Nephrol Dial Transplant (2000) 15: 717-718
© 2000 European Renal Association-European Dialysis and Transplant Association
Case Report
Concurrent pheochromocytoma, diabetes insipidus and cerebral venous thrombosis—a possible unique pathophysiological mechanism
1 Nephrology, University of Milan, San Raffaele Hospital, 2 Division of Internal Medicine, Cernusco S.N. Hospital and 3 INB, CNR, HSR Hospital, University of Milano Bicocca, Milan, Italy
Keywords: catecholamines; cerebral venous thrombosis; diabetes insipidus; hypertension; pheochromocytoma; vasopressin
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Introduction |
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Here we describe a case of concurrent cerebral venous thrombosis, pheochromocytoma and diabetes insipidus and present a hypothesis regarding a unique pathophysiological mechanism.
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Case |
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A 38-year-old Caucasian man underwent right adrenalectomy for pheochromocytoma in December 1996. Three months previously, he had suffered from headache, nausea, vomiting and seizures and was unable to maintain a standing position. An extended cerebral venous thrombosis was diagnosed based on MRI findings. Two days after neurological symptoms regressed, blood pressure and urinary catecholamine levels increased [epinephrine (normal values 1.5–2.2 µg/ 24 h): 122 µg/24 h; norepinephrine (normal values 12–85 µg/24 h): 637 µg/24 h. The levels were confirmed on two subsequent assays performed 2 months later: epinephrine 656 and 492; norepinephrine 2443 and 1464]. Twenty days after polyuria and polydipsia were evident, the patient tested positive for dehydration and desmopressin, leading to the diagnosis of central diabetes insipidus. No organic lesions in the pituitary gland were found at a repeat brain MRI, which documented a complete revascularization of cerebral venous sinuses (a partial revascularization was already present 13 days after the remission of neurological symptoms).
The location of the pheochromocytoma was ambiguous. An abnormally increased right adrenal gland (4–5 cm) was found by echography and then confirmed by computed tomography (CT) and MRI. However, both meta-iodobenzylguanidine (MIBG) and octreotide scintigraphy were negative [1]. Pheochromocytoma was localized definitively in November 1996 by two subsequent positron emission tomography (PET) studies.
The first PET study was performed following administration of hydroxyephedrine (Figure 1
), a radiotracer with a close structural similarity to norepinephrine, which accumulates specifically in organs with rich sympathetic innervation, particularly heart and adrenal medulla [2].
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The second followed administration of 2-[fluorine- 18]-fluoro-2-deoxy-D-glucose (FDG), which is a tracer of tumour viability [3]. No extra-adrenal localizations of the tumour were observed.
Following adrenalectomy, blood pressure normalization (with normal levels of urinary catecholamines: epinephrine, 5.5 µg/24 h; norepinephrine, 35 µg/24 h) and a complete remission of diabetes insipidus (with a negative dehydration test) were observed. The antihypertensive drugs and desmopressin were withdrawn. Brain MRI of the pituitary gland was superimposable to that before adrenalectomy.
Anticoagulant therapy was stopped 2 years later. Two months after discontinuation, the absence of procoagulant risk factors was confirmed by a second complete screening.
Relapses of hypertension, polyuria and polydipsia, as well as recurrence of the tumour have not been seen after 28 months of follow-up.
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Discussion |
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The absence of both pocoagulant risk factors and organic lesions of the pituitary gland suggested the possibility of a unique pathophysiological mechanism.
Cerebral venous thrombosis is a common paraneoplastic syndrome seen in many malignant tumours [4]. This patient did not show any extra-adrenal localization of pheochromocytoma. However, even if no metastases were found, malignancy of pheochromocytoma could not be excluded because there is no reliable morphological marker of malignancy for these tumours [5]. Thus, central venous thromboembolism could be considered to be a paraneoplastic syndrome sustained by procoagulant substances secreted by tumor cells already shifting toward malignancy.
To date, an association between pheochromocytoma and diabetes insipidus has not been reported. When no organic lesions of the pituitary are found, central diabetes insipidus is classified as idiopathic. However, high blood pressure levels cause a haemodynamic effect, mediated by peripheral baroreceptors, leading to suppression of antidiuretic hormone (ADH) secretion [6]. In addition, norepinephrine has a direct inhibitory effect on ADH secretion [7]. Thus, elevated blood pressure levels associated with very high norepinephrine levels could be responsible for diabetes insipidus (both haemodynamic and pharmacologic induction).
Unfortunately, we did not perform special stainings to test production of procoagulant substances by tumour cells nor did we evaluate ADH production before and after adrenalectomy. However, both the complete remission of diabetes insipidus associated with adrenalectomy and the absence of other thrombotic events after 28 months of follow-up strongly support the hypothesis of an unique pathophysiological mechanism. Thus, when thrombotic syndromes or polyuria and polydipsia appear in hypertensive patients, the presence of pheochromocytoma should be suspected.
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Notes |
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Correspondence and offprint requests to: Paola Stella, MD, Divisione di Nefrologia, Dialisi ed Ipertensione, Ospedale San Raffaele, Via Olgettina 60, I-20132 Milano, Italy.
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References |
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Tenenbaum F, Lumbroso J, Schlumberger M, Mure A, Plouin PF, Caillou B, Parmentier C. Comparison of radiolabeled octreotide and meta-iodobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma. J Nucl Med1995; 36: 1–6
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Rosenpire KC, Haka MS, Jewett DM et al. Synthesis and preliminary evaluation of [11C]metahydroxyephedrine: a false neurotransmitter agent for heart neuronal imaging. J Nucl Med1990; 31: 1328–1334
[Abstract/Free Full Text] -
Shulkin BL, Koeppe RA, Francis IR, Deeb GM, Loyd RV, Thompson NW. Pheochromocytoma that do not accumulate metaiodobenzylguanidine: localization with PET and administration of FDG. Radiology1993; 186: 711–715
[Abstract/Free Full Text] - Monreal M, Fernandez-Llamazares J, Perandreu J, Urrutia A, Sahuquillo JC, Contel E. Occult cancer in patients with venous thromboembolism: which patients, which cancers. Thromb Haemost1997; 78: 1316–1318[Web of Science][Medline]
- Rosai J. Adrenal gland and other paraganglia. In: Rosai J. eds. Ackerman's Surgical Pathology. Mosby-Year Book, St. Louis, MO, 1996; 1015–1040
- Schrier RW, Berl T, Anderson RJ, McDonald KM. Nonosmolar control of renal water excretion. In: Andreoli TE et al., eds. Disturbances in body fluid osmolality. American Physiological Society, Bethesda, 1977; 149–164
- Robertson GL. Posterior pituitary. In: Felig P, Baxter JD, Frohman LA, eds. Endocrinology and Metabolism. McGraw Hill, New York, 1995; 386–432
Revision received 23.11.99.
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