The Evaluation and Management of Methimazole-Induced Agranulocytosis in the Pediatric Patient: A Case Report and Review of the Literature.

INTRODUCTION: Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of propylthiouracil (PTU) is also contraindicated. Few reports exist about the optimal alternative treatment regimens for the management of thyrotoxicosis in these medically complex patients in the pediatric population. CASE REPORT: We report prolonged saturated solution of potassium Iodide (SSKI) use (29 days) in a 17-year-old female with GD and MMI-induced agranulocytosis, who presented with septic shock. Her treatment course also included beta-blockade, cholestyramine, and granulocyte colony stimulating factor. We performed a review of the literature on the use of SSKI in the management of thyrotoxicosis, as well as best practices from the view of endocrinology, infectious disease, hematology, surgery, and intensivists, for the evaluation and management of MMI-induced agranulocytosis. DISCUSSION: The management of MMI-induced agranulocytosis and associated sequelae require subspecialty input and intensive evaluation and monitoring. Alternative treatments to manage hyperthyroidism and control symptoms of thyrotoxicosis during agranulocytosis are a bridge to definitive therapy, and include beta-blockade, SSKI, cholestyramine, steroids, lithium, and plasmapheresis.

Hyperparathyroidism in a Fracture Population.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that results in excess parathyroid hormone (PTH) secretion and hypercalcemia. PHPT is usually caused by an adenoma and its presentation is often asymptomatic, though it can negatively impact the skeleton via osteoporosis mostly affecting cortical bone and fracture. The diagnosis of PHPT is made by clinical presentation and biochemical and hormonal assessment. Surgical treatment guided by ultrasound sonography and/or 99mTc-sestamibi scintigraphy is generally curative. Normocalcemic hyperparathyroidism (NPHPT) is a variant of hyperparathyroidism defined by normal serum calcium and persistently elevated serum PTH levels. Limited data exist on NPHPT's effects on the skeleton, though current evidence suggests a positive correlation between the disorder and the presence of osteoporotic fractures. Taken together, patients affected by the various manifestations of hyperparathyroidism and their associated homeostatic disturbances represent a not insignificant portion of fracture patients seen in a fracture liaison service.

Unusual appearance of an adrenal ganglioneuroma.

Ganglioneuromas are rare tumors that occur spontaneously or arise from a poorly differentiated neuroblastic tumor. Although they are typically described in the pediatric population, they can occur in adults. Ganglioneuromas are often discovered incidentally and their typical imaging appearance, although non-specific, is that of a well-defined solid mass. We are presenting a case of a fat-containing adrenal lesion in a 53-year-old male. The extensive lipomatous changes within the lesion led to the presumption that it represented an adrenal myelolipoma. Pathology revealed a ganglioneuroma with extensive lipomatous changes. This is an uncommon presentation of an adrenal ganglioneuroma mimicking an adrenal myelolipoma. The diagnosis of an adrenal ganglioneuroma raises the possibility of syndromic associations for which patients may undergo genetic testing. We provide a review of typical imaging features of an adrenal ganglioneuroma and provide insight into the situations in which a ganglioneuroma can be suggested as a diagnostic consideration.

Post-thyroidectomy emergency room visits and readmissions: Assessment from the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP).

BACKGROUND: This study analyzed independent factors associated with post-thyroidectomy Emergency Room (ER) visits and Hospital Readmissions (HR). METHODS: This is a retrospective review from the CESQIP registry of 8381 thyroidectomy patients by 173 surgeons at 46 institutions. A total of 7142 ER visits and 7265 HR were analyzed. Multivariable logistic regression analysis was performed to determine the risk factors for an ER visit or HR. RESULTS: Within 30-days of surgery, rates of all ER visits were 3.4% (n = 250) and all HR were 2.3% (n = 170). Hypocalcemia was the reason for 21.9% of ER encounters and 36.4% of HR. BMI >40 kg/m2 was a risk factor for both ER visit (OR1.86) and HR (OR1.94). Surgical duration >3 h (OR2.63), and transection of recurrent laryngeal nerve (OR4.58) were risk factors for HR. CONCLUSIONS: Strategies to decrease hypocalcemia and improve perioperative care of patients with BMI >40 kg/m2 may improve post-thyroidectomy outcome.

Outpatient Total Thyroidectomy Is Safe for Moderate-Volume Surgeons.

Traditionally, total thyroidectomy (TT) was an inpatient procedure, but recent trends indicate that patients are often discharged on the day of surgery. This has been proven safe for high-volume surgeons but has not been studied for low (<10 TT per year) and moderate volume surgeons (<24 TT per year). Retrospective review was performed for 414 total thyroidectomies between 2005 and 2013. Emergency department visits and readmissions within 30 days of surgery were captured, but were considered the same for the purpose of this analysis. Patients were identified as outpatient if the day of discharge matched the day of surgery. The groups were compared based on demographic variables, comorbidities, postop calcium supplementation, and serum calcium. We found that moderate-volume surgeons were more likely to perform outpatient TT than low-volume surgeons (31.6% vs 6.0%, P < 0.001), but there was no correlation between length of stay and readmission (P = 0.688). Readmitted patients had lower postop serum calcium (8.3 mg/dL) than patients who were not readmitted (8.8 mg/dL, P = 0.006). Our data show that moderate-volume surgeons performing outpatient TT have an acceptable safety profile with respect to emergency department visits and hospital readmissions, and that same day discharge had no bearing on readmission.

Frozen section analysis in the post-Bethesda era.

BACKGROUND: The utility of frozen section (FS) for indeterminate thyroid nodules is controversial. In 2009, the Bethesda System for Reporting Thyroid Cytopathology was established to further subcategorize indeterminate fine-needle aspiration results (follicular lesions, FL) into Bethesda category 3 (BC3) and Bethesda category 4 (BC4). We hypothesize that FS will have less utility in the evaluation of BC3 lesions when compared to BC4. MATERIALS AND METHODS: A total of 479 patients who underwent thyroid lobectomy from January 2008 to July 2014 were retrospectively reviewed. Patients without appropriate Bethesda categorization were excluded. A total of 135 patients (65 FL, 45 BC3, 25 BC4) comprised the study groups. The sensitivity and specificity of FS within these three categories were determined. RESULTS: In the FL group, 6 of 65 patients were found to have thyroid cancer. Three were identified on frozen section (FS) resulting in a sensitivity and specificity of 50% and 100%, respectively. Thus, FS changed the operation in 3 of 65 cases (4.6%). In the BC3 group, 5 of 45 patients were found to have cancer. One was identified on FS resulting in a sensitivity and specificity of 20% and 100%, respectively. Thus, FS changed the operation in 1 of 45 patients (2.2%). In the BC4 group, 4 of 25 patients were found to have cancer. Two were identified on FS resulting in a sensitivity and specificity of 50% and 100% respectively. Thus, FS changed the operation in 2 of 25 patients (8%). CONCLUSIONS: There is improved utility of FS in BC 4 patients as 8% avoided reoperation. However, this benefit hinges on surgeon practice regarding the management of differentiated thyroid cancer >1 cm and <4 cm.

Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways.