Search

ContextThe burden of cirrhosis from nonalcoholic fatty liver disease (NAFLD) is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) are beneficial vs nonalcoholic steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH.Evidence acquisitionEvidence from observational studies, randomized controlled trials, and meta-analyses.Evidence synthesisEndocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (ie, people with obesity, prediabetes, or T2D). With no US Food and Drug Administration (FDA)-approved agents, weight loss is central to successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently, the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management.ConclusionA paradigm change is developing between the endocrinologist’s greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.

BACKGROUND AND AIMS Peroxisome proliferator-activated receptor (PPAR)-γ agonists decrease hepatic/visceral fat (VF) and improve necroinflammation despite subcutaneous (SC) fat weight-gain. Understanding the impact of changes in VF, VF-to-SC fat distribution (VF/SC) and adiponectin (ADPN) levels in relation to histological improvement after weight-loss or pioglitazone is relevant as novel PPAR-γ agonists are being developed for treating non-alcoholic steatohepatitis (NASH). METHODS Fifty-five patients with NASH received a -500 kcal/d hypocaloric diet and were randomized (double-blind) to pioglitazone (45 mg/d) or placebo for 6-months. Before and after treatment patients underwent a liver biopsy and measurement of hepatic/peripheral glucose fluxes, hepatic/adipose tissue-IR and, in 35 patients, hepatic and VF/SC-fat was measured by magnetic resonance spectroscopy/imaging. Data were examined by multivariable statistical analyses combined with machine-learning techniques (partial least square discriminant analysis [PLS-DA]). RESULTS Both pioglitazone (despite weight-gain) and placebo (if weight-loss) reduced steatosis but only pioglitazone ameliorated necroinflammation. Using machine-learning PLS-DA showed that the treatment differences induced by a PPAR-γ agonist vs placebo on metabolic variables and liver histology could be best explained by the increase in ADPN and a decrease in VF/SC, and to a lesser degree, improvement in oral glucose tolerance test-glucose concentrations and ALT. Decrease in steatosis and disease activity score (ballooning plus lobular inflammation) kept a close relationship with an increase in ADPN (r = -.71 and r = -.44, P

Introduction Zoledronic acid, used for treatment of osteoporosis, Paget's disease of the bone, hypercalcemia of malignancy etc. is a bisphosphonate known for its anti-resorptive effect. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which is transient and attributed to an acute phase reaction post zoledronic acid infusion. [1] A less common adverse reaction is ocular inflammation, including uveitis, iritis and episcleritis. [1] The incidence of ocular inflammation is 0.2 - 0.8%. [2] Development of ocular symptoms have been reported to occur between 1 to 7 days post zoledronic acid infusion. [2] We report a case of acute unilateral episcleritis following zoledronic acid infusion for treatment of osteoporosis. Clinical case: A 58-year-old female with a past medical history significant for glaucoma and gastroesophageal reflux (GERD) presented for management of osteoporosis. She could not tolerate oral bisphosphonates due to gastrointestinal side effects. She was therefore switched to intravenous zoledronic acid therapy. On day 1 post zoledronic acid infusion of 5mg dose, she developed diffuse joint and muscle pain as well as right eye pain, redness, photophobia, blurred vision and tearing. As her ocular symptoms progressed by day 5 post zoledronic acid infusion, she presented urgently to ophthalmology clinic when she was diagnosed with episcleritis of the right eye secondary to the zoledronic acid infusion. Patient was started on prednisolone acetate eyedrops twice a day. Three days after starting the eyedrops, patient reported complete resolution of her ocular symptoms. Further treatment for osteoporosis with zoledronic acid was discontinued. Conclusion We present a case of right eye episcleritis occurring 24 hours post zoledronic acid infusion leading to significant ocular discomfort and concern for the patient. Ocular inflammation is an uncommon occurrence post zoledronic acid infusion, hence is not often discussed during routine patient counseling in regards to risks and benefits of this particular treatment. We therefore stress the need for both provider and patient awareness regarding this uncommon ocular side effect related to zoledronic acid use. It is important to inform the patient and educate providers about the possibility of this acute phase reaction occurring post treatment with zoledronic acid to aid in prompt diagnosis and treatment. Our patient responded well to treatment with prednisolone acetate ophthalmologic drops. A rechallenge with zoledronic acid has not been pursued. References: 1. Jin X, Shou Z, Shao Y, Bian P. Zoledronate-induced acute anterior uveitis: a three-case report and brief review of literature. Arch Osteoporos.2021;16(1): 104. Published 2021 Jun 28. doi: 10.1007/s11657-021-00964-z 2. Patel DV, Horne A, House M, Reid IR, McGhee CN. The incidence of acute anterior uveitis after intravenous zoledronate. Ophthalmology. 2013 Apr;120(4): 773-6. doi: 10.1016/j. ophtha.2012.10. 028. Epub 2013 Jan 3. PMID: 23290982 Presentation: No date and time listed

Access to specialized diabetes care is limited due to shortage of endocrinologists and distance to specialty clinics. In addition, referrals to out-of-network providers frequently results in suboptimal care coordination. Tele-mentoring models such as ECHO (Extension for Community Healthcare Outcomes) extends specialty knowledge to primary care providers. Prior to the implementation of a series of ECHO sessions, we assessed provider confidence in managing type 2 diabetes (T2D) . Methods: Prescribing providers (PP) from three VA Health Care Systems in Florida (North Florida/South Georgia) , Texas (Valley Coastal Bend) and Wisconsin (Milwaukee) were invited to participate. We asked questions about practice patterns, prescription habits, and confidence level treating T2D. Results: A total of 49 PP completed the assessment. Mean age was 42.5 years and 74% were females. They were clinical pharmacists (63%) , physicians (22%) , ARNP (8%) , and the rest were trainees. Clinical experience < 5 year was present in 14.2%, whereas 67% had > years. Half of the providers felt very or extremely confident managing a complicated case (A1c>8% on two oral agents) , whereas only 14% of providers felt either “not at all” or somewhat confident. Most of the providers felt very or extremely confident obtaining a diabetes-focused history (63%) , educating patients about complications (69%) , or changing insulin regimens (61%) . Although most of the providers prescribed a glucose meter very often or always (81%) , only 6% of them prescribed a continuous glucose monitor frequently. When sending a referral, 32% mentioned either lack of local endocrinologists or long waiting time as main barriers. Providers felt that patients prefer to stay with their local VA PCP for diabetes care instead of seeing a specialist (65%) Conclusions: A third of providers perceive significant barriers to access specialized diabetes care. There are opportunities to improve provider confidence and skills managing diabetes. Disclosure C.E.Mendez: Advisory Panel; Monarch Medical Technologies . K.Hazen: None. L.M.Semeah: None. J.A.Leey: None. E.A.Mattox: None. S.Kadiyala: None. M.Xhikola: None. K.Yantsides: None. A.D.Oien: None. I.O'shaughnessy: None. A.E.Hansen: None. J.Lucas: None. Funding Veterans Rural Health Resource Center - 00RH

Introduction/Background Galactorrhea in men is rare, with a reported prevalence of 5.5%. It tends to occur bilaterally rather than unilaterally. Among the etiologies of galactorrhea, pharmacologic agents, pituitary tumors, and hypothalamic and pituitary-stalk lesions tend to account for most cases. Here we describe a rare cause of unilateral galactorrhea due to previous herpes zoster in the T4 dermatome. Clinical Case A 76-year-old male with history of hypertension, Crohn's disease, and chronic migraine headaches presented to the Endocrine clinic for evaluation of intermittent unilateral galactorrhea, which had been ongoing for the past 5 years. The patient had no known precipitating events, but he had noticed that galactorrhea was more pronounced in the spring-summer seasons, during which time he used to work outdoors more. No history of cancer, hypothalamic-pituitary disease, or other endocrinopathies. The patient was a former smoker and denied marijuana or alcohol use. He reported a family history of breast cancer in his maternal grandmother. He had no biological children. Active medications included sumatriptan as needed for migraines. Physical examination was notable for gynecomastia that was more prominent on the left. Tenderness to palpation was noticed over the left breast with no exudate expressed from the nipples. Genital exam revealed decreased testicular volume at approximately 10 ml each. Laboratory evaluation revealed normal renal function, prolactin, estradiol, β-HCG, TSH, and normal male karyotype. Testosterone level was low with elevated LH and FSH, suggesting primary hypogonadism. Mammogram and US of the breast were not concerning for malignancy. MRI brain was without pituitary abnormalities. After a detailed discussion on a subsequent follow-up visit, the patient recalled an episode of herpes zoster infection over his left breast about 5 years ago and since had been experiencing left breast pain and nipple discharge. Discussion and conclusion We present a unique case of post-herpetic galactorrhea in an elderly male patient. In the literature, there are case reports that describe galactorrhea in patients post chest wall injuries or chest surgeries, and there was one case report of galactorrhea in a postmenopausal female post zoster infection. A possible mechanism of galactorrhea is thought to be stimulation of the lactational neural arch, and in our case, possibly stimulated by the zoster infection. Prior herpes zoster infection and post-herpetic neuralgia are likely causes for underlying intermittent unilateral galactorrhea. Albeit rare, clinicians should be aware of this etiology when comprehensively evaluating for galactorrhea. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Introduction Denosumab is a receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor used for treatment of osteoporosis and bone metastases in patients with solid tumors. Denosumab induced hypophosphatemia has been reported in less than 1% of patients, and in most cases described as mild to moderate in severity. We present a case of severe hypophosphatemia after denosumab treatment for diffuse bone metastases due to prostate cancer. Case report A 78-year-old male patient with history of diffuse bone metastases due to prostate cancer, schizophrenia on treatment and intermittent alcohol use, presented to the hospital with suicidal ideation and worsening fatigue. Patient was found to have a phosphorus levels of Discussion In patients treated with denosumab, the primary concern is potential post-treatment hypocalcemia, however, our case brings attention to severe hypophosphatemia as a serious side effect to treatment with denosumab. Multiple specialties are involved in the treatment of osteoporosis and metastatic bone lesions, and each should be aware that denosumab can lead to lower serum phosphate levels due to its effects on bone resorption and reduction of proximal tubular reabsorption of the phosphate resulting in clinical symptoms of muscle weakness, bone pain, fractures and even stupor, coma and death. We therefore conclude that monitoring phosphate levels should be part of the pre- and post-treatment evaluation in patients who are candidates for treatment with denosumab, particularly high-dose denosumab. Presentation: No date and time listed

Background Carnitine Palmitoyltransferase II deficiency (CPT II) is a disorder of long-chain fatty-acid oxidation. Clinical presentations include a lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form. The myopathic form is the most common disorder of lipid metabolism affecting skeletal muscle. Individuals with CPT II deficiency are unable to metabolize long-chain fatty acids and can have myalgia. The incidence of statin-induced muscle symptoms is 1.5% to 5%. Individuals with CPT II deficiency have been reported to have an increased incidence of statin-associated myopathy. Yet, it remains crucial to place patients with high ASCVD risk on the appropriate statin therapy. Case Presentation We present a 70-year-old male with medical history of CPT II deficiency (myopathic form), hyperlipidemia with significant hypertriglyceridemia, hypertension, type 2 diabetes mellitus, carotid artery stenosis, atrial fibrillation, and recurrent pancreatitis. Family history was positive for hyperlipidemia and premature coronary artery disease. After history of recurrent pancreatitis and severe myalgias, patient was diagnosed with CPT II deficiency at the age of 30 years. The myalgias were managed by increased carbohydrates intake for many years. Multiple low potency statins, and fenofibrate were attempted but he developed severe myalgia with elevated CPK levels. Eventually he was started on ezetimibe 10 mg daily with fish oil 2000 mg twice daily but his LDL-C continued to rise. CMP and TSH were within normal limits. Nuclear stress test was normal but his ASCVD risk score was 39%. Given the patient's CPT II deficiency and high risk for ASCVD score, statin was recommended for primary prevention. After a thorough discussion of risks and benefits of lipid-lowering therapy, the patient was started on pitavastatin 2 mg twice-weekly regimen and ezetimibe 10mg was continued. Eight weeks later, his LDL-C reduced from 132 mg/dl to 94 mg/dl (n Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Dysfunctional mitochondrial function plays an important role in the progression of nonalcoholic steatohepatitis (NASH). Mitochondrial (mt) respiratory function assessed by oxidative phosphorylation/ OXPHOS (activated respiration with mt complex I [OXPHOS CI] and mt complex I + II [OXPHOS CI+II] substrates) and electron transport system capacity [ETC] were measured using high-resolution respirometry (Oroboros Oxygraph 2k). The aim of this study was to assess mitochondrial function in patients a) with vs. without NASH, and b) NASH with vs. without fibrosis. Liver tissue was obtained from 40 patients (age: 52 ± 12 yrs; BMI: 39.4 ± 8.4 kg/m2; HbA1c: 6.9 ± 1.5%) with NAFLD and obesity or T2DM either by percutaneous liver biopsy (n=28) or during bariatric surgery (n=12). Patients with vs. without NASH (n=20 in each group) were more insulin resistant/ IR (HOMA-IR: 8.1 ± 4.2 vs. 4.5 ± 2.7 mg/dl x μU/ml; Adipo-IR: 10.4 ± 7.2 vs. 6.2 ± 3.8 mmol/L x µU/mL) and had higher OXPHOS CI+II (all p Conclusion: In patients with NASH vs. simple steatosis, there is an early hepatic mitochondrial adaptation to severe insulin resistance. This adaptation is impaired when disease activity worsens, being most evident once patients develop steatohepatitis with significant fibrosis. Disclosure S. Kalavalapalli: None. D. Poulton: None. L. Mansour: None. S. Shrestha: None. F. Bril: None. S. K. Subbarayan: None. S. Kadiyala: None. K. Cusi: None. D. Barb: None. E. Godinez: None. R. Lomonaco: None. J. Friedman: Consultant; Self; Ethicon, Inc. S. Wohlgemuth: None. N. Fanous: None. R. E. Dillard: None. T. M. Cowan: None.

A 67-year-old male was admitted with shortness of breath and diarrhea. His COVID-19 polymerase chain reaction test was positive, and he was found to be in acute heart failure. Troponin levels were elevated, echocardiogram showed ejection fraction of 24%, and his electrocardiogram was normal. Inflammatory markers were elevated. Further testing revealed suppressed thyroid-stimulating hormone and elevated free thyroxine (T4). Differential diagnosis at this point included possible myocarditis from the viral illness, exacerbation of heart failure from the viral infection or from thyrotoxicosis was considered. Patient’s heart failure improved with initiation of heart failure therapies; however, biochemically, his thyroid function tests (TFTs) did not improve, despite empiric methimazole. Thyroid antibody tests were unremarkable. Thyroid ultrasound showed mildly enlarged thyroid gland with no increased vascularity and 5-mm bilateral cysts. Thyroid dysfunction was attributed to subacute thyroiditis from COVID-19, methimazole was tapered, and prednisone was initiated. The patient’s TFTs improved. With the ongoing COVID-19 pandemic, it is imperative that clinicians keep a broad differential in individuals presenting with heart failure, and obtaining baseline TFTs may be reasonable. Rapid treatment of the underlying thyroiditis is important in these patients to improve the cardiovascular outcomes. In our experience, steroid therapy showed a rapid improvement in the TFTs.

A 70-year-old female with unspecified diabetes presented to the emergency department complaining of nausea, dizziness, and anorexia for 4 days. She was diagnosed with diabetes at age 37 years. In her record, both type 1 diabetes and type 2 diabetes were listed as diagnoses. No prior C-peptide or serum antibodies were available. She had peripheral neuropathy and early stage 3 chronic kidney disease without proteinuria.

Introduction: In patient with diabetes and refractory epilepsy requiring vagal nerve stimulator (VNS), glycemic management can be challenging. Clinical experience is limited in this scenario. Case Report: A 67-year-old male, BMI 30 kg/m2, with history of type 2 diabetes and hemispheric hemangioma complicated by seizure disorder is referred to our diabetes clinic for evaluation of persistent hyperglycemia. The patient reports 25-year history of seizures that have been difficult to control with antiepileptic drugs alone and eventually requiring VNS placement. Patient has normal kidney (eGFR > 60mL/min) and liver function. His antiepileptic drug regimen consisted of gabapentin and as needed lorazepam. He was never on glucocorticoids. Glycated hemoglobin (HgA1c) at our initial evaluation was 10.1%. His anti-glycemic regimen consisted of glipizide monotherapy. Fasting and pre-prandial blood glucose were in the 200-400mg/dL range with occasional values higher than 500mg/dL. This was confirmed with 14-day continuous glucose monitoring that showed average blood glucose of 287mg/dL with 100 percent above target (higher than 180 mg/dL). We optimized therapy by adding once daily glargine, pioglitazone and continued glipizide. At follow up visit, HgA1c still remained high at 10.5%, despite medication adherence. Patient emphasized that hyperglycemia was related to VNS use and given documented hyperglycemia with blood glucose range 500–600 mg/dL when on higher output current of 2 milliamps, his neurologist approved a trial off VNS for 4 weeks. His glucose improved to average less than 200 mg/dL and HgA1c decreased to 9.1% on the same anti-glycemic regimen. Device was re-started due to recurrence of seizures, however the output current and “on time” were reduced to minimal effective range for optimizing seizure therapy while avoiding hyperglycemia. Subsequent HgA1C improved to 8.7%. Discussion: VNS is a FDA approved device for epilepsy and depression. It works by intermittent stimulation or “on/off” periods. In animal studies, elevation of blood glucose was noted with afferent stimulation. Conversely, efferent activation lowers blood glucose. There are limited human studies on the effects of vagal nerve stimulation on glycemic control. The few available, showed variation in blood glucose based on output current and length of on/off period. This should be factored in during glycemic evaluation and management and close collaboration with neurology is essential. Reference: (1) Strauss H, et al. Cervical Vagal Nerve Stimulation Impairs Glucose Tolerance and Suppresses Insulin Release in Conscious Rats. Physiological Reports 2018; 6(24): 1–9 (2) Strauss H, et al. Effect of Vagus Nerve Stimulation on Blood Glucose Concentration in Epilepsy Patients - Importance of Stimulation Parameters. Physiological Reports 2019; 7(14): 1–10

The underlying mechanisms responsible for the development and progression of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) are unclear. Since the thyroid hormone regulates mitochondrial function in the liver, we designed this study in order to establish the association between plasma free T4 levels and hepatic triglyceride accumulation and histological severity of liver disease in patients with T2DM and NAFLD. This is a cross-sectional study including a total of 232 patients with T2DM. All patients underwent a liver MR spectroscopy (1H-MRS) to quantify hepatic triglyceride content, and an oral glucose tolerance test to estimate insulin resistance. A liver biopsy was performed in patients with a diagnosis of NAFLD. Patients were divided into 5 groups according to plasma free T4 quintiles. We observed that decreasing free T4 levels were associated with an increasing prevalence of NAFLD (from 55% if free T4≥1.18 ng/dL to 80% if free T41H-MRS (p