QUIZ PAGE JUNE 2015 A Young Woman With Hypertension CLINICAL PRESENTATION A 24-year-old pregnant woman presented with hypertension at 7 weeks’ gestation. Two years earlier, she had been evaluated for elevated blood pressure (BP) of 150 to 170/110 to 120 mm Hg and found to have a serum potassium level of 2.6 mmol/L (reference range, 3.6-4.6 mmol/L) and plasma renin concentration of 362 mIU/L (reference range, 2.8-40 mIU/L) in the supine position. She underwent renal angiography, for which there were no findings of note. The patient was prescribed amlodipine, 5 mg, and irbesartan, 150 mg/d, and her BP responded promptly by decreasing to 115/70 mm Hg. Upon presentation, the patient denied symptoms aside from nocturia. She had no headache, chest pain, or edema. Her family history was not notable for any diseases or syndromes. She was not taking antihypertensive medication, and BP was 156/110 mm Hg. The rest of her examination findings were unremarkable, and she had no apparent obesity. She had a serum potassium
- What are the causes of hypertension in a
young woman? - What induces a high renin state? - How can this patient’s diagnosis be
confirmed? - What therapeutic approach should be
advised?
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level of 3.0 mmol/L, serum bicarbonate level of 23 mmol/L, serum creatinine level of 0.64 mg/dL (57 mmol/L; corresponding to estimated glomerular filtration rate . 90 mL/min/1.73 m2 as calculated by the 4-variable MDRD [Modification of Diet in Renal Disease] Study equation), and spot urine albumin-creatinine ratio of 42 mg/mmol. Plasma renin concentration was 846 mIU/L (reference range, 2.8-40 mIU/L) in the supine position, and serum aldosterone level was 2,370 pmol/L (reference range, 30-444 pmol/L) in the supine position.
QUIZ PAGE JUNE 2015
ANSWERS
DISCUSSION - What are the causes of
hypertension in a young woman? The most common causes of hypertension in a young woman are essential hypertension or hypertension as part of metabolic syndrome. Secondary causes include fibromuscular dysplasia, overproduction of aldosterone, and hormonal causes such as those related to oral contraceptive use or pregnancy-induced hypertension. In this age group, additional endocrine explanations for secondary hypertension include thyroid or parathyroid disorders and low vitamin D levels. A rare but important cause is coarctation of the aorta. Finally, exogenous factors such as licorice consumption, substantial alcohol intake, and use of nonsteroidal anti-inflammatory drugs should be investigated and/or ruled out.
In the present case, the patient was pregnant, but hypertension in gestational week 7 should not be regarded as gestational hypertension or preeclampsia.
hyperplasia. As for primary causes of hypertensive high renin states, renin-producing renal tumors can be seen with simultaneous high aldosterone levels.
- What induces a high
- How can this patient’s
renin state? Renin is produced by juxtaglomerular cells in the kidney and plays a major role in BP regulation by inducing the reninangiotensin-aldosterone system. Hypertensive high renin states can be secondary or primary. Secondary causes of a high renin state include renovascular disease, most commonly fibromuscular dysplasia of the renal artery in young women. Additionally, hypertensive states per se are associated with a slight increase in renin levels, but this is much more pronounced in the malignant hypertensive condition. This might be explained by renovascular ischemia due to intimal
diagnosis be confirmed? Duplex ultrasound examination of the kidneys and echocardiography were performed to exclude renal artery stenosis and coarctation of the aorta. Magnetic resonance tomography of the upper abdomen identified a mass in the caudal area of the left kidney (Fig 1). Plasma renin and aldosterone concentrations in the left renal vein were 1,230 mIU/L and .3,900 pmol/L, respectively. In a peripheral vein, values were 726 mIU/L and 1,330 pmol/L, respectively. This high secretion of renin from the left tumor-containing kidney supports the diagnosis of reninoma.
(A) Magnetic resonance tomogram shows a mass extending from the caudal pole of the left kidney. (B) 111In-octreotide scintigraphy (maximum intensity projection) shows high uptake of the radionuclide in the mass (arrow).
QUIZ PAGE
Figure 1.
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Am J Kidney Dis. 2015;65(6):xvii-xix
Figure 2. Histopathology of the renal mass. (A) Tumor cells form loosely cohesive sheets with little cytologic atypia (hematoxylin-eosin stain; original magnification, 3400). (B) Tumor cells show cytoplasmic and membranous labeling by antibodies against somatostatin receptor subtype 2 (SSTR2; detection using Dako EnVision system [horseradish peroxidase– based staining]).
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In-octreotide scintigraphy was performed, showing high uptake of the radionuclide in the left renal mass (Fig 1). This uptake is due to high expression of somatostatin receptor type 2 (SSTR2) by the tumor cells.1 This was further supported by immunohistochemical analysis of the surgical specimen, which demonstrated strong membranous staining of tumor cells by a monoclonal anti-SSTR2 antibody2 (Fig 2). - What therapeutic
approach should be advised?
Am J Kidney Dis. 2015;65(6):xvii-xix
FINAL DIAGNOSIS Hypertension due to a juxtaglomerular cell tumor (reninoma) secreting large amounts of renin.
REFERENCES 1. Weckbecker G, Lewis I, Albert R, Schmid HA, Hoyer D, Bruns C. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov. 2003;2(12):999-1017. 2. Körner M, Waser B, Schonbrunn A, Perren A, Reubi JC. Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am J Surg Pathol. 2012;36(2):242-252. 3. Corvol P, Pinet F, Plouin P-F, Bruneval P, Menard J. Reninsecreting tumors. Endocrinol Metab Clin North Am. 1994;23:255-270. 4. Theodoropoulou M, Stalla GK. Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol. 2013;34(3):228-252.
CASE PROVIDED AND AUTHORED BY Svante Jansson, MD, PhD,1 Johan Fredén Lindqvist, MD,2 Karin Manhem, MD, PhD,3 Ola Nilsson, MD, PhD,6 Thord Rosén, MD, PhD,5 and Hans Herlitz, MD, PhD,4 1Sahlgrenska University Hospital, Institute of Clinical Sciences/Department of Surgery; 2Department of Clinical Physiology and Nuclear Medicine; 3 Department of Molecular and Clinical Medicine/Cardiology/ 4 Nephrology/ 5Endocrinology; and 6 Department of Pathology, Sahlgrenska Academy, University of Gothenburg, Sweden. Address correspondence to Hans Herlitz, PhD, MD, Institute of Medicine, Department of Molecular and Clinical Medicine/Nephrology, Sahlgrenska University Hospital, Gothenburg, Sweden 41345. E-mail: [email protected] Ó 2015 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015. 01.027 SUPPORT: None. FINANCIAL DISCLOSURE: The authors declare that they have no relevant financial interests.
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Most reninomas are benign, but metastatic cases have been reported.3 The patient underwent surgical resection of the tumor with normalization of BP (110/70 mm Hg without medication) and renin and aldosterone levels (18.0 mU/L and 232 pmol/L, respectively). Because the tumor was clearly visible on 111In-octreotide scintigraphy and expressed SSTR on immunohistochemical staining, a neuroendocrine phenotype for the tumor was identified. This suggests the opportunity to control hormone secretion and tumor cell
proliferation in these tumors by long-acting somatostatin analogues or targeted radiotherapy in the case of unresectable masses.4
- What are the causes of hypertension in a
young woman? - What induces a high renin state? - How can this patient’s diagnosis be
confirmed? - What therapeutic approach should be
advised?
xvii
QUIZ PAGE
Am J Kidney Dis. 2015;65(6):xvii-xix
level of 3.0 mmol/L, serum bicarbonate level of 23 mmol/L, serum creatinine level of 0.64 mg/dL (57 mmol/L; corresponding to estimated glomerular filtration rate . 90 mL/min/1.73 m2 as calculated by the 4-variable MDRD [Modification of Diet in Renal Disease] Study equation), and spot urine albumin-creatinine ratio of 42 mg/mmol. Plasma renin concentration was 846 mIU/L (reference range, 2.8-40 mIU/L) in the supine position, and serum aldosterone level was 2,370 pmol/L (reference range, 30-444 pmol/L) in the supine position.
QUIZ PAGE JUNE 2015
ANSWERS
DISCUSSION - What are the causes of
hypertension in a young woman? The most common causes of hypertension in a young woman are essential hypertension or hypertension as part of metabolic syndrome. Secondary causes include fibromuscular dysplasia, overproduction of aldosterone, and hormonal causes such as those related to oral contraceptive use or pregnancy-induced hypertension. In this age group, additional endocrine explanations for secondary hypertension include thyroid or parathyroid disorders and low vitamin D levels. A rare but important cause is coarctation of the aorta. Finally, exogenous factors such as licorice consumption, substantial alcohol intake, and use of nonsteroidal anti-inflammatory drugs should be investigated and/or ruled out.
In the present case, the patient was pregnant, but hypertension in gestational week 7 should not be regarded as gestational hypertension or preeclampsia.
hyperplasia. As for primary causes of hypertensive high renin states, renin-producing renal tumors can be seen with simultaneous high aldosterone levels.
- What induces a high
- How can this patient’s
renin state? Renin is produced by juxtaglomerular cells in the kidney and plays a major role in BP regulation by inducing the reninangiotensin-aldosterone system. Hypertensive high renin states can be secondary or primary. Secondary causes of a high renin state include renovascular disease, most commonly fibromuscular dysplasia of the renal artery in young women. Additionally, hypertensive states per se are associated with a slight increase in renin levels, but this is much more pronounced in the malignant hypertensive condition. This might be explained by renovascular ischemia due to intimal
diagnosis be confirmed? Duplex ultrasound examination of the kidneys and echocardiography were performed to exclude renal artery stenosis and coarctation of the aorta. Magnetic resonance tomography of the upper abdomen identified a mass in the caudal area of the left kidney (Fig 1). Plasma renin and aldosterone concentrations in the left renal vein were 1,230 mIU/L and .3,900 pmol/L, respectively. In a peripheral vein, values were 726 mIU/L and 1,330 pmol/L, respectively. This high secretion of renin from the left tumor-containing kidney supports the diagnosis of reninoma.
(A) Magnetic resonance tomogram shows a mass extending from the caudal pole of the left kidney. (B) 111In-octreotide scintigraphy (maximum intensity projection) shows high uptake of the radionuclide in the mass (arrow).
QUIZ PAGE
Figure 1.
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Am J Kidney Dis. 2015;65(6):xvii-xix
Figure 2. Histopathology of the renal mass. (A) Tumor cells form loosely cohesive sheets with little cytologic atypia (hematoxylin-eosin stain; original magnification, 3400). (B) Tumor cells show cytoplasmic and membranous labeling by antibodies against somatostatin receptor subtype 2 (SSTR2; detection using Dako EnVision system [horseradish peroxidase– based staining]).
111
In-octreotide scintigraphy was performed, showing high uptake of the radionuclide in the left renal mass (Fig 1). This uptake is due to high expression of somatostatin receptor type 2 (SSTR2) by the tumor cells.1 This was further supported by immunohistochemical analysis of the surgical specimen, which demonstrated strong membranous staining of tumor cells by a monoclonal anti-SSTR2 antibody2 (Fig 2). - What therapeutic
approach should be advised?
Am J Kidney Dis. 2015;65(6):xvii-xix
FINAL DIAGNOSIS Hypertension due to a juxtaglomerular cell tumor (reninoma) secreting large amounts of renin.
REFERENCES 1. Weckbecker G, Lewis I, Albert R, Schmid HA, Hoyer D, Bruns C. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov. 2003;2(12):999-1017. 2. Körner M, Waser B, Schonbrunn A, Perren A, Reubi JC. Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am J Surg Pathol. 2012;36(2):242-252. 3. Corvol P, Pinet F, Plouin P-F, Bruneval P, Menard J. Reninsecreting tumors. Endocrinol Metab Clin North Am. 1994;23:255-270. 4. Theodoropoulou M, Stalla GK. Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol. 2013;34(3):228-252.
CASE PROVIDED AND AUTHORED BY Svante Jansson, MD, PhD,1 Johan Fredén Lindqvist, MD,2 Karin Manhem, MD, PhD,3 Ola Nilsson, MD, PhD,6 Thord Rosén, MD, PhD,5 and Hans Herlitz, MD, PhD,4 1Sahlgrenska University Hospital, Institute of Clinical Sciences/Department of Surgery; 2Department of Clinical Physiology and Nuclear Medicine; 3 Department of Molecular and Clinical Medicine/Cardiology/ 4 Nephrology/ 5Endocrinology; and 6 Department of Pathology, Sahlgrenska Academy, University of Gothenburg, Sweden. Address correspondence to Hans Herlitz, PhD, MD, Institute of Medicine, Department of Molecular and Clinical Medicine/Nephrology, Sahlgrenska University Hospital, Gothenburg, Sweden 41345. E-mail: [email protected] Ó 2015 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015. 01.027 SUPPORT: None. FINANCIAL DISCLOSURE: The authors declare that they have no relevant financial interests.
xix
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Most reninomas are benign, but metastatic cases have been reported.3 The patient underwent surgical resection of the tumor with normalization of BP (110/70 mm Hg without medication) and renin and aldosterone levels (18.0 mU/L and 232 pmol/L, respectively). Because the tumor was clearly visible on 111In-octreotide scintigraphy and expressed SSTR on immunohistochemical staining, a neuroendocrine phenotype for the tumor was identified. This suggests the opportunity to control hormone secretion and tumor cell
proliferation in these tumors by long-acting somatostatin analogues or targeted radiotherapy in the case of unresectable masses.4
