Abstract

Amiodarone, a medication commonly used for management of cardiac arrhythmias, is known for its multitude of side effects notoriously affecting thyroid gland dysfunction such as hypothyroidism and hyperthyroidism. Amiodarone induced thyrotoxicosis (AIT) types I and II has been well described. We present a case that demonstrates the development of the full

autoimmune Grave’s spectrum. A 77 year-old man with atrial fibrillation was treated with amiodarone and required consultative assistance because of development of ophthalmopathy including periorbital edema in conjunction with thyrotoxicosis. His presentation was heralded by diplopia and ptosis. Suppressed TSH, elevated T3 and T4 levels, and elevated thyroid stimulating immunoglobulin were all notable new findings in support of this clinical

development. Pretibial myxedema with classic peau d’orange was also a clinically relevant finding. Earlier consulting physicians offered antibiotic treatment for possible cellulitis and lower extremity duplex testing, which was negative for deep venous thrombosis. These features are unique from the more commonly understood AIT types 1 and 2 and may be related to the increased number of 1a-positive T-cells which have been linked to possible pathogenesis of thyrotoxicosis in autoimmune mediated Grave’s disease. There has been well documented elevation of thyroid anti-microsomal antibodies following exposure to the amiodarone molecule and subsequent reduction of levels following cessation of treatment.

The patient required methimazole, which is known to not only help to reduce endogenous thyroid function, but is also associated with immune modulating effects. It has been known to be associated with reduction of thyroid stimulating immunoglobulins as well as reduction of T-cell activation. Additional treatment included glucocorticoid treatment and use of teprotumumab.

Historically, the impact of amiodarone in creating thyroid dysfunction has been attributed to by the significant iodine component of the amiodarone molecule. This case, however, offers a different perspective in pathogenesis–one that underscores the complexity of immune responsiveness and the potential evolution of autoimmune processes even in patients with a less predictable demographic.

Biography

Dr Haenel has been a clinical endocrinologist with a flare for teaching for 26 years. He is originally from Philadelphia, PA and was raised and educated in the Philadelphia area until his fellowship training in Endocrinology, Diabetes, and Medical Genetics from the Medical University of South Carolina in Charleston, SC, US (1997-99). Following completion of his training, he practiced with his father in NJ for 15 years and went on to become head of endocrinology at Kennedy Hospital (currently Jefferson Health). He has been actively involved with teaching students and residents and went on to develop and head Rowan-SOM endocrinology fellowship program. Upon moving back to Charleston, SC in 2014 he has remained actively involved in clinical and educational medicine. He works at Roper/St Francis Health and is the medical director of student education VCOM-Spartanburg. He also serves as chair of AOBIM (responsible for creation and maintenance of board certification exams) and endocrinology section head. He is a frequently invited lecturer and has received numerous awards for excellence in patient care and golden apples for his teaching acumen. He lives in Charleston with his wife of 28 years, who works locally as a dentist and educator, and their three children.

Abstract
Introduction: The National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) of the United States of America defines pharmacogenomics as the area of medicine whose primary objective is to evaluate the relationship between the genetic profile and the variability in responses to drug therapy, and toxicities. Among all leukemias, acute myeloid leukemia (AML) is the most frequent in the adult population, characterized by the disordered growth of immature blood cells called myeloblasts. Various obstacles, like the need for early diagnosis, the biochemical characteristics of the disease itself, the emergency profile of starting treatment, and the difficulty of accessing new non-cytotoxic chemotherapy treatments, may influence therapeutic success. However, among these challenges, the genotypic variability of patients in respect to the metabolism of drugs used to treat AML stands out. This variability can contribute to increases in toxicity of medications and influence the clinical outcome. Cytochrome P450 (CYP450) is a superfamily of enzymes related to various reactions in the body. In the human genome, 57 CYP450 genes that encode functional proteins have been found and grouped according to their homology. A significant number of copy number variations have been noted in these genes, which may influence the biotransformation of drugs. The genes that encode the glutathione S-transferases (GST) enzymes present considerable polymorphisms depending on ethnic variations and can suffer both homozygous gene deletions, leading to loss of function, and heterozygous deletions or duplications, leading to loss or gain of function. Therefore, mutations can guide changes in the biotransformation of drugs. Objective: This study aimed to determine the frequency of genetic alterations as deletions and duplications in cytochrome P450 (CYP450) and glutathione S-transferases (GST) genes, as well as to investigate whether there is a relationship between these alterations and neutrophilic hematologic recovery in adult patients diagnosed with acute myeloid leukemia. Method: DNA samples from 70 patients diagnosed with acute myeloid leukemia were evaluated using the Multiplex Ligation-dependent Probe Amplification (MLPA) technique. The presence or absence of polymorphisms was compared regarding the time to neutrophilic recovery- (neutrophil count ≥1.0 x 10⁹/L) using Kaplan-Meier curves, with the comparison between the curves being performed using the non-parametric log-rank test. Neutrophil toxicity was analyzed in 46 patients (65.7%), as 24 patients died before completing induction therapy. Minor neutrophil toxicity was characterized by a recovery time of up to 21 days to achieve ≥1.0 x 10⁹/L neutrophils, while major toxicity takes longer than 21 days to recover. The neutrophilic recovery time (NRT) of 21 days was chosen because it allows for the start of a new cycle of chemotherapy in most protocols for the treatment of AML. Results: The median age of the participants was 57 years, with a higher proportion of females (57.2%) and white individuals (61.4%). A striking observation is that 76 occurrences of polymorphisms were verified in the 54 patients, with some patients presenting polymorphisms in more than one family of genes. Consistent duplications in CYP450 and GST, deletions in CYP450 and GST, deletions in CYP450 and duplications in GST, and duplications in CYP450 and deletions in GST. The following genes were analyzed: GSTP1, CYP1A1, CYP1A2, CYP2B6, CYP2C9, and CYP2C19. However, none of the patients had any polymorphisms in these genes. The robust Fisher’s exact test we applied to evaluate neutrophilic recovery time between groups with and without polymorphisms obtaining a p-value = 0.0287, and Kaplan-Meier curves revealed that the median NRT for patients with polymorphisms of CYP450 and GST was 21 days, while the median NRT for the group without polymorphisms was 12 days (p-value = 0.0056). Conclusion: The study demonstrated that CYP450 and GST genes are polymorphic, and these polymorphisms may lead to longer neutrophilic recovery after induction treatment of acute myeloid leukemia remission. In conclusion, pharmacogenomics is a crucial factor in pharmacotherapy and should be considered.

Biography
Dr. Gilmar De A. França holds a Master of Science degree from the School of Medicine of the University of São Paulo, São Paulo, Brazil, with an emphasis in Molecular Biology and Hematology. He is a specialist in Clinical Oncology from Hospital Sírio-Libanês, São Paulo, Brazil, and a specialist in Clinical Pharmacy from Hospital Israelita Albert Einstein, São Paulo, Brazil. Currently, he serves as a Professor of Molecular Biology and Biotechnology in the Pharmacy program at Faculdade Oswaldo Cruz, São Paulo, Brazil, and as a Pharmacist at Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.

Abstract

Background: Limb-Girdle Muscular Dystrophy (LGMD) is a rare heterogeneous group of Neuromuscular disorders distinguished by progressive weakness of limb-girdle muscles. Diagnosis of LGMD is a challenging task and requires multiple obligatory assays. Through Next-Generation Sequencing (NGS)  ameliorate the speed, cost, and resolution of diagnosis, enabling the simultaneous analysis of multiple genes and genetic variants and bestow the better understanding of the molecular mechanisms underlying LGMD and its subtypes

Objective: To study the epidemiology, clinical features, the genetic variability in patients diagnosed with LGMD through Next Generation Sequencing.

Material and Method – A retrospective study of 27 patients suspected of LGMD was done to study the phenotypic presentation and the genotypic alteration of the patients, presenting to a tertiary care center in Rajasthan were studied.

Results: Out of the twenty-seven patients suspected of LGMD, nineteen patients took genetic tests, while eight patients underwent biopsy. Among the nineteen patients, seventeen patients were identified with pathogenic mutations. Autosomal Recessive (LGMD-R) was the most common subgroup in this cohort. In the LGMD R1 subgroup, the most common mutation was c.2051–1 G > T and the exon hotspot was 18–22. The deleterious mutations in the LGMD R2subgroup were distributed along the entire coding sequence, without any hotspot. However, C2E, C2F, and DysF domains contain variants at higher frequencies. The types of mutations were mostly point mutations (34 % of missense mutations and 66 % of nonsense mutations). We identified one novel mutation which was considered as a stop codon. Patients (n = 8) who underwent muscle biopsy for immunohistochemistry, had absent/reduced sarcoglycan uptake (n = 4) or absent dysferlin (n = 2) on the sarcolemma, while the remaining two biopsies were inconclusive (due to multiple protein deficiencies).

Biography 

Dr. Urvashi Vijay is a Research Scientist-C at SMS Medical College, Jaipur, with a Ph.D. in Biotechnology and extensive experience in molecular biology, clinical microbiology, and translational research. Her academic journey spans prestigious institutions such as Banasthali University, The IIS University, and Birla Institute of Scientific Research.

She has made notable contributions in the fields of infectious diseases, cancer genomics, neurogenetics, and public health, including collaborative projects funded by ICMR, DHR-MDRU, and WHO. Her work involves multidisciplinary approaches combining advanced molecular techniques, next-generation sequencing, and clinical diagnostics.

Dr. Vijay has authored over 20 peer-reviewed publications and book chapters with reputed publishers such as Elsevier, and she has served as a reviewer for journals like Science of the Total Environment, Water Research, and Elyon Cancer Journal. She is a member of several scientific societies, including the Association of Microbiologists of India and STOX.

Her current research includes genomic studies in muscular dystrophies, enteroviral infections, and non-invasive biomarkers for cancer. Passionate about innovation and collaboration, she continues to drive translational research forward through both bench work and clinical integration.