Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BACKGROUND: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

Disparities in access to high-volume parathyroid surgeons in the United States: A call to action.

BACKGROUND: Parathyroidectomy by a high-volume surgeon is associated with a reduced risk of perioperative complications and of failure to cure primary and secondary hyperparathyroidism. There are limited data on disparities in access to high-volume parathyroid surgeons in the United States. METHODS: We used publicly available 2019 Medicare Provider Utilization and Payment data to identify all surgeons who performed >10 parathyroidectomies for Medicare fee-for-service beneficiaries, anticipating that fee-for-service beneficiaries likely represent only a subset of their high-volume practices. High-volume parathyroid surgeon characteristics and geographic distribution were evaluated. Inequality in the distribution of surgeons was measured by the Gini coefficient. The association between neighborhood disadvantage, based on the Area Deprivation Index, and proximity to high-volume parathyroid surgeons was evaluated using a one-way analysis of variance with Bonferroni-corrected pairwise comparisons. A sensitivity analysis was performed restricting to high-volume parathyroid surgeons within each hospital referral region, evidence-based regional markets for tertiary medical care. RESULTS: We identified 445 high-volume parathyroid surgeons who met inclusion criteria with >10 parathyroidectomies for Medicare fee-for-service beneficiaries. High-volume parathyroid surgeons were 71% male sex, and 59.8% were general surgeons. High-volume parathyroid surgeons were more likely to practice in a Metropolitan Statistical Area with a population >1 million than in less populous metropolitan or rural areas. The number of high-volume parathyroid surgeons per 100,000 fee-for-service Medicare beneficiaries in the 53 most populous Metropolitan Statistical Areas ranged from 0 to 4.94, with the highest density identified in Salt Lake City, Utah. In 2019, 50% of parathyroidectomies performed by high-volume parathyroid surgeons were performed by 20% of surgeons in this group, suggesting unequal distribution of surgical care (Gini coefficient 0.41). Patients in disadvantaged neighborhoods were farther from high-volume parathyroid surgeons than those in advantaged neighborhoods (median distance: disadvantaged 27.8 miles, partially disadvantaged 20.7 miles, partially advantaged 12.1 miles, advantaged 8.4 miles; P < .001). This association was also shown in the analysis of distance to high-volume parathyroid surgeons within the hospital referral region (P < .001). CONCLUSION: Older adults living in disadvantaged neighborhoods have less access to high-volume parathyroid surgeons, which may adversely affect treatment and outcomes for patients with primary and secondary hyperparathyroidism. This disparity highlights the need for actionable strategies to provide equitable access to care, including improved regionalization of high-volume parathyroid surgeon services and easing travel-related burdens for underserved patients.

A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVE: Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS: A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS: Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION: Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

Emerging diagnostic methods and imaging modalities in cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice.

Indigenous maternal health and health services within Canada: a scoping review.

BACKGROUND: Globally, there are disparities in access to maternal health care services and equity in maternal health outcomes between Indigenous and non-Indigenous populations. While the literature is growing, it has not been systematically synthesized. This review addresses this gap by synthesizing the existing literature on the organizational structure of maternity care, accessibility and delivery of services, and clinical disparities impacting Indigenous maternal health within Canada. It also identifies current knowledge gaps in research on these topics. METHODS: A scoping review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines and the extension for scoping reviews. The search for relevant papers was performed in PubMed, CINAHL, and SCOPUS electronic databases and included any empirical literature written in English and published during 2006 - 2021. The research team inductively coded 5 articles to develop a coding scheme, which was then applied to the remaining articles. RESULTS: A total of 89 articles were included in the review, of which 32 were qualitative papers, 40 quantitative, 8 were mixed-methods publications, and 9 were review papers. The analysis of the articles resulted in identifying a range of overarching themes pertaining to the maternal health of Indigenous women within Canada including provision of services, clinical issues, education, health disparities, organization, spatial context, and impact of informal support. The results suggest that physical, psychological, organizational, and systemic barriers inhibit the quality-of-care pregnant Indigenous women receive, and that maternal health services are not consistently provided in a culturally safe manner. Results also suggest that, compared to non-Indigenous pregnant women, Indigenous women are more likely to develop clinical complications during pregnancy, reflecting the structural impacts of colonization that continue to negatively influence Indigenous maternal health and well-being. CONCLUSIONS: There are many complex barriers that prevent Indigenous women from receiving high quality and culturally appropriate maternal care. Possible areas that could address the service gaps illuminated through this review include the implementation of cultural considerations across health care jurisdictions within Canada.

Physicians' views of patient-planetary health co-benefit prescribing: a mixed methods systematic review.

Health professionals are increasingly called to become partners in planetary health. Using patient-planetary health (P-PH) co-benefit prescribing framing, we did a mixed methods systematic review to identify barriers and facilitators to adopting P-PH co-benefit prescribing by physicians and mapped these onto the Capability, Opportunity, Motivation, and Behaviour (COM-B) model and Theoretical Domains Framework (TDF). We searched electronic databases from inception until October, 2022, and did a content analysis of the included articles (n=12). Relevant categories were matched to items in the COM-B model and TDF. Nine barriers and eight facilitators were identified. Barriers included an absence of, or little, knowledge of how to change practice and time to implement change; facilitators included having policy statements and guidelines from respected associations. More diverse study designs that include health professionals, patients, and health-care system stakeholders are needed to ensure a more holistic understanding of the individual, system, and policy levers involved in implementing clinical work informed by planetary health.

Implementation of a formal sleep center-based screening protocol for primary aldosteronism in patients with obstructive sleep apnea.

BACKGROUND: There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS: Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS: A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION: Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

BACKGROUND: Although the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. METHODS: All patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. RESULTS: A total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). CONCLUSION: Thyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.

DNA Methylation Profiling in Rare Sellar Tumors.

The histologic diagnosis of sellar masses can be challenging, particularly in rare neoplasms and tumors without definitive biomarkers. Moreover, there is significant inter-observer variability in the histopathological diagnosis of many tumors of the CNS, and some rare tumors risk being misclassified. DNA methylation has recently emerged as a useful diagnostic tool. To illustrate the clinical utility of machine-learning-based DNA methylation classifiers, we report a rare case of primary sellar esthesioneuroblastoma histologically mimicking a non-functioning pituitary adenoma. The patient had multiple recurrences, and the resected specimens had unusual histopathology. A portion of the resected sellar lesion was profiled using clinically validated whole-genome DNA methylation and classification. DNA was extracted from the tissue, hybridized on DNA methylation chips, and analyzed using a clinically validated classifier. DNA methylation profiling of the lesion showed that the tumor classified best with the esthesioneuroblastoma reference cohort. This case highlights the difficulty in diagnosing atypical sellar lesions by standard histopathological methods. However, when phenotypic analyses were nonconclusive, DNA methylation profiling resulted in a change in diagnosis. We discuss the growing role of DNA methylation profiling in the classification and diagnosis of CNS tumors, finding that utilization of DNA methylation studies in cases of atypical presentation or diagnostic uncertainty may improve diagnostic accuracy with therapeutic and prognostic implications.

Preoperative differentiation of hypophysitis and pituitary adenomas using a novel clinicoradiologic scoring system.

PURPOSE: Hypophysitis can clinically and radiologically mimic other nonfunctioning masses of the sella turcica, complicating preoperative diagnosis. While sellar masses may be treated surgically, hypophysitis is often treated medically, so differentiating between them facilitates optimal management. The objective of our study was to develop a scoring system for the preoperative diagnosis of hypophysitis. METHODS: A thorough literature review identified published hypophysitis cases, which were compared to a retrospective group of non-functioning pituitary adenomas (NFA) from our institution. A preoperative hypophysitis scoring system was developed and internally validated. RESULTS: Fifty-six pathologically confirmed hypophysitis cases were identified in the literature. After excluding individual cases with missing values, 18 hypophysitis cases were compared to an age- and sex-matched control group of 56 NFAs. Diabetes insipidus (DI) (p < 0.001), infundibular thickening (p < 0.001), absence of cavernous sinus invasion (CSI) (p < 0.001), relation to pregnancy (p = 0.002), and absence of visual symptoms (p = 0.007) were significantly associated with hypophysitis. Stepwise logistic regression identified DI and infundibular thickening as positive predictors of hypophysitis. CSI and visual symptoms were negative predictors. A 6-point hypophysitis-risk scoring system was derived: + 2 for DI, + 2 for absence of CSI, + 1 for infundibular thickening, + 1 for absence of visual symptoms. Scores ≥ 3 supported a diagnosis of hypophysitis (AUC 0.96, sensitivity 100%, specificity 75%). The scoring system identified 100% of hypophysitis cases at our institution with an estimated 24.7% false-positive rate. CONCLUSIONS: The proposed scoring system may aid preoperative diagnosis of hypophysitis, preventing unnecessary surgery in these patients.

Determinants of Surgical Remission in Prolactinomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors. METHODS: We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at <1 year and >1 year after operation, respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (ORs) were calculated, stratified by radiologic size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis. RESULTS: Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission (OR, 0.20; 95% confidence interval [CI], 0.16-0.24) and lower rates of remission at follow-up (OR, 0.11; 95% CI, 0.053-0.22). Postoperative remission was less likely in tumors with extrasellar or suprasellar extension (OR, 0.16; 95% CI, 0.06-0.43) and tumors with cavernous sinus invasion (OR, 0.03; 95% CI, 0.01-0.13). Female gender and absence of preoperative dopamine agonist treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission, I2 = 94%; follow-up remission, I2 = 86%; recurrence, I2 = 68%). CONCLUSIONS: Transsphenoidal surgery for prolactinomas may be particularly effective in small, noninvasive, treatment-naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.

Tumor volume improves preoperative differentiation of prolactinomas and nonfunctioning pituitary adenomas.

PURPOSE: Both prolactinomas and nonfunctioning adenomas (NFAs) can present with hyperprolactinemia. Distinguishing them is critical because prolactinomas are effectively managed with dopamine agonists, whereas compressive NFAs are treated surgically. Current guidelines rely only on serum prolactin (PRL) levels, which are neither sensitive nor specific enough. Recent studies suggest that accounting for tumor volume may improve diagnosis. The objective of this study is to investigate the diagnostic utility of PRL, tumor volume, and imaging features in differentiating prolactinoma and NFA. METHODS: Adult patients with pathologically confirmed prolactinoma (n = 21) or NFA with hyperprolactinemia (n = 58) between 2013 and 2020 were retrospectively identified. Diagnostic performance of clinical and imaging variables was analyzed using receiver-operating characteristic curves to calculate area under the curve (AUC). RESULTS: Tumor volume and PRL positively correlated for prolactinoma (r = 0.4839, p = 0.0263) but not for NFA (r = 0.0421, p = 0.7536). PRL distinguished prolactinomas from NFAs with an AUC of 0.8892 (p < 0.0001) and optimal cut-off value of 62.45 ng/ml, yielding a sensitivity of 85.71% and specificity of 94.83%. The ratio of PRL to tumor volume had an AUC of 0.9647 (p < 0.0001) and optimal cut-off value of 21.62 (ng/ml)/cm3 with sensitivity of 100% and specificity of 82.76%. Binary logistic regression found that PRL was a significant positive predictor of prolactinoma diagnosis, whereas tumor volume, presence of cavernous sinus invasion, and T2 hyperintensity were significant negative predictors. The regression model had an AUC of 0.9915 (p < 0.0001). CONCLUSIONS: Consideration of tumor volume improves differentiation between prolactinomas and NFAs, which in turn leads to effective management.

Does glucose influence multidien cycles of interictal and/or ictal activities?

PURPOSE: There are multidien patterns of seizure occurrence. Predicting seizure risk may be easier with biomarker correlates to multidien patterns. We hypothesize multiday hyper or hypoglycemia contributes to seizure risk. METHODS: In a type I diabetic (T1D) with focal onset epilepsy with continuous glucose monitoring (CGM) and responsive neurostimulation (RNS) devices, we studied multiday interictal activities (IEA), seizures, and glucose. Hourly CGM data was matched to hourly RNS captures of interictal and ictal activities over 33 months. RNS detection settings were unchanged. Multidien cycles were analyzed, active blocks of IEA and ictal episodes defined, and tissue glucose averages studied. RESULTS: Average glucose was 161 mg/dl. A 40-day cycle of interictal and ictal activities occurred, though no similar glucose cycle was evident. Glucose elevations relative to patient average were associated with increases in IEA but not seizure. Frequent seizures were not associated with obvious elevations or decreases of glucose from baseline, most seizures occurred at +/- 10 mg/dl of average daily glucose (i.e. 150-170 mg/dl). CONCLUSION: Tissue glucose may influence IEA but may not influence multiday seizure activity or very frequent seizures. In an ambulatory T1D patient multiday hypo or hyperglycemic extremes do not appear to provoke seizure activities.

Are there mortality risks for patients with epilepsy who use cannabis treatments as monotherapy?

Mortality associated with cannabis used for treatment of epilepsy is not well documented. We discuss two fatalities in the setting of epilepsy and self-determined therapy with cannabis (SDTC). One patient had probable sudden unexpected death in epilepsy, the second death was due to seizure-associated drowning. Both directed SDTC over conventional anti-seizure medications. Where recreational cannabis is legal, decisions to use cannabis are often self-directed and independent of physician advice of cannabis risks, in part because physicians may not be aware of the risk of SDTC. Further study of morbidity and mortality of SDTC in patients with epilepsy is needed.