Persistent Insulin Autoimmune Syndrome in a Caucasian Male in the Absence of Triggers.

Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence of insulin autoantibodies (IAAs) in patients who were never exposed to exogenous insulin and with no evidence of pancreatic abnormalities. IAS is much more frequent in East Asians, especially the Japanese population, compared to the lower incidence in Caucasians. However, it can be associated with other autoimmune diseases or drug use like methimazole and alpha-lipoic acid (ALA). We report a case of a 47-year-old Caucasian male presenting with a 12-month history of worsening episodes of fasting and post-prandial hypoglycemia associated with symptoms of dizziness, tremors, palpitations, and unconsciousness associated with hypoglycemia. Symptoms resolved with the administration of carbohydrate-containing foods, establishing Whipple's triad. At an outside facility, he had initial labs that showed elevated insulin levels (141 µU/ml) with normal glucose, C-peptide, and proinsulin levels, but there was no availability of an IAA lab assay. Given his symptoms, severity, and frequency of hypoglycemia, he was admitted to the hospital for a 72-hour fast, which showed the lowest glucose level of 64 mg/dl with inappropriately high insulin of 22.2 µU/ml, low C-peptide of 0.57 ng/ml, and undetectable proinsulin of <1.6 pmol/L, but with IAA being >50 U/ml (0.0-0.4 U/ml). He was treated with intensive dietary counseling with a low-carbohydrate diet and prednisone 20 mg twice daily initially. Additionally, he could not tolerate octreotide, diazoxide, and acarbose due to side effects. He is currently on prednisone 10 mg daily and nifedipine with no further hypoglycemic episodes, but still has a high IAA of >50 U/ml and serum insulin levels of 70-112 µU/ml. Our case highlights the importance of recognizing hypoglycemia and checking for IAA levels as first-line diagnostic tests, in the absence of which there could be a delay in diagnosis and leading to unnecessary lab and imaging testing. Our case is unique since it happened in a Caucasian without any prior exposure to a triggering factor and has not undergone self-remission yet, which happens in most of IAS cases.

Extra-pulmonary Cutaneous Sarcoidosis Presenting With Granulomatous Cranial Lesions and Cardiac Complications: A Case Report.

Sarcoidosis is a non-caseating granulomatous disorder affecting multiple organs. Although the lungs are the most common site of presentation, extra-pulmonary manifestations involving the skin and heart can occur. Sarcoidosis affecting skull bone is uncommon and involvement of skin, heart, and skull bone all together, without pulmonary manifestations, is extremely rare. We report a 63-year-old Caucasian woman with a past history of cutaneous sarcoidosis and granulomatous skull bone lesions who presented with recurrent syncope. An ambulatory cardiac monitor detected intermittent high-grade atrioventricular block and cardiac MRI confirmed the diagnosis of cardiac sarcoidosis. This case represents an extremely unique journey of sarcoidosis and suggests potential consideration for cardiac sarcoidosis screening in patients with a history of extra-cardiac manifestations.

Coexistence of a Calcium-Sensing Receptor Mutation and Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the main differential diagnoses in a patient presenting with parathyroid hormone (PTH)-mediated hypercalcemia. PHPT is most often caused by a single-gland parathyroid adenoma and FHH is the result of an inactivating mutation of the calcium-sensing receptor (CaSR) gene. In this paper, we present a unique case of the co-existence of an inactivating CaSR gene mutation and PHPT due to a single-gland parathyroid adenoma. The patient is a 67-year-old female with a history of recurrent nephrolithiasis who presented with hypercalcemia, elevated PTH level, and hypocalciuria. As a result of the patient's hypocalciuria, familial hypocalciuric hypercalcemia was suspected, and genetic testing was pursued. CaSR gene analysis revealed a heterogeneous inactivating mutation of the CaSR gene. Additionally, nuclear imaging with technetium sestamibi revealed a large focus of activity on the right side of the neck suspicious of a parathyroid adenoma. This was resected and confirmed to be a hypercellular parathyroid adenoma. Two years after her surgery, the patient continues to have normal calcium levels with no further episodes of nephrolithiasis. She is currently undergoing treatment for osteoporosis and is being periodically monitored for recurrence of hypercalcemia due to the presence of the inactivating CaSR gene mutation. This case highlights an exceedingly rare case of a patient with both an inactivating CaSR gene mutation and PHPT due to a single parathyroid adenoma, and it underscores the importance of further research to determine any potential relationship between the two.

The Role of Gut Microbiome Supplementation in COVID-19 Management.

COVID-19, which is caused by the RNA virus, SARS-CoV-2, mainly affects the respiratory system and has a varied clinical presentation. However, several studies have shown that COVID-19 can also affect the gastrointestinal (GI) system. Patients can experience various GI symptoms, such as vomiting and diarrhea, and the virus has been detected in the stool samples of patients hospitalized with COVID-19. There have also been rare reports of COVID-19 presenting with isolated GI symptoms and lack of respiratory symptoms, and the virus has also been detected for prolonged periods in the fecal samples of COVID-19 patients. Major alterations in the gut microbiome in the form of depletion of beneficial organisms and an abundance of pathogenic organisms have been reported in the fecal samples of hospitalized COVID-19 patients. Although the US FDA has approved several drugs to manage COVID-19, their efficacy remains modest. So, there is a constant ongoing effort to investigate novel treatment options for COVID-19. Health supplements like probiotics, prebiotics, postbiotics, and synbiotics have been popularly known for their various health benefits. In this review, we have summarized the current literature, which shows the potential benefit of these health supplements to mitigate and/or prevent the clinical presentation of COVID-19.

Gut microbiome supplementation as therapy for metabolic syndrome.

The gut microbiome is defined as an ecological community of commensal symbiotic and pathogenic microorganisms that exist in our body. Gut microbiome dysbiosis is a condition of dysregulated and disrupted intestinal bacterial homeostasis, and recent evidence has shown that dysbiosis is related to chronic inflammation, insulin resistance, cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM), and obesity. It is well known that obesity, T2DM and CVD are caused or worsened by multiple factors like genetic predisposition, environmental factors, unhealthy high calorie diets, and sedentary lifestyle. However, recent evidence from human and mouse models suggest that the gut microbiome is also an active player in the modulation of metabolic syndrome, a set of risk factors including obesity, hyperglycemia, and dyslipidemia that increase the risk for CVD, T2DM, and other diseases. Current research aims to identify treatments to increase the number of beneficial microbiota in the gut microbiome in order to modulate metabolic syndrome by reducing chronic inflammation and insulin resistance. There is increasing interest in supplements, classified as prebiotics, probiotics, synbiotics, or postbiotics, and their effect on the gut microbiome and metabolic syndrome. In this review article, we have summarized current research on these supplements that are available to improve the abundance of beneficial gut microbiota and to reduce the harmful ones in patients with metabolic syndrome.

Gut microbiota interactions with anti-diabetic medications and pathogenesis of type 2 diabetes mellitus.

Microorganisms including bacteria, viruses, protozoa, and fungi living in the gastrointestinal tract are collectively known as the gut microbiota. Dysbiosis is the imbalance in microbial composition on or inside the body relative to healthy state. Altered Firmicutes to Bacteroidetes ratio and decreased abundance of Akkermansia muciniphila are the predominant gut dysbiosis associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and metabolic syndrome. Pathophysiological mechanisms linking gut dysbiosis, and metabolic diseases and their complications include altered metabolism of short-chain fatty acids and bile acids, interaction with gut hormones, increased gut microbial metabolite trimethylamine-N-oxide, bacterial translocation/Leaky gut syndrome, and endotoxin production such as lipopolysaccharides. The association between the gut microbiota and glycemic agents, however, is much less understood and is the growing focus of research and conversation. Recent studies suggest that the gut microbiota and anti-diabetic medications are interdependent on each other, meaning that while anti-diabetic medications alter the gut microbiota, the gut microbiota also alters the efficacy of anti-diabetic medications. With increasing evidence regarding the significance of gut microbiota, it is imperative to review the role of gut microbiota in the pathogenesis of T2DM. This review also discusses the interaction between gut microbiota and the various medications used in the treatment of T2DM.

Real-time continuous glucose monitoring improves glycemic control and reduces hypoglycemia: Real-world data.

AIM: To study the effect of real time continuous glucose monitor (RT-CGM) use on glycemic parameters in patients with diabetes mellitus (DM) in real world practice. METHODS: We retrospectively studied 91 adult subjects with DM who had been using Dexcom™ RT-CGM. Two consecutive hemoglobin A1c (HbA1c), both prior to and after at least 3 months of RT-CGM initiation, were collected. A total of 31 subjects completed a 5-14 day user blinded CGM using a Freestyle Libre™ prior to RT-CGM initiation. The first two week period following at least 3 months use of RT-CGM was analyzed for CGM metrics. RESULTS: A total of 51.6 % of subjects had T1DM, 34.1 % used continuous subcutaneous insulin infusion (CSII), and 62.6 % had DM for > 10 years. Both HbA1c obtained following RT-CGM initiation decreased significantly compared to baseline (8.11 + 1.47% vs 7.69 + 1.25 %; P = 0.002 & 8.16 + 1.51 % vs 7.62 + 1.06 %; P = 0.001). Subjects with baseline HbA1c > 7.0 % showed even more robust reduction in both HbA1c after RT-CGM initiation (8.74 + 1.24 % vs 7.99 + 1.22 %; P = 0.000 & 8.74 + 1.32 % vs 7.85 + 1.07 %; P = 0.001). On comparison of CGM metrics, there was a significant reduction in time spent in hypoglycemia (sugars < 70 mg/dl) including severe hypoglycemia (sugars < 54 mg/dl) after initiation of the RT-CGM (9.16 + 8.68 % vs 1.29 + 2.21 %; P = <0.001 & 4.58 + 5.43 % vs 0.28 + 0.58 %; P = <0.001). CoV of glucose was also decreased significantly (39.61 + 9.36 % vs 31.06 + 6.74 %; P = <0.001) with RT- CGM use. CONCLUSION: RT-CGM use for at least 3 months in patients with DM results in meaningful HbA1c reductions with stable glycemic control without increasing the risk of hypoglycemia.

Elevated Graves' Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis.

Subacute thyroiditis can be rarely associated with autoimmune thyroid disorders. It includes Graves' disease which is characterized by the presence of a highly specific antibody known as thyroid-stimulating hormone (TSH) receptor antibody (TRAb). There are three types of TRAb: TSH receptor stimulating antibody (TSAb) which stimulates the TSH receptor causing Graves' disease, TSH receptor blocking antibody (TBAb) which blocks the TSH receptor causing hypothyroidism, and a neutralizing antibody which does not alter the thyroid function. There are two assays used to check the TRAb: the thyroid-stimulating immunoglobulin (TSI) assay and the TSH receptor-binding inhibitor immunoglobulin (TBII) assay out of which the TSI assay measures the stimulating antibody which is specific for graves' disease. Although autoimmune thyroid disorders can rarely occur following subacute thyroiditis, their clinical presentation is usually compatible with the type of antibody detected in the patient's serum. We present a unique case of a 44-year-old patient who presented with subacute thyroiditis followed by the development of persistent hypothyroidism even in the presence of elevated Graves' disease-specific TSI and TRAb.

Severe Symptomatic Hypercalcemia in a Patient With Familial Hypocalciuric Hypercalcemia.

One of the less common causes of hypercalcemia is familial hypocalciuric hypercalcemia (FHH). It is an autosomal-dominant genetic condition, which presents asymptomatically in most patients while some may have mild symptoms. The serum calcium levels are mildly elevated with mild elevation in parathyroid hormone, which rarely requires management with pharmacologic agents. We present an unusual case report of a 76-year-old woman, confirmed to have FHH type 1 mutation, presented with symptomatic hypercalcemia probably set off by metabolic stresses of her age and needing intensive treatment with intravenous bisphosphonates, calcitonin and cinacalcet.

Case of COVID-19 presenting with gastrointestinal symptoms.

Patients with coronavirus disease 2019 (COVID-19) predominantly present with the pulmonary symptoms such as fever, cough, and shortness of breath. We present a case of an 83 years old patient with COVID-19 who presented with only gastrointestinal symptoms without respiratory complaints. Our case raises the concern regarding our current lack of understanding of extrapulmonary manifestations of COVID-19. Given genetic homology between 2019 severe acute respiratory syndrome coronavirus (SARS-CoV) 2 and SARS-CoV, our case underscores the urgent need for further studies to understand the role of the gastrointestinal system in 2019 SARS-CoV-2 transmission and COVID-19 pathogenesis.