Wiebke Fenske

Laparoscopic Versus Open Adrenalectomy for Adrenocortical Carcinoma: Surgical and Oncologic Outcome in 152 Patients

BACKGROUND The role of laparoscopic adrenalectomy in the treatment of patients with adrenocortical carcinoma (ACC) is controversial. OBJECTIVE Our aim was to compare oncologic outcome in patients with ACC who underwent either open adrenalectomy (OA) or laparoscopic adrenalectomy (LA) for localised disease. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective analysis of 152 patients with stage I-III ACC with a tumour < or =10 cm registered with the German ACC Registry. INTERVENTION Patients were stratified into two groups according to the surgical procedure (LA or OA). For comparison, we used both a matched pairs approach by selecting for each patient from the LA group (n=35) one corresponding patient from the OA group (n=117) and multivariate analysis in all 152 patients. MEASUREMENTS Disease-specific survival was chosen as the predefined primary end point. Secondary end points were recurrence-free survival, frequency of tumour capsule violation and postoperative peritoneal carcinomatosis, and incidence and reasons for conversion from LA to OA. RESULTS AND LIMITATIONS LA and OA did not differ with regard to the primary end point using either the matched pairs approach (hazard ratio [HR] for death: 0.79; 95% confidence interval [CI], 0.36-1.72; p=0.55) or multivariate analysis (HR for death: 0.98; 95% CI, 0.51-1.92; p=0.92). Similarly, adjusted recurrence-free survival was not different between LA and OA (HR: 0.91; 95% CI, 0.56-1.47; p=0.69). Frequency of tumour capsule violation and peritoneal carcinomatosis were comparable between groups. In 12 of 35 patients of the LA group, surgery was converted to open surgery with no impact on the clinical outcome. CONCLUSIONS For localised ACC with a diameter of < or =10 cm, LA by an experienced surgeon is not inferior to OA with regard to oncologic outcome.

Copeptin in the Differential Diagnosis of Hyponatremia

BACKGROUND Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. METHODS In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). RESULTS Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r(2) = 0.62, P < 0.001) or urine osmolality (r(2) = 0.39, P = 0.001) was observed. Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used. The combined information of plasma copeptin less than 3 pmol/liter and urine osmolality less than 200 mOsm/kg ensured primary polydipsia in 100% of suspected patients. CONCLUSION Copeptin measurement reliably identifies patients with primary polydipsia but has limited utility in the differential diagnosis of other hyponatremic disorders. In contrast, the copeptin to U-Na ratio is superior to the reference standard in discriminating volume-depleted from normovolemic hyponatremic disorders.

Improved Survival in Patients with Stage II Adrenocortical Carcinoma Followed Up Prospectively by Specialized Centers

CONTEXT Median survival in stage II adrenocortical carcinoma (ACC) differs widely in published series ranging between 23 and more than 60 months. We hypothesized that these results may have been affected by a referral bias because many patients may contact specialized centers only after recurrence. OBJECTIVE The objective of the study was a comparison of outcome in patients with stage II ACC who were followed up prospectively early after surgery and were counseled by a specialized center (prospective group) with patients who registered with the German ACC registry later than 4 months after diagnosis (retrospective group). PATIENTS/METHODS The study was a cohort analysis in 149 adult patients with stage II ACC. RESULTS Patients who were followed up prospectively (n = 30) had a lower recurrence rate and a superior 5-yr survival compared with the 119 patients in the retrospective group (30 vs. 74%, P < 0.01 and 96 vs. 55%, P < 0.05, respectively). In the retrospective group, 67% of the patients had registered only after disease recurrence. In the remaining patients, the recurrence rate was low (21%), and the 5-yr survival was greater than 95%. More patients in the prospective group received adjuvant mitotane (53 vs. 16%, P < 0.001), and adjuvant mitotane was associated with improved survival [hazard risk 0.35 (95% confidence interval 0.13-0.97); P = 0.04]. However, the survival advantage was maintained when only patients without mitotane therapy were analyzed. CONCLUSIONS Patients who are followed up prospectively after surgery for stage II ACC and receive early specialized care have a much better prognosis than previously reported due to a major referral bias in previous series and use of adjuvant mitotane. These findings will impact on the perception of prognosis in newly diagnosed stage II ACC.

Value of Fractional Uric Acid Excretion in Differential Diagnosis of Hyponatremic Patients on Diuretics

BACKGROUND The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e.g. >100 mOsm/kg), clinical euvolemia, and a urinary sodium (Na) excretion (U-Na) more than 30 mmol/liter. However, in hyponatremic patients taking diuretics, this definition is unreliable due to the natriuretic effect of diuretics. Here, we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD, regardless of the use of diuretics. METHODS A total of 86 consecutive hyponatremic patients (serum Na <130 mmol/liter) was classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, and fractional excretion (FE) of Na, urea, and uric acid (UA) were measured in all subjects. The accuracy to diagnose SIAD was assessed using receiver operating characteristic analysis. RESULTS A total of 31 patients (36%) had a diagnosis of SIAD, and 55 (64%) were classified as non-SIAD. There were 57 patients (68%) who were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the receiver operating characteristic curve 0.96; 0.92-1.02). However, in patients on diuretics, the diagnosis was unreliable (area under the curve 0.85; 0.73-0.97). There, FE-UA performed best compared with all other markers tested (area under the curve 0.96; 0.92-1.12), resulting in a positive predictive value of 100% if a cutoff value of 12% was used. CONCLUSION FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagnostic accuracy in hyponatremic patients with and without diuretic treatment.

Utility and Limitations of the Traditional Diagnostic Approach to Hyponatremia: A Diagnostic Study

BACKGROUND The differential diagnosis of hyponatremia is often challenging because of its association with multiple underlying pathophysiological mechanisms, diseases, and treatment options. Several algorithms are available to guide the diagnostic approach to hyponatremia, but their diagnostic and clinical utility has never been evaluated. We aimed to assess in detail the diagnostic utility as well as the limitations of the existing approaches to hyponatremia. METHODS Each of the 121 consecutive subjects presenting with hyponatremia (serum sodium <130 mmoL/L) underwent 3 different and independent diagnostic and therapeutic approaches: inexperienced doctor applying an established Algorithm, intensive care senior physicians acting as Senior Physician, and senior endocrinologist serving as Reference Standard. RESULTS The overall diagnostic agreement between Algorithm and Reference Standard was 71% (respective Cohens kappa and delta values were 0.64 and 0.70), the overall diagnostic agreement between Senior Physician and Reference Standard was 32% (0.20 and 0.19, respectively). Regarding the therapeutic consequences, the diagnostic accuracy of the Algorithm was 86% (0.70 and 0.72, respectively) and of the Senior Physician was 48% (0.01 and 0.04, respectively). In retrospect, by disregarding the patients extracellular fluid volume and assessing the effective arterial blood volume by determination of the fractional urate excretion, the Algorithm improved its diagnostic accuracy to 95%. CONCLUSION Although the Algorithm performed reasonably well, several shortcomings became apparent, rendering it difficult to apply the Algorithm without reservation. Whether some modifications may enhance its diagnostic accuracy and simplify the management of hyponatremia needs to be determined.

Dysnatraemia in heart failure

To investigate in detail the correlates of dysnatremia, and to estimate its differential prognostic relevance in patients with heart failure with reduced or preserved LVEF.

High incidence of hyponatremia in trained rowers during a four-week training camp

Results Hyponatremia ([Na] < 135 mmol/L) was observed in 70% of the rowers. The highest incidence amounted to 43% at day 18, when training volume was highest. [Na] decreased from 143 ± 8.7 mmol/L (baseline) to 134.5 ± 5.4 mmol/L (day 18, p< 0.01). Hyponatremia was associated with body mass gain in the preceding 24 hours (p<0.01). [Na] returned to normal values at day 28 (139.8 ± 3.9 mmol/L). Relative fluid intake (L/m body surface area) increased from day 7 (males: 2.79 ± 0.78 L/m; females: 2.20 ± 0.70 L/m) to day 28 (3.88 ± 0.69 L/m and 2.65 ± 0.93 L/m; p<0.05). No athlete developed symptomatic hyponatremia.

Copeptin: a marker for ADPKD progression?

Autosomal dominant polycystic kidney disease (ADPKD) accounts for ∼5–10% of patients with end-stage renal disease (ESRD) [1]. Mutations in the PKD1 and PKD2 gene, encoding polycystin-1 (PC-1) and -2 (PC-2), account for ∼85 and 15% of diseases, respectively. PC-1 interacts with PC-2 to build a multifunctional signalling complex that regulates intracellular Ca 2+ signalling, and epithelial development and repair, which are essential mechanisms for maintaining a differentiated phenotype of renal epithelial cells [2, 3]. The exact pathology underlying renal cyst formation is still unknown, but it is generally accepted that adenosine3′-5′-cyclic monophosphate (cAMP) agonists accelerate cyst growth by stimulating mural epithelial cell proliferation and transepithelial Cl − secretion coupled to osmotic water flow [4].