Alaleh Mazhari

A primer on concentrated insulins: what an internist should know

ABSTRACT The common insulin concentration in most preparations of insulin is 100 units per mL or U-100. Human regular U-500 insulin was the first concentrated insulin introduced and it has been available in the United States since the 1950s. Humulin R is the only human regular U-500 available on the market. Human regular U-500 is five times more concentrated than U-100 and because of its pharmacodynamic properties, works as both a basal and a bolus insulin. Human regular U500 allows for delivery of a larger insulin dose with a smaller volume leading to better absorption compared to U-100 and has traditionally been used in patients with moderate to severe insulin resistance. More recently other forms of concentrated insulin have become available and the newer concentrated insulin preparations can be used in diabetic patients with or without insulin resistance. Our intent is to provide primary care physicians with a review of the pharmacology and current literature on concentrated insulins as well as recommendations for patient selection, dose initiation, and dose adjustment.

Neurology of the pituitary

The anterior pituitary hormones are essential for reproduction, growth, metabolic homeostasis, stress response, and adaptation to changes in the external environment. Each pituitary hormone is secreted in a distinctive pulsatile manner reflecting its regulation by the central nervous system through a complex interaction between hypothalamic neuroendocrine pathways, feedback effects from peripheral target gland hormones, and intrapituitary mechanisms. While the most common cause of a pituitary mass is an adenoma, the differential diagnosis is broad and includes pituitary hyperplasia, lymphocytic hypophysitis, craniopharyngioma among others. Patients with pituitary adenomas can be asymptomatic or present with symptoms due to mass effect, pituitary hormone dysfunction, or both. Prolactinomas represent 40% of pituitary adenomas, the majority of which are microadenomas. Hyperfunction of growth hormone and ACTH are far less common, while TSH-producing tumors are exceedingly rare. Hypopituitarism in patients with pituitary adenomas can be partial or complete. The clinical picture will depend on the type, degree, and rapidity of onset of pituitary hormone deficiency. An MRI specifically focused on the sellar region is the imaging modality of choice to detect pituitary pathology. Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness.

Effect of Silicone Gluteal Implant on Bone Mineral Density Evaluation by DXA Scan

Aamna Hassan,* Erin Grady, Joseph Ringelstein, James R. Halama, Alaleh Mazhari, and Nicholas C. Friedman Department of Nuclear Medicine, Hines VA Medical Center, Hines, IL, USA; Department of Nuclear Medicine, Loyola University Medical Center, Maywood, IL, USA; Department of Radiology, Section of Nuclear Medicine, Loyola University Medical Center, Maywood, IL, USA; and Department of Endocrinology, Loyola University Medical Center, Maywood, IL, USA

SELECTIVE HYPOALDOSTERONISM: A REVIEW.

OBJECTIVE Selective hypoaldosteronism (SH) is a condition manifested by hyperkalemia due to low aldosterone secretion with normal cortisol. One of the obstacles in diagnosis is the awareness of the condition itself. The objective of this review is to highlight what is known about the epidemiology, pathophysiology, etiology, presentation, diagnosis, and treatment of SH. METHODS Literature search was performed on PubMed and Ovid Medline for articles which contained hypoaldosteronism as a major topic. RESULTS The recent literature on this topic is surprisingly limited. Few recent review articles were found, none of which were in English and less than 5 years old. Case reports and genetic literature were also included in this review, as they contain the most recent reports of SH in the literature. CONCLUSION Awareness about SH will hopefully help physicians to identify patients at risk as well as decide on treatment if any therapy is required.

Cathepsins K and S: Role in Bone, Adipocytes, and Glucose Regulation

Cathepsins are a diverse group of proteases that are increasingly being recognized for their role in various disease states. The focus of this article is to review the data regarding the activity of cathepsin K and cathepsin S in adipocyte differentiation and function as well as glucose metabolism. Data from animal and human studies have shown up-regulation of cathepsin K expression in white adipose tissue of overweight/obese mice and humans. Cathepsin K appears to affect adipocyte differentiation as well as weight gain. Data from studies using cathepsin K blocking agents suggest that by blocking cathepsin K, there is reduction in adipocyte differentiation and weight gain. Cathepsin K also may play a role in glucose metabolism with higher cathepsin K levels being associated with insulin resistance. Cathepsin S is also overexpressed in adipose tissue of overweight/obese subjects. Both murine and human models have been studied to further investigate its role in adipocytes and obesity. Cathepsin S appears to be involved in glucose dysregulation as well as pathogenesis of diabetes mellitus. Further studies are necessary to better characterize the role of cathepsin K and S and to examine whether there is potential for targeted therapy for prevention and treatment of obesity as well as diabetes mellitus.

Response to: ‘Pharmacokinetic/pharmacodynamic properties and efficacy/safety of U-500R from randomized clinical studies’

We thank the authors of the letter to the editor for the information provided regarding the article we recently published in Postgraduate Medicine [1]. We are grateful to have received the insightful paper on the pharmacokinetics and pharmacodynamics of human regular U-500 insulin and human regular U-100 insulin [2]. We were remiss in not including this data suggesting no absorption difference to balance information from other authors that there is an absorption advantage to human regular U-500 insulin. The letter to the editor states ‘These properties of U-500 R are unique and cannot be equated to those of intermediate-acting human neutral protamine Hagedorn (NPH) insulin [4], contrary to what was stated in the review [1].’ The properties referred to are the time course of action of the two insulins. Actually, we did not equate the two but rather stated that the two insulins were similar in time course of action, which they are. The randomized controlled trial, to which the author(s) of the letter refer, was e-published in January of 2016 which is after our paper was submitted [3]. We do acknowledge, however, that the Hood et al. [4] initial data was inadvertently not referenced in our paper. The ranges of therapeutic options described in our paper include both the two and three time per day dosing regimen compared in the RCT. Sincerely, Barnosky A, Shah L, Meah F, Emanuele N, Emanuele MA, Mazhari A Declaration of interest