Characterization of Thyroid Nodules by 4-Dimensional Computed Tomography: Initial Experience.

OBJECTIVE: We aimed to evaluate the use of 4-dimensional computed tomography (4DCT) for characterization of thyroid nodules. METHODS: Our study drew from 100 consecutive patients with primary hyperparathyroidism who underwent 4D parathyroid CT imaging for adenoma localization. Included subjects had tissue sampling of a thyroid nodule within 3 months of 4DCT. RESULTS: Twenty subjects (18 women and 2 men) had thyroid nodules that were pathologically confirmed. Precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules (36 vs 61 HU, P = 0.05). Arterial phase and delayed phase nodule attenuations were not significantly different in malignant and benign nodules (128 vs 144 HU, P = 0.7; 74 vs 98 HU, P = 0.3). CONCLUSIONS: Our initial experience with a small group of patients was unable to support the use of 4DCT for characterizing thyroid nodules; however, precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules.

A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment.

BACKGROUND: Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1-VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1-FGFR4), platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer (RR-DTC). METHODS: Fifty-eight patients with RR-DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFR-targeted therapy was permitted. The primary endpoint was the objective response rate (ORR) based on independent imaging review. Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors also were assessed. RESULTS: After ≥14 months of follow-up, patients had an ORR of 50% (95% confidence interval [CI], 37%-63%) with only partial responses reported. The median time to response was 3.6 months, the median response duration was 12.7 months, and the median PFS was 12.6 months (95% CI, 9.9-16.1 months). The ORR for patients who had received previous VEGF therapy (n = 17) was 59% (95% CI, 33%-82%). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3 and 4 treatment-emergent adverse events, regardless of their relation to treatment, occurred in 72% of patients and most frequently included weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). CONCLUSIONS: In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. Cancer 2015;121:2749-2756. © 2015 American Cancer Society.

Vitamin D deficiency: a simple algorithm employing weekly administration of 50,000 IU of vitamin D.

OBJECTIVE: Vitamin D deficiency affects parathyroid hormone levels and is endemic in the American population due to diet and lifestyle. The aim of this study was to evaluate a treatment algorithm using weekly doses of 50,000 IU of Vitamin D2 for thyroid and parathyroid surgery patients. STUDY DESIGN: Prospective, non-randomized. SETTING: University health sciences center. SUBJECTS AND METHODS: Patients at a thyroid center being treated for benign and malignant thyroid diseases or parathyroid disease. Subjects with total vitamin D levels less than 30 ng/dl were prospectively treated with weekly doses of 50,000 IU of vitamin D2 (D2) for durations dependent upon initial vitamin D (25-hydroxyvitamin D) levels. Vitamin D levels were measured after the treatment intervals and change in levels from baseline was determined. RESULTS: Subjects receiving 8 weeks of therapy demonstrated an average increase in vitamin D level of 13.4 ng/ml, 10 weeks of therapy showed an increase of 16.35 ng/ml, and 12 weeks showed an average increase of 21.6 ng/ml. The treatment groups had success rates of 82%, 75%, and 71% after 8, 10, and 12 weeks of therapy respectively. When only compliant patients were evaluated (defined as greater than 3-ng/ml increase after therapy), the success rates after 8, 10, and 12 weeks increased to 95%, 79%, and 71% respectively. CONCLUSIONS: A simple algorithm using 50,000 IU of vitamin D2 corrects its deficiency in the majority of subjects treated. This is a simple method of treatment for thyroid and parathyroid patients who are vitamin D deficient. Thyroid and parathyroid conditions are frequently treated by otolaryngologists and vitamin D deficiency can complicate their diagnosis and/or management.

Incidence of diffuse FDG uptake in the thyroid of patients with hypothyroidism.

Positron emission tomography (PET) positive lesions are common in the thyroid. The uptake can be focal or diffuse. Diffuse thyroid uptake is thought to be indicative of autoimmune thyroiditis and not for lesions of malignant potential. Hashimoto's thyroiditis as a cause for diffusely positive thyroid glands has been demonstrated. We determine the incidence of diffuse thyroid PET positivity in hypothyroid patients, presumed to have Hashimoto's thyroiditis. The study design was retrospective database and electronic medical record review. The study setting includes tertiary care and academic health sciences center. The subjects were patients at our medical center who underwent positron emission tomography. Hypothyroid patients were identified who had total body PET imaging performed for any reason. Patients were excluded if they were not taking levothyroxine, had a history of neck surgery, neck irradiation, Graves' disease, taking lithium, thalidomide, amiodarone or interleukin. Patients remaining after the application of these exclusion criteria were presumed to be hypothyroid from Hashimoto's thyroiditis. Only 9.5% of PET scans of hypothyroid patients display diffuse thyroid activity. Only a small minority of presumed Hashimoto's thyroiditis patients will display diffuse thyroid activity after PET imaging. The etiology of this effect is unknown. Diffuse thyroid activity rarely requires surgical intervention.

Breast cancer prevention in older women: an algorithm to choose an optimal preventive agent.

BACKGROUND: Breast cancer is a significant cause of morbidity and mortality in older women. The current study presents new, comprehensive guidelines for providing chemoprevention to older women. OBJECTIVE: The objective of this study was to develop and pilot test a chemopreventive choice algorithm to assess its feasibility for older women at high risk of breast cancer. DESIGN: The study observed outcomes of 23 older adult females being treated with one of the four different chemopreventive agents. A novel algorithm protocol was utilized for individualized chemopreventive selection. SETTING: The study was conducted in a high-risk outpatient clinic for older women. PARTICIPANTS: Older outpatient females at high risk (N=23) were offered chemopreventive options based on individual criteria. INTERVENTION: Literature review for breast cancer chemopreventive agents informed our development of a logic-based algorithm to guide treatment protocol and chemopreventive choice optimization. Selective estrogen receptive modulators (SERMs) were avoided in women with endometrial cancer risk (ie, pre-hysterectomy individuals), but used in women with low thromboembolic event (TE) risk. Raloxifene was used with osteoporotic women. Aromatase inhibitors (AIs) were used in women with high TE risk. Women without TE risks are advised to take SERMs. When bone density decreased due to AI use, women were switched to raloxifene. MEASUREMENTS/RESULTS: Of 23 participants of age ranging from 59 to 80 years (mean=72.6), two women developed estrogen receptor-positive breast cancer. Two participants, one who declined chemoprevention and one treated with an AI, developed breast cancer. All initial chemopreventive agents were selected according to the algorithm. Although minor adverse events occurred, each was managed by discontinuation or replacement of the chemopreventive agent. Discontinuation was most commonly due to side effect concerns or cost rather than experienced side effects. CONCLUSION: Outcomes of the initial utilization of the chemopreventive agent choice algorithm support the viability of the protocol, but further evaluation with a larger and more diverse sample is required.

Relationship of Vitamin D Deficiency and Intraoperative Parathyroid Hormone Elevation in Completion and Total Thyroidectomy.

OBJECTIVE: To quantify how frequently intraoperative parathyroid hormone levels increase during thyroid surgery and to explore a possible relationship between secondary hyperparathyroidism due to vitamin D deficiency and elevation in intraoperative parathyroid hormone. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: A total of 428 consecutive patients undergoing completion and total thyroidectomy by the senior author over a 7-year period were included for analysis. All patients had baseline and postexcision intraoperative parathyroid hormone levels as well as vitamin D levels from the same laboratory. Institute of Medicine criteria were employed for vitamin D stratification (>30, normal; 20-29.9, insufficient; <20, deficient) . Other data analyzed include sex, age, neck dissection status, and parathyroid autotransplantation. RESULTS: A total of 118 patients (27.6%) had an intraoperative parathyroid hormone elevation above baseline. Patients with vitamin D deficiency were significantly more likely to experience hormone elevation ( P = .04). When parathyroid hormone rose, it did so by a mean 32.1 pg/mL. Patients with vitamin D deficiency demonstrated significantly larger hormone increases ( P = .03). CONCLUSION: Elevation in intraoperative parathyroid hormone levels above baseline after completion and total thyroidectomy occurs in over one-fourth of cases and is significantly associated with vitamin D deficiency. This study is the first to report this observation. We hypothesize that vitamin D deficiency in these patients may create a subclinical secondary hyperparathyroidism that leads to intraoperative parathyroid hormone elevation when the glands are manipulated. Additional studies will be needed to explore this physiologic mechanism and its clinical significance.

AHNS Series: Do you know your guidelines? Optimizing outcomes in reoperative parathyroid surgery: Definitive multidisciplinary joint consensus guidelines of the American Head and Neck Society and the British Association of Endocrine and Thyroid Surgeons.

BACKGROUND: Revision parathyroid is challenging due to possible diagnostic uncertainty as well as the technical challenges it can present. METHODS: A multidisciplinary panel of distinguished experts from the American Head and Neck Society (AHNS) Endocrine Section, the British Association of Endocrine and Thyroid Surgeons (BAETS), and other invited experts have reviewed this topic with the purpose of making recommendations based on current best evidence. The literature was also reviewed on May 12, 2017. PubMed (1946-2017), Cochrane SR (2005-2017), CT databases (1997-2017), and Web of Science (1945-2017) were searched with the following strategy: revision and reoperative parathyroidectomy to ensure completeness. RESULTS: Guideline recommendations were made in 3 domains: preoperative evaluation, surgical management, and alternatives to surgery. Eleven guideline recommendations are proposed. CONCLUSION: Reoperative parathyroid surgery is best avoided if possible. Our literature search and subsequent recommendations found that these cases are best managed by experienced surgeons using precision preoperative localization, intraoperative parathyroid hormone (PTH), and the team approach.

Methylation status of genes in papillary thyroid carcinoma.

OBJECTIVES: To determine the methylation status of gene promoter regions using methylation-specific polymerase chain reaction in genes encoding for thyrotropin receptor (TSHR), E-cadherin (ECAD), sodium iodide symporter protein (NIS-L), ataxia telangiectasia mutated (ATM), and death-associated protein kinase (DAPK) proteins and if methylation status correlates with patient variables, tumor factors, or outcome measures among patients with papillary thyroid carcinoma. DESIGN: Database query and retrospective medical chart review for patients with well-differentiated thyroid cancer and nonmalignant thyroid conditions treated at our institutions (1996-2004). Methylation-specific polymerase chain reaction was performed, and results were compared with controls for these genes. Methylation status was then compared with patient variables, tumor factors, and outcome measures for patients with thyroid carcinoma and controls. PATIENTS: The study population comprised 32 patients with papillary thyroid carcinoma and 27 controls. RESULTS: In our patients, all 5 genes were methylated more frequently in papillary thyroid carcinoma than in controls. NIS-L trended toward a more advanced stage at presentation. NIS-L methylation in cancer cells was not associated with methylation in adjacent benign tissue, unlike the other 4 genes. Neither age nor sex affected methylation status, and methylation status did not correlate with extent of the primary tumor or presence of nodal metastasis at diagnosis. Tumors recurred less frequently in patients with TSHR methylation than in patients with unmethylated TSHR promoter regions. CONCLUSIONS: Promoter methylation may be a marker for malignancy in thyroid carcinoma. Furthermore, methylation status of tumors as determined by methylation-specific polymerase chain reaction may help in determining patient prognosis.

A retrospective study of the association between megestrol acetate administration and mortality among nursing home residents with clinically significant weight loss.

BACKGROUND: Megestrol acetate (MA) is a progestin widely used to treat weight loss and cachexia in patients suffering from AIDS or cancer. Although MA is also frequently prescribed for similarly malnourished elderly individuals, the efficacy and morbidity of MA treatment in this patient population remain unclear. OBJECTIVE: The goal of this study was to examine the effects of MA therapy on weight and overall mortality in elderly nursing home residents. METHODS: This was a case-control cohort study of 17,328 nursing home residents admitted to Beverly Healthcare nursing home between January 1, 2000, and December 31, 2003, who had lost either 5% of total body weight within 3 months or 10% of total body weight within 6 months. Residents within this weight loss group who received MA therapy--within 30 days of their weight loss documentation--were matched (1:2) with non-MA-treated residents with respect to age, sex, race, weight, and first notation of weight loss. Residents were further matched by propensity score for activities of daily living, cognitive functioning, number of medications taken during the 7 days before data entry, clinical condition (unstable, acute episode of a recurrent problem, end-stage disease), cancer diagnosis, and human immunodeficiency virus diagnosis. RESULTS: A total of 709 patients (mean [SD]age, 84.1 [9.7]years; 70.9% female) who received MA therapy were matched with 1418 non-MA-treated patients (mean [SD] age, 84.2 [9.0] years; 70.9% female). Of the 709 MA patients, 281 (39.6%) were alive and in the nursing home at last follow-up, 149 (21.0%) were alive and discharged to another facility or to home, and 279 (39.4%) died in the nursing home. For the controls, 651 (45.9%) were alive and in the nursing home, 308 (21.7%) were discharged to another facility or to home, and 459 (32.4%) died in the nursing home. The median survival of MA-treated residents (23.9 months; 95% CI, 20.2-27.5) was significantly less than untreated residents (31.2 months; 95% CI, 27.8-35.9) (P < 0.001). Median weight and median of weight differences were unchanged after 6 months of treatment with MA compared with matched controls. CONCLUSIONS: MA treatment of elderly nursing home residents with significant weight loss was associated with a significant increase in all-cause mortality without a significant increase in weight. Randomized, prospective studies of the use of MA in elderly nursing home residents are necessary to more fully evaluate morbidity and mortality associated with this therapy.

Incidence of thyroid carcinoma in fluorodeoxyglucose positron emission tomography-positive thyroid incidentalomas.

OBJECTIVE: Fluorodeoxyglucose (FDG) whole body positron emission tomography (PET) scan may show clinically occult second lesions. Such lesions in the thyroid are increasingly common. There are several recent reports of a high probability of malignancy in these lesions ranging from 14% to 63%. STUDY DESIGN AND SETTING: This is a retrospective review of 15,711 PET scans at a multi-disciplinary thyroid clinic at a tertiary care university medical center. Twenty-two patients were referred with thyroid PET "incidentalomas." The review included 18 FDG-PET scans, ultrasound guided fine needle aspiration biopsies, and thyroid surgery pathology. Aspiration cytology or pathology were the main outcome measures. RESULTS: Three patients had malignancy of the PET-positive thyroid lesions. Papillary thyroid micro carcinomas were detected in four of the specimens that showed a benign pathology of the dominant nodule. CONCLUSION: Our experience shows a 14% malignancy rate for the dominant (imaged) nodule and a total malignancy rate of 32% when the incidental micro carcinomas are included. Both of these rates are significantly lower than results published previously.

Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D.

OBJECTIVES: Vitamin D is vitally important in maintaining skeletal health. A low plasma vitamin D concentration is associated with increased parathyroid hormone secretion, increased bone turnover, osteomalacia, and osteoporosis. As a result, vitamin D deficiency is associated with a higher incidence of hip and other fractures. Although Vitamin D deficiency has been reported in long-term care facilities, optimal methods of replenishment have not been defined. The objective of the present study was to identify the pattern of calcium and vitamin D supplementation in nursing home residents and to identify vitamin D deficiency in residents already on supplement therapy. DESIGN: Retrospective chart review. SETTING: Five academic nursing homes staffed by faculty from the University of Arkansas for Medical Sciences. PARTICIPANTS: Elderly residents aged 65 and older receiving calcium and vitamin D supplements. MEASUREMENTS: Data on dose, frequency, and levels of calcium and vitamin D were collected. The medication list and creatinine levels were also recorded. RESULTS: Forty-four (40%) residents were receiving 1000 mg, 48 (44%) were receiving 1200 mg, and 9 (8.2%) were receiving 1500 mg of calcium carbonate. Similarly, 79 (72%) residents were on 400 IU, 13 (12%) were on 600 IU, and only 8 (7%) were on 800 IU of vitamin D3 (cholecalciferol). Low levels of Vitamin D 25 (OH) D (values <30 ng/mL) were identified in 49.4% of residents; 16% were found to have deficiency (<20 ng/mL). CONCLUSION: Despite clear benefit, nursing home residents were not supplemented adequately with calcium and vitamin D.

Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.

BACKGROUND: The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic BrafV600E with and without Pten insufficiency. METHODS: After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis. RESULTS: Although mice harboring BrafV600E mutations were smaller in body size compared with their wild-type (WT) littermates, the size of their thyroid glands and deep cervical lymph nodes were significantly larger. Additionally, the tumor-draining lymph nodes showed increased and enlarged lymphatic sinuses that were distributed throughout the cortex and medulla. Tumor-reactive lymphadenopathy and histiocytosis, but no frank metastases, were observed in all mice harboring BrafV600E mutations. CONCLUSIONS: The tumor-draining lymph nodes undergo significant structural alterations in immunocompetent mice, and this may represent a primer for papillary thyroid carcinoma (PTC) metastasis.

Considerations in incorporating office-based ultrasound of the head and neck.

OBJECTIVE: The purpose of this study was to determine the cost considerations and strategies for incorporating ultrasound (US) in a head and neck practice. STUDY DESIGN AND SETTING: A retrospective chart review of office-based US procedures from 2001 to 2005 was completed at our academic medical center. Billing and coding for US and US guided fine needle aspiration (USFNA) were examined. RESULTS: The appropriate CPT codes are 76536 for US and 76942 and 10022 for USFNA-related procedures. The USFNA codes should be used repeatedly for correct coding of biopsies from multiple sites. Cost (equipment) sharing between specialties is a potential strategy for office-based US incorporation. CONCLUSION: Based on practice volume, specific CPT coding, and Medicare reimbursements, office-based US equipment and certification costs could be offset in 1 year. SIGNIFICANCE: Office-based US can be readily incorporated with significant benefits to patients. Billing and usage strategies were identified that would improve the economics of providing office-based US.

Postoperative Calcium Management in Same-Day Discharge Thyroid and Parathyroid Surgery.

OBJECTIVE: To describe a safe and effective postoperative prophylactic calcium regimen for same-day discharge thyroid and parathyroid surgery. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral academic institution. SUBJECTS AND METHODS: In total, 162 adult patients who underwent total thyroidectomy, completion thyroidectomy, unilateral parathyroidectomy, parathyroidectomy with bilateral neck exploration, or revision parathyroidectomy were identified preoperatively to be candidates for same-day discharge. All patients in this study were successfully discharged the same day on our standard prophylactic calcium regimen. RESULTS: Less than 1% (1/162) of patients re-presented to the hospital within 30 days of surgery, and that patient was successfully discharged from the emergency department after negative workup for hypocalcemia. There was no significant difference between preoperative and postoperative calcium levels in the total/completion thyroidectomy groups (9.3 vs 9.2 mg/dL, respectively; P = .14). The average postoperative calcium level in the parathyroid group was well within normal limits (9.5 mg/dL), and the difference in postoperative calcium levels between revision and primary parathyroidectomy cases was not significantly different (P = .34). CONCLUSION: The reported calcium regimen demonstrates a safe, effective, and objective means of postoperative calcium management in outpatient thyroid and parathyroid surgery in appropriately selected patients.

A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer.

PURPOSE: Positive results of phase I studies evaluating lenvatinib in solid tumors, including thyroid cancer, prompted a phase II trial in advanced medullary thyroid carcinoma (MTC). EXPERIMENTAL DESIGN: Fifty-nine patients with unresectable progressive MTC per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 within the prior 12 months received lenvatinib (24-mg daily, 28-day cycles) until disease progression, unmanageable toxicity, withdrawal, or death. Prior anti-VEGFR therapy was permitted. The primary endpoint was objective response rate (ORR) by RECIST v1.0 and independent imaging review. RESULTS: Lenvatinib ORR was 36% [95% confidence interval (CI), 24%-49%]; all partial responses. ORR was comparable between patients with (35%) or without (36%) prior anti-VEGFR therapy. Disease control rate (DCR) was 80% (95% CI, 67%-89%); 44% had stable disease. Among responders, median time to response (TTR) was 3.5 months (95% CI, 1.9-3.7). Median progression-free survival (PFS) was 9.0 months (95% CI, 7.0-not evaluable). Common toxicity criteria grade 3/4 treatment-emergent adverse events included diarrhea (14%), hypertension (7%), decreased appetite (7%), fatigue, dysphagia, and increased alanine aminotransferase levels (5% each). Ret proto-oncogene status did not correlate with outcomes. Low baseline levels of angiopoietin-2, hepatocyte growth factor, and IL8 were associated with tumor reduction and prolonged PFS. High baseline levels of VEGF, soluble VEGFR3, and platelet-derived growth factor BB, and low baseline levels of soluble Tie-2, were associated with tumor reduction. CONCLUSIONS: Lenvatinib had a high ORR, high DCR, and a short TTR in patients with documented progressive MTC. Toxicities were managed with dose modifications and medications.

Effects of megestrol acetate on pituitary function and end-organ hormone secretion: a post hoc analysis of serum samples from a 12-week study in healthy older men.

BACKGROUND: Megestrol acetate (MA) is a synthetic progestin commonly used to promote weight gain in malnourished older individuals. In small studies, MA administration has been associated with reduced serum cortisol concentrations in patients with cancer or AIDS. The impact of MA on the pituitary secretion of adrenocorticotropic hormone (ACTH) and other hormones is unclear, and the prevalence and extent of hypocortisolemia in older individuals after MA treatment is unknown. A randomized, placebo-controlled study of the effects of testosterone (T) and resistance training (RT) on body composition after MA administration in older men has been reported previously. OBJECTIVE: The purpose of this post hoc analysis was to examine the effect of 12 weeks of MA on pituitary function and end-organ hormone secretion in healthy older individuals using frozen serum samples from that study. METHODS: The previous study was conducted at the Department of Geriatrics, Donald W. Reynolds Center on Aging and the General Clinical Research Center at The University of Arkansas for Medical Sciences, Little Rock, Arkansas. Healthy male volunteers aged 60 to 85 years were recruited from the center and were randomly assigned to 1 of 4 study groups: RT + T, T, RT + placebo (P), or P. Subjects enrolled in the RT groups underwent supervised upper- and lower-body strength-training exercises 3 d/wk at 80% of 1 repetition maximum. Subjects in the groups to receive T received injections of testosterone enanthate 100 mg i.m. QW for 12 weeks. Subjects receiving P were given 1-mL saline injections i.m. QW for 12 weeks. All subjects received MA 800 mg p.o. QD concurrently for 12 weeks. For the present analysis, serum concentrations of the pituitary hormones follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), ACTH, prolactin (PRL), and luteinizing hormone (LH), as well as the end-organ hormones estradiol (E2), cortisol, free T4, and T, were measured in samples obtained at baseline (week 0) and after 12 weeks of MA treatment. RESULTS: Serum samples from 21 men (mean [SD]age, 67.0 [7.3]years; mean [SD] body mass index, 23.1 [10.4] kg/m2; mean [SD] percentage of body fat, 22.5% [8.8%]; RT + T, T, RT + P, and P groups, n = 4, 5, 6, and 6 subjects, respectively) were available from the original study. The mean percentage changes from baseline in serum pituitary hormone concentrations after 12 weeks of MA administration were as follows: TSH, -14.7%; ACTH, -89.5%; PRL, 162.2%; and LH, -49.0%; (P = 0.03, <0.001, <0.001, and <0.001, respectively). The mean (SD) percentage changes from baseline in serum end-organ hormone concentrations with MA at 12 weeks were as follows: E2, 181.6%; and cortisol, -90.8% (both, P < 0.001). In the P and RT + P groups, the mean percentage changes from baseline in T were -84% and -85%, respectively (both, P < 0.001). FSH and free T4 concentrations were not significantly changed. CONCLUSIONS: This analysis of serum samples from healthy older men suggests that MA administration significantly affected the secretion of several pituitary hormones and end-organ hormone synthesis. Most notably, ACTH secretion and serum cortisol levels were statistically significantly suppressed in 20 of 21 subjects, without the development of clinically significant adrenal suppression.

Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent of Concurrent Bisphosphonate Therapy in Elderly Adults.

OBJECTIVES: To measure the effect of proton pump inhibitors (PPIs), with and without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and calcium. DESIGN: Retrospective chart review of individuals 60 years and older. Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D (<30 ng/mL) were excluded. SETTING: Academic geriatric outpatient center in southern midwest. PARTICIPANTS: Individuals aged 60 and older with concurrent calcium, PTH, vitamin D, and creatinine laboratory measurements (N = 80) meeting labeled criteria. MEASUREMENTS: Serum calcium, PTH, vitamin D, and creatinine. RESULTS: Chronic PPI exposure was associated with statistically significantly higher PTH (65.5 vs 30.3 pg/mL, P < .001; normal range 10-55 pg/mL) and lower calcium (9.1 vs 9.4 mg/dL, P = .02; normal range 8.5-10.5 mg/dL) than no PPI exposure. Chronic PPI exposure with concurrent BP therapy was associated with statistically significantly higher PTH (65.2 vs 43.4 pg/mL, P = .05) and lower calcium (9.2 vs 9.6 mg/dL, P = .04) than BP therapy only. CONCLUSION: Based on the present study, chronic PPI exposure in elderly adults is associated with mild hyperparathyroidism regardless of concurrent oral BP administration.

Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.

OBJECTIVE: To evaluate 4-dimensional (4D) computed tomography (CT) for the localization of parathyroid adenomas previously considered nonlocalizing on ultrasound and single-photon emission CT with CT scanning (SPECT-CT). To measure radiation exposure associated with 4D-CT and compared it with SPECT-CT. STUDY DESIGN: Case series with chart review. SETTING: University tertiary hospital. SUBJECTS AND METHODS: Nineteen adults with primary hyperparathyroidism who underwent preoperative 4D CT from November 2013 through July 2014 after nonlocalizing preoperative ultrasound and technetium-99m SPECT-CT scans. Sensitivity, specificity, predictive values, and accuracy of 4D CT were evaluated. RESULTS: Nineteen patients (16 women and 3 men) were included with a mean age of 66 years (range, 39-80 years). Mean preoperative parathyroid hormone level was 108.5 pg/mL (range, 59.3-220.9 pg/mL), and mean weight of the excised gland was 350 mg (range, 83-797 mg). 4D CT sensitivity and specificity for localization to the patient's correct side of the neck were 84.2% and 81.8%, respectively; accuracy was 82.9%. The sensitivity for localizing adenomas to the correct quadrant was 76.5% and 91.5%, respectively; accuracy was 88.2%. 4D CT radiation exposure was significantly less than the radiation associated with SPECT-CT (13.8 vs 18.4 mSv, P = 0.04). CONCLUSION: 4D CT localizes parathyroid adenomas with relatively high sensitivity and specificity and allows for the localization of some adenomas not observed on other sestamibi-based scans. 4D CT was also associated with less radiation exposure when compared with SPECT-CT based on our study protocol. 4D CT may be considered as first- or second-line imaging for localizing parathyroid adenomas in the setting of primary hyperparathyroidism.