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Patient: Female, 37-year-old Final Diagnosis: Diabetic ketoacidosis • Fournier’s gangrene Symptoms: Dysuria • pain Medication: Canagliflozin Clinical Procedure: Incision and drainage Specialty: Endocrinology and Metabolic • General and Internal Medicine Objective: Adverse events of drug therapy Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors have become an appealing treatment for diabetes due to their favorable cardiac and renal outcomes. However, reports continue to emerge describing potentially life-threatening adverse events such as Fournier’s gangrene and diabetic ketoacidosis associated with their use. Herein, we present a case of simultaneous Fournier’s gangrene and diabetic ketoacidosis after initiation of treatment with canagliflozin. Case Report: A 37-year-old female with diabetes presented to the hospital with a chief complaint of left gluteal pain associated with dysuria 1 month after canagliflozin was added to her regimen. On initial evaluation, the patient was afebrile and hemodynamically stable. Physical examination revealed suprapubic tenderness and induration in the left gluteal region extending to the perineum. Laboratory testing was significant for anion gap metabolic acidosis with the presence of serum ketones. Computed tomography of abdomen and pelvis revealed features suggestive of Fournier’s gangrene. The patient was treated for Fournier’s gangrene and diabetic ketoacidosis. Management included empirical antibiotic treatment, multiple surgical explorations with debridement as well as insulin infusion with aggressive fluid resuscitation. The patient was discharged with a urinary catheter, vacuum dressing, and colostomy with instructions to start a basal bolus insulin regimen and discontinue canagliflozin. Conclusions: This is the first case describing a simultaneous occurrence of Fournier’s gangrene and diabetic ketoacidosis with SGLT2 inhibitor therapy. Considering the growing popularity of these drugs, it is important to be aware of their more serious and potentially fatal complications. It is also important to promptly terminate SGLT2 inhibitors when harmful adverse effects are suspected.

Background Identifying the etiology of hormonal insufficiency is important for correct diagnosis and for appropriate hormone supplementation. Usually multiple hormone deficiencies are driven by pituitary pathology, but here we present a case that poses a unique diagnostic and therapeutic dilemma. Clinical Case A 55 y/o lady with HTN and recently diagnosed metastatic Renal Cell Carcinoma (RCC) presented with weakness, dizziness, altered mental status, polydipsia and polyuria. Her metastases included the bilateral adrenal glands, thyroid, brain, and she had a sellar lesion displacing the pituitary as well as infundibular thickening. She had been treated with dexamethasone due to vasogenic edema, whole brain radiation, and was going to start immunotherapy (Ipilumimab&Nivolumimab). On exam she had relative hypotension and tachycardia (BP 115/58, HR 108). She was diagnosed with non-PTH mediated hypercalcemia (Ca 13.9/ 15.3 corrected for albumin 2.3, PTH 6.5, PTH-RP 69, Vitamin D-25 19.4). Her calcium normalized after fluid resuscitation and bisphosphonate treatment, but weakness and hypotension persisted. We tested thyroid and adrenal function given the location of her lesions, recent whole brain radiation, and recent steroid use. Her TSH was 0.017 (0.270 - 4.200 µIU/mL), fT4 0.84 (0.80 - 1.50 ng/dL), T3 0.59 (72.0 - 153.0 ng/dL), ACTH was 1.7 (7.2-63.3 pg/ml), cortisol 1.3 (6.0 - 18.4 ug/dL), aldosterone 3 (< or = 28 ng/dL), renin 7.87 (0.25 - 5.82 ng/mL/h), renin/aldosterone 0.4 (0.9 - 28.9). At 30 minutes after cosyntropin administration cortisol was 7.7 ug/dL, aldosterone 26 ng/dL, and at 60 minutes cortisol was 10.3 ug/dL. Hydrocortisone was initiated while tapering off dexamethasone, and levothyroxine was offered but declined. She opted to postpone further workup. Conclusion This patient presents a dilemma in identifying the primary causes of hormonal abnormalities given potential pituitary and primary thyroid and adrenal disease. The thyroid abnormalities could represent sick euthyroid physiology with lower T4 to T3 conversion or the effects of steroids which can also suppress TSH vs. hypothalamic or pituitary disease. Primary hypothyroidism from gland destruction was unlikely. The low ACTH and cortisol levels were expected since she was on dexamethasone, but low aldosterone with raised renin activity was concerning for primary adrenal insufficiency. However, after cosyntropin the suboptimal cortisol yet preserved aldosterone response supported secondary or tertiary adrenal insufficiency, and only cortisol was supplemented. Understanding her endocrine disease had implications for longer term management given that replacement may only need to be temporary and adrenal recovery might be possible. Further, the use of a 30 minute aldosterone level can be helpful in cases where multiple factors and discrepant laboratory findings may exist.

Background Unintentional weight loss, ascites, and altered mental status typically raise concerns for hepatologic-cardiac-oncologic disease. Herein we present a case that after exhaustive workup the etiology of the aforementioned findings was attributed to a combination of anorexia and severe hypothyroidism, states where slowed metabolism and altered nutritional status can interact synergistically. Clinical Case A 71 y/o lady with a history of hypothyroidism after RAI for Graves’ disease, anxiety, depression, presented with 20-30 lbs unintentional weight loss over 5 months. She had poor appetite, nausea, constipation, increased abdominal girth, anasarca, fatigue, weakness, and altered mental status. On exam she had bradycardia, hypotension and hypothermia (BP 97/51, HR 54, RR 18, Temp 94, BMI 15.8). Labs revealed a TSH of 36, FT4 0.98, Tbili 0.3, alk phos 491, AST 435, ALT 651, gGT 151, albumin 2.3, prealbumin 14.7, INR 1.03, and pancytopenia. Treatment with IV levothyroxine resulted in mental status improvement. Over the next few months extensive testing revealed mild element deficiencies (zinc 44- nl range 60 - 130 mcg/dL, vit A 32- nl range 38 - 98 mcg/dL), no evident infectious/hematologic or inflammatory disease. Despite 3 paracenteses, 2 liver biopsies, multiple imaging studies (abdominal U/S, ECHO, XRs, CT chest/abdomen/pelvis, MRI abdomen/pelvis, enterography, MRI brain, PET scan), EGD/colonoscopy, bone marrow bx, and explorative laparoscopic abdominal surgery, no clear explanation was found. During the workup her liver enzymes remained elevated, TSH and fT4 normalized, but T3 remained low at 50 (76 - 181 ng/dL). Psychiatric evaluation revealed mild cognitive impairment, presumed to be secondary to depression and underlying disease. By exclusion, she was diagnosed with anorexia with a possible component of persistent hypothyroidism. She was fed through NG tube and followed closely by nutrition with a personalized high protein and calorie meal plan. Eight months later she had gained 5 lbs, her liver enzymes/electrolytes and CBC normalized, and most of her symptoms resolved. Conclusion Hypothyroidism can cause LFT abnormalities, and though rare, there are >50 cases of hypothyroidism induced ascites reported. Usually LFTs and ascites normalize promptly with hormone supplementation. However, our patient’s case was complicated by severe anorexia, with nutritional status essentially equivalent to kwashiorkor sufferers. Though extremely rare in the developed world and in adults, kwashiorkor like physiology has been described in patients with anorexia, with impressive liver abnormalities, presumed to be due to autophagy. Though certainly this is a rare diagnosis, it does point to the fact that in our test driven culture, it is worth pausing, re-evaluating history and physical and thinking outside the box prior to subjecting our patients to countless tests and procedures.

Introduction Sodium glucose co-transporter 2 (SGLT2) inhibitors have become an appealing treatment for diabetes due to their favorable cardiac and renal outcomes. However, reports continue to emerge describing potentially life-threatening adverse events such as Fournier’s gangrene (FG) and diabetic ketoacidosis (DKA) associated with their use. Herein, we report a case of simultaneous FG and DKA in a patient taking canagliflozin. Case Presentation A 37-year-old woman with a history of type 2 diabetes mellitus, peripheral neuropathy, and morbid obesity (BMI of 45.8 kg/m2) presented to the hospital with left gluteal pain associated with dysuria despite 5-day treatment with trimethoprim/sulfamethoxazole for a presumed urinary tract infection. Approximately 1 month prior, sitagliptin and canagliflozin were added to her regimen due to poor glycemic control on metformin (HbA1c 9.8%). On examination her temperature was 36.9oC, pulse 117 beats/minute, blood pressure 144/79 mmHg and respiratory rate was 19 bpm. She appeared lethargic and had suprapubic tenderness and induration in the left gluteal region extending to the perineum. Laboratory findings revealed an arterial pH of 7.23 and PCO2 of 34 mmHg, a blood glucose of 402 mg/dL, serum bicarbonate 12mmol/L (20-30mmol/L), an elevated anion gap of 24mmol/L (7-17mmol/L) and a lactate of 1.8 mmol/L. Urinalysis showed 4+ glucose and 1+ ketones. Serum β-hydroxybutyrate was 2.49 mmol/L (0.02-0.27mmol/L). A CT scan of the abdomen and pelvis showed marked inflammatory changes with subcutaneous edema and air within the medial left gluteal soft tissues and locules of air extending into the presacral soft tissues suggestive of Fournier’s gangrene. The diagnoses of Fournier’s gangrene and DKA were made. The patient was started on empirical antibiotic treatment and required six surgical explorations with debridement. Interestingly, initial DKA management included only subcutaneous insulin. Only when serum ketones were identified and the anion gap persisted, insulin infusion with aggressive fluid resuscitation was initiated with successful resolution of anion gap metabolic acidosis. She was discharged with a urinary catheter, vacuum dressing, colostomy with instructions to start insulin glargine 18U and discontinue the oral anti-diabetic medications. Discussion To the best of our knowledge, this is the first case describing the simultaneous occurrence of two potentially fatal adverse effects of SGLT2 inhibitor therapy; Fournier’s gangrene and DKA. In light of the FDA’s warnings and the growing popularity of SGLT2 inhibitor therapy it is important to be mindful of their more serious and potentially fatal complications. It is also important to promptly terminate SGLT2 inhibitors when harmful adverse effects are suspected to prevent further progression.

Human pesticide exposure can occur both occupationally and environmentally during manufacture and after the application of indoor and outdoor pesticides, as well as through consumption via residues in food and water. There is evidence from experimental studies that numerous pesticides, either in isolation or in combination, act as endocrine disruptors, neurodevelopmental toxicants, immunotoxicants, and carcinogens. We reviewed the international literature on this subject for the years between 1990 and 2017. The studies were considered in this review through MEDLINE and WHO resources. Out of the n = 1817 studies identified, n = 94 were reviewed because they fulfilled criteria of validity and addressed associations of interest. Epidemiological studies have provided limited evidence linking pre- and post-natal exposure to pesticides with cancers in childhood, neurological deficits, fetal death, intrauterine growth restriction, preterm birth, and congenital abnormalities (CAs). In this review, the potential association between pesticide exposure and the appearance of some human CAs (including among others musculoskeletal abnormalities; neural tube defects; urogenital and cardiovascular abnormalities) was investigated. A trend towards a positive association between environmental or occupational exposure to some pesticides and some CAs was detected, but this association remains to be substantiated. Main limitations of the review include inadequate exposure assessment and limited sample size. Adequately powered studies with precise exposure assessments such as biomonitoring, are warranted to clarify with certainty the potential association between pesticide exposure and human CAs.

BACKGROUND Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. OBJECTIVES The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. METHODS Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. RESULTS Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. CONCLUSIONS This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

Background Leptin is an adipocyte-derived peptide hormone that acts in the hypothalamus to stimulate pathways that inhibit feeding and promote energy expenditure. Mutations in the gene encoding leptin or its receptor (LR) are rare and typically lead to extreme obesity. We describe a patient who presented with severe hypertriglyceridemia, non-alcoholic fatty liver (NAFL) and a clinical phenotype of partial lipodystrophy, who upon whole exome sequencing harbored a novel homozygous mutation in the Ig domain of the LR. Clinical case A 45-year-old woman with a past medical history of hypertension presented with abdominal pain and was diagnosed with hypertriglyceridemic pancreatitis. She denied alcohol or recreational drug use. Her BMI was 26 kg/m2, BP 167/109 mmHg, HR 106, and she had prominent central obesity with a paucity of adipose tissue on the extremities and gluteal region. Triglycerides (Tg) were 2,076 mg/dl, lipase 366 u/l, A1c of 6.0%, ALT 70 u/l, AST 27 u/l. Proteinuria was present, but serum and urine protein electrophoreses were normal. Abdominal CT was suggestive of liver steatosis and pancreatitis. Given her lipodystrophic features, elevated Tg, and fatty liver, we performed whole exome sequencing which revealed a novel homozygous mutation in the leptin receptor (p.S389N) that is predicted to be deleterious. Compared to other reported cases with LR mutations, our patient did not report excessive appetite and denied frequent childhood infections. Further workup showed low fasting leptin, 4.2 ng/ml (8.0-38.9 ng/ml for women with BMI 25-30s), fasting glucose of 114mg/dl and insulin of 21 ulU/ml. IGF-I was 141 ng/ml, FSH 4.6 mIU/mL, LH 3.8 U/ml, estradiol 60 pg/Ml, free testosterone 2.1 pg/ml, TSH 2.67 mlu/l, fT4 1.3ng/dl. Her family history was significant for pancreatitis in mother and maternal grandfather, nonalcoholic steatohepatitis (NASH) in her 14-year-old son and liver problems in her sister, but so far, no other members have been tested for the mutation. She was treated with fenofibrate for hypertriglyceridemia with subsequent decrease of Tg levels to 503 mg/dl. Conclusion Our case is unique in that our patient’s clinical features are less severe in comparison to those reported with other LR mutations. Given that this is a novel homozygous mutation in the Ig region of the LR, and it is predicted to be deleterious, it is still unclear how it relates to her lipodystrophic features and overall clinical presentation. This case highlights the gap in knowledge and the diversity in clinical presentations that may accompany LR mutations and would have been missed if it were not for whole exome sequencing. At the same time, this case raises questions regarding the role of the leptin in hypertriglyceridemia, NASH and NAFL, and to what degree emerging therapies for leptin deficiency can prevent the progression of NASH and NAFL disease, since currently there are no clear therapeutic guidelines.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i’s) are the newest class of anti-hyperglycemic drugs. Their mechanism of action involves increasing urinary glucose excretion by preventing glucose reabsorption in the proximal renal tubules, yet they can also promote ketogenesis under certain circumstances. Numerous reports suggest an association between SGLT2i’s and diabetic ketoacidosis (DKA), but the medical literature remains sparse. Since the use of these drugs for diabetes has increased dramatically due to favorable cardiac outcomes, identification of patients at greatest risk for this life-threatening complication is essential. Therefore, in an effort to better understand the circumstances in which SGLT2i associated DKA occurs we reviewed all available cases at our hospital over a 5-year period. Patients and Methods: We retrospectively reviewed all cases of ketoacidosis associated with SGLT2i use at our hospital from 2013 to October 2018 using an electronic medical record search algorithm. Terms included canagliflozin, dapagliflozin, empagliflozin, SGLT2 inhibitors, metabolic acidosis, ketoacidosis, diabetes, and DKA. Patients that developed DKA without being treated with SGLT2i were excluded. Results: We identified 77 cases, 21 of which met criteria for DKA associated with SGLTi use. 64% were female and 36% were male, average age was 57.8 years, BMI 29.8 kg/m2, and mean diabetes duration was 11 years. The majority carried diagnoses of T2DM (94%) and 83.4% had no history of DKA prior to using an SGLT2i. The most common presenting symptoms were nausea, vomiting (38%), abdominal pain (28.5%) and altered mental status (19%). Common precipitants were poor oral intake (57.14%) and infection (23.8%). Average blood glucose concentrations at presentation were 329 + 36 mg/dl, interestingly, 52% of the episodes were euglycemic DKA (euDKA) with blood glucose

Background: Combined use of Glucagon-like peptide-1 receptor agonists (GLP-1RA) & sodium-glucose cotransporter 2 inhibitors (SGLT2i) may provide particular advantages for treating type 2 diabetes mellitus (DM2). Both promote weight loss and have favorable effects on cardiovascular outcomes while minimizing hypoglycemic events, however, in some circumstances their combination might result in previously unexpected side effects. We describe a case where initiation of a GLP1RA appeared to induce euglycemic diabetic ketoacidosis (euDKA) in a patient taking an SGLT2i. Clinical Case: A 52-year-old woman with hyperlipidemia and DM2 presented with 3 days of nausea & vomiting. Approximately 1 week prior she started liraglutide due to suboptimal glycemic control on dapagliflozin (HbA1c 8%). She reported no fevers, chills, cough, dysuria, diarrhea or sick contacts. She had headache without meningeal signs. Laboratory findings were significant for leukocytosis (15.400/µL), low bicarbonate (12 mmol/L), hyperglycemia (206 mg/dL), low lactate (0.9 mmol/L) and glucosuria/ketonuria (+4). Venous blood gas revealed metabolic acidosis with pH 7.18, pCO2 37, HCO3 13.4. Based on these findings, the patient was diagnosed with euDKA due to dapagliflozin in the setting of liraglutide associated nausea. Insulin drip and IV fluids were initiated with rapid resolution of the metabolic disturbance. No infectious process was identified. Prior to starting dapagliflozin 10 months ago, she was on metformin, long acting and pre-meal insulin. She had ketoacidosis 8 months prior when liraglutide was first prescribed, but at the time it was attributed to infection in the setting of dapagliflozin, liraglutide and metformin use, and metformin and liraglutide were stopped, but dapagliflozin was continued. Conclusion: EuDKA is defined as diabetic ketoacidosis without marked hyperglycemia, generally

Introduction Sarcoidosis is a granulomatous disease that can affect multiple organ systems including the central nervous system in 5-15% of patients, yet it is a rare cause of intrasellar lesions (

Objective: To demonstrate important points regarding the possible hypoglycemic effects of sulfasalazine and suggest possible underlying mechanism(s) accounting for sulfasalazine-induced hypoglycemia.Methods: We describe a case of reversible sulfasalazine-induced hypoglycemia, review the literature, and discuss a potential mechanism accounting for sulfasalazine-induced hypoglycemia.Results: A 63-year-old man with Crohn disease treated with sulfasalazine and type 2 diabetes complicated by end-stage renal disease was admitted for treatment of persistent hypoglycemia. Insulinoma was initially suspected, but localization studies including endoscopic ultrasound were negative. This raised the possibility of sulfasalazine-induced hypoglycemia. Three days after sulfasalazine was stopped, he became normoglycemic. Hypoglycemia has not recurred since discontinuing sulfasalazine.Conclusion: Clinicians should be aware of the potential hypoglycemic effect of sulfasalazine. Doses should be reduced in patients with impaired renal function, and it should be discontinued if otherwise unexplained hypoglycemia develops.Abbreviations: CT = computed tomography; ESRD = end-stage renal disease