Diagnosis and management of diabetes insipidus for the internist: an update.

Diabetes insipidus is a disorder characterized by excretion of large amounts of hypotonic urine. Four entities have to be differentiated: central diabetes insipidus resulting from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, nephrogenic diabetes insipidus resulting from resistance to AVP in the kidneys, gestational diabetes insipidus resulting from an increase in placental vasopressinase and finally primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Distinguishing between the different types of diabetes insipidus can be challenging. A detailed medical history, physical examination and imaging studies are needed to detect the aetiology of diabetes insipidus. Differentiation between the various forms of hypotonic polyuria is then done by the classical water deprivation test or the more recently developed hypertonic saline or arginine stimulation together with copeptin (or AVP) measurement. In patients with idiopathic central DI, a close follow-up is needed since central DI can be the first sign of an underlying pathology. Treatment of diabetes insipidus or primary polydipsia depends on the underlying aetiology and differs in central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia. This review will discuss issues and newest developments in diagnosis, differential diagnosis and treatment, with a focus on central diabetes insipidus.

Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis.

BACKGROUND: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response. METHODS: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis. RESULTS: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR. CONCLUSION: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.

Mid-regional pro-atrial natriuretic peptide and the assessment of volaemic status and differential diagnosis of profound hyponatraemia.

BACKGROUND: Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is associated with extracellular and cardiac fluid volume. METHODS: A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L(-1) ) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-proANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. RESULTS: MR-proANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia (P = 0.0002). The area under the curve (AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval (CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-proANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure (P = 0.012). MR-proANP predicted the syndrome of inappropriate antidiuresis (SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). CONCLUSION: MR-proANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-proANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia.

[Hormones as biomarkers for diagnosis and prognosis]. / Hormone als Biomarker für Diagnose und Prognose.

Procalcitonin is a biomarker for estimating the likelihood of a bacterial infection. Procalcitonin-guided antibiotic therapy can reduce antibiotic overuse in respiratory tract infections. The differential diagnosis of water-electrolyte imbalances is challenging. Copeptin is co-secreted with arginine vasopressin (AVP) and is a reliable surrogate of plasma AVP. Copeptin may become a useful diagnostic tool in patients with polydipsia-polyuria syndrome and hyponatremia. Copeptin is also known to mirror different levels of stress. It appears to have an interesting potential as a new prognostic biomarker in patients with ischemic stroke. Biomarkers should not be used without the clinical context. They are meant to complement clinical judgment based upon a synthesis of available clinical and laboratory features in each patients.

Eosinophilic myositis/perimyositis: frequency and spectrum of cutaneous manifestations.

BACKGROUND: Eosinophilic myositis/perimyositis (EM/P) are a group of rare idiopathic muscle disorders associated with eosinophilia. OBJECTIVE: We describe the frequency and spectrum of cutaneous manifestations in EM/P and compare them with the idiopathic hypereosinophilic syndrome (HES). METHODS: We review the literature on EM/P and describe an additional case associated with angioedema. RESULTS: Of a total of 26 reported patients with EM/P, cutaneous manifestations were observed in 10. These were, in order of frequency, deep subcutaneous induration, erythema, angioedema, urticaria, and papular lesions. CONCLUSION: Skin lesions occur less frequently in EM/P than in HES. Although erythematous papulonodular lesions and urticaria/angioedema are most commonly observed in HES, the most frequent skin manifestations of EM/P are subcutaneous induration and erythema. In HES, angioedema has been correlated with a favorable prognosis. At least some of these patients apparently have an idiopathic eosinophilic disorder distinct from HES, including EM/P. In contrast to HES, the overall prognosis of EM/P is good, particularly when muscle lesions are focal, and the principal histopathologic finding is perimysial infiltrates.