Postpartum sacral insufficiency fractures.

Postpartum sacral insufficiency fracture is an uncommon occurrence that is often under-diagnosed because its symptoms of low back, buttock and groin pains may initially be attributed to physiologic biomechanical changes caused by pregnancy or to intervertebral disc disease. We present a case of bilateral sacral insufficiency fractures in a 37-year-old postpartum woman with osteopenic bone mineral density confirmed by dual energy X-ray absorptiometry. The symptoms were initially suspected to be of discogenic cause, and the fractures were incidentally appreciated at the edge of a lumbar spine magnetic resonance image. Therefore, it is important to keep in mind this potential diagnosis when examining imaging studies of postpartum patients. For women who present other risk factors of osteoporosis, imaging of the entire sacrum should be part of the imaging studies. If sacral stress fractures are diagnosed, further evaluation for bone mineral density and underlying metabolic bone disease is recommended.

Menin missense mutants encoded by the MEN1 gene that are targeted to the proteasome: restoration of expression and activity by CHIP siRNA.

CONTEXT: In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known. OBJECTIVE: Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology. METHODS: Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells. RESULTS: The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-ß up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-ß inhibition of cell numbers. CONCLUSION: When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases.

Life-threatening hyponatremia following a low-iodine diet: a case report and review of all reported cases.

OBJECTIVE: To report a case of life-threatening hyponatremia as a complication of a 4-week long low-iodine diet and highlight the risk factors for this complication by reviewing all previously reported cases. METHODS: The clinical and biochemical data from the study patient are presented and the pertinent literature is reviewed. A risk analysis for this complication is highlighted. RESULTS: A 66-year-old Vietnamese woman had a total thyroidectomy and bilateral neck lymph node dissection for papillary thyroid carcinoma. A whole body radioiodine scan demonstrated 2 foci of activity in the anterior neck. The patient received recombinant human thyrotropin (rhTSH) and was admitted for radioiodine therapy. She had strictly adhered to a low-iodine diet for 4 weeks in preparation for ablation. The patient was on a thiazide diuretic for her hypertension, which was discontinued on admission. On admission, the patient started feeling light-headed, dizzy, and nauseated. Blood tests revealed a critical serum sodium concentration of 107 mEq/L. Further investigations confirmed hypotonic hyponatremia, which had developed despite being euthyroid after receiving rhTSH. The patient was managed accordingly and made a full recovery. CONCLUSIONS: This case, in addition to the reviewed cases, emphasizes the importance of preventing and managing this rare but relatively dangerous complication. Based on an analysis of the reviewed cases, the risk factors for developing this complication are a prolonged low-iodine diet, the elimination of salt from the diet, and the use of thiazide diuretics. All patients in the reported cases were older than 65 years of age.

Long-term fracture risk following renal transplantation: a population-based study.

Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965-1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject's complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected ( P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6-6.4] and vertebral (SIR, 23.1; 95% CI, 12.3-39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1-12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.