolytic activity.3,4 We describe a case of adrenocorticotropin (ACTH)-dependent CS with left ventricular thrombosis that led to acute mesenteric ischaemia. To our best knowledge, this case is the first presentation of mesenteric ischaemia in a patient with CS.
The Case A 36-year-old man with a 6 years history of ACTHdependent CS (Table 1) was admitted to the hospital complaining of intractable abdominal pain, nausea and vomiting for 10 hours. He was a known case of CS with central obesity, purple striae, diabetes and hypertension. Elevated serum levels of ACTH had been detected; however, despite performing a pituitary MRI, thoracic spiral computerised tomography (CT) scan, bronchoscopy and abdominal CT scan, the source of ACTH production had not been localised. Thus, bilateral adrenalectomy (BAL) had been Correspondence to: Masoud Rahmanian, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Talar-e-Honar Alley, Shahid Sadoughi Blvd., Yazd, Iran. Email: [email protected].
ß Acta Clinica Belgica 2015
performed 4 years ago. After the operation, the CS remained active, and a reevaluation 3 years later demonstrated a pituitary with suspicious appearance. He was scheduled for further localising studies including scintigraphy and Inferior Petrosal Sinus Sampling (IPSS) but he suddenly developed low grade fever, severe generalised abdominal pain, nausea and vomiting. On examination, the patient had the blood pressure of 182/112 mmHg and oral temperature of 37.9uuC. Cardiac auscultation was regular and the abdomen was soft without tenderness. Laboratory results are noted in Table 2. The results of coagulation tests are presented in Table 3. After 4 hours of admission, for evaluation of undiagnosed severe abdominal pain, a CT scan was performed to evaluate the undiagnosed severe abdominal pain that revealed superior mesenteric artery occlusion (Fig. 1). A transthoracic echocardiogragh revealed a large left ventricular clot. He had no history of thrombosis or cardiac problems. He was transferred to the operation room emergently. During laparotomy, diffuse ischaemia of small intestine was observed and nonviable portions were excised. After 2 days, another operation was performed, and all parts of the small intestine from 15 cm distal to the ligament of Treitz were excised because of necrosis. After the operation, he gradually deteriorated and developed multiple abscesses in the abdominal and pelvic cavity. He admitted in the intensive care unit, but despite treatment with broad spectrum antibiotics and surgical abscess drainage, the patient died 4 weeks later.
Rahmanian et al.
Table 1 Cushing screening confirmatory and localising tests Test
Result
Reference range
Urinary Free cortisol (UFC) (before adrenalectomy) Serum cortisol after low dose dexamethasone suppression test ACTH UFC (after adrenalectomy)
358
Up to 50 mg/24 h
7
109 139
v2 mg/dl 10–60 pg/dl Up to 50 mg/dl
Table 2 Laboratory results
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
Test
Result Reference value
Cell blood count (CBC) White blood cell (|103 mm{3) Polymorphonuclear (%) Lymphocyte (%) Haemoglobin (g/dl) Platelet (|103/ mm3) Urea nitrogen (mg/dl) Creatinine (mg/dl) Alanine aminotransferase (U/L) Aspartate aminotransferase (U/L) Alkaline phosphatase Blood gas pH HCO3 (meq/l) PCO2 (mmHg) ESR (mm/h) Amylase (U/L) Lipase (U/L) Lactate dehydrogenase (U/L) Creatine phosphokinase (U/L)
18 78 20 15.5 220 19 1.1 40 51
4–7 40–70 20–50 14–18 150–450 7–20 0.6–1.2 7–41 12–38
346 7.49 7.35–7.45 22 22–30 29 32–45 59 50 20–96 32 3–43 981 115–221 439 51–294
Table 3 Coagulation study results Factor Prothrombin time (PT)(s) Partial thromboplastin time (PTT) (s) D-dimer (ng/Ml) Protein C (%) Protein S (%) Antithrombin III (%) Fibrinogen (mg/dl) Factor VIII (%) Anticardiolipin IgG (GPL) Anticardiolipin IgM (MPL)
Result 12 25 2990 13.8 53.8 105 440 w160 v1 v1
Reference value 12–15 26–39 220–740 70–140 70–140 70–130 200–400 50–150 0–15 0–15
Acute abdominal pain in Cushing syndrome patient
Discussion Endogenous CS may result from inappropriate secretion of ACTH from a pituitary adenoma, or rarely ectopic ACTH producing tumours5 or excessive production of cortisol from an adrenocortical tumour. Hypercortisolism has various consequences, such as central obesity, easy bruising, supraclavicular fat pad deposition, hypertension, diabetes, psychosis and osteoporosis.6 The principal cause of death among CS patients is cardiac complications.7,8 Venous thromboembolism (VTE) is also increased in CS especially after surgery. Some studies showed excessive amounts of factor VIII, factor IX, Von Willebrand Factor (VWF), fibrinogen and Plasminogen-activator inhibitor (PAI).9,10 This evidence suggests that CS involves a hypercoagulable state. However, aside from VTE, there are no data regarding increased risk of arterial thrombosis in CS. Major causes of acute mesenteric ischaemia are superior mesenteric artery embolism and thrombosis.11 Superior mesenteric artery embolism is most frequently due to left heart thrombosis, and left heart thrombosis in a patient without structural heart disease is a sign of a hypercoagulable state. The patient history and absence of fever prior to the beginning of abdominal pain were in favour of a non-infectious clot. The study of coagulation factors in this patient revealed elevated levels of factor VIII and fibrinogen. Increased levels of these factors during an inflammatory process can be a reaction to acute phases, but we were not able to differentiate these, from elevation due to CS activity, because the patient did not recover from his critical illness. Dexamethasone increases VWF release from endothelial cells.12 Because VWF carries factor VIII, a concordant increase in VWF and factor VIII is observed in hypercortisolism. Although bilateral adrenalectomy (BAL) is a safe and effective treatment for symptomatic relief in patients with Cushing disease who have unsuccessful trans-
Figure 1 Two consecutive sections (A and B) of abdominal computerised tomography (CT) angiogram.
Rahmanian et al.
Acute abdominal pain in Cushing syndrome patient
sphenoidal surgery (TSS),13 adrenal seeding during surgery and autografting of adrenal tissue within the abdominal cavity can cause recurrent CS.14
Conclusion
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
The present case showed that a hypercoagulable state during CS can lead to catastrophic thromboembolic events. Previous case reports and studies confirmed that venous thrombosis increases in CS, and this case showed that unusual arterial or ventricular thrombosis probably increases in hypercortisolism. This report is the first presentation of CS with left ventricular thrombus formation causing lethal acute mesenteric ischaemia. Because of the increased incidence of thromboembolic events in CS, anticoagulant prophylaxis, especially in preoperative periods, can reverse this condition.3
Acknowledgements The authors wish to thank the patient and his family. We also thank Dr. Ahmad Shojaoddiny-Ardekani and Fateme Sadat Haghighi for their assistance in preparing the manuscript.
2
3
4 5
6
7
8
9
Disclaimer Statements Contributors Masoud Rahmanian: Endocrinologist Jamal Jafari nedooshan: Surgeon Funding None. Conflicts of interest There are no conflicts of interest relevant to this study. Ethics approval None required.
References 1 Stuijver DJ, van Zaane B, Feelders RA, Debeij J, Cannegieter SC, Hermus AR, et al. Incidence of venous thromboembolism in
10
11 12
13
14
patients with Cushing’s syndrome: a multicenter cohort study. J Clin Endocrinol Metab. 2011;96(11):3525–32. Pereira AM, Delgado V, Romijn JA, Smit JW, Bax JJ, Feelders RA. Cardiac dysfunction is reversed upon successful treatment of Cushing’s syndrome. Eur J Endocrinol. 2010;162(2):331–40. Manetti L, Bogazzi F, Giovannetti C, Raffaelli V, Genovesi M, Pellegrini G, et al. Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing’s syndrome: results from a prospective study before and after surgery. Eur J Endocrinol. 2010;163(5):783–91. Trementino L, Arnaldi G, Appolloni G, Daidone V, Scaroni C, Casonato A, et al. Coagulopathy in Cushing’s syndrome. Neuroendocrinology. 2010;92(Supp l):55–9. Hasani-Ranjbar S, Rahmanian M, Ebrahim-Habibi A, Soltani A, Soltanzade A, Mahrampour E, et al. Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation. Fam Cancer. 2014;13:267–725. Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88(12):5593–602. Etxabe J, Vazquez JA. Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf). 1994;40(4):479–84. Lindholm J, Juul S, Jorgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, et al. Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab. 2001;86(1):117–23. Ambrosi B, Sartorio A, Pizzocaro A, Passini E, Bottasso B, Federici A. Evaluation of haemostatic and fibrinolytic markers in patients with Cushing’s syndrome and in patients with adrenal incidentaloma. Exp Clin Endocrinol Diabetes. 2000;108(4):294–8. Kastelan D, Dusek T, Kraljevic I, Polasek O, Giljevic Z, Solak M, et al. Hypercoagulability in Cushing’s syndrome: the role of specific haemostatic and fibrinolytic markers. Endocrine. 2009;36(1):70–4. Reinus JF, Brandt LJ, Boley SJ. Ischemic diseases of the bowel. Gastroenterol Clin North Am. 1990;19(2):319–43. Casonato A, Pontara E, Boscaro M, Sonino N, Sartorello F, Ferasin S, et al. Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing’s syndrome. Blood Coagul Fibrinolysis. 1999;10(3):145–51. Thompson SK, Hayman AV, Ludlam W, Devensey C, Loriaux L, Sheppard B. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushings disease. Ann Surg. 2007;245(5):790–4. Agboola-Abu CF, Ohwovoriole AE, Kuku SF. A follow up report: recurrent cushings syndrome after bilateral adrenalectomy. West Afr J Med. 2001;20(1):56–60.
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Acute abdominal pain in a man with Cushing syndrome M. Rahmanian, J. J. Nedooshan, S. Rafat, R. Rafie, M. Rafiei & R. N. Moghadam To cite this article: M. Rahmanian, J. J. Nedooshan, S. Rafat, R. Rafie, M. Rafiei & R. N. Moghadam (2015) Acute abdominal pain in a man with Cushing syndrome, Acta Clinica Belgica, 70:5, 372-374, DOI: 10.1179/2295333715Y.0000000025 To link to this article: http://dx.doi.org/10.1179/2295333715Y.0000000025
Published online: 06 May 2015.
Submit your article to this journal
Article views: 11
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20 Download by: [University of Western Ontario]
Date: 16 March 2016, At: 08:25
Case Report
Acute abdominal pain in a man with Cushing syndrome M. Rahmanian*1, J. J. Nedooshan2, S. Rafat3, R. Rafie4, M. Rafiei 5, R. N. Moghadam1 Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, 2Department of Surgery, Shahid Sadoughi University of Medical Sciences, Yazd, Iran, 3Department of Cardiology, Mortaz Hospital of Yazd, Yazd, Iran, 4Kaiser Permanente Southern California Medical Center, 1526 Edgemont Street, Los Angeles, CA, 5Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
1
Arterial thrombosis or emboli have rarely been reported in Cushing syndrome (CS). Here we describe the first case of mesenteric ischaemia secondary to ventricular emboli in a patient with CS. Laboratory evaluation showed increased fibrinogen and factor VIII. Previous studies showed that venous thromboembolism (VTE) increases in CS. This case for the first time described arterial system thrombosis and emboli in a patient with adrenocorticotropin (ACTH)-dependent CS. Keywords: Cushing syndrome, Mesenteric ischaemia, Thromboembolism
Introduction Thromboembolism is a well-known complication of Cushing syndrome (CS), which is appearing at twice the rate observed in the general population,1 especially after surgical procedures.2 The exact mechanism of the hypercoagulable state in hypercortisolism is not clear; however, some studies have shown increased procoagulant factor production and decreased fibrinolytic activity.3,4 We describe a case of adrenocorticotropin (ACTH)-dependent CS with left ventricular thrombosis that led to acute mesenteric ischaemia. To our best knowledge, this case is the first presentation of mesenteric ischaemia in a patient with CS.
The Case A 36-year-old man with a 6 years history of ACTHdependent CS (Table 1) was admitted to the hospital complaining of intractable abdominal pain, nausea and vomiting for 10 hours. He was a known case of CS with central obesity, purple striae, diabetes and hypertension. Elevated serum levels of ACTH had been detected; however, despite performing a pituitary MRI, thoracic spiral computerised tomography (CT) scan, bronchoscopy and abdominal CT scan, the source of ACTH production had not been localised. Thus, bilateral adrenalectomy (BAL) had been Correspondence to: Masoud Rahmanian, Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Talar-e-Honar Alley, Shahid Sadoughi Blvd., Yazd, Iran. Email: [email protected].
ß Acta Clinica Belgica 2015
performed 4 years ago. After the operation, the CS remained active, and a reevaluation 3 years later demonstrated a pituitary with suspicious appearance. He was scheduled for further localising studies including scintigraphy and Inferior Petrosal Sinus Sampling (IPSS) but he suddenly developed low grade fever, severe generalised abdominal pain, nausea and vomiting. On examination, the patient had the blood pressure of 182/112 mmHg and oral temperature of 37.9uuC. Cardiac auscultation was regular and the abdomen was soft without tenderness. Laboratory results are noted in Table 2. The results of coagulation tests are presented in Table 3. After 4 hours of admission, for evaluation of undiagnosed severe abdominal pain, a CT scan was performed to evaluate the undiagnosed severe abdominal pain that revealed superior mesenteric artery occlusion (Fig. 1). A transthoracic echocardiogragh revealed a large left ventricular clot. He had no history of thrombosis or cardiac problems. He was transferred to the operation room emergently. During laparotomy, diffuse ischaemia of small intestine was observed and nonviable portions were excised. After 2 days, another operation was performed, and all parts of the small intestine from 15 cm distal to the ligament of Treitz were excised because of necrosis. After the operation, he gradually deteriorated and developed multiple abscesses in the abdominal and pelvic cavity. He admitted in the intensive care unit, but despite treatment with broad spectrum antibiotics and surgical abscess drainage, the patient died 4 weeks later.
Rahmanian et al.
Table 1 Cushing screening confirmatory and localising tests Test
Result
Reference range
Urinary Free cortisol (UFC) (before adrenalectomy) Serum cortisol after low dose dexamethasone suppression test ACTH UFC (after adrenalectomy)
358
Up to 50 mg/24 h
7
109 139
v2 mg/dl 10–60 pg/dl Up to 50 mg/dl
Table 2 Laboratory results
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
Test
Result Reference value
Cell blood count (CBC) White blood cell (|103 mm{3) Polymorphonuclear (%) Lymphocyte (%) Haemoglobin (g/dl) Platelet (|103/ mm3) Urea nitrogen (mg/dl) Creatinine (mg/dl) Alanine aminotransferase (U/L) Aspartate aminotransferase (U/L) Alkaline phosphatase Blood gas pH HCO3 (meq/l) PCO2 (mmHg) ESR (mm/h) Amylase (U/L) Lipase (U/L) Lactate dehydrogenase (U/L) Creatine phosphokinase (U/L)
18 78 20 15.5 220 19 1.1 40 51
4–7 40–70 20–50 14–18 150–450 7–20 0.6–1.2 7–41 12–38
346 7.49 7.35–7.45 22 22–30 29 32–45 59 50 20–96 32 3–43 981 115–221 439 51–294
Table 3 Coagulation study results Factor Prothrombin time (PT)(s) Partial thromboplastin time (PTT) (s) D-dimer (ng/Ml) Protein C (%) Protein S (%) Antithrombin III (%) Fibrinogen (mg/dl) Factor VIII (%) Anticardiolipin IgG (GPL) Anticardiolipin IgM (MPL)
Result 12 25 2990 13.8 53.8 105 440 w160 v1 v1
Reference value 12–15 26–39 220–740 70–140 70–140 70–130 200–400 50–150 0–15 0–15
Acute abdominal pain in Cushing syndrome patient
Discussion Endogenous CS may result from inappropriate secretion of ACTH from a pituitary adenoma, or rarely ectopic ACTH producing tumours5 or excessive production of cortisol from an adrenocortical tumour. Hypercortisolism has various consequences, such as central obesity, easy bruising, supraclavicular fat pad deposition, hypertension, diabetes, psychosis and osteoporosis.6 The principal cause of death among CS patients is cardiac complications.7,8 Venous thromboembolism (VTE) is also increased in CS especially after surgery. Some studies showed excessive amounts of factor VIII, factor IX, Von Willebrand Factor (VWF), fibrinogen and Plasminogen-activator inhibitor (PAI).9,10 This evidence suggests that CS involves a hypercoagulable state. However, aside from VTE, there are no data regarding increased risk of arterial thrombosis in CS. Major causes of acute mesenteric ischaemia are superior mesenteric artery embolism and thrombosis.11 Superior mesenteric artery embolism is most frequently due to left heart thrombosis, and left heart thrombosis in a patient without structural heart disease is a sign of a hypercoagulable state. The patient history and absence of fever prior to the beginning of abdominal pain were in favour of a non-infectious clot. The study of coagulation factors in this patient revealed elevated levels of factor VIII and fibrinogen. Increased levels of these factors during an inflammatory process can be a reaction to acute phases, but we were not able to differentiate these, from elevation due to CS activity, because the patient did not recover from his critical illness. Dexamethasone increases VWF release from endothelial cells.12 Because VWF carries factor VIII, a concordant increase in VWF and factor VIII is observed in hypercortisolism. Although bilateral adrenalectomy (BAL) is a safe and effective treatment for symptomatic relief in patients with Cushing disease who have unsuccessful trans-
Figure 1 Two consecutive sections (A and B) of abdominal computerised tomography (CT) angiogram.
Rahmanian et al.
Acute abdominal pain in Cushing syndrome patient
sphenoidal surgery (TSS),13 adrenal seeding during surgery and autografting of adrenal tissue within the abdominal cavity can cause recurrent CS.14
Conclusion
Downloaded by [University of Western Ontario] at 08:25 16 March 2016
The present case showed that a hypercoagulable state during CS can lead to catastrophic thromboembolic events. Previous case reports and studies confirmed that venous thrombosis increases in CS, and this case showed that unusual arterial or ventricular thrombosis probably increases in hypercortisolism. This report is the first presentation of CS with left ventricular thrombus formation causing lethal acute mesenteric ischaemia. Because of the increased incidence of thromboembolic events in CS, anticoagulant prophylaxis, especially in preoperative periods, can reverse this condition.3
Acknowledgements The authors wish to thank the patient and his family. We also thank Dr. Ahmad Shojaoddiny-Ardekani and Fateme Sadat Haghighi for their assistance in preparing the manuscript.
2
3
4 5
6
7
8
9
Disclaimer Statements Contributors Masoud Rahmanian: Endocrinologist Jamal Jafari nedooshan: Surgeon Funding None. Conflicts of interest There are no conflicts of interest relevant to this study. Ethics approval None required.
References 1 Stuijver DJ, van Zaane B, Feelders RA, Debeij J, Cannegieter SC, Hermus AR, et al. Incidence of venous thromboembolism in
10
11 12
13
14
patients with Cushing’s syndrome: a multicenter cohort study. J Clin Endocrinol Metab. 2011;96(11):3525–32. Pereira AM, Delgado V, Romijn JA, Smit JW, Bax JJ, Feelders RA. Cardiac dysfunction is reversed upon successful treatment of Cushing’s syndrome. Eur J Endocrinol. 2010;162(2):331–40. Manetti L, Bogazzi F, Giovannetti C, Raffaelli V, Genovesi M, Pellegrini G, et al. Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing’s syndrome: results from a prospective study before and after surgery. Eur J Endocrinol. 2010;163(5):783–91. Trementino L, Arnaldi G, Appolloni G, Daidone V, Scaroni C, Casonato A, et al. Coagulopathy in Cushing’s syndrome. Neuroendocrinology. 2010;92(Supp l):55–9. Hasani-Ranjbar S, Rahmanian M, Ebrahim-Habibi A, Soltani A, Soltanzade A, Mahrampour E, et al. Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation. Fam Cancer. 2014;13:267–725. Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88(12):5593–602. Etxabe J, Vazquez JA. Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin Endocrinol (Oxf). 1994;40(4):479–84. Lindholm J, Juul S, Jorgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, et al. Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab. 2001;86(1):117–23. Ambrosi B, Sartorio A, Pizzocaro A, Passini E, Bottasso B, Federici A. Evaluation of haemostatic and fibrinolytic markers in patients with Cushing’s syndrome and in patients with adrenal incidentaloma. Exp Clin Endocrinol Diabetes. 2000;108(4):294–8. Kastelan D, Dusek T, Kraljevic I, Polasek O, Giljevic Z, Solak M, et al. Hypercoagulability in Cushing’s syndrome: the role of specific haemostatic and fibrinolytic markers. Endocrine. 2009;36(1):70–4. Reinus JF, Brandt LJ, Boley SJ. Ischemic diseases of the bowel. Gastroenterol Clin North Am. 1990;19(2):319–43. Casonato A, Pontara E, Boscaro M, Sonino N, Sartorello F, Ferasin S, et al. Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing’s syndrome. Blood Coagul Fibrinolysis. 1999;10(3):145–51. Thompson SK, Hayman AV, Ludlam W, Devensey C, Loriaux L, Sheppard B. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushings disease. Ann Surg. 2007;245(5):790–4. Agboola-Abu CF, Ohwovoriole AE, Kuku SF. A follow up report: recurrent cushings syndrome after bilateral adrenalectomy. West Afr J Med. 2001;20(1):56–60.
![[73-year-old man with acute abdominal pain].](/assets/img/hold.png)
