Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

A Rare Presentation of Infantile Virilization Secondary to Malignant Etiology.

Adrenocortical tumor is a rare malignancy (1-2/million) in children with a heterogenous presentation and generally poor prognosis. We report two cases of adrenocortical carcinoma who presented primarily with virilization along with cushingoid features and hypertension. Both children were managed with surgical resection of tumor, steroid replacement, and antihypertensives.

Arjuna's recollections - Part III (or) an endocrine version of the "Motorcycle Diaries".

The ultimate dream of every young student stepping into the hallowed portals of a medical college is to achieve the holy grail of medical education, a DM seat. However, the real battle begins only after the DM seat is won. The residency is a veritable roller coaster ride all through the three years, with the student alternating between exhilaration and despondency, wisdom and foolishness, hope and despair and ecstasy and agony. The long working hours, logistic difficulties, interpersonal conflicts and resource limitations are the anvils on which the callow postgraduates are beaten into shape, to bring to fore, their inner steel. While the DM residency does succeed in shaping the students into capable and empathic healthcare professionals of the highest order, on quite a few occasions, it leaves behind a host of bittersweet memories, that prompt the student to look back often, not with fondness, but with a sense of regret and heartache. Encompassing all these experiences, is an unvarnished first-hand account of my peregrinations as an endocrine resident at Osmania Medical College.

Type 1 diabetes: Syndromes in resource-challenged settings.

Type 1 Diabetes is a complex disorder that is made more complex by the myriad of co-morbid conditions associated with it. Mauriac Syndrome is a well-known but nowadays uncommon condition that presents with growth retardation secondary to poor glycaemic control. Limited Joint Mobility is an often-missed association of diabetes. Its importance lies in the fact that it can cause significant impairment of fine movements in T1DM children. It also indicates poor glycaemic control over a long period of time and can be used as a surrogate marker for development of diabetic microvascular complications. Anaemia in T1DM is protean and can develop due to a combination of nutritional factors, chronic renal disease, coeliac disease and worm infestation. Management is etiological. Vitamin deficiencies are ubiquitous in T1DM and if left untreated, can lead to neurological, haematological and skeletal dysfunction. The best-known co-morbid conditions are the local site reactions clubbed together under the moniker lipodystrophies. These can be either atrophic or hypertrophic and are usually due to repeated injections at the same site, improper technique and needle re-use. Management is often difficult and they are best prevented by appropriate diabetes education and emphasis on proper injection techniques at the time of T1DM diagnosis, with periodic reinforcement. Amyloidosis is a little known condition that shares a lot of features in common with the lipodystrophies and often needs to be differentiated from lipohypertrophy. T1DM is a disease which is often associated with a poor quality of life and these co-morbid conditions also need to be treated for effective general and psychological well-being.

Weight management in Ramadan.

Ramadan fasting is associated with significant weight loss in both men and women. Reduction in blood pressure, lipids, blood glucose, body mass index and waist and hip circumference may also occur. However, benefits accrued during this month often reverse within a few weeks of cessation of fasting, with most people returning back to their pre-Ramadan body weights and body composition. To ensure maintenance of this fasting induced weight loss, health care professionals should encourage continuation of healthy dietary habits, moderate physical activity and behaviour modification, even after conclusion of fasting. It should be realized that Ramadan is an ideal platform to target year long lifestyle modification, to ensure that whatever health care benefits have been gained during this month, are perpetuated.

The endocrine quiz.

With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject.

Hypothyroidism in pregnancy.

Pregnancy is a period that places great physiological stress on both the mother and the fetus. When pregnancy is compounded by endocrine disorders such as hypothyroidism, the potential for maternal and fetal adverse outcomes can be immense. While a lot of attention has been focused on the adverse fetal outcomes consequent to hypothyroidism, attention is also being gradually directed towards the adverse maternal outcomes of this disorder. Role of antibody positivity in influencing outcomes in a euthyroid woman, also needs further clarification. Prompt diagnosis and treatment of hypothyroidism in pregnancy is very essential. Subclinical hypothyroidism also needs to be detected and treated to prevent adverse outcomes, especially maternal. Since women with hypothyroidism during pregnancy, especially of the autoimmune variety might have a flare up of the disorder post-partum, or might continue to require thyroxine replacement post-partum, adequate follow-up is mandatory. While targeted case finding is generally practised, recent evidence seems to indicate that universal screening might be a better option. In conclusion, routine screening, early confirmation of diagnosis and prompt treatment. Allied with regular post-partum follow up, is required to ensure favourable maternal and fetal outcomes.

Prolactin and cancer: Has the orphan finally found a home?

Prolactin has, for long, been associated with galactorrhea and infertility in women while its role in men is largely unknown. Recently, expression of prolactin in various other tissues like the breast, prostate, decidua, and the brain has been recognized. This has led to evaluation of paracrine and autocrine actions of prolactin at these tissues and a possible role in development of various cancers. Increased expression of PRL receptors has also been implicated in carcinogenesis. Breast cancer has the strongest association with increased prolactin and prolactin receptor levels. Prostate cancer also has reported significant association, while the role of prolactin in colorectal, gynecological, laryngeal, and hepatocellular cancers is more tenuous. Prolactin/prolactin receptor pathway has also been implicated in development of resistance to chemotherapy. Thus, the effects of this pathway in carcinogenesis seem widespread. At the same time, they also offer an exciting new approach to hormonal manipulation of cancers, especially the treatment-resistant cancers.

Where do conventional OADs stand.

The last two decades have witnessed unprecedented activity in the field of OADs with many new drugs becoming available. Concerns with OAD include cardiovascular safety, fear about hypoglycemia, weight gain etc. In this article we attempt to review OADs , sulfonylureas in particular, in the light of the newer agents.

Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study.

PURPOSE: To assess if interval changes in metabolic status in normal cerebral tissue after radiation therapy (RT) can be detected by 2D CSI (chemical shift imaging) proton spectroscopy. MATERIALS AND METHODS: Eleven patients with primary brain tumors undergoing cranial radiation therapy (RT) were included. 2D-CSI MRS was performed before, during, and after the course of RT with the following parameters: TE/TR 144/1500 ms, field of view (FOV) 24, thickness 10 mm, matrix 16 x 16. The metabolic ratios choline/creatine (Cho/Cr), N-acetylaspartate (NAA)/Cr, and NAA/Cho in normal brain tissue were calculated. RESULTS: NAA/Cr and Cho/Cr were significantly decreased at week 3 during RT and at 1 month and 6 months after RT compared to values prior to RT (P < 0.01). The NAA/Cr ratio decreased by -0.19 +/- 0.05 (mean +/- standard error [SE]) at week 3 of RT, -0.14 +/- 0.06 at the last week of RT, -0.14 +/- 0.05 at 1 month after RT, and -0.30 +/- 0.08 at 6 months after RT compared to the pre-RT value of 1.43 +/- 0.04. The Cho/Cr ratio decreased by -0.27 +/- 0.05 at week 3 of RT, -0.11 +/- 0.05 at the last week of RT, -0.26 +/- 0.05 at 1 month after RT and -0.25 +/- 0.07 at 6 months after RT from the pre-RT value of 1.29 +/- 0.03. Changes in Cho/Cr were correlated with the interaction of the radiation dose and dose-volume at week 3 of RT, during the last week of RT (P < 0.005), and at 1 month after RT (P = 0.017). CONCLUSION: The results of this study suggest that MRS can detect early metabolic changes in normal irradiated brain tissue.

Estimating blood-brain barrier opening in a rat model of hemorrhagic transformation with Patlak plots of Gd-DTPA contrast-enhanced MRI.

Patlak plot processing of Gd-shifted T1 relaxation-time images from a rat model of hemorrhagic transformation yielded estimates and maps of the blood-to-brain influx rate constant of Gd-DTPA (K1). The Patlak plots also produced a heretofore unrecognized parameter, the distribution space of the intravascular-Gd-shifted protons (Vp), an index of blood-to-tissue transfer of water. The K1 values for Gd-DTPA were very high for the regions of blood-brain barrier (BBB) opening and were similar to those of 14C-sucrose concurrently obtained by quantitative autoradiographic (QAR) analysis. In these same ROI's, Vp was five-fold greater than normal, which suggests that the permeability of the BBB to water was also increased. The 14C-sucrose space of distribution in the ischemic ROI's was around 8%, thus indicating a sizable interstitial space. The spatial resolving power of Gd-DTPA-deltaT1 imaging was rather good, although no match for 14C-sucrose-QAR. This study shows that quantitative deltaT1-MRI estimates of regional blood-brain transfer constants of Gd-DTPA and water distribution are possible when Patlak plots are employed to process the data. This approach may be useful for tracking the time-course of BBB barrier function in both animals and humans.

Functional MRI-BOLD of brainstem structures during visually triggered migraine.

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.

Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness?

OBJECTIVE: The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2' in the PAG, red nucleus (RN), and substantia nigra (SN). R2' is a measure of non-heme iron in tissues. METHODS: Seventeen patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla magnetic resonance imaging system. For each subject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2' (R2* - R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2' values of the EM, CDH, and N groups were compared using analysis of variance, Student t test, and correlation analysis. RESULTS: In the PAG, there was a significant increase in mean R2' and R2* values in both the EM and CDH groups (P<.05) compared with the N group, but no significant difference in these values was demonstrated between the EM and CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2' in the EM and CDH groups. A decrease in mean R2' and R2* values also was observed in the RN and SN of the CDH group compared with the N and EM groups (P<.05), explained best by flow activation due to head pain. CONCLUSIONS: Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeated migraine attacks. These results support and emphasize the role of the PAG as a possible "generator" of migraine attacks, potentially by dysfunctional control of the trigeminovascular nociceptive system.

Automated three-dimensional signature model for assessing brain injury in emergent stroke.

This presentation will focus on the value of established and newer MR methods that can be applied to the diagnosis and management of ischemic stroke with emphasis on future applications of MR to provide previously unmet needs of the treating clinician and clinical trials. Time alone is an inadequate indicator of the therapeutic window, especially when the time of stroke onset is uncertain. Thus, there is a need to predict the evolution of stroke in a way that more precisely and with greater resolution identifies the progression of cellular damage at the moment of investigation. This also would be of value for thrombolysis when knowledge of the degree and extent of tissue necrosis and the consequent potential for brain hemorrhage is of the utmost importance. To provide this, we perform postprocessing of diffusion-, T(1)- and T(2)-weighted images to produce the apparent diffusion coefficient of water, and T(1) and T(2) maps that are then further processed to provide maps and quantitation of the tissue signatures of ischemic histopathology. By these means, we can accomplish objective volumetric analysis of infarct size and of the proportions of potentially viable and salvageable tissue. We will show how this has the potential to predict long-term stroke outcome and facilitate decision-making in terms of safety of reperfusion strategies and the appropriateness of cytoprotective treatment. The value of our approach is to replace time as the therapeutic window and extend the opportunity of treatment to those patients presenting beyond the stringent time limits employed in current investigative clinical trials. Further, used as a surrogate marker of clinical outcome, this form of stroke analysis may speed proof of principle clinical trials in small numbers of stroke patients.

Magnetic resonance assessment of acute and chronic stroke.

This article describes the important role of magnetic resonance imaging (MRI) in noninvasively assessing human focal ischemic stroke. Conventional MRI, diffusion-weighted and/or perfusion-weighted imaging have been used to facilitate both the qualitative and quantitative evaluation of heterogeneity of ischemic brain tissue. Further, by combining 2 or more magnetic resonance parameters, tissue-signature models have been developed that may be used as surrogate markers of tissue histopathology to characterize ischemic tissue as salvageable, necrotic, or tissue in transition to necrosis. Magnetic resonance tissue-signature models and results are presented. Dynamic changes in the evolution of ischemic tissue to infarction are also discussed. Recovery from acute stroke was studied with blood oxygenation level-dependent functional MRI to investigate the neural mechanisms for recovery from aphasia after stroke.

Time course of ADCw changes in ischemic stroke: beyond the human eye!

BACKGROUND AND PURPOSE: Using newly developed computerized image analysis, we studied the heterogeneity of apparent diffusion coefficient of water (ADCw) values in human ischemic stroke within 10 hours of onset. METHODS: Echo-planar trace diffusion-weighted images from 9 patients with focal cortical ischemic stroke were obtained within 10 hours of symptom onset. An Iterative Self-Organizing Data Analysis (ISODATA) clustering algorithm was implemented to segment different tissue types with a series of DW images. ADCw maps were calculated from 4 DW images on a pixel-by-pixel basis. The segmented zones within the lesion were characterized as low, pseudonormal, or high, expressed as a ratio of the mean+/-SD of ADCw of contralateral noninvolved tissue. RESULTS: The average ADCW in the ischemic stroke region within 10 hours of onset was significantly depressed compared with homologous contralateral tissue (626.6+/-76.8 versus 842.9+/-60.4x10(-6) mm2/s; P<0.0001). Nevertheless, ISODATA segmentation yielded multiple zones within the stroke region that were characterized as low, pseudonormal, and high. The mean proportion of low:pseudonormal:high was 72%:20%:8%. CONCLUSIONS: Despite low average ADCW, computer-assisted segmentation of DW MRI detected heterogeneous zones within ischemic lesions corresponding to low, pseudonormal, and high ADCw not visible to the human eye. This supports acute elevation of ADCw in human ischemic stroke and, accordingly, different temporal rates of tissue evolution toward infarction.