Department of Medicine, Division of Nephrology and Osteology, University of Hamburg, Hamburg, Germany
Keywords: diagnosis; hypertension; reninaldosterone levels
Case presentation
A 26-year-old actress was urgently admitted to the hospital because of a blood pressure of 220/120 mmHg. She had been well until 3 months earlier when she noticed the regular appearance of headaches. Her past medical history was unrevealing. She had stopped taking oral contraceptives 3 months prior to admission. At the time of hospitalization she did not take any medication. There was no family history of hypertension. She smoked up to 30 cigarettes a day and had lost 5 kg of body weight over the last 3 months. She had a lean body-mass-index of 17.6. The physical examination was unremarkable. There were no signs of peripheral oedema. The patient appeared in psychological distress. Laboratory values showed a serum creatinine of 1.1 mg/dl, BUN 15 mg/dl, sodium 138 mmol/l, potassium 3.0 mmol/l, chloride 96 mmol/l. Venous blood gases revealed a pH of 7.38 and serum bicarbonate of 28.3 mmol/l. Creatinine clearance was 79 ml/min, albumin excretion was 231 mg/24 h, potassium excretion 129 mmol/24 h, sodium excretion 63 mmol/24 h, and chloride excretion 73 mmol/24 h. Twenty four hour blood pressure monitoring (while taking clonidine and nifedipine) showed no single systolic blood pressure value >160 mmHg, but frequent diastolic readings of >100 mmHg (Figure 1). However, the physiological dip at nighttime was preserved. Ultrasould examination of the kidneys revealed a difference in lengths (right kidney: 10.3 cm; left kidney: 13.0 cm). Sonographically the left kidney appeared to be a double kidney with a duplex ureter. Duplex sonography of the well-visible renal arteries and determination of various intrarenal resistance indices gave no evidence of renal artery stenosis. A captopril renal radionuclide study with 99mTc-mercaptoacetyltriglycine (MAG-3) revealed no signs of renal artery stenosis, but there was a reduction of the clearance of the right kidney to 33% of normal. Normal values were obtained for epinephrine, noradrenaline, and cortisol in plasma and urine. The plasma renin activity under standardized conditions in the supine patient was strongly increased to 18 µg/l/h (normal range supine patient: 0.51.6 µg/l/h). The plasma aldosterone was increased almost six times (78.4 ng/dl; normal range of adults in supine position: 2.914.5 ng/dl). This was confirmed by an elevated aldosterone excretion rate in a 24-h urine collection. The patient was confronted with a suspected diagnosis of diuretic abuse which she denied. She was discharged on clonidine (150 µg per day) and a daily potassium supplement of 40 mval.
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Discussion
This case has numerous interesting medical aspects, however, we would like to elaborate on one of the more frequent mishaps which one encounters in the process of diagnostic reasoning. As physicians we often arrive at the correct diagnosis by recognizing familiar patterns of disease presentations. The syndrome of hypertension with hypokalaemia and metabolic alkalosis is a well-known pattern and usually does not give us a hard time in making the correct diagnosis. The differential diagnosis includes primary hyperaldosteronism such as Conn's disease or secondary hyperaldosteronism due to renal artery stenosis or renin secreting tumours. The initial approach of the diagnostic process in this case was straight forward. The hypokalaemia was due to renal potassium wasting; furthermore, elevated plasma aldosterone and renin levels were established, and this constellation excludes primary hyperaldosteronism. The next step in the differential was to look for the various causes of hypertension due to secondary hyperaldosteronism in conjunction with elevated renin levels. This differential diagnosis includes renal artery stenosis, renin secreting tumours and Cushing's Syndrome. The a priori likelihood of the latter was very low since the patient was lean and did not have any signs of virilization. Moreover, the renin levels are low in Cushing's syndrome. Renin secreting tumours are always located within the kidney and none of the imaging techniques including a CT-scan showed a tumour [1]. Inherited diseases such as Bartter's and Gitelman's syndrome were not further considered because they are associated with hypotension whilst our patient had hypertension.
The diagnosis of renal artery stenosis had the highest a prior likelihood. To confirm this hypothesis a duplex ultrasound of the kidneys and a captopril enhanced renal radionuclide scan were performed. However, both tests were negative. Was the diagnosis of renal artery stenosis excluded convincingly at this point? The physicians in charge thought so and refrained from further testing, i.e. performing the gold standard test of angiography to verify a renal artery stenosis. They began looking for a competing diagnosis and discharged the patient with the diagnosis of putative diuretic abuse, despite the fact that the a priori likelihood of this diagnosis was rather low, since the patient was hypertensive and denied taking diuretics. The test to increase the a posteriori likelihood of this diagnosis, i.e. toxicology screens for diuretics, was not performed [2].
The most intriguing question remains: why was the diagnosis with the highest pretest probability rejected? Several reasons may have to be considered. First, the disease presentation had rapidly changed during the patients stay in hospital. The predominant presenting symptom of severe hypertension disappeared with two drug treatment; this does not correspond to the type of hypertension that is commonly found in patients with renal artery stenosis. It was not taken into consideration, however, that clonidine may be very effective in lowering blood pressure in hyperaldosteronism [3]. In addition, the patient stopped smoking during her hospital stay. Smoking causes significant renal vasoconstriction [4]. A moderate renal artery stenosis at the time of initial presentation could have become clinically evident due to heavy smoking. Cessation of smoking may well have resulted in a reduction of renal vasoconstriction, thereby blunting our diagnostic tools. Secondly, the negative test results and the incomplete interpretation of the results was used as evidence against renal artery stenosis. Although the non-invasive tests are generally appropriate for the diagnosis of renal artery stenosis, the limitations of these tests were not appropriately considered, (the negative predictive value of the radionuclide scan is 8590% and that of duplex ultrasound in experienced hands as high as 97%) [5,6]. The captopril scintigraphy showed no reduction in glomerular filtration after administration of an ACE inhibitor. The significant reduction of the base line clearance of the right kidney was ignored [8]. The initial renal ultrasound demonstrated a size difference of the kidneys of almost 3 cm which was mistakenly interpreted by the investigator as a duplex ureter of the larger kidney. Finally, the patient's personality played an important role. She was an actress, smoked heavily, was rather unwilling to comply with in-hospital rules and seemed very concerned about keeping her body weight. This kind of attitude is not unusual in the setting of diuretic abuse.
Two and a half years later the patient was referred again for repeat work-up of persistently elevated renin and aldosterone levels. She was not hypertensive (on treatment) and the potassium was in the normal range. The physicians in charge opted to repeat all previously negative tests. This time the correct diagnosis was made. The duplex ultrasound revealed a renal artery stenosis that was confirmed by the renal angiography.
Teaching point
This is an excellent example of premature closure of diagnostic reasoning [7], an obstacle we encounter frequently when the diagnostic process becomes cumbersome. The findings in this case were not consistent with the diagnosis of diuretic abuse, and the diagnosis with the highest a priori likelihood was rejected because the results of imaging techniques were partly not interpreted correctly and were trusted beyond their limitations.
As long as there is a strong clinical suspicion of a certain disease, do not get lost in your diagnostic work-up and refrain from blaming it on your patient.
Notes
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Correspondence and offprint requests to: Ingo Krenz, MD, University of Hamburg, University Hospital Eppendorf, Department of Medicine, Division of Nephrology and Osteology, Pavillion 61, Martinistraße 52, D-20246 Hamburg, Germany.
References