Surgical Management of Normocalcemic Primary Hyperparathyroidism and the Impact of Intraoperative Parathyroid Hormone Testing on Outcome.

Objective To review our surgical experience and the impact of intraoperative parathyroid hormone (IOPTH) testing among patients with normocalcemic primary hyperparathyroidism. Study Design Case series with chart review. Setting Academic referral hospital. Subject and Methods Normocalcemic hyperparathyroidism (NCHPT) patients were identified with normal-range blood ionized calcium and serum elevated parathyroid hormone. Patient demographics, intraoperative findings, IOPTH dynamics, and biochemical outcomes were compared with those of classic primary hyperparathyroidism (PHPT) patients. Results Of the 2120 patients who underwent parathyroidectomy, 616 patients met the inclusion criteria: 119 (19.5%) patients had NCHPT, and 497 (80.5%) had classic PHPT. NCHPT patients had higher rates of multigland hyperplasia as compared with classic PHPT (12% vs 4%, P = .002) and smaller gland size ( P < .001). Of 119 NCHPT patients, 114 (97%) achieved >50% drop in IOPTH intraoperatively, as opposed to 492 (99%) among 497 classic PHPT patients ( P = .014). IOPTH drop >50% had an equivalent positive predictive value for long-term cure in both groups. Conclusions Surgeons treating NCHPT patients should suspect the presence of multigland disease and have a low threshold for converting to bilateral exploration depending on IOPTH decay dynamics.

RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review.

BACKGROUND: Molecular markers associated with thyroid malignancy are increasingly being used as differential diagnostic tools for thyroid nodules. However, little has been reported recently regarding the prevalence of these markers in benign lesions. The literature was systematically reviewed to examine studies that reported on the prevalence of these markers in benign thyroid lesions. METHODS: Appropriate studies published between January 1, 2000, and April 30, 2015, and cataloged in PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for by combining different keywords for "thyroid tumor" with both general and specific keywords for "molecular marker" by using "AND" as the Boolean operator. All studies meeting criteria that reported the prevalence of RAS mutations, and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangements in benign thyroid lesions were included for study. RESULTS: A total of 64 articles (including 8162 patients, of whom 42.5% had benign lesions) that met all the study criteria were systematically reviewed and abstracted. Among 35 studies examining RAS mutations, the reported prevalence of RAS mutation in benign lesions ranged from 0% to 48%. In 38 studies examining RET/PTC rearrangements, the prevalence in benign lesions ranged from 0% to 68%. PAX8/PPAR-gamma rearrangements were examined in 27 studies, with the prevalence in benign lesions ranging from 0% to 55%. CONCLUSION: The presence of these biomarkers and the tremendous variation in reports of their prevalence in benign lesions suggests the need for caution when including these markers in diagnostic decisions. Further understanding of the importance of these markers, as well as newly discovered markers of thyroid malignancy, may be required in order to avoid overtreatment of patients with benign thyroid tumors.

Characterizing the operative findings and utility of intraoperative parathyroid hormone (IOPTH) monitoring in patients with normal baseline IOPTH and normohormonal primary hyperparathyroidism.

BACKGROUND: During parathyroidectomy with intraoperative parathyroid hormone monitoring, the successful removal of a hypersecreting gland(s) resulting in normocalcemia is indicated by a >50% decrease in intraoperative parathyroid hormone level, typically into the normal range. Some patients, however, will have baseline parathyroid hormone levels within the normal range. We sought to determine the utility of intraoperative parathyroid hormone testing in these patients. METHODS: We retrospectively studied all patients who underwent parathyroidectomy for primary hyperparathyroidism at our institution over a 10-year period. RESULTS: Overall, 317 (17%) patients had parathyroid hormone within the normal range at the onset of operation (baseline intraoperative parathyroid hormone), and 1,544 (83%) had classic primary hyperparathyroidism. The intraoperative parathyroid hormone degradation was slower in normal baseline intraoperative parathyroid hormone patients than classic primary hyperparathyroidism patients, though this did not reach statistical significance (P < .254). A >50% intraoperative parathyroid hormone decrease predicted cure in 98.7% of normal baseline patients and 98.8% of classic primary hyperparathyroidism patients (P = .810). Normal baseline patients had a lesser cure rate the longer it took to achieve a 50% decrease intraoperatively; however, the cure rate was constant at any time point the 50% decrease occurred in patients with classic primary hyperparathyroidism (P < .05). CONCLUSION: The 50% rule delineating operative cure can be applied with equal confidence to patients with normal range, baseline intraoperative parathyroid hormone. Moreover, the time at which the 50% drop is achieved impacts operative success rates in these patients.

Nerve growth factor promoter activity revealed in mice expressing enhanced green fluorescent protein.

Nerve growth factor (NGF) and its precursor proNGF are perhaps the best described growth factors of the mammalian nervous system. There remains, however, a paucity of information regarding the precise cellular sites of proNGF/NGF synthesis. Here we report the generation of transgenic mice in which the NGF promoter controls the ectopic synthesis of enhanced green fluorescent protein (EGFP). These transgenic mice provide an unprecedented resolution of both neural cells (e.g., neocortical and hippocampal neurons) and non-neural cells (e.g., renal interstitial cells and thymic reticular cells) that display NGF promoter activity from postnatal development to adulthood. Moreover, the transgene is inducible by injury. At 2 days after sciatic nerve ligation, a robust population of EGFP-positive cells is seen in the proximal nerve stump. These transgenic mice offer novel insights into the cellular sites of NGF promoter activity and can be used as models for investigating the regulation of proNGF/NGF expression after injury.