An Overlooked Disease: Minimal Autonomous Cortisol Secretion (MACS). A Narrative Review.

BACKGROUND: A far more common disease than Cushing's syndrome is subclinical hypercortisolism or mild autonomous cortisol secretion (MACS), with an overall prevalence of 0.2-2%. OBJECTIVE: This review aims to shed light on the prevalence, screening and diagnostic criteria, comorbidities, and management of Mild Autonomous Cortisol Secretion (MACS). METHODS: Studies eligible targeted MACS regarding prevalence, screening, comorbidities, management, and clinical outcome. This is a mini-review. IRB approval was not needed. RESULTS: The 1 mg Dexamethasone suppression test (DST) remains the first screening test. MACS is associated with adverse cardiometabolic and renal outcomes, osteoporosis and osteopenia, immunodeficiency, depression, coagulopathy, and sarcopenia. Surgery is the gold standard treatment. Medical therapy is recommended when surgery is contraindicated or not feasible. Clinically silent hypercortisolism is a frequent entity that necessitates early detection and treatment. The production of cortisol should be looked at as a spectrum where subtle, undetectable levels can still be produced. They know its association with adverse health outcomes. CONCLUSION: MACS is no longer considered an asymptomatic disorder; repeated hormonal and functional tests are crucial to prevent multiorgan damage.

Sodium-Glucose Co-Transporter Protein 2 Inhibitors Induced Hypercalcemia: A Case Series and Literature Review.

BACKGROUND: Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents. To our knowledge, hypercalcemia has not been labeled as a side effect of this class; nevertheless, 2 cases have been reported over the last few years. CASE REPORT: We present a case series of 3 patients with type 2 diabetes mellitus (T2DM) in whom hypercalcemia developed when they were started on canagliflozin and dapagliflozin treatment. In cases 1 and 2, hypercalcemia developed shortly after increasing the canagliflozin dose. In both cases, calcium levels returned to the normal range 1 week after discontinuing canagliflozin treatment. In case 3, laboratory workup revealed an elevated serum calcium level shortly after switching the therapy to dapagliflozin. DISCUSSION: The first reported case of hypercalcemia related to SGLT2 inhibitor use was described in relation to canagliflozin. High calcium level was also reported in a patient after introducing dapagliflozin. In our cases, hypercalcemia was first noted after increasing the dose of canagliflozin and after introducing dapagliflozin. Although the exact causes are unknown, we propose a comprehensive multifactorial mechanism. CONCLUSION: This is the first reported case series of hypercalcemia associated with SGLT2 inhibitors. Although the exact mechanisms remain uncertain, these drugs may predispose individuals to hypercalcemia. Monitoring for signs and symptoms of hypercalcemia or better switching to more selective SGLT2 inhibitors in at-risk patients could potentially prevent this complication.

Efficacy and safety of a generic rosuvastatin in a real-world setting: prospective, observational clinical study in Lebanese patients.

BACKGROUND: No published studies have assessed the efficacy and safety of rosuvastatin generics. OBJECTIVES: Primary objective to assess the safety and efficacy of a generic rosuvastatin in reducing plasma low-density-lipoprotein cholesterol (LDL-C) in Lebanese dyslipidemic patients. Changes in high-density lipoprotein cholesterol, triglycerides and adverse effects were secondary objectives. DESIGN: Prospective, observational, non-comparative. SETTING: Multiple outpatient clinics in Lebanon. PATIENTS AND METHODS: Dyslipidemic patients requiring statin therapy were followed for 2 months after prescription of a generic rosuvastatin at the physician's discretion. Efficacy and safety measurements were collected from medical records. MAIN OUTCOME MEASURES: Efficacy was assessed based on the evaluation of mean and percent change in LDL-C between baseline and week 8 as well as the proportion of patients reaching target LDL-C levels. Safety was assessed based on the evaluation of the incidence of adverse events (AEs) during the study period. RESULTS: Two months after initiation of generic rosuvastatin, LDL-C levels in the 313 eligible patients who completed the study significantly decreased from 4.3 (0.8) mmol/L (168.2 [31.3] mg/dL) at baseline to 2.7 (0.7) mmol/L (105.9 [25.5] mg/dL) (P < .001). The mean percent change in LDL-C level was highest in subjects receiving generic rosuvastatin at a dose of 40 mg/day (-47.4%), followed by 20 mg/day (-36.8%), and 10 mg/ day (-31.4%); 82.5% of patients reached the target LDL-C level as set by their physician at baseline. Thirteen patients (4%) reported six AEs during treatment: abdominal pain, headache, stomach ache, insomnia, musculoskeletal pain/myalgia and nausea. No clinically significant changes in serum creatinine, serum creatine kinase, or liver function tests were reported. One patient withdrew because of an adverse event. CONCLUSIONS: Generic rosuvastatin was efficacious and safe in reducing LDL-C levels and helping the majority of patients achieve LDL-C targets after a short treatment period. LIMITATIONS: The observational nature, and a control group, and the relatively short duration of follow-up limit the generalizability of results. The authors received fees for study activities at patient visits from an independent clinical research organization subcontracted by the sponsor.

Effect of gender, puberty, and vitamin D status on biochemical markers of bone remodedeling.

Peak bone mass, a determinant of osteoporosis at older ages, is affected by genetic, nutritional, lifestyle, and hormonal factors. Adolescence is a critical time for peak bone mass accrual, and boys achieve a higher peak bone mass than girls. We have reported vitamin D insufficiency in adolescents in our population, but its impact on bone remodeling is unclear. We systematically evaluated the impact of puberty, gender, and vitamin D status on biochemical markers of bone remodeling. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), C-terminal telopeptide of type I collagen crosslinks (S-CTX), and 25 OH vitamin D were measured in 172 healthy students from private schools in the fall of 1999: There were 92 girls and 80 boys, age 10-17 years. In girls, all markers of bone turnover changed significantly with pubertal stage, were maximal at midpuberty, and decreased toward adult levels by Tanner stage V. Conversely in boys, these markers increased during early pubertal stages but had not normalized by Tanner stage V. Levels of all biochemical markers were significantly higher in boys compared to girls even after adjustment for age, body weight, and Tanner stage, P < 0.0001. In the subgroup of girls, those with vitamin D insufficiency, serum levels of BAP and S-CTX were highest. However, in multiple regression analyses, gender was the only consistent correlate of all three markers of bone remodeling. In conclusion, after adjusting for age, weight, and Tanner stages, changes in bone remodeling markers were most powerfully affected by gender. The latter may have important implications on gender differences in peak bone mass.