Testing for Primary Hyperparathyroidism in 17,491 Patients With Hypercalcemia.

BACKGROUND: Primary hyperparathyroidism (PHPT) is underdiagnosed and associated with many adverse health effects. Historically, many hypercalcemic patients have not received parathyroid hormone (PTH) testing; however, underlying reasons are uncertain. Our goals are to determine the PTH testing rate among hypercalcemic individuals at a large academic health system and to assess for characteristics associated with testing versus not testing for PHPT to inform future strategies for closing testing gaps. METHODS: This retrospective study included adult patients with ≥1 elevated serum calcium result between 2018 and 2022. Based on the presence or absence of a serum PTH result, individuals were classified as "screened" versus "unscreened" for PHPT. Demographic and clinical characteristics of these groups were compared. RESULTS: The sample comprised 17,491 patients: 6567 male (37.5%), 10,924 female (62.5%), mean age 59 y. PTH testing was performed in 6096 (34.9%). Characteristics independently associated with the greatest odds of screening were 5+ elevated calcium results (odds ratio [OR] 5.02, P < 0.0001), chronic kidney disease (OR 3.63, P < 0.0001), maximum calcium >12.0 mg/dL (OR 2.48, P < 0.0001), and osteoporosis (OR 2.42, P < 0.0001). Characteristics associated with lowest odds of screening were age <35 y (OR 0.60, P < 0.0001), death during the study period (OR 0.68, P < 0.0001), age ≥85 y (OR 0.70, P = 0.0007), and depression (OR 0.84; P = 0.0081). CONCLUSIONS: Only 35% of hypercalcemic patients received PTH testing. Although the presence of PHPT-associated morbidity was generally associated with increased rates of screening, hypercalcemic patients with depression were 16% less likely to be tested.

Multidisciplinary Endocrine Tumor Board: Assessment of the Patient Experience.

Research surrounding tumor boards has focused on patient outcomes and care coordination. Little is known about the patient experience with tumor boards. This survey examined aspects of the patient experience for patients presented at our multidisciplinary endocrine tumor board (ETB). A 15-item survey was distributed via the online patient portal to patients over the age of 18 whose case had been discussed at our ETB over an 18-month period. Descriptive statistics were reported, and a Fisher's exact test was used to examine relationships between variables. A total of 47 patients completed the survey (46%). A majority (72%) report their provider explained what the ETB is, and 77% report being informed their case would be discussed. Most patients were satisfied their case was being discussed (72%). A number of patients did report moderate or severe anxiety knowing their case was being discussed (15%). Sixty-four percent of patients report the ETB recommendations were clearly explained; however, satisfaction with the recommendations was slightly lower (53%). Despite the somewhat low satisfaction with the recommendations, 75% of patients felt more confident in their treatment plan knowing their case was discussed. Finally, if given the chance, 66% responded that they would have been interested in participating in their own ETB discussion. This study provides some insight into the patient experience surrounding tumor board discussions. Overall, patients are satisfied when their case is discussed at ETB. Patients can also experience anxiety about these discussions, and many patients desire to be present for their own discussions.

Precision nephrotoxicity testing using 3D in vitro models.

Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

Opportunistic CT Assessment of Parathyroid Glands: Utility of Radiologist-Recommended Biochemical Evaluation for Diagnosing Primary Hyperparathyroidism.

BACKGROUND. Existing gaps in primary hyperparathyroidism (PHPT) diagnosis and treatment have prompted calls for systemic change in the approach to this disease. One proposed change is opportunistic assessment for enlarged parathyroid glands on routine CT examinations, to target biochemical testing to individuals most likely to have un-diagnosed PHPT. OBJECTIVE. The purpose of our study was to assess the utility of a radiologist recommendation for biochemical testing in patients with a suspected enlarged parathyroid gland on routine CT for identifying previously undiagnosed PHPT. METHODS. This retrospective study included patients without known or suspected PHPT who underwent routine CT (i.e., performed for reasons other than known or suspected parathyroid disease) between August 2019 and September 2021 in which the clinical CT report included a radiologist recommendation for biochemical testing to evaluate for possible PHPT because of a suspected enlarged parathyroid gland. Neuroradiologists at the study institution included this recommendation on the basis of individual judgment without formal criteria. The EHR was reviewed to identify patients who underwent subsequent laboratory evaluation for PHPT. An endocrine surgeon used available laboratory results and clinical data to classify patients as having PHPT, secondary hyper-parathyroidism, or no parathyroid disorder independent of the CT findings. RESULTS. The sample comprised 39 patients (median age, 68 years; 20 women, 19 men) who received the radiologist recommendation for biochemical evaluation. Of these patients, 13 (33.3%) received the recommended biochemical evaluation. Of the 13 tested patients, three (23.1%) were classified as having PHPT, four (30.8%) as having secondary hyperparathyroidism, and six (46.2%) as having no parathyroid disorder. Thus, the number of patients needing to receive a radiologist recommendation for biochemical testing per correct PHPT diagnosis was 13.0, and the number of patients needing to undergo laboratory testing per correct PHPT diagnosis was 4.3. One of the three patients classified as having PHPT underwent surgical resection of the lesion identified by CT, which was shown on histopathologic evaluation to represent hypercellular parathyroid tissue. CONCLUSION. Radiologist recommendations for biochemical testing in patients with suspected enlarged parathyroid glands on routine CT helped to identify individuals with undiagnosed PHPT. CLINICAL IMPACT. Opportunistic assessment for enlarged parathyroid glands on routine CT may facilitate PHPT diagnosis.

Multiple endocrine neoplasia 2A presenting in a family with a history of Hirschprung's disease.

Hirschprung's disease co-occurs with multiple endocrine neoplasia type 2A infrequently but at a higher rate with certain RET mutations. We present a case of a patient evaluated for an adrenal incidentaloma with a history of familial Hirschprung's. Our patient was found to have synchronous pheochromocytoma and medullary thyroid carcinoma illustrating the importance of genetic testing in these patients to determine appropriate screening for endocrine tumors.

Gaps in pre-rituximab hepatitis B screening: an institutional experience.

The aim of the study was to evaluate the pretreatment workup of patients referred to our tertiary care center with low-grade lymphoma for compliance with National Comprehensive Cancer Network guidelines. This was a retrospective chart review. The study included all new patients with low-grade lymphoma who were diagnosed and treated at our center from January 1, 2005, to December 30, 2011. All the major facets of pretreatment workup were examined, including bone marrow biopsy, lactate dehydrogenase, hepatitis B screening, performance status of the patient, and diagnostic radiological studies. A total of 53 new patients were identified, of whom 36 (68%) had pretreatment workup and treatment at our center. The median age at diagnosis was 67. Fifty-four percent of the patients had bone marrow biopsy done. Radiological diagnostic studies were conducted in 97% of the patients. Hepatitis B screening was done in 19% of the total patients and 25% of the patients who received rituximab. Lactate dehydrogenase levels were checked in 72% of the patients. A significant deviation from the National Comprehensive Cancer Network guidelines for low-grade lymphoma pretreatment workup was observed for hepatitis B screening. Measures to ensure that patients have hepatitis B screening before rituximab were implemented. Studies such as these help to improve patient care.

Corrections for mRNA extraction and sample normalization errors find increased mRNA levels may compensate for cancer haplo-insufficiency.

The relative mRNA levels of differentially expressed (DE) and housekeeping (HK) genes of six aneuploid cancer lines with large-scale genomic changes identified by SNP/SKY analysis were compared with similar genes in diploid cells. The aneuploid cancer lines had heterogeneous genomic landscapes with subdiploid, diploid, and supradiploid regions and higher overall gene copy numbers compared with diploid cells. The mRNA levels of the haploid, diploid, and triploid HK genes were found to be higher after correction of easily identifiable mRNA measurement errors. Surprisingly, diploid and aneuploid HK gene mRNA levels were the same by standard expression array analyses, despite the higher copy numbers of the cancer cell HK genes. This paradoxical result proved to be due to inaccurate inputs of true intra-cellular mRNAs for analysis. These errors were corrected by analyzing the expression intensities of DE and HK genes in mRNAs extracted from equal cell numbers (50:50) of intact cancer cell and lymphocyte mixtures. Correction for both mRNA extraction/sample normalization errors and total gene copy numbers found the SUIT-2 and PC-3 cell lines' cancer genes both had ~50% higher mRNA levels per single allele than lymphocyte gene alleles. These increased mRNA levels for single transcribed cancer alleles may restore functional mRNA levels to cancer genes rendered haplo-insufficient by the genetic instability of cancer. © 2013 Wiley Periodicals, Inc.