In-patient Tolvaptan use in SIADH: care audit,therapy observation and outcome analysis

Background

Indications for use of tolvaptan in SIADH-associated hyponatraemia remain controversial. We audited our local guidelines for Tolvaptan use in this situation to review treatment implications including drug safety, hospital admission episode analysis (episodes of liver toxicity, CNS myelinolysis, sodium-related re-admission rates), morbidity; mortality and underlying aetiologies.

Methods

We report a retrospective case series analysis of on-going treatment outcomes (case-note review) for 31 patients (age 73.3 ± 10.5 years, 55% females) consecutively treated with Tolvaptan as in-patient for confirmed SIADH with persistent S/Na⁺ < 125 mmol/L despite removal of reversible causes and 24-48 h fluid restriction, and include longer-term outcome data (re-treatment/readmissions/mortality) for up to 4 years of follow-up. A minimum of 6 months follow-up data were reviewed unless the patient died before that period.

Results

Short-term outcomes were favourable; 94%-achieved treatment targets after a mean of 3.48 ± 2.46 days. There was statistically significant rise in S/Na⁺ level after Tolvaptan treatment (before treatment: mean sodium 117.8 ± 3.73, 108–121 mmol/L and after treatment: mean sodium 128.7 ± 3.67, 125–135.2 mmol/L, P < .001). Although the target S/Na⁺ level was >125 mmol/L in fact one third (35%) of the patients achieved a S/Na⁺ level of >130 mmol/L by the time of hospital discharge. No patient experienced S/Na⁺ rise >12 mmol/L/24 h, drug-associated liver injury or CNS-myelinolysis. The average length of hospital stay following start of Tolvaptan treatment was 3.2 days. Relapse of hyponatraemia occurred in 26% of the patients, requiring retreatment with Tolvaptan. In all patients where either relapse of hyponatraemia occurred or readmission was necessary, SIADH was associated with malignancy, which was present overall in 60% of the group studied.

Conclusions

This study confirms the safety and efficacy of Tolvaptan in the treatment of SIADH-related significant, symptomatic hyponatraemia when used under specialist guidance and strict monitoring. A sodium level relapsing below the treatment threshold by 1 week after discontinuation is a good indicator of a patient group with re-treatment/longer-term therapy needs, all of whom had underlying malignancy. The criteria set locally in our trust to initiate Tolvaptan use also identifies a group where further investigation for underlying malignancy should be considered.

     

Profound Hypokalemia in Diabetic Ketoacidosis: A Therapeutic Challenge

ObjectiveTo describe profound hypokalemia in a comatose patient with diabetic ketoacidosis.MethodsWe present a case report, review the mechanisms for the occurrence of hypokalemia in diabetic ketoacidosis, and discuss its management in the setting of hyperglycemia and hyperosmolality.ResultsA 22-year-old woman with a history of type 1 diabetes mellitus was admitted in a comatose state. Laboratory tests revealed a blood glucose level of 747 mg/dL, serum potassium of 1.9 mEq/L, pH of 6.8, and calculated effective serum osmolality of 320 mOsm/kg. She was intubated and resuscitated with intravenously administered fluids. Intravenous administration of vasopressors was necessary for stabilization of the blood pressure. Intravenous infusion of insulin was initiated to control the hyperglycemia, and repletion of total body potassium stores was undertaken. A total of 660 mEq of potassium was administered intravenously during the first 12.5 hours. Despite such aggressive initial repletion of potassium, the patient required 40 to 80 mEq of potassium daily for the next 8 days to increase the serum potassium concentration to normal.ConclusionProfound hypokalemia, an uncommon initial manifestation in patients with diabetic ketoacidosis, is indicative of severe total body potassium deficiency. Under such circumstances, aggressive potassium repletion in a comatose patient must be undertaken during correction of other metabolic abnormalities, including hyperglycemia and hyperosmolality. Intravenously administered insulin should be withheld until the serum potassium concentration is ≥ 3.3 mEq/L. (Endocr Pract. 2005;11:331-334)     

Hyponatremia in the postoperative craniofacial pediatric patient population: a connection to cerebral salt wasting syndrome and management of the disorder.

Hyponatremia after cranial vault remodeling has been noted in a pediatric patient population. If left untreated, the patients may develop a clinical hypoosmotic condition that can lead to cerebral edema, increased intracranial pressure, and eventually, to central nervous system and circulatory compromise. The hyponatremia has traditionally been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); however, in our patients the treatment has been resuscitation with normal saline as opposed to fluid restriction (the accepted treatment of SIADH), thus placing the diagnosis of SIADH in question. Patients who developed hyponatremia after intracranial injury or surgery were, until recently, grouped together as having SIADH. However, there are diagnosis and treatment differences between SIADH and another distinct but poorly understood disorder that is designated cerebral salt wasting syndrome (CSW). CSW is associated with increased urine output and increased urine sodium concentration and volume contraction, and it is frequently seen after a central nervous system trauma. We therefore developed a prospective study to evaluate the cause of the sodium imbalance.Ten consecutive pediatric patients who underwent intracranial surgery for various craniosynostotic disorders were postoperatively monitored in the pediatric intensive care unit for hemodynamic, respiratory, and fluid management. The first four patients were evaluated for electrolyte changes and overall fluid balance to determine the consistency with which these changes occurred. The remaining six patients had daily (including preoperative) measurement of serum electrolytes, urine electrolytes, urine osmolarity, serum antidiuretic hormone (ADH), aldosterone, and atrial natriuretic hormone (ANH). All patients received normal saline intravenous replacement fluid in the postoperative period.All of the patients developed a transient hyponatremia postoperatively, despite normal saline resuscitation. Serum sodium levels as low as 128 to 133 mEq per liter (normal, 137 to 145 mEq per liter) were documented in the patients. All patients had increased urine outputs through the fourth postoperative day (>1 cc/kg/h). The six patients who were measured had an increased ANH level, with a peak value as high as 277 pg/ml (normal, 25 to 77 pg/ml). ADH levels were low or normal in all but one patient, who had a marked increase in ADH and ANH. Aldosterone levels were variable. On the basis of these results, all but one patient showed evidence of CSW characterized by increased urine output, normal or increased urine sodium, low serum sodium, and increased ANH levels. The other patient had similar clinical findings consistent with CSW but also had an increase in ADH, thus giving a mixed laboratory picture of SIADH and CSW.The association of CSW to cranial vault remodeling has previously been ignored. This study should prompt reevaluation of the broad grouping of SIADH as the cause of all hyponatremic episodes in our postoperative patient population. An etiologic role has been given to ANH and to other, as yet undiscovered, central nervous system natriuretic factors. All of the patients studied required normal saline resuscitation, a treatment approach that is contrary to the usual management of SIADH. These findings should dictate a change in the postoperative care for these patients. After cranial vault remodeling, patients should prophylactically receive normal saline, rather than a more hypotonic solution, to avoid sodium balance problems.     

Tolvaptan inhibits ERK-dependent cell proliferation, Cl⁻ secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin

In autosomal dominant polycystic kidney disease (ADPKD), arginine vasopressin (AVP) accelerates cyst growth by stimulating cAMP-dependent ERK activity and epithelial cell proliferation and by promoting Cl(-)-dependent fluid secretion. Tolvaptan, a V2 receptor antagonist, inhibits the renal effects of AVP and slows cyst growth in PKD animals. Here, we determined the effect of graded concentrations of tolvaptan on intracellular cAMP, ERK activity, cell proliferation, and transcellular Cl(-) secretion using human ADPKD cyst epithelial cells. Incubation of ADPKD cells with 10(-9) M AVP increased intracellular cAMP and stimulated ERK and cell proliferation. Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ～10(-10) M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation. Basolateral application of AVP to ADPKD cell monolayers grown on permeable supports caused a sustained increase in short-circuit current that was completely blocked by the Cl(-) channel blocker CFTR(inh-172), consistent with AVP-induced transepithelial Cl(-) secretion. Tolvaptan inhibited AVP-induced Cl(-) secretion and decreased in vitro cyst growth of ADPKD cells cultured within a three-dimensional collagen matrix. These data demonstrate that relatively low concentrations of tolvaptan inhibit AVP-stimulated cell proliferation and Cl(-)-dependent fluid secretion by human ADPKD cystic cells.     

The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment

Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin‐regulated water reabsorption via aquaporin‐2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2‐mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin–cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney. In MDCK, tolvaptan prevented dDAVP‐induced increase in ser256‐AQP2 and osmotic water permeability. A similar effect on ser256‐AQP2 was found in V1aR ?/? mice, thus confirming the V2R selectively. Of note, calcium calibration in MDCK showed that tolvaptan per se caused calcium mobilization from the endoplasmic reticulum resulting in a significant increase in basal intracellular calcium. This effect was only observed in cells expressing the V2R, indicating that it requires the tolvaptan–V2R interaction. Consistent with this finding, tolvaptan partially reduced the increase in ser256‐AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium‐inhibitable AC type VI. Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance.     

Hypertension in a Patient with Aldosterone Deficiency

ObjectiveTo describe a patient with aldosterone synthase deficiency, who presented with failure to thrive, hypovolemic hyponatremia, and the unexpected finding of hypertension.MethodsWe present a case report, review the related literature, and outline a possible mechanism for the concomitant occurrence of high blood pressure and hyponatremia in this patient.ResultsA 5-month-old infant with unambiguous female genitalia was admitted to our hospital with failure to thrive and hyponatremia. Her blood pressure was 115/88 mm Hg (> 95% for age). The serum sodium concentration was 123 mEq/L (normal for age, > 130), and the potassium level was 5.3 mEq/L (normal, 3.5 to 5.3). A direct renin measurement by immunochemiluminescence assay was 11,400 μU/mL (normal, < 5), and the aldosterone level was 4 ng/dL (normal, 2 to 70). These findings indicated a diagnosis of aldosterone synthase deficiency. Treatment with fludrocortisone and sodium chloride was begun, but the hypertension worsened. Therapy with an angiotensin-converting enzyme inhibitor was transiently required.ConclusionAngiotensin II, a potent vasoconstrictor, is an intermediate in the renin-angiotensin system. We believe that this protein was the cause of the hypertension in the setting of aldosterone deficiency in our patient. (Endocr Pract. 2005;11:104-107)     

Formulation and in-vitro characterization of fast-disintegrating herbal extract sublingual immunotherapy tablet for peanut-induced allergic asthma

BackgroundAllergen immunotherapy (AIT) involves the regimen of gradually incrementing doses of the allergen, thereby inducing desensitization and tolerance. Sublingual Immunotherapy tablets (SLIT-tablets) have been formulated for several allergies and had manifested efficacy for allergic rhinitis and allergic asthma. SLIT promises an alternative method to other routes of AIT enabling patients to self-administer AIT.ObjectiveThe study aimed to formulate fast disintegrating SLIT containing crude peanut extract for peanut-induced allergic asthma.MethodsThe crude peanut extract was prepared by a simple extraction method and was subjected to quantitative and qualitative analysis. The extract was also characterised for its physical properties. The preformulation study for the extract and excipients of the tablet was performed using FT-IR spectroscopy and Differential scanning calorimetry. The tablet powder blends were characterised for pre-compression properties. The SLIT tablets were developed by direct compression and the post-compression evaluation was performed.ResultsThe results of the quantitative and qualitative analysis of extract confirmed the presence of peanut proteins in the extract. The preformulation studies using FT-IR spectroscopy and Differential Scanning Calorimetry revealed that there is no significant interaction between the CPE and excipients. The pre-compression characterisation showed that the powder blends had good flowproperties. Three doses of SLIT tablets were formulated with each dose containing four batches and the tablet of each dose was optimized by studying the effect of varying concentrations of super disintegrants on disintegration time and dissolution rate. The post compression characterization of the tablets was performed and the optimized batch of the three doses with the concentration of 5% crospovidone and 2% croscarmellose sodium showed less wetting time and high-water absorption ratio, shorter disintegration time of 14secs and maximum drug release of >90% within 2–3 min.ConclusionThe results indicated the suitability of formulated SLIT tablets for peanut induced allergic asthma.     

Detailed evaluation of Mobius3D dose calculation accuracy for volumetric-modulated arc therapy

PurposeTo perform a detailed evaluation of dose calculation accuracy and clinical feasibility of Mobius3D. Of particular importance, multileaf collimator (MLC) modeling accuracy in the Mobius3D dose calculation algorithm was investigated.MethodsMobius3D was fully commissioned by following the vendor-suggested procedures, including dosimetric leaf gap (DLG) optimization. The DLG optimization determined an optimal DLG correction factor which minimized the average difference between calculated and measured doses for 13 patient volumetric-modulated arc therapy (VMAT) plans. Two sets of step-and-shoot plans were created to examine MLC and off-axis open fields modeling accuracy of the Mobius3D dose calculation algorithm: MLC test set and off-axis open field test set. The test plans were delivered to MapCHECK for the MLC tests and an ionization chamber for the off-axis open field test, and these measured doses were compared to Mobius3D-calculated doses.ResultsThe mean difference between the calculated and measured doses across the 13 VMAT plans was 0.6% with an optimal DLG correction factor of 1.0. The mean percentage of pixels passing gamma from a 3%/1 mm gamma analysis for the MLC test set was 43.5% across the MLC tests. For the off-axis open field tests, the Mobius3D-calculated dose for 1.5 cm square field was −4.6% lower than the chamber-measured dose.ConclusionsIt was demonstrated that Mobius3D has dose calculation uncertainties for small fields and MLC tongue-and-groove design is not adequately taken into consideration in Mobius3D. Careful consideration of DLG correction factor, which affects the resulting dose distributions, is required when commissioning Mobius3D for patient-specific QA.     

Severe Hyponatre mia Due to Rosiglita zone Use in an Elderly Woman With Diabetes Mellitus: A Rare Cause of Syndrome of Inappropriate Antidiuretic Hormone Secretion

ObjectiveTo describe the first case of syndrome of inappropriate antidiuretic hormone secretion with lifethreatening hyponatremia due to rosiglitazone therapy.MethodsWe describe the clinical, laboratory, and imaging findings of the study patient.ResultsAn 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient’s plasma sodium concentration has remained in the reference range at follow-up visits.ConclusionsThis is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition. (Endocr Pract. 2008;14:1017-1019)     

Investigation and management of moderate to severe inpatient hyponatraemia in an Australian tertiary hospital

Background

Hyponatraemia is the most common electrolyte disturbance amongst hospitalised patients. Both American and European guidelines recommend fluid restriction as first line treatment for SIADH, however differ on second line recommendations. The objective of this study was to examine investigation and management of hyponatraemia in hospitalised patients in an Australian tertiary hospital.

Methods

A retrospective audit was conducted of electronic medical records and laboratory data of inpatients with serum sodium (Na) ≤125?mmol/L, admitted over a 3?month period to the Princess Alexandra Hospital, Brisbane, Australia. The main outcomes measured included: demographic characteristics, investigations, accuracy of diagnosis, management strategy, change in Na and patient outcomes.

Results

The working clinical diagnosis was considered accurate in only 37.5% of cases. Urine Na and osmolality were requested in 72 of 152 patients (47.4%) and in 43 of 70 euvolaemic patients (61.4%). Thyroid function tests (67.1%) and morning cortisol (45.7%) were underutilized in the euvolaemic group. In the SIADH cohort, fluid restriction resulted in a median (IQR) 7.5?mmol/L (4–10.5) increase in Na after 3?days; no treatment resulted in a median 0?mmol/L (??0.5–1.5) change. Oral urea was utilized in 5 SIADH patients where Na failed to increase with fluid restriction alone. This resulted in a median 10.5?mmol/L (3.5–13) increase in Na from baseline to day 3. There were no cases of osmotic demyelination. The median length of stay was 8?days (4–18.5). Mortality was 11.2% (17 patients). There was a weak but significant correlation between nadir serum Na and mortality (R?=?0.18, P?=?0.031).

Conclusion

Inpatient hyponatraemia is often inadequately investigated, causing errors in diagnosis. Treatment is heterogeneous and often incorrect. In cases with hyponatraemia refractory to fluid restriction, oral urea presents an effective alternative treatment.

     

Low Potassium Dialysate as a Protective Factor of Sudden Cardiac Death in Hemodialysis Patients with Hyperkalemia

AimHyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD.MethodsWe conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed.ResultsThere were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13–0.85).ConclusionsUsing low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.     

Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients

Background and Aim

Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.

Methods

To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.

Results

During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.

Conclusions

These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.     

Rhabdomyolysis after Withdrawal of Thyroid Hormone in a Patient with Papillary Thyroid Cancer

ObjectiveTo report a case of rhabdomyolysis presenting with severe hyperkalemia after withdrawal of thyroid hormone in a patient with differentiated thyroid cancer.MethodsWe describe the clinical and laboratory findings of the study patient and review the relevant literature.ResultsA 54-year-old man with progressive generalized weakness and myalgias presented with acute renal failure and hyperkalemia. He had undergone total thyroidectomy for papillary thyroid cancer 6 weeks earlier and had discontinued thyroid hormone 2 weeks before his current presentation in preparation for thyroid remnant ablation. He had a history of multiple colon and small-bowel resections for familial adenomatous polyposis and desmoid tumor. He was severely dehydrated on examination. Laboratory tests results included the following values: creatine phosphokinase, 5265 U/L (reference range, 52-336 U/L); creatinine, 2.1 mg/dL; potassium, > 8.0 mEq/L; and thyrotropin, 92.2 mIU/L. His condition was diagnosed as rhabdomyolysis, and his fluid deficit and hyperkalemia were treated aggressively. Cardiac status remained stable, and both acute renal failure and hyperkalemia improved. He then received remnant ablation, and thyroid hormone was restarted. His muscle complaints resolved over the following 3 months.ConclusionsHypothyroidism-induced rhabdomyolysis can occur during thyroid hormone withdrawal and can present with life-threatening hyperkalemia. Patients undergoing thyroid hormone withdrawal should be assessed for risk of rhabdomyolysis, and preventive strategies should be implemented, including prevention of dehydration.The use of recombinant thyrotropin, rather than thyroid hormone withdrawal, should be considered in those who are at high risk for such complications. (Endocr Pract. 2008;14:1023-1026)     

Tratamiento con equinocandinas en un paciente crítico sometido a técnica continua de reemplazo renal

BackgroundCritically ill patients with invasive candidiasis (IC) often suffer renal failure, which sometimes requires continuous renal replacement techniques (CRRT). Echinocandins are the first line treatment for IC in critically ill patients with mild or severe illness. Their elimination during CRRT should be negligible due to their pharmacokinetic and pharmacodynamic (PK/PD) profile, and dose adjustment are not needed, as suggested by the few reported clinical studies.Clinical caseThis is the case of a 66 year old male who underwent surgery due to peritonitis secondary to intestinal suture dehiscence. The patient was admitted to ICU with septic shock symptoms and multiple organ dysfunction syndrome (MODS), and CRRT was started. Anidulafungin was prescribed at the usual dosage due to the IC risk factors present, and the observation of yeasts in the peritoneal fluid. Anidulafungin was selected due to the hepatic failure suffered by the patient. An isolate of Candida albicans susceptible to fluconazole was cultured from peritoneal fluid and rectal exudates. However, anidulafungin was maintained due to the MODS and observing the clearance of fluconazole during CRRT. The patient's condition improved favourably, being moved to the surgical ward 20 days after the surgery.ConclusionsEchinocandins, due to their PK/PD profile, could be safely given at usual doses to critically ill patients undergoing CRRT. However, new studies are required to strengthen this recommendation. Its extrahepatic metabolism makes anidulafungin a more attractive option among echinocandins and other antifungals when used in patients with different degrees of hepatic failure     

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Coproporphyria: Case Report and Review of Literature

ObjectiveTo remind physicians to consider the hepatic porphyrias in the differential diagnosis of the syndrome of inappropriate antidiuretic hormone secretion.MethodsWe present a case report of a patient seen in the hospital for severe hyponatremia, who was discovered to have the syndrome of inappropriate antidiuretic hormone secretion attributable to coproporphyria. Results of laboratory tests of the patient and her family are presented.ResultsA 54-year-old woman was seen in the hospital because of severe hyponatremia accompanied by generalized seizures. Her serum sodium concentration was 112 mEq/L, with concomitant serum and urine osmolalities of 235 and 639 mOsm/kg, respectively. Renal, thyroid, and adrenal functions were normal. Brain, chest, abdominal, and pelvic imaging studies were negative for occult malignant disease. Urinary excretions of porphobilinogen and aminolevulinic acid were substantially elevated. Results of follow-up urine, plasma, and fecal porphyrin studies were consistent with coproporphyria. Results of porphyrin metabolic studies of the patient’s family showed normal findings in her parents and a minimally increased fecal coproporphyrin concentration and urinary uroporphyrin excretion in her sister.ConclusionAn endocrinology consultation is often requested for patients with hyponatremia. It is important to consider the acute hepatic porphyrias in the differential diagnosis, even though these are rare disorders and the family history may not always be helpful because of the high frequency of asymptomatic carriers. (Endocr Pract. 2007;13:164-168)     

Dosimetric study of Hounsfield number correction effect in areas influenced by contrast product in lungs case

BackgroundThe aim of the study was dosimetric effect quantification of exclusive computed tomography (CT) use with an intravenous (IV) contrast agent (CA ), on dose distribution of 3D-CRT treatment plans for lung cancer. Furthermore, dosimetric advantage investigation of manually contrast-enhanced region overriding, especially the heart.Materials and methodsTen patients with lung cancer were considered. For each patient two planning CT sets were initially taken with and without CA. Treatment planning were optimized based on CT scans without CA. All plans were copied and recomputed on scans with CA. In addition, scans with IV contrast were copied and density correction was performed for heart contrast enhanced. Same plans were copied and replaced to undo dose calculation errors that may be caused by CA. Eventually, dosimetric evaluations based on dose volume histograms (DVHs) of planning target volumes (PTV) and organs at-risk were studied and analyzed using the Wilcoxon’s signed rank test.ResultsThere is no statistically significant difference in dose calculation for the PTV maximum, mean, minimum doses, spinal cord maximum doses and lung volumes that received 20 and 30 Gy, between planes calculated with and without contrast scans (p > 0.05) and also for contrast scan, with manual regions overriding.ConclusionsDose difference caused by the contrast agent is negligible and not significant. Therefore, there is no justification to perform two scans, and using an IV contrast enhanced scan for dose calculation is sufficient.     

Finding the right balance between resistance and sensitivity: a review of the cardiac manifestations of the syndrome of resistance to thyroid hormone and the implications for treatment

ObjectiveTo review cardiac manifestations in the syndrome of resistance to thyroid hormone (RTH) and to question the general recommendation that the thyroidstimulating hormone (TSH) value be the guide to thyroid hormone replacement.MethodsThe syndrome of RTH is caused by mutations in the carboxyterminal portion of the β isoform of the thyroid hormone receptor, resulting in variable clinical manifestations. It is generally recommended that the replacement of thyroid hormone in patients with RTH be guided by the serum TSH concentration. The variable responsiveness of tissues to thyroid hormone, however, makes it difficult to balance the correct replacement dose. We present a case that brings into question the conventional wisdom about the replacement dose of thyroid hormone in this scenario, and we review the pertinent literature.ResultsA 54- year-old man with RTH was treated with levothyroxine and increasing doses of liothyronine sodium as part of an evaluation of RTH. On day 10 of theprotocol, he developed atrial fibrillation despite a normal level of TSH (1.1 mIU/L). Administration of liothyronine was discontinued, and cardioversion was planned; however, the patient’s heart rhythm converted spontaneously to normal sinus rhythm.ConclusionReplacement of thyroid hormone in patients with RTH should include careful monitoring of thyrotoxic cardiac side effects in addition to consideration of normalization of the TSH level. (Endocr Pract. 2012;18:252- 255)     

Continuous collection and analysis of bovine oviduct fluid: preliminary results

Oviduct fluid was collected by cannulating the oviducts of nine cows. The fluid was analyzed for sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), inorganic phosphorus (Pi), magnesium (Mg) concentration and osmolarity (Osm). The mean concentrations +/- the standard error of the means of the constituents were: Na (140.7 +/- 0.37 mEq/L), K (5.12 +/- 0.08 mEq/L), Cl (101.8 +/- 1.54 mEq/L), Ca (1.88 +/- 0.08 mEq/L), Pi (1.97 +/- 0.07 mEq/L), and Mg (1.00 +/- 0.03 mEq/L). Osmolarity was 281.0 +/- 2.56 m Osmols. Significantly lower concentrations of Na (117.4 +/- 2.58 mEq/L) were found in the fluid collected from the oviduct ipsilateral to the ovulating ovary on the day of ovulation. This decrease in Na concentration did not occur in fluid from the contralateral oviduct. The lowest concentrations of Ca were found during days 18 through 21, while the highest were found during days 2 through 6. No significant cyclic changes in the other constituents were observed although the concentrations tended to be highest during days 18 through 21 and lowest on day 1. The concentrations of many of the constituents analyzed were different than those previously reported for bovine oviduct fluid (1).     

小剂量甲状腺素联合厄贝沙坦氢氯噻嗪治疗老年重症心力衰竭的效果观察

目的:探究使用小剂量甲状腺素联合厄贝沙坦氢氯噻嗪治疗老年重症心力衰竭(CHF)中的治疗效果。方法:将37例本院老年CHF患者随机分做实验组(19例)及对照组(18例)。对照组予厄贝沙坦氢氯噻嗪片及美托洛尔治疗;实验组予厄贝沙坦氢氯噻嗪片、美托洛尔及左旋甲状腺素钠片治疗。对比治疗前后两组患者心力衰竭症状、心功能及甲状腺素水平的变化。结果:实验组总有效率(94.7%)高于对照组(77.8%),差异具有统计学意义(P0.05);两组患者左心室射血分数(LVEF)水平及胱抑素C水平增加,纽约心脏病协会分级(NYHA)及B型脑钠肽水平均降低(P0.05);与对照组相比,实验组LVEF及胱抑素C水平较高,NYHA分级及B型脑钠肽水平较低,差异存在统计学意义(P0.05);两组血清三碘甲状腺原氨酸(T3)、血清甲状腺素(T4)水平均升高(P0.05),与对照组相比,实验组血清T3、T4水平较高,差异具有统计学意义(P0.05)。结论:小剂量甲状腺素联合厄贝沙坦氢氯噻嗪治疗老年CHF的效果显著,可以明显改善心力衰竭症状、提高LVEF水平,降低NYHA分级及血清中B型脑钠肽水平。