The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules.

Background: Thyroid nodules with indeterminate cytology are increasingly subjected to molecular testing. We evaluated the diagnostic performances of Afirma Genomic Sequencing Classifier (GSC) and ThyroSeq v3 in thyroid nodules with high versus low/intermediate suspicion ultrasound classification. Methods: In this prospective cohort study, we analyzed all Bethesda III and IV thyroid nodules that underwent fine-needle aspiration biopsies in the University of California Los Angeles Health System from July 2017 to April 2020. All patients underwent molecular testing with Afirma GSC or ThyroSeq v3 as part of an institutional randomized trial (NCT02681328). Nodules were categorized according to the American Thyroid Association (ATA) ultrasound risk classification. The benign call rate and the positive predictive value of molecular testing were compared between ATA high suspicion versus all other categories. Results: A total of 343 patients with 375 indeterminate thyroid nodules were included. The malignancy rate in ATA high suspicion nodules was not significantly increased by a suspicious Afirma GSC result (77.8% for all ATA high suspicion nodules vs. 87.5% for nodules with ATA high suspicion and suspicious Afirma GSC results, positive likelihood ratio [LR] = 2.0, 95% confidence interval [CI 0.5-8.0], p = 1.0) or by a positive ThyroSeq v3 result (80.0% vs. 80.0%, positive LR = 1.0 [CI 1.0-1.0], p = 1.0). The rate of malignancy in ATA low/intermediate suspicion nodules increased from 21.0% to 56.3% with a suspicious Afirma GSC result (positive LR = 4.8 [CI 3.4-6.9], p < 0.0001) and decreased to 3.8% with a benign Afirma GSC result (negative LR = 0.1 [CI 0.07-0.3], p < 0.0001). Similarly, the rate of malignancy in ATA low/intermediate suspicion nodules increased from 24.3% to 66.7% with a positive ThyroSeq v3 result (positive LR = 6.2 [CI 4.0-9.7], p < 0.0001) and decreased to 2.1% with a negative ThyroSeq v3 result (negative LR = 0.07 [CI 0.02-0.3], p < 0.0001). Conclusions: Afirma GSC and ThyroSeq v3 performed well in ruling out malignancy in sonographically low/intermediate suspicion thyroid nodules but has limited diagnostic value in sonographically high suspicion nodules. Molecular testing can prognosticate more aggressive thyroid cancers, which can inform treatment decisions.

Utilizing point-of-care A1c to impact outcomes - can we make it happen in primary care?

PURPOSE OF REVIEW: Hemoglobin A1c testing provides a marker of glycemic control and is the standard for diabetes risk assessment. According to the Centers for Disease Control (CDC), only 67.3-71.4% of diabetic patients between 2011 and 2016 had at least two A1c levels tested per year. Moreover, 27.8% had uncontrolled diabetes with an A1c of ≥8.0%, increasing the risk of microvascular complications. Lack of monitoring presents a significant barrier, and improving ease of testing could improve glycemic control. RECENT FINDINGS: Point-of-care (POC) A1c testing, obtained via capillary blood with results provided in 5-6 min, is available and used frequently in endocrine clinics. However, POC A1c testing is not standard in primary care, where 90% of type 2 diabetes patients are treated. Barriers include access and costs of POC A1c machines and standardization of testing in the primary care setting. Review of literature, however, suggests that POC A1c testing in primary care may lead to A1c reduction whereas being potentially cost-effective and strengths the patient-physician relationship. SUMMARY: POC A1c testing in primary care, if widely available and integrated into workflow, has the potential to positively impact diabetes care. Real-time feedback may change patient and physician behaviors, allowing earlier therapeutic intensification.

Newly discovered endocrine functions of the liver.

The liver, the largest solid visceral organ of the body, has numerous endocrine functions, such as direct hormone and hepatokine production, hormone metabolism, synthesis of binding proteins, and processing and redistribution of metabolic fuels. In the last 10 years, many new endocrine functions of the liver have been discovered. Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones [including 25-hydroxyvitamin D, insulin-like growth factor 1 (IGF-1), and angiotensinogen], hepatic metabolism of hormones (including thyroid hormones, glucagon-like peptide-1, and steroid hormones), and actions of specific binding proteins to glucocorticoids, sex steroids, and thyroid hormones. These studies have furthered insight into cirrhosis-associated endocrinopathies, such as hypogonadism, osteoporosis, IGF-1 deficiency, vitamin D deficiency, alterations in glucose and lipid homeostasis, and controversially relative adrenal insufficiency. Several novel endocrine functions of the liver have also been unraveled, elucidating the liver's key negative feedback regulatory role in the pancreatic α cell-liver axis, which regulates pancreatic α cell mass, glucagon secretion, and circulating amino acid levels. Betatrophin and other hepatokines, such as fetuin-A and fibroblast growth factor 21, have also been discovered to play important endocrine roles in modulating insulin sensitivity, lipid metabolism, and body weight. It is expected that more endocrine functions of the liver will be revealed in the near future.

Development of Inappropriate Vasopressin Secretion in Association With Lumbar Cerebrospinal Fluid Drainage in an Adult With Traumatic Basilar Skull Fracture.

OBJECTIVE: Hyponatremia associated with cerebrospinal fluid (CSF) drainage is primarily limited to pediatric patients. Only 1 case in an adult, after pituitary surgery, has been described. We present the first adult case, to our knowledge, of lumbar CSF drainage associated with the syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with a traumatic basilar skull fracture. METHODS: Serum and urine samples were evaluated for hyponatremia. Computed tomography and magnetic resonance imaging were performed to evaluate the fractures. RESULTS: A 31-year-old woman was hospitalized with traumatic facial and skull base fractures and managed conservatively. Four days into her hospital stay, she underwent lumbar CSF drainage for 6 days to treat a CSF leak. On examination, the patient remained hemodynamically stable and euvolemic. Sodium levels decreased from 142 to 136 mmol/L (normal, 135-146 mmol/L) on the day before and after lumbar drain placement, respectively, down to a nadir of 124 mmol/L over 3 subsequent days. Serum osmolality was 260 mOsm/kg (275-295 mOsm/kg); urine osmolality, 482 mOsm/kg; urine Na, 175 mmol/L; and thyroid-stimulating hormone, 4.0 µIU/mL (0.3-4.7 µIU/mL). The patient received treatment with sodium tablets, fluid restriction, and hypertonic saline for a diagnosis of SIADH. Sodium levels normalized from 131 to 136 mmol/L within 16 hours after lumbar drain removal. CONCLUSION: This case illustrated a temporal association of SIADH with CSF drainage in an adult. Although this could be coincidental because a basilar skull fracture can lead to SIADH, it raises the possibility that CSF lumbar drainage contributed to the patient's SIADH.

Skeletal Complications With GNAS Mutation: An Unusual Case With Osteoma Cutis, Gout, and Synovial Chondromatosis in a Patient With Pseudopseudohypoparathyroidism.

OBJECTIVE: We present a patient with pseudopseudohypoparathyroidism (PPHP) who developed both gout and synovial chondromatosis, in addition to the classical Albright's hereditary osteodystrophy phenotype. METHODS: The patient's clinical course, laboratory data, and imaging are presented. RESULTS: The patient is a 40-year-old male with no pertinent family history who presented with findings of Albright's hereditary osteodystrophy, including short stature, obesity, rounded face, shortened fourth and fifth digits, and osteoma cutis (heterotopic subcutaneous ossification), which required surgical removal for pain relief. Genetic testing confirmed a GNAS mutation, and labs showed normal parathyroid hormone, calcium, and phosphorus levels, diagnostic of PPHP. The patient later developed gout and synovial chondromatosis, a rare benign process where the synovial membrane forms calcified loose bodies within the joint. CONCLUSION: The patient case highlights the musculoskeletal complications of PPHP. Though PPHP has been rarely associated separately with gout or synovial chondromatosis, this is the first reported patient to have developed both conditions. This case raises the significance of multidisciplinary follow up for potential orthopedic complications. Moreover, the case underscores the importance of genetics and epigenetics in skeletal health, independent of calcium homeostasis in the blood.

Association between site-specific bone mineral density and glucose homeostasis and anthropometric traits in healthy men and women.

OBJECTIVE: Patients with type 2 diabetes mellitus have an increased risk of fracture despite normal or increased bone mineral density (BMD). Studies on the relationship of glucose homeostasis with BMD phenotypes have been inconclusive because distinguishing the roles of insulin resistance and hyperglycaemia in bone remodelling is challenging. In this study, we sought to define the relationship of site-specific BMD with glucose homeostasis traits and anthropometric traits. DESIGN/PATIENTS/MEASUREMENTS: In a cross-sectional study, we examined 787 subjects from the Mexican-American Coronary Artery Disease (MACAD) cohort who had undergone euglycaemic-hyperinsulinaemic clamps, oral glucose tolerance testing and dual X-ray absorptiometry. Glucose homeostasis traits included insulinogenic index (IGI30), insulin sensitivity (M value), insulin clearance (MCRI), fasting insulin, fasting glucose and 2-hour glucose. Univariate and multivariate analyses were performed to assess the association of glucose homeostasis and anthropometric traits with site-specific BMD. RESULTS: Two-hour glucose was negatively associated with arm BMD in women, which remained significant in multivariate analysis (ß = -.15, P = .0015). Positive correlations between fasting insulin and BMD at weight-bearing sites, including pelvis (ß = .22, P < .0001) and legs (ß = .17, P = .001) in women and pelvis (ß = .33, P < .0001) in men, lost significance after multivariate adjustment. Lean mass exhibited strong independent positive associations with BMD at multiple sites in both sexes. CONCLUSION: Our findings suggest that (i) anabolic effects of insulin might work via mechanical loading from lean mass; (ii) a direct negative effect of increasing glucose might be more prominent at cortical-bone-rich sites in women; and (iii) lean mass is a strong positive predictor of bone mass.

THYMIC CARCINOID WITH ADRENOCORTICOTROPIC HORMONE-PRODUCING ECTOPIC CUSHING SYNDROME AND EMPTY SELLA.

OBJECTIVE: Ectopic Cushing's syndrome secondary to thymic carcinoid is a rare disorder that may be difficult to diagnose and manage. METHODS: We describe a case of severe Cushing's syndrome secondary to a large adrenocorticotropic hormone (ACTH) producing thymic carcinoid in a patient with history of primary hyperaldosteronism. RESULTS: A 43-year-old female with a 20-year history of an aldosterone-secreting adrenocortical adenoma status post right adrenalectomy presented with acute onset of proximal muscle weakness, swelling, facial hirsutism, and severe hypokalemia. Ectopic Cushing's Syndrome was suspected based on the sudden symptom onset and markedly elevated 24-hr urine cortisol and ACTH levels. MRI revealed an empty pituitary sella and a large (7.3 cm) mediastinal mass visible on chest CT. The mass was resected by video-assisted thoracoscopic surgery, resulting in resolution of symptoms and cortisol levels. Pathology assessment confirmed well-differentiated thymic carcinoid with positive ACTH staining. CONCLUSION: The case highlights clinical features, challenges in diagnostic work up, treatment modalities, and associated endocrine findings in a thymic carcinoid abutting the heart and presenting with ectopic ACTH secretion.

Maternal and cord blood vitamin D status and childhood infection and allergic disease: a systematic review.

CONTEXT: It is unclear how in utero vitamin D deficiency affects the extraskeletal health of children, despite the known risks for adverse pregnancy/birth outcomes. OBJECTIVE: This systematic review seeks to assess the effect of in utero vitamin D exposure on childhood allergy and infection outcomes using the PRISMA guidelines. DATA SOURCES: MEDLINE, Cochrane Library, and Web of Science databases were searched. STUDY SELECTION: Literature published through April 2015 was searched for studies reporting on the association between maternal pregnancy or cord blood vitamin D status and childhood allergy and infection. DATA EXTRACTION: Of 4175 articles identified, 43 studies met the inclusion criteria. They examined a wide variety of outcomes, using many different vitamin D cutoff values in their analyses. DATA SYNTHESIS: For most outcomes, results were inconsistent, although there appeared to be a protective effect between higher in utero vitamin D status and childhood lower respiratory tract infection (5 of 10 studies). CONCLUSIONS: More research is needed on childhood allergy and infection outcomes, and future studies should standardize outcome reporting, especially with regard to cutoff values for vitamin D concentrations. Evidence of a protective association between in utero vitamin D exposure and lower respiratory tract infection was found, while the other outcomes were either understudied or showed inconsistent results.PROSPERO registration no. CRD42013006156.