An update on subclinical hypothyroidism and subclinical hyperthyroidism.

Subclinical thyroid dysfunction is characterized by normal levels of peripheral thyroid hormone, paired with a TSH level that is either lower than (subclinical hyperthyroidism) or higher than (subclinical hypothyroidism) the normal laboratory reference range. Slight shifts in peripheral hormone levels result in significant serum TSH changes. The exact upper limit of normal TSH and the management of subclinical hypothyroidism are still controversial. For those with TSH between high upper limit of normal and 10 mIU/L, the authors suggest selective use of thyroxine therapy. The authors agree with the general consensus in favor of therapy for those with serum TSH levels above 10 mIU/L. This recommendation is compatible with guidelines of American Thyroid Association and American Association of Clinical Endocrinologists. For subclinical hyperthyroidism persistent serum TSH <0.1 mIU/L should be treated particularly if the etiology is nodular toxic goiter. For serum TSH between 0.1 mIU/L and lower limit of normal, serum TSH co-morbidities such as cardiac risk factors and osteoporosis may favor therapy.

Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis.

CONTEXT: Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly. OBJECTIVE: The aim of this systematic review is to summarize the existing evidence on vitamin D use and the risk of falls. DATA SOURCES: We searched electronic databases from inception through August 2010. STUDY SELECTION: Eligible studies were randomized controlled trials in which the intervention was vitamin D and the incidence of falls was reported. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics, quality, and outcomes data. DATA SYNTHESIS: Odds ratio and associated 95% confidence interval were estimated from each study and pooled using the random effects model. RESULTS: We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96). This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D. The quality of evidence was low to moderate because of heterogeneity and publication bias. CONCLUSIONS: Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.

Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis.

CONTEXT: Several studies found association between vitamin D levels and hypertension, coronary artery calcification, and heart disease. OBJECTIVE: The aim of this study was to summarize the evidence on the effect of vitamin D on cardiovascular outcomes. DESIGN AND METHODS: We searched electronic databases from inception through August 2010 for randomized trials. Reviewers working in duplicate and independently extracted study characteristics, quality, and the outcomes of interest. Random-effects meta-analysis was used to pool the relative risks (RR) and the weighted mean differences across trials. RESULTS: We found 51 eligible trials with moderate quality. Vitamin D was associated with nonsignificant effects on the patient-important outcomes of death [RR, 0.96; 95% confidence interval (CI), 0.93, 1.00; P = 0.08], myocardial infarction (RR, 1.02; 95% CI, 0.93, 1.13; P = 0.64), and stroke (RR, 1.05; 95% CI, 0.88, 1.25; P = 0.59). These analyses were associated with minimal heterogeneity. There were no significant changes in the surrogate outcomes of lipid fractions, glucose, or diastolic or systolic blood pressure. The latter analyses were associated with significant heterogeneity, and the pooled estimates were trivial in absolute terms. CONCLUSIONS: Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D. The quality of the available evidence is low to moderate at best.

Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008.

BACKGROUND: Invasive fibrous thyroiditis (IFT) is the rarest form of thyroiditis, and reports are often limited to case reports and small case series. In this study, we aimed to summarize our institutional experience with IFT since 1976. METHODS: We retrospectively reviewed the cases of all patients with IFT evaluated at Mayo Clinic, Rochester, Minnesota, from 1976 through 2008, with special emphasis on clinical presentation, associated risk factors, associated comorbid conditions, complications, and treatment. RESULTS: Twenty-one patients met our inclusion criteria of (i) IFT confirmed by pathologic review at our institution and (ii) evidence of extension of fibrosis outside the thyroid capsule. Most patients (17, 81%) were women (mean age, 42 years). Presenting symptoms included pain (24%), dysphagia (33%), vocal cord paralysis (29%), and tracheal narrowing (48%). Three patients had associated hypoparathyroidism. Sixteen (76%) had a history of tobacco use, and 10 (48%) were current smokers. Fibrosing mediastinitis was present in four, orbital fibrosis in one, retroperitoneal fibrosis in three, and pancreatic fibrosis in one (38% had extracervical fibrotic processes). Eighteen patients had partial thyroidectomy, 7 (39%) of whom had surgical complications involving vocal cords and parathyroid. Two required tracheostomy. Thirteen had corticosteroid therapy; six received tamoxifen. There was no cause-specific mortality, and the fibrotic process stabilized or partially resolved in all patients. CONCLUSIONS: IFT often is associated with a systemic extracervical fibrotic process and tobacco use. Attempted thyroid resection often results in postoperative complications. Long-term follow-up showed no deaths from IFT and showed stability of the thyroiditis.

Clinical review: Adult height in patients with congenital adrenal hyperplasia: a systematic review and metaanalysis.

CONTEXT: Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients. OBJECTIVE: Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files. STUDY SELECTION: Eligible studies included patients diagnosed with CAH before age 5 and followed to final height. DATA EXTRACTION: Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each study's risk of bias. DATA SYNTHESIS: The sd score (SDS) for final height and corrected height (defined as final height SDS - midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I(2) statistic was used to assess inconsistency in results across studies. RESULTS: We found 35 eligible studies, most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated with age at diagnosis, gender, type and dose of steroid, and age of onset of puberty. Mineralocorticoid users had a better height outcome in comparison with the nonusers (P = 0.02). CONCLUSION: Evidence derived from observational studies suggests that the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than expected given parental height.

Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.

CONTEXT: Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear. OBJECTIVE: The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia. DATA SOURCES: We searched electronic databases between 2002 and March 2008. STUDY SELECTION: We selected published randomized trials of CSII vs. MDI. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events. DATA SYNTHESIS: We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes. CONCLUSIONS: Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.

Rituximab: applications in dermatology.

Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used extensively for B-lymphocytic malignancies. In addition, applications for autoimmune diseases have emerged in recent years. Case reports support the use of rituximab in certain dermatologic conditions, including paraneoplastic pemphigus, pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies. Clinical trials are lacking and would be an appropriate next step.