Inferior vena cava ultrasound and other techniques for assessment of intravascular and extravascular volume: an update.

Goals of volume management are to accurately assess intravascular and extravascular volume and predict response to volume administration, vasopressor support or volume removal. Data are reviewed that support the following: (i) Dynamic parameters reliably guide volume administration and may improve clinical outcomes compared with static parameters, but some are invasive or only validated with mechanical ventilation without spontaneous breathing. (ii) Ultrasound visualization of inferior vena cava (IVC) diameter variations with respiration reliably assesses intravascular volume and predicts volume responsiveness. (iii) Although physiology of IVC respiratory variations differs with mechanical ventilation and spontaneous breathing, the IVC collapsibility index (CI) and distensibility index are interconvertible. (iv) Prediction of volume responsiveness by IVC CI is comparable for mechanical ventilation and spontaneous breathing patients. (v) Respiratory variations of subclavian/proximal axillary and internal jugular veins by ultrasound are alternative sites, with comparable reliability. (vi) Data support clinical applicability of IVC CI to predict hypotension with anesthesia, guide ultrafiltration goals, predict dry weight, predict intra-dialytic hypotension and assess acute decompensated heart failure. (vii) IVC ultrasound may complement ultrasound of heart and lungs, and abdominal organs for venous congestion, for assessing and managing volume overload and deresuscitation, renal failure and shock. (viii) IVC ultrasound has limitations including inadequate visualization. Ultrasound data should always be interpreted in clinical context. Additional studies are required to further assess and validate the role of bedside ultrasonography in clinical care.

Hepatorenal syndrome misdiagnosis may be reduced using inferior vena cava ultrasound to assess intravascular volume and guide management.

Hepatorenal syndrome (HRS) is a diagnosis of exclusion defined as acute kidney injury (AKI) with cirrhosis and ascites, with serum creatinine unresponsive to standardized volume administration and diuretic withdrawal. Persistent intravascular hypovolemia or hypervolemia may contribute to AKI and be revealed by inferior vena cava ultrasound (IVC US), which may guide additional volume management. Twenty hospitalized adult patients meeting HRS-AKI criteria had IVC US to assess intravascular volume after receiving standardized albumin administration and diuretic withdrawal. Six had IVC collapsibility index (IVC-CI) ≥50% and IVCmax ≤0.7 cm suggesting intravascular hypovolemia, 9 had IVC-CI <20% and IVCmax >0.7 cm suggesting intravascular hypervolemia, and 5 had IVC-CI ≥20% to <50% and IVCmax >0.7 cm. Additional volume management was prescribed in the 15 patients with either hypovolemia or hypervolemia. After 4-5 days, serum creatinine levels decreased ≥20% without hemodialysis in 6 of 20 patients - 3 with hypovolemia received additional volume, and 2 with hypervolemia plus one with 'euvolemia' and dyspnea were volume restricted and received diuretics. In the other 14 patients, serum creatinine failed to persistently decrease ≥20% or hemodialysis was required indicating that AKI did not improve. In summary, fifteen of 20 patients (75%) were presumed to have intravascular hypovolemia or hypervolemia by IVC ultrasound. Six of the 20 patients (40%) improved AKI by 4-5 days of follow-up with additional IVC US-guided volume management, and thus had been misdiagnosed as HRS-AKI. IVC US may more accurately define HRS-AKI as being neither hypovolemic nor hypervolemic, and guide volume management, decreasing the frequency of HRS-AKI misdiagnosis.

Comparison of subclavian vein to inferior vena cava collapsibility by ultrasound in acute heart failure: A pilot study.

BACKGROUND: Management of acute decompensated heart failure (ADHF) requires accurate assessment of relative intravascular volume, which may be technically challenging. Inferior vena cava (IVC) collapsibility with respiration reflects intravascular volume and right atrial pressure (RAP). Subclavian vein (SCV) collapsibility may provide an alternative. HYPOTHESIS: The purpose of this study was to examine the relationship between SCV collapsibility index (CI) and IVC CI in ADHF. METHODS: This was a prospective study of non-ventilated patients with ADHF who had paired IVC and SCV ultrasound assessments. As SCV CI is highly position-dependent, measurements were performed supine at 30-45°. RESULTS: Thirty-three patients were included with 36 encounters. The sample size was adequately powered for receiver-operator characteristic (ROC) analysis. SCV CI correlated with IVC CI during relaxed breathing (R = .65, n = 36, p < .001) and forced inhalation (R = .47, n = 36, p = .0036). SCV CI < 22% and >33% corresponded to IVC CI < 20% and >50% suggesting hypervolemia (sensitivity/specificity: 72%) and hypovolemia (sensitivity/specificity: 78%), respectively. Moderate to severe tricuspid regurgitation (TR) compared to less than moderate TR was associated with lower SCV CI (medians: 12.4% vs. 25.3%, p = .022) and IVC CI (medians: 9.6% vs. 35.6%, p = .0012). SCV CI and IVC CI were not significantly different among chronic kidney disease stages. CONCLUSION: In non-ventilated ADHF, SCV CI at 30-45° correlates with paired IVC CI, and may provide an alternative to IVC CI for assessment of relative intravascular volume, which may facilitate clinical management. Moderate to severe TR decreases SCV CI and IVC CI and may result in overestimation of relative intravascular volume.

Inferior Vena Cava Collapsibility Index: Clinical Validation and Application for Assessment of Relative Intravascular Volume.

Accurate assessment of relative intravascular volume is critical to guide volume management of patients with acute or chronic kidney disorders, particularly those with complex comorbidities requiring hospitalization or intensive care. Inferior vena cava (IVC) diameter variability with respiration measured by ultrasound provides a dynamic noninvasive point-of-care estimate of relative intravascular volume. We present details of image acquisition, interpretation, and clinical scenarios to which IVC ultrasound can be applied. The variation in IVC diameter over the respiratory or ventilatory cycle is greater in patients who are volume responsive than those who are not volume responsive. When 2 recent prospective studies of spontaneously breathing patients (n = 214) are added to a prior meta-analysis of 181 patients, for a total of 7 studies of 395 spontaneously breathing patients, IVC collapsibility index (CI) had a pooled sensitivity of 71% and specificity of 81% for predicting volume responsiveness, which is similar to a pooled sensitivity of 75% and specificity of 82% for 9 studies of 284 mechanically ventilated patients. IVC maximum diameter <2.1 cm, that collapses >50% with or without a sniff is inconsistent with intravascular volume overload and suggests normal right atrial pressure (0-5 mmHg). Inferior vena cava collapsibility (IVC CI) < 20% with no sniff suggests increased right atrial pressure and is inconsistent with overt hypovolemia in spontaneously breathing or ventilated patients. These IVC CI cutoffs do not appear to vary greatly depending on whether patients are breathing spontaneously or are mechanically ventilated. Patients with lower IVC CI are more likely to tolerate ultrafiltration with hemodialysis or improve cardiac output with ultrafiltration. Our goal for IVC CI generally ranges from 20% to 50%, respecting potential biases to interpretation and overriding clinical considerations. IVC ultrasound may be limited by factors that affect IVC diameter or collapsibility, clinical interpretation, or optimal visualization, and must be interpreted in the context of the entire clinical situation.

Comparison of Respiratory Variations of Subclavian Vein and Inferior Vena Cava in Hospitalized Patients with Kidney Disease.

BACKGROUND: Accurate assessment of relative intravascular volume is critical for appropriate volume management of patients with kidney disease. Respiratory variations of inferior vena cava (IVC) diameter have been used and may correlate with those of subclavian vein (SCV) by bedside ultrasound. The purpose of this study was to assess the relationship between SCV and IVC respiratory variations by bedside ultrasound in a large group of hospitalized patients with acute and/or chronic kidney disease. METHODS: We compared 160 paired SCV and IVC bedside ultrasound studies from 102 semi-recumbent hospitalized adult patients with kidney disease. Patient encounters in which the SCV or IVC could not be clearly visualized were excluded. Collapsibility index=(Dmax-Dmin)/Dmax*100%; D=venous diameter. RESULTS: Relationships between SCV collapsibility index and IVC collapsibility index were not different for longitudinal and transverse views of the SCV. Correlation of SCV collapsibility index with IVC collapsibility index was 0.75 for mechanical ventilation (n=65, P<0.0001) and 0.67 for spontaneous breathing (n=95, P<0.0001). IVC collapsibility index cut-offs <20% for hypervolemia and >50% for hypovolemia corresponded to SCV collapsibility index cut-offs of <22% and >39%, respectively, for both mechanical ventilation and spontaneous breathing encounters. Using these cut-offs for SCV collapsibilities, assessment as hypervolemia versus not-hypervolemia had maximal sensitivity and specificity for predicting respective IVC collapsibility cut-offs of 88% for mechanical ventilation and 74% for spontaneous breathing, and assessment as hypovolemia versus not-hypovolemia had maximal sensitivity and specificity of 91% and 70%, respectively. Concordance, defined as agreement between assessment using SCV CI and assessment using IVC CI, was 85% for mechanical ventilation and 72% for spontaneous breathing when differentiating hypervolemia versus not-hypervolemia and was 89% and 71% respectively when differentiating hypovolemia versus not-hypovolemia. CONCLUSION: Assessment using SCV collapsibility index in the semi-recumbent position has a reasonable concordance with assessment using IVC collapsibility index for both spontaneous breathing and mechanical ventilation, in a wide range of hospitalized patients with concurrent kidney disease, and may be a useful adjunct to assess relative intravascular volume in patients with kidney disease.

Changes in cardiac output with hemodialysis relate to net volume balance and to inferior vena cava ultrasound collapsibility in critically ill patients.

Cardiac output may increase after volume administration with relative intravascular volume depletion, or after ultrafiltration (UF) with relative intravascular volume overload. Assessing relative intravascular volume using respiratory/ventilatory changes in inferior vena cava (IVC) diameters may guide volume management to optimize cardiac output in critically ill patients requiring hemodialysis (HD) and/or UF.We retrospectively studied 22 critically ill patients having relative intravascular volume assessed by IVC Collapsibility Index (IVC CI) = (IVCmax-IVCmin)/IVCmax*100%, within 24 h of cardiac output measurement, during 37 intermittent and 21 continuous HD encounters. Cardiac output increase >10% was considered significant. Net volume changes between cardiac outputs were estimated from "isonatremic volume equivalent" (0.9% saline) gains and losses.Cardiac output increased >10% in 15 of 42 encounters with IVC CI <20% after net volume removal, and in 1 of 16 encounters with IVC CI ≥20% after net volume administration (p = 0.0136). All intermittent and continuous HD encounters resulted in intradialytic hypotension. Net volume changes between cardiac output measurements were significantly less (median +1.0 mL/kg) with intractable hypotension or vasopressor initiation, and net volume removal was larger (median -22.9 mL/kg) with less severe intradialytic hypotension (p < 0.001). Cardiac output increased >10% more frequently with least severe intradialytic hypotension and decreased with most severe intradialytic hypotension (p = 0.047).In summary, cardiac output may increase with net volume removal by ultrafiltration in some critically ill patients with relative intravascular volume overload assessed by IVC collapsibility. Severe intradialytic hypotension may limit volume removal with ultrafiltration, rather than larger volume removal causing severe intradialytic hypotension.

Relationship of inferior vena cava collapsibility to ultrafiltration volume achieved in critically ill hemodialysis patients.

BACKGROUND: Ultrasound (US) assessment of intravascular volume may improve volume management of dialysis patients. We investigated the relationship of intravascular volume evaluated by inferior vena cava (IVC) US to net volume changes with intermittent hemodialysis (HD) in critically ill patients. METHODS: A retrospective cohort of 113 intensive care unit patients in 244 encounters had clinical assessment of intravascular volume followed by US of respiratory/ventilatory variation of IVC diameter, and had HD within 24 h. IVC collapsibility index (IVC CI)=(IVCmax-IVCmin)/IVCmax*100%. Volume management was guided by clinical data plus IVC US findings. Intradialytic hypotension (IDH) was categorized by severity from none to inability to tolerate HD. RESULTS: Linear regression correlating n-weighted proportions of encounters achieving net volume removal of ≥0.5 L, ≥1.0 L, ≥1.5 L, and ≥2.0 L strongly correlated across the range of IVC CI (R2=0.87-0.64). Sensitivity and specificity analysis showed IVC CI was a better predictor than IVCmax of achieving net ultrafiltration (UF) volumes. Mean central venous pressure, pulmonary artery occlusion pressure, and cardiac output were poor predictors by logistic regression and receiver operating curve analyses. IVC CI <20% was the approximate optimal cutoff for achieving ≥0.5 L to ≥2.0 L net UF volumes. Net volume change achieved tended to be less than recommended and may have been limited by the development of IDH. Severity of IDH did not correlate with UF rate in mL/kg/h. χ2 analysis showed pre-US clinical intravascular volume assessments had poor concordance with IVC CI categories. CONCLUSION: IVC US may be a useful tool for predicting whether critically ill patients will achieve volume removal with HD.

Focused Real-Time Ultrasonography for Nephrologists.

We propose that renal consults are enhanced by incorporating a nephrology-focused ultrasound protocol including ultrasound evaluation of cardiac contractility, the presence or absence of pericardial effusion, inferior vena cava size and collapsibility to guide volume management, bladder volume to assess for obstruction or retention, and kidney size and structure to potentially gauge chronicity of renal disease or identify other structural abnormalities. The benefits of immediate and ongoing assessment of cardiac function and intravascular volume status (prerenal), possible urinary obstruction or retention (postrenal), and potential etiologies of acute kidney injury or chronic kidney disease far outweigh the limitations of bedside ultrasonography performed by nephrologists. The alternative is reliance on formal ultrasonography, which creates a disconnect between those who order, perform, and interpret studies, creates delays between when clinical questions are asked and answered, and may increase expense. Ultrasound-enhanced physical examination provides immediate information about our patients, which frequently alters our assessments and management plans.

A systematic literature search and review of sodium concentrations of body fluids
.

BACKGROUND: Wide ranges of sodium concentrations for different body fluid losses have been noted with minimal substantiating data and variability among sources, leading to use of "cumulative fluid balance" regardless of composition in hospitalized patients. AIMS: To define the sodium concentrations of fluid losses from the body. METHOD: We performed a systematic search and literature review in adult humans using PubMed database. RESULTS: Inclusion criteria were met for 107 full-text articles. Mean sodium concentrations were significantly lower for acidic (mean ± SD: 44 ± 12 mEq/L) than for alkaline (55 ± 13 mEq/L) gastric fluid, higher for bile (185 ± 24 mEq/L) or pancreatic fluid (156 ± 3 mEq/L) than for all other body fluids, and similar for intact small bowel (119 ± 14 mEq/L) and ileostomy outputs (116 ± 25 mEq/L). Sodium concentrations were significantly greater for cholera-induced diarrhea (128 ± 18 mEq/L) and lower for osmotic-induced diarrhea (28 ± 16 mEq/L) than all other causes of diarrhea. For osmotic diarrheas, sorbitol-induced diarrhea sodium concentration was higher (63 ± 17 mEq/L) than for carbohydrate malabsorption (43 ± 20 mEq/L), lactulose (26 ± 19 mEq/L), Idolax (16 ± 13 mEq/L), or polyethylene glycol (13 ± 7 mEq/L). For secretory diarrheas, sodium concentration for idiopathic causes (53 ± 22 mEq/L) was lower than for neuroendocrine and villous tumors (75 ± 13 mEq/L) or nonosmotic laxatives (88 ± 33 mEq/L). For pleural, peritoneal, and edema fluid, sodium concentrations (137 ± 13 mEq/L) were similar to plasma. No data were found for wound fluid. Sodium concentration for sweat was 44 ± 17 mEq/L. CONCLUSIONS: This is the first in-depth review of verifiable sodium concentrations of body fluids most commonly lost in hospitalized patients. Sodium concentrations are fluid-specific and consistent. Sodium concentrations for diarrhea are associated with specific mechanisms/causes. These data should be useful to more accurately replace sodium and water content for specific body fluid losses.
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Is an isolated TSH elevation in chronic nonthyroidal illness "subclinical hypothyroidism"?

CONTEXT: Elevated TSH with normal T4 frequently occurs with chronic kidney, liver, and heart diseases. Whether isolated TSH elevations represent mild thyroid gland failure has not been established. EVIDENCE ACQUISITION: PubMed was searched for longitudinal studies in chronic heart, liver, or kidney disease documenting persistent isolated TSH elevations or progression to overt hypothyroidism. EVIDENCE SYNTHESIS: Four articles met inclusion criteria. In 16 end-stage renal failure patients, four had isolated TSH elevations. All normalized within 14 months. In 452 systolic heart failure patients, 20 had isolated TSH elevations, five of 20 were persistent, and none progressed to overt hypothyroidism within 6 months. In 207 untreated chronic hepatitis C patients, 12 had isolated TSH elevations and four had increased TSH with reduced free T4; all were female, and 14 had positive antithyroid antibodies. After 1 year, two of 12 developed "clinical hypothyroidism." In 72 chronic hepatitis C patients, nine females had positive antithyroid antibodies. Two antibody-negative patients had TSH 5-6 mU/L with reduced free T4. After 1 year, three of four with positive antithyroid antibodies and baseline TSH < 4 mU/L had elevated TSH with reduced free T4. CONCLUSIONS: In chronically ill patients, there is inadequate evidence to determine: 1) that isolated TSH elevations usually persist or progress to overt hypothyroidism; 2) the etiology and clinical significance of isolated TSH elevations; and 3) whether levothyroxine therapy is indicated for persistent isolated TSH elevations. Thus, isolated TSH elevations in chronic renal, cardiac, or liver diseases have not been documented to indicate mild thyroid gland failure.

Serum 25-hydroxyvitamin D deficiency; a risk factor for chronic kidney disease in ambulatory indigent patients.

OBJECTIVE: To assess whether 25-hydroxyvitamin D (25[OH]D) deficiency is a risk factor for chronic kidney disease (CKD) in ambulatory indigent patients. METHODS: Data for all serum 25(OH)D concentrations measured during 2010 in our ambulatory nondialysis-dependent patients were analyzed along with CKD-related parameters. Patients were stratified into groups based on 25(OH)D levels of <10, 10 to 19, 20 to 29, and ≥30 ng/mL. CKD was defined by estimated glomerular filtration rate (eGFR; Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] equation) and abnormal urine protein to creatinine ratios. CKD-associated parameters included serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25[OH]2D), alkaline phosphatase, albumin, corrected calcium, and total CO2 levels. RESULTS: A total of 2,811 patients had 25(OH)D levels measured. Patients with 25(OH)D levels <10 ng/mL had significantly increased relative risk (RR) of an eGFR <15 mL/min/1.73 m2 (RR, 4.0), an eGFR of 15 to 29 mL/min/1.73 m2 (RR, 2.6), urine protein to creatinine ratio >3.5 g/g (RR, 5.6), and serum PTH >100 pg/mL (RR, 2.8) compared to patients with a 25(OH)D level ≥30 ng/mL. Patients with 25(OH)D levels of 10 to19 ng/mL had significantly increased RR of a urine protein to creatinine ratio >3.5 g/g (RR, 4.8) and serum PTH >100 pg/mL (RR, 1.5) compared to patients with 25(OH)D levels ≥30 ng/mL. CONCLUSION: 25(OH)D deficiency (<10 ng/mL) was associated with reduced eGFR, nephrotic-range proteinuria, and increased PTH levels in our population of ambulatory urban indigent patients.

Vitamin D deficiency in urban indigent patients in Southern California.

OBJECTIVE: To determine the prevalence of 25-hydroxy (OH) vitamin D deficiency in ambulatory and hospitalized patients from a large urban county medical center in Southern California, and assess the effects of season, ethnicity, age, location of care, and comorbidities on prevalence. METHODS: Data for all serum 25(OH)-D2 and -D3 concentrations measured during 2010, along with associated demographic characteristics and comorbidity data, were analyzed. 25(OH) D concentrations were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Of 210,695 patients, serum 25(OH) D concentrations were measured for 3,276 (1.6%), 78% of whom were Hispanic, 69% female, 14% hospitalized, and 86% ambulatory. Median patient age was 54 years. Prevalence of 25(OH) D <10 ng/mL was 6.5% overall, 5.5% in Hispanics, 6.7% in Asians, 15.5% in African Americans, and 8.9% in whites. Prevalence was significantly higher in African Americans than in Hispanics (relative risk (RR): 2.79), males (RR: 2.07), hospitalized patients (RR: 4.96), and winter (RR: 1.34). Prevalence of 25(OH) D <20 ng/mL was 35% overall, 34% in Hispanics, 32% in Asians, 49% in African Americans, and 33% in whites, and was significantly higher in African Americans than Hispanics (RR: 1.45), males (RR: 1.32), hospitalized patients (RR: 2.02), and younger patients (RR: 1.21, age ≤30; 1.16, age 31-50) versus those age 51 to 70 years, and in winter (RR: 1.21). CONCLUSION: Our study estimated the prevalence of 25(OH) D deficiency and identified at-risk patient groups in Southern California; 25(OH) D deficiency should be suspected, diagnosed, and adequately treated to improve the health status in at-risk urban indigent patient populations.

Low pleural fluid-to-serum glucose gradient indicates pleuroperitoneal communication in peritoneal dialysis patients: presentation of two cases and a review of the literature.

BACKGROUND: Transudative pleural effusions due to pleuroperitoneal communication occur in 1.6-10% of patients receiving peritoneal dialysis (PD) and usually have overtly elevated glucose concentrations. METHODS: We report two cases of verified pleuroperitoneal communication with minimally elevated pleural fluid glucose levels. We reviewed the literature of all PD patients with pleuroperitoneal communication that reported pleural glucose levels to assess their clinical and laboratory features and pleural fluid-to-serum glucose gradients. RESULTS: We evaluated a total of 47 reported patients on PD with diagnosed pleuroperitoneal communication. Onset of the transudative pleural effusion after initiating PD was <3 months in only 48%. Shortness of breath was reported in 96%. Pleural effusions were right sided in 87%. Pleural fluid-to-serum glucose gradients varied from 2 to 1885 mg/dL, with 20% ≤50 mg/dL, 13% being 51-100 and 67% >100 mg/dL. All pleural fluid-to-serum glucose ratios were >1. CONCLUSIONS: With a transudative pleural effusion in patients receiving PD, a pleural fluid-to-serum glucose ratio >1 is consistent with a pleuroperitoneal communication. In questionable cases, independent verification is necessary.

Clinical review: Thyroid hormone therapy for postoperative nonthyroidal illnesses: a systematic review and synthesis.

CONTEXT: Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial. OBJECTIVE: The aim was to conduct a systematic review evaluating effects and risks of postoperative T(3) therapy in adults. DATA SOURCES: Electronic databases and reference lists through March 2010 were searched. STUDY SELECTION: Studies with comparable control groups comparing T(3) to placebo therapy in randomized controlled trials were selected. DATA EXTRACTION: Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T(3) was given in high doses (0.175-0.333 µg/kg · h) for 6 to 9 h, in four studies iv T(3) was given in low doses (0.0275-0.0333 µg/kg · h for 14 to 24 h), and in three studies T(3) was given orally in variable doses and durations. DATA SYNTHESIS: Both high- and low-dose iv T(3) therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T(3) therapy and could not be assessed for low-dose iv or oral T(3). Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T(4) were inconclusive. LIMITATIONS: Numbers of usable unique studies and group sizes were small. Duration of T(3) therapy was short, and dosages and routes of administration varied. CONCLUSIONS: Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.

Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review.

CONTEXT: Thyroid hormone therapy to enhance weight loss in obesity during caloric deprivation and to improve morbidity and mortality in adults with nonthyroidal illnesses remains controversial. OBJECTIVE: The aim of this study was to conduct a systematic review evaluating effectiveness and risks of T(3) and/or T(4) therapy in these populations. DATA SOURCES: Electronic databases and reference lists were searched. STUDY SELECTION: Studies with comparable control groups comparing T(3) and/or T(4) therapy to placebo in randomized controlled trials (RCTs) or prospective observational studies were selected. DATA EXTRACTION: Three reviewers performed serial abstraction. DATA SYNTHESIS: During caloric deprivation of obese subjects, T(3) therapy decreased serum TSH and T(4) concentrations. Consistent effects of T(3) or T(4) on weight loss, protein breakdown, metabolic rate, and heart rate could not be established. In euthyroid cardiac patients, T(3) decreased TSH and free T(4) levels, without consistent effects of T(3) or T(4) on heart rate, cardiac output, or systemic vascular resistance. Mortality increased 3.3-fold with T(4) therapy in acute renal failure patients, whereas an effect in cardiac, critically ill, and burn patients could not be established. Equivalence testing indicated that larger RCTs are required to determine whether thyroid hormone therapy alters end-points in obesity or nonthyroidal illnesses. LIMITATIONS: Numbers of usable unique studies were small, numbers of patients in each study were inadequate, end-points were variable, few RCTs were performed, and study quality of non-RCTs was poor. CONCLUSIONS: Available data are inconclusive regarding effectiveness of thyroid hormone therapy in treating obesity or nonthyroidal illnesses, whereas data support that such therapy induces subclinical hyperthyroidism.

Assessing thyroid hormone status in a patient with thyroid disease and renal failure: from theory to practice.

A 35-year-old Asian male, treated for hyperthyroidism, systemic lupus erythematosis, and uremia presented with low serum total thyroxine (T4) and normal serum thyrotropin (TSH) levels. He had been receiving prednisone and methimazole for 15 weeks. Free T4 measured by direct equilibrium dialysis was in the hypothyroid range (0.3 ng/dL; normal, 0.8-2.7). Two possibilities were considered: (1) a weakly bound dialyzable inhibitor in uremic serum that interfered with this serum free T4 determination or (2) hypothyroidism with persistent TSH suppression because of prior hyperthyroidism. To determine whether a weakly bound inhibitor was involved, the patient's serum was serially diluted using two diluents: (1) an ultrafiltrate of the patient's serum, which would contain any unbound inhibitor, as well as free T4 and (2) an inert diluent. Free T4 measurements were similar with both, providing evidence against the presence of a dialyzable and ultrafilterable inhibitor. In conclusion, this patient was hypothyroid because of antithyroid drug administration, associated with prolonged central TSH suppression from preexisting hyperthyroidism. Discontinuation of methimazole resulted in normalization of serum total T4 and TSH values. Thus, paired, serial serum dilutions, using two different diluents, provided evidence for differentiation of appropriately low free T4 measurements (because of hypothyroidism), from spuriously low free T4 measurements (because of an interfering inhibitor).