4D SPECT/CT: A Hybrid Approach to Primary Hyperparathyroidism.

Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT. Using the input from radiologists, endocrinologists, and surgeons, we apply patient criteria such as large body habitus, concomitant multiglandular disease, multinodular thyroid disease, confusing previous imaging, and unsuccessful previous surgery to create an imaging paradigm that uses 4D SPECT/CT yet is cost-effective, accurate, and limits extraneous radiation exposure. 4D SPECT/CT capitalizes on the strengths of SPECT and 4D CT and addresses limitations that exist when these modalities are used in isolation. In select patients with complicated clinical parameters, preoperative imaging with 4D SPECT/CT can improve accuracy yet remain cost-effective.

Kids These Days: Social Media's Influence on Adolescent Behaviors.

We live in an electronic world with near-ubiquitous access to smartphones and social media. One consequence of this new reality is that children and teenagers may be unduly swayed by social media influencers who promote skincare products and practices, colloquially referred to as "skinfluencers," and enjoy unfettered access to emerging trends-not all of which lead to positive results. Herein, we describe two cases of adolescents presenting to a pediatric dermatology department after trying different beauty trends endorsed by social media influencers. The first patient developed allergic contact dermatitis to "snail slime" (96% Snail Secretion Filtrate; COSRX), a popular over-the-counter skincare product that has received notable attention on social media platforms due to its purported skin hydrating effects. The second patient presented urgently due to her mother's concerns of "overnight moles," which, in fact, the patient had acquired after applying makeup using a social media-endorsed "freckle stamp." Clinicians should be aware of these emerging trends to properly educate, manage, and treat patients susceptible to their influence-especially within the particularly impressionable teenage population.

12 tips for developing Physician Education.

The education of a physician is a life-long process. Healthcare is a dynamic field characterized by continuous advancements in medicine, evolving treatment options, changing regulations, care models, and technology. Physicians must keep up-to-date with new practices, procedures, medications, and diseases and fulfill the educational requirements to maintain their medical licensure. Continuing education for physicians serves the essential purpose of nurturing lifelong learning, ensuring that medical practices align with the latest standards, and ultimately enhancing the quality of patient care and outcomes. In a broader context, physician education encompasses all activities designed to enhance skills, professional performance, and relationships that physicians employ to provide services to patients and the public and to improve collaborations within the field. This paper outlines a step-by-step plan for designing high-quality education programs for physicians. It aims to assist in ongoing education, aligning their practices with the latest medical care standards, and optimizing their clinical performance to improve patient and community health.

Bilateral accessory axillary breast tissue in a premenarchal female.

A 9-year-old premenarchal female presented to pediatric dermatology with a 6-month history of periodically tender, bilateral and symmetric axillary masses. Magnetic resonance imaging and subsequent surgical excision confirmed the diagnosis of bilateral accessory axillary breast tissue. Accessory axillary breast tissue is a rare condition seen most in pubertal, pregnant and breastfeeding women. However, it can arise in pre-adolescent patients and should be added to the differential diagnosis of an axillary mass.

Outcomes of subtotal parathyroidectomy for renal hyperparathyroidism.

BACKGROUND: Renal hyperparathyroidism due to end-stage kidney disease is associated with considerable morbidity, and when refractory is treated with parathyroidectomy. Recurrent renal hyperparathyroidism is a major surgical complication, yet initial target parathyroid remnant size and outcomes, including rates of recurrence are not well elucidated. METHODS: This is a single-institution retrospective cohort study of patients who underwent initial subtotal parathyroidectomy for renal hyperparathyroidism on dialysis, from 1990-2022. The subtotal parathyroidectomy was defined as resection of 3 parathyroid glands ± partial resection of the fourth gland leaving a remnant of ∼75-100 mg, and postresection intraoperative parathyroid hormone goal was 150-250 pg/mL. Clinical data were examined for outcomes. RESULTS: Among 204 patients who met inclusion criteria, 139 (68%) had follow-up data; 58% (80/139) were women and median age was 45 years. Surgical complications included 2 hematomas (1.4%), 1 recurrent laryngeal nerve injury (<1%), and no patient required readmission for intravenous calcium. Using a target remnant size of 75-100 mg, recurrent renal hyperparathyroidism was uncommon (14/139, 10%) and arose at a median interval of 58.6 months (range, 8-180). In cases of recurrence, the postresection intraoperative parathyroid hormone level was less likely to drop <250 pg/mL (40%, 4/10 vs nonrecurrence 65%, 80/123; P = .11) with a slightly lower median decrease (70% vs 81% in nonrecurrence, P = .8); however, neither were significant. Recurrence did not occur in the 19 patients who later received kidney transplantation (P = .2). CONCLUSION: In subtotal parathyroidectomy for renal hyperparathyroidism, use of a target 75-100 mg remnant size results in low complication rates. Durable cure appears to be more likely with renal transplantation.

Sex differences in patients with primary hyperparathyroidism.

BACKGROUND: Differences in presenting symptoms of primary hyperparathyroidism and outcomes of parathyroidectomy between sexes have been described, but whether these can be assessed by perioperative use of a validated tool, such as the Pasieka Parathyroidectomy Assessment Score, is unknown. METHOD: All patients with primary hyperparathyroidism were asked to complete symptom assessment at the preoperative and postoperative visits. The assessment included a query for 13 Pasieka Parathyroidectomy Assessment Score parameters evaluated using a visual analog scale as described by Pasieka (summative score 0-1,300), and general quality of life and wellness. A review of a prospectively maintained database of primary hyperparathyroidism patients (January 2016-December 2019) was performed, and those who had a 6-month cure after initial parathyroidectomy were included. RESULTS: The study cohort was mostly women (77%, 541/701). The median preoperative Pasieka Parathyroidectomy Assessment Score was higher in women (155, 0-1,190) than in men (80.5, 0-855, P < .001), although there were similar rates of asymptomatic primary hyperparathyroidism (Pasieka Parathyroidectomy Assessment Score = 0, 12.5% vs 7%, P = .042). After curative parathyroidectomy, women reported a substantial reduction in symptomatology, with Pasieka Parathyroidectomy Assessment Score declining by 35% at initial postoperative visit (median, 155 vs 100, P < .001), further decreasing to 48% by 6 months (155 vs 80, P < .001). The Pasieka Parathyroidectomy Assessment Score in men did change but to a much smaller degree at both the initial postoperative visit (80.5 vs 70; P = .036) and at 6 months (80.5 vs 57.5; P = .048). CONCLUSION: When assessed with the Pasieka Parathyroidectomy Assessment Score, improvement in symptoms was clearly demonstrated for women after curative parathyroidectomy. Whether symptom improvement also occurs in men is less apparent but may be due to disparities in the development and validation of outcomes tools in general.

Normocalcemic hyperparathyroidism: Intervention to differentiate primary from secondary hyperparathyroidism.

BACKGROUND: Normocalcemic hyperparathyroidism can occur, but surgery should not be considered until common etiologies for secondary hyperparathyroidism are comprehensively excluded. Calcium deficiency is an underrecognized cause of normocalcemic parathyroid hormone elevation, and we aim to determine if the implementation of a preoperative calcium challenge can be used to reduce unnecessary parathyroidectomy. METHODS: Consecutive patients referred for parathyroidectomy (1/21-6/22) with normocalcemia (serum calcium <10 mg/dL) and concurrently elevated parathyroid hormone levels were routinely treated with supplemental calcium and vitamin D3, and follow-up laboratory studies were assessed. RESULTS: A total of 29/314 (9%) patients had normocalcemic parathyroid hormone elevation with mean calcium, parathyroid hormone, and vitamin D 25OH levels of 9.5 ± 0.3 mg/dL, 109.9 ± 34.9 pg/mL, and 42.7 ± 23.8 ng/mL respectively. Confounding factors included estimated glomerular filtration rate <60 in 2, loop diuretic use in 4, and prior gastric bypass or gastric sleeve surgery in 4. Follow-up biochemical evaluation was available in 27 (92%); results were unchanged in 7 patients (26%); normalization of parathyroid hormone levels with persistently normal calcium levels occurred in 15 (55%), thus confirming secondary hyperparathyroidism and hypercalcemia with elevated parathyroid hormone levels (classic primary hyperparathyroidism) was diagnosed in 5 (19%). Parathyroid exploration has been completed for 3 of 5 patients with classic primary hyperparathyroidism to date. CONCLUSION: A preoperative calcium challenge was prospectively initiated in normocalcemic patients with parathyroid hormone elevation, and there was high compliance (92%). Short-interval calcium supplementation revealed ∼50% to have resolved secondary hyperparathyroidism due to insufficient calcium intake, which avoided unnecessary surgery. In contrast, classic patients were unveiled in 20%, allowing for prompt and correct surgical intervention.

Whole-Exome Sequencing of a Case of Squamoid Eccrine Ductal Carcinoma Reveal Similarities With Cutaneous Squamous Cell Carcinoma.

ABSTRACT: Squamoid eccrine ductal carcinoma (SEDC) is a poorly documented but likely underrecognized sweat gland malignancy with significant risk for local recurrence and potential for metastasis and rare disease-related mortality. Histopathologically, the tumor demonstrates a biphasic differentiation pattern: superficially, the tumor has squamous differentiation [indistinguishable from well-differentiated cutaneous squamous cell carcinoma (cSCC)], while the deeper aspect has a more infiltrative pattern with prominent ductal differentiation. Diagnosis of SEDC relies upon histopathologic examination alone. Its pathogenesis is poorly understood, and its genomic features have yet to be described. In this article, we characterize the genomic features in a case of SEDC through whole-exome sequencing, then compare its features with cSCC and other eccrine ductal carcinomas. Whole-exome sequencing revealed 30 mutations/Mb with 21 pathogenic or likely pathogenic mutations in total, identified across 14 different genes. The genomic abnormalities identified in this case of SEDC overlap considerably with those found in cSCC but not those of other sweat gland malignancies. The clinical and histopathologic features of SEDC previously reported and the genetic features determined from this case suggest that this tumor may arise initially as a well-differentiated cSCC that subsequently undergoes divergent differentiation focally to resemble a sweat gland malignancy. Genetic analyses of additional cases are warranted to clarify this consideration.

Molecular Testing Predicts Incomplete Response to Initial Therapy in Differentiated Thyroid Carcinoma Without Lateral Neck or Distant Metastasis at Presentation: Retrospective Cohort Study.

Background: Molecular testing (MT) is emerging as a potential prognostic factor that can be available before treatment of differentiated thyroid carcinoma begins. Among patients eligible for either lobectomy or total thyroidectomy as their initial therapy, our study aims were to assess (1) if conventionally available preoperative factors are associated with incomplete response to initial therapy, and (2) if MT results can be a surrogate for the ATA Risk Stratification System (RSS) to estimate risk of recurrence. Methods: The data of consecutive thyroid cancer patients without preoperative lateral neck disease or distant metastasis who underwent index thyroidectomy between November 1, 2017 and October 31, 2021 were reviewed. Logistic regression models including preoperative variables such as MT and/or the postoperatively available RSS were constructed to predict disease recurrence, either structural or biochemical. Model discrimination using the c-statistic and goodness-of-fit test were compared. Results: Among 945 patients studied, 50 (5.2%) recurred with 18-month median follow-up. Recurrences were detected in 17 (2.9%), 20 (6.7%), and 13 (22.8%) patients with RSS-low, -intermediate, and -high cancers, respectively (p < 0.001). In multivariable analysis, only tumor size was associated with recurrence (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.5). In a different model analyzing 440 (46.6%) patients with available MT results, recurrence was associated with both larger tumor size (OR 1.4 [95% CI 1.1-1.8]) and MT results (p < 0.001). Including MT improved the c-statistic by 27%, which was statistically no different than the model incorporating only the RSS (p = 0.15). Conclusions: Disease recurrence was observed across all ATA RSS categories in short-term follow-up, and tumor size was the only conventional preoperative factor associated with recurrence. When MT results were incorporated, they not only improved predictive ability beyond tumor size alone, but also yielded similar ability as the gold standard ATA RSS. Thus, MT results might aid the development of novel preoperative risk stratification algorithms.

Changes in thyroid nodule cytology rates after institutional implementation of the Thyroid Imaging Reporting and Data System.

BACKGROUND: The American College of Radiology Thyroid Imaging Reporting and Data System for ultrasound classification of malignancy risk was developed to better triage thyroid nodules for fine-needle aspiration biopsy. To examine further, we compared thyroid cytologic classification rates in nodules before and after institutional Thyroid Imaging Reporting and Data System implementation. METHODS: Cytology diagnoses by Bethesda criteria (categories I-VI) from January 2014 to October 2021 were retrieved; observed changes in yearly category frequency were analyzed by linear regression; and pooled cohorts of pre- (2014-2018) and post-Thyroid Imaging Reporting and Data System (2019-2021) cytology call rates were compared. RESULTS: Overall, 7,413 cytologic specimens were included (range/year 715-1,444). From 2014 to 2021, the proportion of benign (Bethesda category II) diagnosis per year declined stepwise from 49.7% to 19.4%, and atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda category III) increased sequentially from 21.3% to 51.5%. Between 2014 and 2021, Bethesda category III diagnosis increased on average by 4.8% per year (95% confidence internal, 3.29-5.54; P < .001) and Bethesda category II results decreased on average by 4.4% per year (95% confidence interval, 6.29-3.42; P < .001). When comparing pre- and post-Thyroid Imaging Reporting and Data System, the proportion of Bethesda category II cytology results decreased (43.1% vs 21%; P = .001) while Bethesda category III (28.3% vs 47.7%; P = .002) and Bethesda category V (1.1% vs 1.7%; P = .015) results increased. CONCLUSION: After implementation of American College of Radiology Thyroid Imaging Reporting and Data System ultrasound criteria, we observed a 2.5-fold decline in the rate of benign cytology and an increase in the proportion of atypia of undetermined significance/follicular lesion of undetermined significance results.

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes.

BACKGROUND: Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. METHODS: Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. RESULTS: Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group-low, molecular risk group-intermediate, and molecular risk group-high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group-low, molecular risk group-intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group-intermediate, molecular risk group-high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group-high cancers than in molecular risk group-intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9-8.6; P < .001) and more likely in molecular risk group-intermediate than in molecular risk group-low (hazard ratio = 5.0; 95% confidence interval, 2.0-12.5; P < .001). CONCLUSION: Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.

Long-Term Outcomes for Patients with Multiple Endocrine Neoplasia Type 1 and Duodenopancreatic Neuroendocrine Neoplasms.

BACKGROUND: Liver metastasis from duodenopancreatic neuroendocrine neoplasms (DP-NENs) is a major cause of mortality in multiple endocrine neoplasia type 1 (MEN1) patients, yet much of their natural history is unknown. METHODS: This longitudinal, retrospective cohort study analyzed all MEN1 patients with imageable functional (F) and nonfunctional (NF) DP-NENs (1990-2021) for liver metastasis-free survival (LMFS) and overall survival (OS). RESULTS: Of 138 patients, 85 (61.6%) had imageable DP-NENs (28 F, 57 NF), and the mean largest tumor size was 1.8 ± 1.4 cm. Multifocality was present in 32 patients (37.7%). Surgery was performed for 49 patients (57.7%). During an 11-year median follow-up period (IQR, 6-17 years), 23 (27.1%) of the patients had liver metastasis, and 19 (22.4%) patients died. Death was attributed to liver metastasis in 60% of cases. The patients with F-DP-NENs versus NF-DP-NENs more often had liver metastasis (46.4% vs. 15.8%; p = 0.002) but had similar 10-year LMFS (80.9 vs. 87.0%; p = 0.44) and OS (82.7 vs. 94.3%; p = 0.69). The patients with NF-DP-NENs had surgery when their tumors were larger (p < 0.001). Tumor size was not associated with liver metastasis (p = 0.89). The average growth rate was 0.04 cm/year (SE, 0.02 cm/year; p = 0.01) during active surveillance for NF-DP-NENs (n = 38). Liver metastasis developed in four patients with tumors smaller than 2 cm. The risk of liver metastasis was independent of surgery (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.21-2.93; p = 0.72) and death (HR, 0.51; 95% CI, 0.08-3.06; p = 0.46). CONCLUSIONS: Although the observed outcomes in this study were better than historical data, small NF-DP-NENs still developed liver metastasis and liver metastasis remains a major cause of death. These results suggest that size as a sole criterion for surgery may be insufficient to predict tumor behavior.

Changes in frailty after parathyroid and thyroid surgery.

BACKGROUND: Frailty tools assess symptoms and comorbidities that may coincide with those of primary hyperparathyroidism. To test the hypothesis that parathyroidectomy improves frailty, we conducted a prospective cohort comparison of frailty after parathyroid or thyroid surgery. METHODS: The Risk Analysis Index measuring frailty was prospectively administered to patients undergoing curative parathyroid exploration or total thyroidectomy. Risk Analysis Index results at the preoperative, postoperative, and last follow-up visits were assessed longitudinally. RESULTS: Compared to total thyroidectomy patients (n = 142), parathyroid exploration patients (n = 187) were older (P = .001), more often male (P = .05) and had longer surgical follow-up (P < .001). Mean preoperative Risk Analysis Index scores were higher in parathyroid exploration patients (24 ± 9 vs total thyroidectomy 17 ± 8, P < .001). Parathyroid exploration patients demonstrated a significant decrease in Risk Analysis Index score from preoperative to last follow-up (P < .01); total thyroidectomy patients did not (P = .44). Parathyroid exploration patients were also less likely to exhibit a 20% increase in Risk Analysis Index over time, suggesting that parathyroidectomy slowed progression of frailty (2% vs 19%, P = .003). CONCLUSION: In this prospective study of frailty using a validated assessment tool, Risk Analysis Index scores decreased after parathyroid exploration surgery. When compared to total thyroidectomy patients, parathyroid exploration patients were also less likely to suffer a clinically meaningful ≥20% increase in Risk Analysis Index scores after surgery, suggesting that parathyroid exploration patients better maintained baseline health at final follow-up.

Is routine 24-hour urine calcium measurement useful during the evaluation of primary hyperparathyroidism?

BACKGROUND: Primary hyperparathyroidism and familial hypocalciuric hypercalcemia have similar biochemical profiles, and calcium-to-creatinine-clearance ratio helps distinguish the two. Additionally, 24-hour urine calcium >400 mg/day indicates surgery and guidelines recommend obtaining 24-hour urine calcium preoperatively. Our aim was to assess how 24-hour urine calcium altered care in the evaluation of suspected primary hyperparathyroidism. METHODS: Consecutive patients assessed for primary hyperparathyroidism from 2018 to 2020 were reviewed. Primary hyperparathyroidism was diagnosed by 2016 American Association of Endocrine Surgeons Parathyroidectomy Guidelines criteria. 24-hour urine calcium-directed change in care was defined as familial hypocalciuric hypercalcemia diagnosis, surgical deferment for additional testing, or 24-hour urine calcium >400 mg/day as the sole surgical indication. RESULTS: Of 613 patients, 565 (92%) completed 24-hour urine calcium and 477 (84%) had concurrent biochemical testing to calculate calcium-to-creatinine-clearance ratio. 24-hour urine calcium was <100 mg/day in 9% (49/565) and calcium-to-creatinine-clearance ratio was <0.01 in 17% (82/477). No patient had confirmed familial hypocalciuric hypercalcemia, although 1 had a CASR variant of undetermined significance. When calcium-to-creatinine-clearance ratio was <0.01, familial hypocalciuric hypercalcemia was excluded by 24-hour urine calcium >100 mg/day (56%), prior normal calcium (16%), renal insufficiency (11%), absence of familial hypercalcemia (3%), normal repeat 24-hour urine calcium (10%), or interfering diuretic (1%). 24-hour urine calcium-directed change in care occurred in 25 (4%), including 4 (1%) who had genetic testing. Four-gland hyperplasia was more common with calcium-to-creatinine-clearance ratio <0.01 (17% vs calcium-to-creatinine-clearance ratio ≥ 0.01, 4%, P < .001), but surgical failure rates were equivalent (P = .24). CONCLUSION: 24-hour urine calcium compliance was high, and results affected management in 4%, including productive identification of hypercalciuria as the sole surgical indication in 2 patients. When calcium-to-creatinine-clearance ratio <0.01, clinical assessment was sufficient to exclude familial hypocalciuric hypercalcemia and only 1% required genetic testing. 24-hour urine calcium should be ordered judiciously during primary hyperparathyroidism assessment.

How and when is multiglandular disease diagnosed in sporadic primary hyperparathyroidism?

BACKGROUND: In total, ∼15% of patients with sporadic primary hyperparathyroidism have multiglandular disease, which may be suspected preoperatively but can only be confirmed intra or postoperatively. The study aim is to determine how and when patients are diagnosed with multiglandular disease and to what extent different modalities contribute. METHODS: Consecutive cases of sporadic primary hyperparathyroidism (2013-2019) undergoing initial exploration were reviewed from a single-institution prospective database. Preoperative single-photon emission tomography/computed tomography and neck ultrasound were routinely performed to help direct either bilateral or unilateral exploration guided by intraoperative parathyroid hormone monitoring using the dual criteria. Multiglandular disease was defined as either resection of >1 enlarged parathyroid or hypercalcemia at ≥6 months after single gland resection. RESULTS: Of 1,890 patients with sporadic primary hyperparathyroidism, multiglandular disease was identified in 254 (13.4%); 244 (96.1%) were diagnosed intraoperatively and 10 (3.9%) postoperatively. In these multiglandular disease patients, single gland disease was suggested on single-photon emission tomography/computed tomography in 54.0%, ultrasound in 49.2%, and both were concordant for single gland disease in 29.4%. Intraoperative multiglandular disease diagnosis was prompted by an inadequate intraoperative parathyroid hormone monitoring drop in 38.5%, by surgeon interpretation of imaging in 38.1%, by observing ipsilateral gland enlargement in 11.0%, by finding an initial gland <200 mg in 10.3%, and 2.0% had unexpected multiglandular disease during thyroidectomy. Multiglandular disease was diagnosed by postoperative hypercalcemia in 10 of 254 patients (4.9%). CONCLUSION: To avoid failure at parathyroidectomy for primary hyperparathyroidism, expert surgeons use multiple approaches to diagnose and manage multiglandular disease. Preoperative localization studies alone are insufficient, missing multiglandular disease in at least 30% of cases. All examined adjuncts are informative, including intraoperative parathyroid hormone monitoring, imaging, and intraoperative visual cues.