Statin Intolerance: A Review and Update.

OBJECTIVE: To review the evidence of existing literature on the management of statin intolerance. METHODS: We searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022. RESULTS: Statin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins. CONCLUSION: Management of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.

Prevalence and clinical determinants of non-alcoholic fatty liver disease by liver scores in adults with type 1 diabetes.

AIMS: To investigate the prevalence and clinical risk factors for non-alcoholic fatty liver disease (NAFLD) in type 1 diabetes (T1DM) by liver scores. METHODS: A retrospective, unicenter, cross-sectional analysis was performed of adults with T1DM from 2015 to 2018. Steatosis scores (hepatic steatosis index-HSI, Framingham steatosis index-FSI) and fibrosis scores (FIB-4 index, AST-to-platelet ratio index-APRI) were associated with clinical parameters. RESULTS: We identified 447 patients, 38 ± 14.5 yrs, 54 % female, BMI 28 ± 5.9 kg/m2. Liver steatosis was prevalent at 61 % by HSI ≥ 36 and 52 % by FSI ≥ 23. A majority of these individuals had normal liver transaminase levels. The presence of advanced fibrosis was 4 % by APRI > 0.7 and 4 % by FIB-4 > 2.67. BMI ≥ 25 kg/m2 correlated with steatosis scores (P < 0.001) but not fibrosis scores. Older age (≥40 yrs), hypertension, dyslipidemia, and history of cardiovascular disease were associated with steatosis markers. Only 21 % had any abdominal imaging, 2 % had hepatology referral and 1 % had a liver biopsy. Glucagon-like peptide-1 agonist was prescribed in 5 % and thiazolidinedione in 4 %. CONCLUSION: Liver scores indicating steatosis but not fibrosis is common in adults with T1DM with obesity and/or metabolic syndrome, and is associated with older age, hypertension, and dyslipidemia. NAFLD is under-diagnosed and under-investigated; a minority of patients have had any liver evaluation or treatment.

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease, the Impact of Available Lipid-Lowering Medications on Lipoprotein(a): An Update on New Therapies.

OBJECTIVE: To review evidence of existing and new pharmacological therapies for lowering lipoprotein(a) (Lp[a]) concentrations and their impact on clinically relevant outcomes. METHODS: We searched for literature pertaining to Lp(a) and pharmacological treatments in PubMed. We reviewed articles published between 1963 and 2020. RESULTS: We found that statins significantly increased Lp(a) concentrations. Therapies that demonstrated varying degrees of Lp(a) reduction included ezetimibe, niacin, proprotein convertase subtilisin/kexin type 9 inhibitors, lipoprotein apheresis, fibrates, aspirin, hormone replacement therapy, antisense oligonucleotide therapy, and small interfering RNA therapy. There was limited data from large observational studies and post hoc analyses showing the potential benefits of these therapies in improving cardiovascular outcomes. CONCLUSION: There are multiple lipid-lowering agents currently being used to treat hyperlipidemia that also have a Lp(a)-lowering effect. Two RNA therapies specifically targeted to lower Lp(a) are being investigated in phase 3 clinical trials and, thus far, have shown promising results. However, evidence is lacking to determine the clinical relevance of reducing Lp(a). At present, there is a need for large-scale, randomized, controlled trials to evaluate cardiovascular outcomes associated with lowering Lp(a).

Prevalence and Clinical Determinants of Obesity in Adults With Type 1 Diabetes Mellitus: A Single-Center Retrospective Observational Study.

OBJECTIVE: To determine the prevalence of obesity and assess the cardiometabolic risk profile and treatments associated with obesity management in the type 1 diabetes mellitus adult population. METHODS: We reviewed the records of all patients with type 1 diabetes mellitus seen in our institution's outpatient endocrinology clinic between 2015 and 2018. We stratified the patients into 4 weight categories on the basis of body mass index (BMI) (normal, overweight, obesity class I, and combined obesity class II and III) and evaluated their associated clinical characteristics and relevant medications. RESULTS: Of 451 patients, 64% had a BMI of >25 kg/m2, and 25% had a BMI of ≥30 kg/m2. Over 40% of patients with a BMI of >30 kg/m2 had a history of cardiovascular disease. The off-label use of the glucagon-like peptide 1 receptor agonist was 12% and the sodium glucose cotransporter 2 inhibitor use was 5% in those with obesity. Only 2 patients were prescribed phentermine and 3 had undergone bariatric surgery. Hemoglobin A1C and low-density lipoprotein did not significantly differ between the normal weight and obesity groups. The obesity groups had significantly higher levels of median triglycerides and lower high-density lipoprotein than the normal weight group. CONCLUSION: Obesity was prevalent in a population of patients with type 1 diabetes mellitus seen in a specialty clinic. Those with obesity had a higher prevalence of cardiovascular disease than their normal weight counterparts. The use of weight loss medications was scarce. Studies exploring the safety and efficacy of obesity-targeted therapy in the type 1 diabetes mellitus population are needed.

The role of SGLT-2 inhibitors in managing type 2 diabetes.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are an exceptionally versatile class of medication, and their glycemic and nonglycemic benefits could help millions of patients with type 2 diabetes. Of note, they have been shown to improve cardiac and renal outcomes, much-needed benefits in patients with type 2 diabetes, who are at a higher risk for developing cardiac and renal dysfunction than those who do not have diabetes. The indications for SGLT-2 inhibitors may continue to expand as ongoing clinical trials provide more insight into these drugs.

BROWN TUMORS SECONDARY TO PARATHYROID CARCINOMA MASQUERADING AS SKELETAL METASTASES ON 18F-FDG PET/CT: A CASE REPORT.

OBJECTIVE: Brown tumors develop as skeletal manifestations of hyperparathyroidism. Increased osteoclast activity leads to accumulation of highly active giant cells and to excess cortical bone resorption, producing fibrous cysts. Though most often reported in patients with parathyroid adenomas, brown tumors secondary to parathyroid carcinoma create a clinical dilemma. Increased signal uptake on 2-deoxy-2-(fluorine-18)fluoro-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT) seen within brown tumors may be indistinguishable from bone metastases. We report a case of parathyroid carcinoma in a 38-year-old man presenting with osteolytic bone lesions on 18F-FDG PET/CT that were diagnosed as brown tumors by biopsy. METHODS: We describe the patient history, presentation, diagnostic studies, and treatment. RESULTS: We report a case of a 38-year-old man diagnosed with parathyroid carcinoma with associated hypercalcemia and elevated parathyroid hormone levels who had undergone 3 surgical resections for local recurrences and had persistent hypercalcemia. He was found to have multiple osteolytic lesions throughout his skeleton on 18F-FDG PET/CT imaging 2 months after diagnosis. Biopsy of a right scapula lesion confirmed a brown tumor. CONCLUSION: The role of 18F-FDG PET/CT in management of parathyroid carcinoma has not been systematically evaluated. Skeletal manifestations of parathyroid carcinoma may be present in this imaging modality. Clinicians should consider the possibility of brown tumors in patients with parathyroid carcinoma who undergo 18F-FDG PET/CT imaging.

CUSHING DISEASE MASQUERADING AS GLAUCOMA.

OBJECTIVE: Glaucoma is a well-recognized side effect of corticosteroids. However, steroid-induced glaucoma typically refers to that caused by exogenous corticosteroid administration. Glaucoma secondary to endogenous overproduction of corticosteroids has only been reported in a few case reports. We aim to bring attention to glaucoma as a rare but important manifestation of endogenous hypercortisolism. METHODS: Patient history, physical exam, laboratory results, and imaging studies were reviewed. RESULTS: We report a case of glaucoma as the initial presentation of Cushing disease (CD). The patient was diagnosed with glaucoma 16 months prior to his endocrinology evaluation. At our initial encounter, the patient had a cushingoid appearance. Levels of 24-hour urinary cortisol and late-night salivary cortisol were elevated. Serum cortisol was not suppressed by 1 mg of dexamethasone overnight, but it was suppressed by 8 mg of dexamethasone. Adrenocorticotropic hormone was also elevated. All other pituitary hormone axes were unremarkable (thyroid-stimulating hormone, free thyroxine, follicle-stimulating hormone, luteinizing hormone, growth hormone, prolactin, and insulin-like growth factor). Pituitary magnetic resonance imaging suggested a small adenoma (2 to 3 mm); therefore, the patient underwent inferior petrosal sinus sampling. The results were consistent with CD. Transsphenoidal resection was performed and final pathology confirmed an adrenocorticotropic hormone-positive adenoma. Hypercortisolism and intraocular pressures improved after the surgery. CONCLUSION: Glaucoma can lead to irreversible blindness if left untreated or uncontrolled. However, endogenous hypercortisolism-induced glaucoma can be reversed with treatment of the underlying CD. Thus, heightened awareness of extraocular manifestations of secondary causes of glaucoma such as endogenous hypercortisolism is necessary in order to promote prompt evaluation and treatment.

Megestrol Acetate-Induced Symptomatic Hypogonadism in a Male Patient.

The hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis are very sensitive and can be affected by external factors like stress, starvation, and medication. Medication-induced suppression of these axes can cause adrenal insufficiency (AI) and hypogonadism. Exogenous glucocorticoid use is the most common cause of iatrogenic AI. Our aim is to bring attention to another broadly prescribed medication, megestrol acetate (MA), as the cause of suppression of both these axes. We report a case of symptomatic hypogonadism and asymptomatic AI in a male patient secondary to MA. The patient presented with decrease in testicular size and erectile dysfunction. His total testosterone and morning cortisol levels were low, but FH, LH, and TSH were normal. His pituitary MRI was unremarkable. Upon discontinuation of MA, the patient's testosterone and cortisol levels normalized and his symptoms resolved. Hypogonadism and AI are known adverse effects of MA, but symptomatic hypogonadism as the primary manifestation has only been reported once in previous literature. Prolonged hypogonadism can lead to sarcopenia, depression, and osteoporosis, while asymptomatic AI carries the risk of becoming overt AI. Thus, heightened awareness of the impact of MA on both these axes is necessary.