Variable Clinical Presentation Research Articles

COVID and Vaccine-related Cerebral Venous Thrombosis

The coronavirus disease-2019 (COVID-19) pandemic has been a major threat to global health. It primarily affects the respiratory system but multiple organs, including the nervous system, can be affected. Cerebral venous thrombosis (CVT) has been reported among COVID-19 patients as well as among recipients of COVID vaccines. CVT often remains a diagnostic challenge due to highly variable clinical presentation. We underwent a thorough narrative review of the published literature from January 2020 to April 2023 in the Medline (PubMed) database. Our search led to 66 studies in total, 30 related to COVID-CVT and 36 related to COVID vaccine-CVT. We further looked for differences between these COVID-CVT and COVID vaccine-associated-CVT and their possible pathophysiology, treatment options, and prognosis. A few things that were highlighted during our search: COVID increases CVT risk and can happen without respiratory manifestations. COVID-CVT is more common in middle-aged men and has a higher morality compared to traditional non-COVID-CVT. COVID vaccines also increase the risk of CVT but less than the COVID infection. COVID vaccine-CVT is further divided into two groups having either normal platelets or low platelets. The latter group is better reported and has a higher inpatient mortality and disability at discharge but these patients usually recover well in the follow-up period. Non-heparin anticoagulation, immunomodulation, and surgery are the main treatment options.

Diagnosis, Management, and Prognosis of Cystic Fibrosis-Related Liver Disease in Children.

Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease.

DRESS syndrome: More than just a rash.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is rare but carries significant mortality and morbidity, making early identification and definitive management crucial. The diagnosis of DRESS is made clinically and involves consideration of a broad list of differential diagnoses. Given variable clinical presentations among patients with DRESS syndrome, clinicians should look for common findings and other hallmarks of the syndrome while monitoring for known complications. Additionally, clinicians should maintain a high index of suspicion to avoid missing more mild presentations, such as in this case patient with DRESS syndrome minor.

An Observational Study to Correlate the Histopathological and Dermoscopic Features in Leprosy Patients in a Tertiary Care Hospital.

Leprosy is a chronic granulomatous infection with varied clinical presentations. Dermoscopy is a noninvasive technique widely used in the diagnosis of various skin diseases. To see the correlation between the clinical and dermoscopic features with the histopathological findings in leprosy. A prospective observational study was conducted on clinically suspected leprosy patients attending the dermatology outpatient department (OPD) for 18 months. Representative lesions were observed by dermoscopy, and a biopsy was performed, followed by histopathology for final diagnosis. Patients were categorized by Ridley-Jopling classification. A total of 70 clinically suspected leprosy patients were included in the study. Amongst 70 cases, 56 cases were diagnosed as leprosy by dermoscopy, and 53 cases were confirmed as leprosy by histopathology (hematoxylin and eosin [H and E] staining and Fite-Faraco staining). The other six cases were diagnosed as other nonspecific dermatitis by histopathological findings. Eleven cases that were dermoscopically negative were also confirmed by histopathology to be truly negative. There are three inconclusive cases of dermoscopic findings, which were diagnosed as mid-borderline leprosy by histopathology. Dermoscopic and histopathological correlation was found above 87% in all types of leprosy except mid-borderline leprosy, which showed only a 25% correlation. Dermoscopy is a useful noninvasive tool to assess lesions of leprosy, requires less time for diagnosis, skin features are magnified several times and may become evident before clinical presentation. It definitely helps to reduce the number of biopsies in case of diagnosis of leprosy. However, in doubtful cases, histopathology is required for definitive diagnosis as it is the gold standard to date.

Role of vaccination in patients with human monkeypox virus and its cardiovascular manifestations.

Human monkeypox, caused by the monkeypox virus (MPXV), is an emerging infectious disease with the potential for human-to-human transmission and diverse clinical presentations. While generally considered milder than smallpox, it can lead to severe cardiovascular complications. The virus primarily spreads through contact with infected animals or through human-to-human transmission. Cardiovascular involvement in human monkeypox is rare but has been associated with myocarditis, pericarditis, arrhythmias, and even fulminant myocardial infarction. Vaccination plays a crucial role in preventing and controlling monkeypox, but the eradication of smallpox has left global populations vulnerable. This review explores the cardiovascular manifestations of human monkeypox, the role of vaccination in disease prevention, and the importance of continued research and development of effective vaccines to protect against this emerging infectious threat. The global impact of monkeypox outbreaks, particularly on vulnerable populations, further highlights the importance of understanding and addressing this disease.

Ileal perforation-etiopathology and outcome – An observational study

Background: Ileal perforations have a diverse etiology and often present with perforative peritonitis in the surgical emergency. This study is based on the scenario of management of ileal perforation encountered in a tertiary teaching hospital in West Bengal. Aims and Objectives: The aim and objective of this study is to document and evaluate the post-operative outcome based on the diverse etiopathology, clinical presentation, and surgical management performed in patients having ileal perforation. Materials and Methods: A prospective cross-sectional observational study was conducted in the Deben Mahata Government Medical College, Purulia, West Bengal, for a period of 2 years from February 2020 to January 2022 with 60 patients introperatively diagnosed with ileal perforation. Emergency exploratory laparotomy was done in all the cases presenting with perforative peritonitis. Ileal perforation was identified and an edge biopsy was taken. Appropriate surgical treatment in the forms of primary repair/resection-anastomosis/resection-ileostomy was done. The histopathological report was reviewed following surgery. The patients were evaluated in the post-operative period for post-operative morbidity and mortality. Results: Typhoid fever (68.33%) was the predominant cause in our study. The most common symptoms were abdominal pain (93%), fever (85%), and abdominal distension (75%). Widal test was performed preoperatively and was positive in 41 cases (68.33%). In our study, primary repair (58.33%), resection-anastomosis (15%), and resection-ileostomy (26.67%) were the main surgical treatment performed. Sepsis, surgical site infections (SSIs), fecal fistula, and wound dehiscence were the common post-operative complications found. Among them, SSI (51.67%) was the most common post-operative complication (P<0.0001) found and fecal fistula was the most dreaded post-operative complication with 50% mortality. Histopathological reports following surgery showed cases were mainly due to enteric fever (51.67%) and tuberculosis (25%). Conclusion: Early surgical intervention was the mainstay of treatment of ileal perforation. Delayed presentation of perforation is responsible for the development of surgical site infections (SSIs). Uncontrolled generalized sepsis, wound dehiscence, and fecal fistula were the main causes of post-operative mortality.

Comparison of the transarterial, transvenous, and superior ophthalmic vein approaches in the treatment of indirect carotid-cavernous fistulas.

Indirect carotid-cavernous fistulas (CCFs) are abnormal arteriovenous shunting lesions with a highly variable clinical presentation that depends on the drainage pattern. Based on venous drainage, treatment can be either transarterial (TA) or transvenous (TV). The aim of this study was to compare the outcomes of indirect CCF embolization via the TA, TV, and direct superior ophthalmic vein (SOV) approaches. The authors conducted a retrospective analysis of 74 patients admitted to their institution from 2010 to 2023 with the diagnosis of 77 indirect CCFs as confirmed on digital subtraction angiography. A total of 74 patients with 77 indirect CCFs were included in this study. Embolization was performed via the TA approach in 4 cases, the TV approach in 50 cases, and the SOV in 23 cases. At the end of the procedure, complete occlusion was achieved in 76 (98.7%) cases. The rate of complete occlusion at the end of the procedure and at last radiological follow-up was significantly higher in the SOV and TV cohorts than in the TA cohort. The rate of recurrence was highest in the TA cohort (25% for TA vs 5.3% for TV vs 0% for SOV, p = 0.68). The rate of immediate complete occlusion was higher in the TV and SOV cohorts than in the TA cohort while the rate of complete occlusion at final follow-up was highest in the SOV cohort. The SOV approach was significantly associated with higher rates of postoperative complications. Indirect CCFs require careful examination of the fistulous point and the venous drainage to provide the most effective patient-tailored approach.

Clinician's approach for spectrum of orbital diseases: An overview.

To study the varied clinical presentation and outcome of management of orbital diseases and to ascertain the concordance of FNAC with histopathology. This is a prospective interventional study wherein each patient's clinical presentation was noted. Outcome of management was evaluated based on symptomatic relief, regression of signs, noting any intraoperative or postsurgical complication, recurrence, and cosmetic result in terms of surgical scar. Neoplasia was commonest 33/76; (43.42%), followed by infective and inflammatory conditions 21/76; (27.63% cases), thyroid-associated orbitopathy accounting for 12/76 cases (15.78%), whereas cystic lesions and vascular malformations were 4/76 (5.26%) each. Other disorders constituted a mere 2.65%. Proptosis was the commonest mode of presentation. It was seen in seventy out of seventy-six patients (92.1%). In 86.3% of the cases, there was successful surgical outcome. Of 22 surgically managed cases, recurrence was noted in three cases (13.6%). 90% concordance was seen with histopathology in cases where FNAC was done prior to surgery for diagnosing nature of disease. Majority of orbital and adnexal conditions can be provisionally diagnosed based on imaging; however, an adjunct invasive investigation such as FNAC or biopsy may be required. In the present study, in seven cases (9.2%) FNAC was needed, whereas in two cases (2.63%) biopsy was needed. A definitive diagnosis was confirmed by histopathology in 22 surgically managed cases and by excision biopsy in two. 22/76 (28.94%) of the cases needed surgical treatment, and other cases required conservative or palliative approach.

Aetiology of Vascular Purpura in a Single Centre Experience: Contribution of Clinical and Paraclinical Data.

Vascular purpura can be the clinical expression of infectious, inflammatory, drug-related, neoplastic, and endocrine pathologies. To date, there is no consensus codifying the investigation of vascular purpura, especially when it is isolated. We proposed to study through a retrospective study of 73 cases of vascular purpura, occurring during the period 2004-2019 in our internal medicine department, the contribution of various clinical and paraclinical data to the aetiological diagnosis of vascular purpura. Data were considered to be contributory only when they constituted a solid argument in favour of the aetiological diagnosis of vascular purpura. Our series involved 73 patients including 41 women and 32 men (Gender ratio: 0.78). Mean age was 49 ± 17 years [16-80]. Vascular purpura was isolated in 3% of cases. For the remaining patients, it was associated with functional (91%) or physical (48%) manifestations. It was associated with other skin lesions in 45% of cases. The accepted aetiologies were primary vasculitis (26%), drug-related (15%), infectious (11%) and secondary to connectivitis (10%). No cause was found in a third of cases. Clinical data alone made it possible to suggest the aetiology in more than half of cases. Special investigations were contributory in 46% of cases. The course was contributory in 18% of patients for drug-related and paraneoplastic causes. vascular purpura's diverse clinical presentation presents diagnostic challenges. Aetiologies include vasculitis, drug reactions, infections, and connective tissue disorders. Comprehensive clinical assessment is essential.

Is Alzheimer disease a disease?

Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities - amyloid-β plaques and tau protein neurofibrillary tangles - that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-β toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-β has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single 'silver bullet'. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously.

Can head sway patterns differentiate between patients with Meniere's disease vs. peripheral vestibular hypofunction?

Meniere's disease (MD) is defined by episodic vertigo, unilateral sensorineural hearing loss and fluctuating aural symptoms. Due to the variable clinical presentation, objective tests of MD may have significant diagnostic utility. Head kinematics derived from a head-mounted display (HMD) have demonstrated to be sensitive to vestibular dysfunction. The purpose of this pilot study was to investigate whether head sway can differentiate between patients with MD, vestibular hypofunction (VH) and healthy controls. 80 adults (30 healthy controls, 32 with VH, and 18 with MD) were recruited from a tertiary vestibular clinic. All underwent a postural control assessment using the HTC Vive Pro Eye HMD that recorded head sway in the anterior-posterior (AP), medio-lateral (ML), pitch, yaw and roll direction. Participants were tested with 2 levels of visual load: a static versus oscillating star display. Each scene lasted 60 s and was repeated twice. Sway in each direction was quantified using root mean square velocity (VRMS) for the first 20 s and full 60 s of each scene. Static visual: participants with VH showed significantly larger head VRMS than controls in the AP (60 s and 20 s) and pitch (20 s) directions. Dynamic visual: participants with VH showed significantly larger head VRMS than controls all directions for both the 60 and 20 s analysis. Participants with MD did not differ significantly from the control or the VH group. While limited in numbers, Patients with MD had a high variability in head sway in all directions, and their average head sway was between controls and those with VH. A larger sample as well as patients with worse symptoms at time of testing could elucidate whether head sway via HMD could become a viable test in this population. A similar finding between 20- and 60-s scene and the full portability of the system with an in-clinic testing setup could help these future endeavors. Head sway derived from HMD is sensitive to VH and can be clinically useful as an outcome measure to evaluate sensory integration for postural control.

Recent advances in the diagnosis of drug-induced liver injury.

Drug-induced liver injury (DILI) is a major problem in the United States, commonly leading to hospital admission. Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes. In addition, DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease. Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems. This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.

Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.

To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population. Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

Reversible Cerebral Vasoconstriction Syndrome With Typical and Atypical Symptoms: A Case Series.

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) is most commonly characterized by focal or diffuse severe thunderclap headache with or without focal neurological deficits and associated transient focal vasoconstriction of the intracerebral arteries lasting up to three months. We present six patients diagnosed as RCVS, with three patients presenting with focal neurological deficits without headache and the remaining three with severe headache alone. Neuroimaging revealed focal subarachnoid bleed with or without segmental intracerebral vasospasm, which resolved over three months. Despite thunderclap headache being the most prevalent symptom associated with RCVS, the absence of this symptom should not preclude the diagnosis, especially in the presence of cortical subarachnoid hemorrhage (SAH) or focal segmental intracerebral arterial narrowing. Methods This case series is a retrospective analysis of all patients diagnosed with RCVS between 2018 and 2022, focusing on clinical symptoms, imaging findings, and management. Results Six patients (three males and three females) were diagnosed with RCVS between 2018 and 2022. Three patients presented with typical symptoms, while the remaining three presented with atypical symptoms. Neuroimaging findings ranged from normal to focal SAH with or without arterial narrowing. Conclusion This case series underscores the diverse clinical presentations of RCVS, emphasizing that while thunderclap headache is the predominant symptom, its absence should not exclude the possibility of RCVS, especially when accompanied by focal neurological deficits or cortical SAH. Neuroimaging played a crucial role in identifying the spectrum of findings. These findings highlight the importance of comprehensive evaluation and consideration of RCVS in patients presenting with neurological symptoms, even in the absence of typical headache features.

Enlarged tumefactive perivascular, or Virchow-Robin, spaces and hydrocephalus: do we need to treat? Illustrative cases.

Perivascular spaces (PVSs) are spaces in brain parenchyma filled with interstitial fluid surrounding small cerebral vessels. Massive enlargements of PVSs are referred to as "giant tumefactive perivascular spaces" (GTPVSs), which can be classified into three types depending on their localization. These lesions are rare, predominantly asymptomatic, and often initially misinterpreted as cystic tumor formations. However, there are several reported cases in which GTPVSs have induced neurological symptoms because of their size, mass effect, and location, ultimately leading to obstructive hydrocephalus necessitating neurosurgical intervention. Presented here are three diverse clinical presentations of GTPVS. Here, the authors observed an asymptomatic case of type 1 GTPVS and two symptomatic cases of type 3 GTPVS, one causing local mass effect and the other hydrocephalus. GTPVSs are mostly asymptomatic lesions. Patients without symptoms should be closely monitored, and biopsy is discouraged. Hydrocephalus resulting from GTPVS necessitates surgical intervention. In these cases, third ventriculostomy, shunt implantation, or direct cyst fenestration are surgical options. For patients presenting with symptoms from localized mass effect, a thorough evaluation for potential neurosurgical intervention is imperative. Follow-up in type 3 GTPVS is recommended, particularly in untreated cases. Given the infrequency of GTPVS, definitive guidelines for neurosurgical treatment and subsequent follow-up remain elusive.

Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease.

The Ras family of small GTPases coordinates tissue development by modulating cell proliferation, cell-cell adhesion, and cellular morphology. Perturbations of any of these key steps alter nervous system development and are associated with neurological disorders. While the underlying causes are not known, genetic mutations in Ras and Rap GTPase signaling pathways have been identified in numerous neurodevelopmental disorders, including autism spectrum, neurofibromatosis, intellectual disability, epilepsy, and schizophrenia. Despite diverse clinical presentations, intersections between these two signaling pathways may provide a better understanding of how deviations in neurodevelopment give rise to neurological disorders. In this review, we focus on presynaptic and postsynaptic functions of Ras and Rap GTPases. We highlight various roles of these small GTPases during synapse formation and plasticity. Based on genomic analyses, we discuss how disease-related mutations in Ras and Rap signaling proteins may underlie human disorders. Finally, we discuss how recent observations have identified molecular interactions between these pathways and how these findings may provide insights into the mechanisms that underlie neurodevelopmental disorders.

Rare Presentation: Primary Leiomyosarcoma of the Thyroid Gland

Leiomyosarcoma, an uncommon tumor, becomes even rarer when it emerges within the thyroid gland. Diagnosing it accurately is a challenging task due to its atypical location, diverse clinical and radiological presentations, its rarity, and overlapping differential diagnoses. However, immunohistochemistry studies can offer a precise identification. In this article, we present a compelling case of recurrent primary leiomyosarcoma of the thyroid gland in a 23-year-old man, revealed by inspiratory dyspnea caused by a voluminous cervical mass and ultimately confirmed as leiomyosarcoma through histopathological examination.

Giant Cell Tumor of Soft Tissue Masquerading as a Fibroma - A Rare Clinical Entity

Giant cell tumor of the soft tissue (GCT-ST) is a rare and distinctive entity, separate from its bony counterpart, giant cell tumor of bone. This primary soft tissue tumor is often encountered in middle-aged individuals but rarely in children, with common sites including superficial soft tissue of the extremities. GCT-ST typically presents as a painless, slowly growing mass, emphasizing the importance of complete excision to prevent recurrences and metastasis. We present a case of GCT-ST in a 7-year-old boy with a nodular swelling on the right hip, initially suspected to be a fibroma. Histopathological examination revealed characteristic features of GCT-ST, including spindle and stellate cells, multinucleated giant cells, and haemosiderin-laden macrophages with metaplastic osseous tissue. This case adds to the limited literature on GCT-ST, highlighting its diverse clinical presentations and challenging diagnostic nature. The discussion includes a review of reported cases of GCT-ST, which have shown varied clinical presentations and outcomes. Histologically, GCT-ST resembles a giant cell tumor of bone, with positive staining for CD68, SMA, Vimentin, and p63. Imaging studies typically reveal a solid hemorrhagic mass. Differential diagnoses include benign and malignant soft tissue tumors rich in giant cells. Keywords: Giant Cell Tumor of Soft Tissue (GCT-ST), Rare, Fibro-Histiocytic Tumor Of Intermediate Malignancy, Soft Tissue Tumor, Rare Tumors In Children.

Truenat: Can it be A Game Changer in Extrapulmonary Tuberculosis?

Tuberculosis is a leading health problem worldwide, with India accounting for the majority of cases. Owing to the diverse clinical presentation and paucibacillary nature of extrapulmonary tuberculosis, it is tough to diagnosis by routine microbiological methods. Newer chip/cartridge based nucleic amplification tests (NAATs) like Truenat and Xpert have proved to be game changer in diagnosis of pulmonary tuberculosis. However, role of Truenat in extrapulmonary tuberculosis is still to be evaluated. This study was undertaken to evaluate the diagnostic yield of truant in various extrapulmonary tuberculosis. The study was conducted during 01 June 2021 to 31 July 2022. Of the total 1481 samples received during study, 761 (52%) were extrapulmonary samples. The highest yield of 36% was found in pus aspirate, followed by a 12% yield in pleural fluid. Overall yield of 12% in various extrapulmonary samples is encouraging. Further studies are required for evaluating Truenat role in rapid diagnosis of EPTB and rifampicin resistance detection for better patient care.

From Antibodies to Artificial Intelligence: A Comprehensive Review of Diagnostic Challenges in Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) poses diagnostic challenges due to its diverse clinical presentation and the intricacies of autoimmune thyroid diseases. This comprehensive narrative review explores the evolving landscape of diagnostic challenges in HT, aiming to provide a thorough understanding of the complexities involved in its diagnosis. The diagnostic criteria for HT involve a multifaceted approach, including clinical features, laboratory findings, and imaging studies. Serum antibodies against thyroid antigens, primarily thyroperoxidase (TPO) and thyroglobulin, play a crucial role in confirming the autoimmune nature of the disease. However, seronegative HT adds complexity by presenting without detectable antibodies. The significance of addressing diagnostic challenges lies in potential delays and misdiagnoses, emphasizing the need for accurate and timely intervention. The review explores future directions, emphasizing molecular and cellular aspects, genetic factors, and the emerging field of thyroid regeneration. Standardized diagnostic criteria are essential, considering the subjective nature of the current process. The heterogeneity of disease manifestations complicates targeted treatments, necessitating a deeper understanding of clinical presentations and underlying pathophysiology. Future research directions and challenges outlined in this review contribute to advancing our understanding and improving diagnostic precision in HT.