Primary Sellar Neuroblastoma Masquerading as a Pituitary Macroadenoma.

Olfactory neuroblastomas, or esthesioneuroblastomas, are rare and aggressive malignant tumors that typically arise from the olfactory neuroepithelium in the upper nasal cavity. In rare instances, they can be ectopic originating from areas outside the upper nasal cavity such as the sellar region. These tumors, also known as primary sellar neuroblastomas, may be mistaken for pituitary macroadenomas. We present a rare case of a primary sellar neuroblastoma in a 30-year-old woman with a prior diagnosis of presumed prolactinoma, status post transsphenoidal resection, with residual visual deficits, who presented with worsening vision and headaches. Pituitary magnetic resonance imaging showed a large sellar mass causing compression of the optic chiasm, and invasion of the right cavernous sinus and bilateral cavernous internal carotid arteries. The patient underwent a second transsphenoidal resection. Postoperatively, she developed central adrenal insufficiency, central hypothyroidism, central hypogonadism, and transient syndrome of inappropriate antidiuretic hormone secretion. Owing to rapid tumor regrowth, she underwent a craniotomy with plans for radiation treatment. This condition is challenging to diagnose and has poorly defined clinical management guidelines. An early, aggressive approach with surgical intervention is recommended.

Simultaneous Presentation of Secondary Adrenal Insufficiency and Primary Hypothyroidism due to Pembrolizumab: A Case Report.

Checkpoint inhibitors have gained increased traction in recent years as they have improved prognosis in various malignancies. Pembrolizumab, an anti-programmed cell death protein (PD-1) monoclonal antibody, has become a first-line chemotherapeutic agent for stage II non-small cell lung cancer since 2019. Although much more common with nivolumab, several immune-related adverse effects, particularly endocrinopathies, have been linked with pembrolizumab. We describe a case of a 59-year-old man with a history of unspecified lung cancer who presented with severe hyponatremia later attributed to secondary adrenal insufficiency and accompanying primary hypothyroidism secondary to pembrolizumab. Diagnosing adrenal insufficiency in patients on immune checkpoint inhibitors like pembrolizumab can be challenging due to nonspecific symptoms, making it crucial to rule out other causes of hyponatremia. Immunotherapy is known to cause thyroid immune-related adverse events, and anti-thyroid antibodies may not always be present in the diagnosis of hypothyroidism. Although there are some reported cases of pembrolizumab-induced adrenal insufficiency, the link between immunotherapy and endocrine disorders remains unclear. To our knowledge, no case reports exist that describe both primary hypothyroidism and secondary adrenal insufficiency after taking pembrolizumab, although such cases have been documented with axitinib. Timely diagnosis and treatment of adrenal insufficiency is crucial to prevent adverse effects, especially in patients with cancer receiving immunotherapy, as highlighted in this case.

Ischemic stroke: a rare complication of a large multinodular goiter.

Summary: Mass effect from a goiter is a serious complication with potentially life-threatening consequences. In rare instances, a goiter can compress nearby vessels, compromising cerebral blood flow, which can lead to an ischemic stroke. Ischemic strokes generally occur due to atherogenic or embolic phenomenon, albeit a rare etiology can be due to a mechanical obstruction of great vessels of the neck that provide blood supply to the brain. An unusual example of a similar obstruction is the mass effect of an expansive goiter on the carotid artery (CA) in the neck. We present a rare case of a 90-year-old female who had a historically untreated goiter for 13 years. She presented with symptoms of acute stroke, including right-sided weakness and dysarthria. CT angiogram of the neck revealed a massively enlarged thyroid gland causing compression and intermittent obstruction of the blood flow in the left common CA. Subsequently, the patient underwent a total thyroidectomy. Postoperatively, she had a remarkable recovery of her symptoms of right-sided weakness and dysarthria. Acknowledging stroke as a grave mechanical complication of a large multinodular goiter is crucial for timely and appropriate management to avoid serious consequences. Learning points: The natural history of euthyroid multinodular goiters include abnormal enlargement of the thyroid gland, which results in local compression of structures in the neck causing neurovascular injury. Timely diagnosis and surgical management of an enlarging goiter compressing the CA can reduce morbidity from an ischemic stroke. Ischemic stroke is a rare and dangerous complication of a giant multinodular goiter.

IMPACT OF MULTIDISCIPLINARY PROCESS IMPROVEMENT INTERVENTIONS ON GLUCOMETRICS IN A NONCRITICALLY ILL SETTING.

Objective: This study aimed to assess the impact of multidisciplinary process improvement interventions on glycemic control in the inpatient setting of an urban community hospital, utilizing the daily simple average as the primary glucometric measure. Methods: From 2010-2014, five process of care interventions were implemented in the noncritical care inpatient units of the study hospital. Interventions included education of medical staff, implementation of hyperglycemia and hypoglycemia protocols, computerized insulin order entry, and coordination of meal tray delivery with finger stick and insulin administration. Unpaired t tests compared pre- and postintervention process measures. Simple average daily glucose measure was the primary glucometric outcome. Secondary outcome measures included frequency of hyperglycemia and hypoglycemia. Glucose outcomes were compared with an in-network hospital that did not implement the respective interventions. Results: A total of 180,431 glucose measurements were reported from 4,705 and 4,238 patients from the intervention and comparison hospitals, respectively. The time between bolus-insulin administration and breakfast tray delivery was significantly reduced by 81.7 minutes (P<.00005). The use of sliding scale insulin was sustainably reduced. Average daily glucose was reduced at both hospitals, and overall rates of hypoglycemia were low. Conclusion: A multidisciplinary approach at an urban community hospital with limited resources was effective in improving and sustaining processes of care for improved glycemic control in the noncritical care, inpatient setting. Abbreviations: IQR = interquartile range; JMC = Jacobi Medical Center; NCBH = North Central Bronx Hospital.

Treatment of Diabetic Autonomic Neuropathy in Older Adults with Diabetes Mellitus.

OBJECTIVE: To review the epidemiology, pathophysiology, screening and diagnosis, and optimal treatment of diabetic autonomic neuropathy (DAN) and its implications in older adults. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, DATA SYNTHESIS: A search of PubMed using the Mesh terms "diabetes," "type 1," "insulin-dependent," "T1DM," and "diabetic autonomic neuropathy" was performed to find relevant primary literature. Additional search terms "epidemiology," "geriatric," and "risk" were employed. All English-language articles from 2005 to 2015 appearing in these searches were reviewed for relevance. Related articles suggested in the PubMed search and clinical guidelines from the American Diabetes Association and the American Association of Clinical Endocrinologists were reviewed. These uncovered further resources for risk stratification, pathophysiology, diagnosis, and treatment of DAN. DAN is highly prevalent in the diabetes population and increases the risk of morbidity and mortality in older adults, yet, often goes undiagnosed and untreated. Treatment of DAN is complex in the older adult because of poor tolerability of many pharmacologic treatment options; therefore, great care must be taken when selecting therapy as to avoid unwanted adverse effects. CONCLUSION: With increasing life-expectancy of patients with diabetes mellitus, awareness of DAN and its implications to older adults is needed in primary care. Consistent screening and appropriate treatment of DAN in older adults with diabetes mellitus is essential in helping to maintain functional status and avoid adverse events.

Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes.

The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments.

Sensitive quantitative analysis of C-peptide in human plasma by 2-dimensional liquid chromatography-mass spectrometry isotope-dilution assay.

BACKGROUND: Isotope-dilution assays (IDAs) are well established for quantification of metabolites or small drug molecules in biological fluids. Because of their increased specificity, IDAs are an alternative to immunoassays for measuring C-peptide. METHODS: We evaluated a 2-dimensional liquid chromatography-mass spectrometry (2D LC/MS) IDA method. Sample preparation was by off-line solid-phase extraction, and C-peptide separation was performed on an Agilent 1100 2D LC system with a purification method based on high-pressure switching between 2 high-resolution reversed-phase columns. Because of the low fragmentation efficiency of C-peptide, multiple-reaction monitoring analysis was omitted and selective-ion monitoring mode was chosen for quantification. Native and isotope-labeled ([M+18] and [M+30]) C-peptides were monitored in the +3 state at m/z 1007.7, 1013.7, and 1017.7. RESULTS: The assay was linear (r(2) = 0.9995), with a detection limit of 300 amole (1 pg) on column. Inter- and intraday CVs for C-peptide were < or =2%. Comparison with an established polyclonal-based RIA showed high correlation (r = 0.964). Plasma concentrations of total C-peptide measured by RIA were consistently higher than by IDA LC/MS, consistent with the higher specificity of IDAs compared with immunoassays. CONCLUSIONS: The 2D LC/MS IDA approach eliminates matrix effects, enhancing assay performance and reliability, and has a detection limit 100-fold lower than any previously reported LC/MS method. Isotope-labeled C-peptide(s) can be clearly differentiated from endogenous C-peptide by the difference in m/z ratio, so that both peptides can be quantified simultaneously. The method is highly precise, robust, and applicable to pharmacokinetic detection of plasma peptides.

Sensitive LC MS quantitative analysis of carbohydrates by Cs+ attachment.

The development of a sensitive assay for the quantitative analysis of carbohydrates from human plasma using LC/MS/MS is described in this paper. After sample preparation, carbohydrates were cationized by Cs(+) after their separation by normal phase liquid chromatography on an amino based column. Cesium is capable of forming a quasi-molecular ion [M + Cs](+) with neutral carbohydrate molecules in the positive ion mode of electrospray ionization mass spectrometry. The mass spectrometer was operated in multiple reaction monitoring mode, and transitions [M + 133] --> 133 were monitored (M, carbohydrate molecular weight). The new method is robust, highly sensitive, rapid, and does not require postcolumn addition or derivatization. It is useful in clinical research for measurement of carbohydrate molecules by isotope dilution assay.

The thyrotropin reference range should remain unchanged.

CONTEXT: Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis. STUDY SUBJECTS: The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease. INTERVENTION: The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months. RESULTS: About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine. CONCLUSION: Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr.

Acute elevation of NEFA causes hyperinsulinemia without effect on insulin secretion rate in healthy human subjects.

Increased circulating levels of nonesterified free fatty acids (NEFA) have been observed in such hyperinsulinemic states as obesity, impaired glucose tolerance, diabetes, and dyslipidemia where they have been causally linked to the development of insulin resistance and hyperinsulinemia. The concentration of NEFA in plasma is believed to have direct modifying effects on insulin secretion and clearance. It remains controversial whether acute increases in NEFA potentiate insulin secretion in human subjects. We studied the effect of an acute elevation of NEFA during lipid-heparin infusion compared to a glycerol-only control on glucose-stimulated insulin secretion and clearance during a 120-min hyperglycemic (10 mM) clamp in 7 healthy normoglucose-tolerant volunteers. The metabolic clearance rate of C-peptide (MCR(CP)) was measured in each subject during the study by simultaneous infusion of C-peptide. Insulin secretion rate (ISR) was calculated from deconvolution of C-peptide data after correction for the rate of C-peptide infusion. Clearance rate of insulin (MCR(INS)) was calculated based upon endogenous ISR. Plasma glucose (mg/dL): basal (90-115 min) 90.2 +/- 2.8 vs. 90.2 +/- 2.3; clamp (150-240 min) 180.5 +/- 2.8 vs. 180.9 +/- 1.3. Plasma insulin (pmol/L): prebasal (fasting) 29.6 +/- 10.0 vs. 29.8 +/- 10.6; basal (90-115 min) 30.1 +/- 9.2 vs. 34.5 +/- 12.1; second phase clamp (210-240 min) 127.6 +/- 18.2 vs. 182.5 +/- 17.3*. Plasma NEFA (mM): prebasal 0.47 +/- 0.08 vs. 0.52 +/- 0.09; basal 0.35 +/- 0.05 vs. 0.98 +/- 0.02*; clamp (122-240 min) 0.06 +/- 0.02 vs. 0.77 +/- 0.06*. ISR (pmol/min): prebasal 72.7 +/- 7.5 vs. 72.0 +/- 7.9; second phase clamp (210-240 min) 268.5 +/- 27.2 vs. 200.2 +/- 23.7. MCR(INS) (mL/min): prebasal 3393 +/- 488 vs. 3370 +/- 511; clamp 2284 +/- 505 vs. 1214 +/- 153* (*p < 0.05 glycerol vs. intralipid/heparin). This study demonstrates that acute NEFA elevation causes hyperinsulinemia due to a significant decrease in systemic insulin clearance without increasing rates of insulin secretion.