Activating BRAF mutation in sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland: two case reports and review of the literature.

BACKGROUND: Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare form of thyroid carcinoma. The underlying molecular mechanisms of sclerosing mucoepidermoid carcinoma with eosinophilia tumorigenesis remain unknown. CASE PRESENTATION: We present two cases of sclerosing mucoepidermoid carcinoma with eosinophilia, both with a concurrent papillary thyroid carcinoma. Patient 1, a 70-year-old Caucasian woman, presented with sclerosing mucoepidermoid carcinoma with eosinophilia with distant renal metastasis and coexisting papillary thyroid carcinoma. Patient 2, a 74-year-old Caucasian woman with a remote history of thyroid cancer treated with thyroidectomy, presented with locoregionally invasive sclerosing mucoepidermoid carcinoma with eosinophilia and recurrent papillary thyroid carcinoma in the thyroid bed. BRAF mutation studies were performed on the sclerosing mucoepidermoid carcinoma with eosinophilia tumors. In both cases, sclerosing mucoepidermoid carcinoma with eosinophilia was positive for the BRAF V600E mutation by polymerase chain reaction. Patient 1 is the first reported case of sclerosing mucoepidermoid carcinoma with eosinophilia with renal metastasis, to the best of our knowledge. CONCLUSIONS: Our findings suggest, for the first time, to our knowledge, involvement of the RAS-RAF-MEK-ERK signaling pathway in the pathogenesis of sclerosing mucoepidermoid carcinoma with eosinophilia. Thus, BRAF inhibitors may prove to be a useful targeted medical therapy in the treatment of a subset of patients with aggressive sclerosing mucoepidermoid carcinoma with eosinophilia tumors who exhibit BRAF activating mutation.

I-131 uptake in the breast from fat necrosis.

Radioactive iodine I-131 whole-body scintigraphy is used to monitor thyroid cancer metastases after total thyroidectomy. We present a case of a woman who was diagnosed with papillary thyroid cancer and underwent a total thyroidectomy. I-131 scintigraphy revealed abnormal accumulation of radioactive iodine in the right breast causing concern for thyroid cancer metastasis. Mammographic studies confirmed that the abnormal radiotracer accumulation was due to fat necrosis in the breast. I-131 uptake in fat necrosis is a poorly understood process that is not clearly defined in the literature. This case highlights that false-positive uptake of I-131 can mimic metastases of thyroid carcinoma.

Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women's Health Initiative hormone therapy trials.

BACKGROUND: Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results. However, randomized trial evidence on nephrolithiasis risk with estrogen therapy in postmenopausal women is lacking. METHODS: We reviewed the incidence of nephrolithiasis in the Women's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers. A total of 10 739 postmenopausal women with hysterectomy were randomized to receive 0.625 mg/d of conjugated equine estrogens (CEE) or placebo, and 16 608 postmenopausal women without hysterectomy were randomized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate (2.5 mg/d). The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial. RESULTS: Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms. Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years (hazard ratio, 1.21; 95% confidence interval, 1.03-1.44). Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 (95% confidence interval, 1.08-1.78). The increased nephrolithiasis risk was independent of progestin coadministration, and effects did not vary significantly according to prerandomization history of nephrolithiasis. CONCLUSIONS: These data suggest that estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women. These findings should be considered in decision making regarding postmenopausal estrogen use. The mechanisms underlying this higher susceptibility remain to be determined. Trial Registration clinicaltrials.gov Identifier: NCT0000611.

Recurrent thyroid cancer with changing histologic features.

We present the case of a 57-year-old woman diagnosed with breast cancer and a thyroid mass that was suspicious for cancer. The breast cancer was estrogen and progesterone receptor negative, HER2/neu borderline, with a high proliferative index. Treatment of this cancer took precedence. Nine months later, a total thyroidectomy was done for papillary thyroid cancer with metastases to 2 of 8 perithyroid lymph nodes. Postoperative radioactive iodine ablation was given. Recurrent thyroid disease was found in the right neck 1 year later and was resected; no radioactive iodine was given at that time. After 2½ years, the cancer recurred as a more highly aggressive, undifferentiated anaplastic thyroid carcinoma. Treatment is discussed.

Total thyroidectomy for medically refractory amiodarone-induced thyrotoxicosis.

Amiodarone is a class III antiarrhythmic drug widely used for both ventricular and supraventricular tachyarrhythmias. Due to its high iodine content and structural similarity to thyroxine, abnormalities in thyroid function are common in patients taking amiodarone, especially with long-term use. Both hypo- and hyperthyroidism have been associated with amiodarone, with the former far more common in the United States. We present a patient with medically refractory amiodarone-induced thyrotoxicosis after a 2-year history of amiodarone use, resulting in cardiac arrest and encephalopathy. The patient ultimately required total thyroidectomy for symptomatic control.

Concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell endometrial cancer.

A 65-year-old Caucasian woman with a known history of clear cell endometrial cancer presented with hypercalcemia. Further evaluation demonstrated that the patient had primary hyperparathyroidism due to a parathyroid adenoma, as well as an increased parathyroid hormone-related peptide secondary to her malignancy. To the best of our knowledge, this is the first reported case of a female patient with concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy. This case illustrates the importance of considering a broad differential when evaluating patients with hypercalcemia. It also emphasizes the importance of recognizing the biochemical interplay between parathyroid hormone and parathyroid hormone-related peptide.

Comparison of testosterone, alendronate, and a combination of both therapies in men with low bone mineral density.

BACKGROUND: Both bisphosphonates and testosterone are known to improve bone mineral density (BMD) in men with low bone mass, but whether combination therapy is superior to these agents used alone is not clear. We compared the changes in lumbar spine BMD when men with low bone mass were treated with each agent alone or as combination therapy. METHODS: In a retrospective study, we analyzed serum and BMD data from 149 men who had been evaluated in the Endocrinology Clinic at the Dallas Veterans Affairs Medical Center, Dallas, Texas. The subjects were divided into three cohorts: 59 men receiving testosterone therapy alone, 68 men receiving alendronate therapy alone, and 22 receiving combination therapy. RESULTS: Compared with the baseline values, the lumbar spine and BMD increased significantly in each of the testosterone, alendronate, and combination therapy cohorts (median annualized rate of change: 2.1% [p < .001], 2.6% [p < .001], and 2.5% [p = .04], respectively). The combination therapy group did not demonstrate any additional increase in BMD at the lumbar spine or total hip compared with either agent alone. The results did not change after adjusting for differences in baseline weight, age, BMD, or baseline testosterone level. CONCLUSION: The results suggest that the combination of testosterone and alendronate does not appear to be superior to single-drug therapy in our patient population.

Biochemical and stone-risk profiles with topiramate treatment.

BACKGROUND: Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation. METHODS: Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment. RESULTS: Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001). CONCLUSION: Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Post-renal transplantation hypophosphatemia: a review and novel insights.

PURPOSE OF REVIEW: This review intends to elucidate the pathophysiologic mechanism of renal phosphorus loss in the post-renal transplantation population. This review will provide new insight in to the pathophysiologic mechanism(s) responsible for the development of this phenomenon and will also explore the pathogenetic role of persistent phosphorus wasting in the development of post-renal transplantation osteodystrophy. RECENT FINDINGS: Recently, the phosphaturic hormone, fibroblast growth factor-23, has been ascertain to be increased in the sera of patients with chronic kidney and end-stage renal disease. There is new evidence that a non-PTH humoral factor is persistently present in post-renal transplantation patients that is likely responsible for the observed persistent renal phosphorus loss. We offer that fibroblast growth factor-23 (and/or other phosphatonins) is the culprit factor responsible for the phenomenon of persistent hypophosphatemia in post-renal transplantation patients. Moreover, we believe that the phenomenon of persistent renal phosphorus wasting is an important but overlooked cause of osteodystrophy and increased fracture risk in this patient population. SUMMARY: The pathophysiology of post-renal transplantation phosphorus wasting is complex and to date is still not fully recognized. Further studies of the regulatory mechanism of fibroblast growth factor-23 and its metabolism may offer additional insights into phosphorus homeostasis and its clinical application in the post-renal transplantation population.