Immunotherapy and Thyroid Dysfunction: Relevance to Nuclear Medicine.

We report a case of a 66-year-old woman with small cell lung cancer (stage IIB, T2N1M0), who received immunotherapy with nivolumab monthly for 2 months and then presented with thyrotoxic symptoms associated with suppressed thyroid-stimulating hormone levels and elevated free thyroid hormone levels, although previous thyrotropin performed 1 month ago was normal. Thyroid uptake and scan demonstrated diffusely decreased uptake in both thyroid lobes. The 4-hour percentage uptake was 0.7%, and the 24-hour percentage uptake was 0.3%. This was followed by development of hypothyroidism within few weeks. Findings suggested drug-induced thyroiditis secondary to nivolumab therapy.

Hypernatremic disorders in the intensive care unit.

Hypernatremia, defined as plasma sodium concentration >145 mEq/L, is frequently encountered in critically ill patients admitted to the intensive care unit (ICU). Hypernatremia indicates a decrease in total body water relative to sodium and is invariably associated with plasma hyperosmolality though total body sodium content may be normal, decreased, or increased. Hypernatremia usually occurs as a result of impaired thirst or access to water, with or without increased water losses from renal and extrarenal sources. Critically ill patients in ICU are at high risk of hypernatremia because of their inability to control free water intake as a result of sedation, intubation, change in mental status, and fluid restriction for various other reasons. In addition, excessive fluid losses from various renal or nonrenal sources and treatment with sodium containing fluids are commonly encountered in this population, predisposing them to hypernatremia. The consequences of hypernatremia result from osmotic movement of water across the cell membrane, leading to primarily intracellular and variable degree of extracellular volume depletion. The clinical features depend on severity and rapidity of hypernatremia development with abnormal cognitive and neuromuscular function in many cases and potential risk of hemorrhagic complications or death from vascular stretching and rupture in advanced cases. The management of hypernatremia focuses on judicious replacement of free water deficit to restore normal plasma osmolality as well as identification and correction of underlying causes of hypernatremia. Electrolyte-free water replacement is the preferred therapy though electrolyte (sodium) containing hypotonic fluids can also be used in some circumstances. Oral free water replacement guided by thirst is ideal though parenteral fluid replacement is usually necessary in critically ill ICU patients. Various calculations for estimating free water deficit are available and any can be used to guide initial fluid replacement therapy. Rate of correction depends on rapidity of hypernatremia development, though frequent monitoring of plasma sodium levels is essential to ensure appropriate response and to adjust the rate of fluid replacement to prevent the risk of cerebral edema from rapid correction of chronic hypernatremia. Free water requirements should be routinely assessed in ICU patients and judicious electrolyte and free water replacement prescribed for those at risk of hypernatremia.

Hypertension in people with diabetes and the metabolic syndrome: pathophysiologic insights and therapeutic update.

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are emerging as epidemics of the 21st century and are important components of the metabolic syndrome (MS). Evidence demonstrates a relationship between HTN, T2DM, and several vascular and metabolic abnormalities that are components of the MS. HTN affects nearly 70 million Americans and over one billion worldwide; likewise, the MS affects 44% of the US population above the age of 60 years and is rapidly increasing. HTN associated with the MS has certain pathophysiologic characteristics that provide clinical challenges. There is growing evidence that tissue activation of the renin-angiotensin system contributes to endothelial dysfunction, microalbuminuria, insulin resistance, and subsequent increased risk for cardiovascular and chronic kidney disease. The notion that HTN is a metabolic as well as a vascular disease provides a new treatment paradigm.

Bisphosphonates and osteonecrosis of the jaw: a retrospective study.

OBJECTIVE: To assess the prevalence of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonate therapy and in those who were bisphosphonate naïve. METHODS: We undertook a retrospective review of medical records of patients at the New York Harbor Health Care System from 1999 through 2004. Charts were selected for review if patients had a Current Procedural Terminology (CPT) code suggestive of ONJ or if they had ever received bisphosphonate therapy. RESULTS: Among 1,951 medical records reviewed, we identified 2 patients with ONJ who had received bisphosphonates and 2 patients with ONJ who were bisphosphonate naïve. Both patients treated with bisphosphonates had multiple myeloma and were receiving monthly infusions. They had initially received pamidronate before treatment was changed to zoledronic acid. In each case, ONJ was precipitated by a routine dental extraction. The prevalence of ONJ in our patient population receiving intravenously administered bisphosphonates was 1 in 71.5. Of the 2 cases of ONJ in bisphosphonate-naïve patients, osteoradionecrosis was clearly incriminated in 1 patient and potentially the causative factor in the other patient as well. No patients receiving orally administered bisphosphonates had ONJ, nor did this complication occur in any patients receiving parenteral bisphosphonate therapy for disorders such as osteoporosis or Paget's disease of bone. CONCLUSION: Bisphosphonates remain an important option for management of metabolic bone disease and complications of malignant disease. The overall prevalence of ONJ in patients receiving bisphosphonates seems to be very low; however, patients receiving intense parenteral therapy for an underlying malignant condition appear to have a uniquely elevated risk for the development of this complication. A causal relationship between bisphosphonates and ONJ remains to be proved and merits further investigation.

Therapeutic interventions for hypertension in metabolic syndrome: a comprehensive approach.

Hypertension is a major component of the metabolic syndrome and a major cardiovascular risk factor. Both disorders are rapidly increasing in frequency, with hypertension affecting nearly 60 million Americans and over 1 billion people worldwide, and metabolic syndrome affecting 44% of the US population above the age of 60 years. Sedentary lifestyle, together with obesity and aging of the population, are the major contributing factors for this growing epidemic. Hypertension in metabolic syndrome possesses unique pathophysiological aspects that have considerable implications on therapy of this disease. In this article, we review the pathophysiology and provide a rationale for the current therapeutic options in light of the most recent clinical trials in the field.

Antiepileptic drugs and bone metabolism.

Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

The case for low carbohydrate diets in diabetes management.

A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (<30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.

Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study.

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD.A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1.Among 3,206 patients identified, the mean age of the study population was 58.3 +/- 0.24 (Years +/- SEM) and the BMI was 30.6 kg/m2. 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03-0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87-0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007-1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites.There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women.