Panostotic expansile bone disease with massive jaw tumor formation and a novel mutation in the signal peptide of RANK.

Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32-year-old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow-legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF-κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12-base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes and genetic basis of the mendelian disorders of RANK signaling activation.

The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults.

CONTEXT: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance. OBJECTIVE: The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults. METHODS: Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 +/- 0.8 yr) and 12 elderly (70.7 +/- 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion. RESULTS: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion. CONCLUSIONS: BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly.

Using quality-improvement techniques to enhance patient education and counselling of diagnosis and management.

BACKGROUND: Patients recall less than half the information provided to them by their physicians. AIMS: The aim of this study was to use quality-improvement (QI) techniques to enhance patient understanding of diagnosis, management and follow-up at the end of the office visit. METHOD: QI techniques including stakeholder analysis, process mapping and plan-do-study-act (PDSA) cycles were used in a pilot study in an outpatient endocrinology clinic specialising in bone disease. The impact of these interventions was evaluated by pre- and post-intervention patient surveys that included qualitative and quantitative data. RESULTS: A team of endocrinology fellows and faculty with expertise in QI developed a series of tools to encourage conversation and interaction during the encounter and to serve as a reference for patients to take home through five PDSA cycles. The tools were iterations of written materials provided to patients at the end of the clinical encounter. In each cycle, the tools were modified according to feedback from patients and providers. Ninety-three patients participated in this study. Patients were surveyed after the implementation of two of the five cycles. Compared with pre-intervention, modifications during the two cycles were associated with a non-significant increase in patients' understanding of the reasons for testing (from 64% to 80% and 75%); management plan (from 61% to 86% and 79%); and future follow-up plans (from 64% to 86% and 81%); P > 0.05 for all three outcomes. Improvement was not seen in patients' knowledge of their diagnoses (from 74% to 73% and 70%; P > 0.05). CONCLUSION: This pilot study shows how QI tools can be used for creating and initiating system improvements aimed at enhancing patient education and counselling.

Comparison of ultrasound-guided fine-needle aspiration biopsy with core-needle biopsy in the evaluation of thyroid nodules.

OBJECTIVE: To compare the diagnostic rate of ultra-sound-guided fine-needle aspiration biopsy (FNAB) with the diagnostic rate of combined FNAB and core-needle biopsy in the evaluation of nodular thyroid disease. METHODS: We performed a retrospective case-control study by reviewing charts of patients who underwent ultra-sound-guided FNAB and core-needle biopsy of the thyroid at a tertiary referral center from January 1999 to December 2001. Results were classified as diagnostic (negative, suspicious, or positive for malignancy) or nondiagnostic. These findings were compared with an age- and sex-matched control group who underwent only FNAB. Complications between the groups were reviewed. RESULTS: The patient group consisted of 320 patients who underwent 340 ultrasound-guided fine-needle aspiration and core-needle biopsies of the thyroid; the control group consisted of 311 patients who underwent 340 FNABs. There was no significant difference in the nondiagnostic rates between groups--12.9% in patients who had FNAB-only compared with 10.9% in patients who had both procedures (proportion difference, -2.1%; 95% confidence interval, -7.0% to 2.9%; P = .41). There was a trend towards an increased incidence of hematoma and infection in the core biopsy group. In the group that underwent FNAB and core-needle biopsies, 10 patients (3.1%) developed biopsy-specific complications (hematomas in 8 patients, biopsy site infections in 2 patients). In the FNAB-only group, 3 patients (1.0%) developed hematomas; there was no incidence of infection. CONCLUSIONS: In the evaluation of thyroid nodules, the addition of core-needle biopsies to FNAB confers little benefit in decreasing the nondiagnostic rates and may be associated with increased complications. Core-needle biopsies should not be routinely performed in the evaluation of thyroid nodules, but rather, patient selection for the more invasive core biopsy should be done judiciously.

To be or not TB.

A 20-year-old Somali woman presented with a tender, enlarging neck mass in the setting of weight loss and tachycardia. This was initially thought to be a thyroid storm. On further investigation, she had suppurative thyroiditis from Mycobacterium tuberculosis. This case illustrates a high prevalence of extrapulmonary tuberculosis (TB) in foreign-born individuals and the necessity to consider TB in the differential diagnosis of an enlarging neck mass.

Assessment of branched-chain amino Acid status and potential for biomarkers.

BCAAs are not synthesized in the body in humans, but they are crucial in protein and neurotransmitter synthesis. The protein anabolic role of BCAAs seems to be mediated not only by their important role as a promoter of the translation process (and possibly acting at the transcription level) but also by inhibition of protein degradation. Leucine may play a critical role in these signaling pathways. Supplementation with BCAAs spares lean body mass during weight loss, promotes wound healing, may decrease muscle wasting with aging, and may have beneficial effects in renal and liver disease. BCAA supplementation is extensively used in the athletic field with the assumption of improved performance and muscle mass. Measuring serum BCAAs has limited clinical utility beyond the controlled setting because levels are affected by a variety of clinical states, and optimal levels in these scenarios have not been completely elucidated. We discuss the effects diet, hormones, stress, aging, and renal or liver dysfunction have on BCAA levels and how understanding the biological effects of BCAAs may help to develop biomarkers of BCAA status. We also discuss potential biomarkers of BCAA status.