Importance of right communication with healthcare providers and patients about the new levothyroxine formulation: an expert opinion from Asia Pacific Thyroid Advisory Board

\ua9 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Levothyroxine (LT4), being “narrow therapeutic index” drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95–105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

Diagnostic techniques for inflammatory eye disease: past, present and future: a review

Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials

Beta-cell function in type 2 diabetic patients who failed to maintain good glycemic status with a combination of maximum dosages of metformin and sulfonylurea

Tada Kunavisarut, Sutin Sriussadaporn, Raweewan LertwattanarakDivision of Endocrinology and Metabolism, Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground: The aim of this study was to investigate beta-cell function and examine whether sulfonylureas (SUs) are still useful in patients with type 2 diabetes (T2DM) who failed to maintain optimal glycemic control with a combination of maximum dosages of metformin and SU.Method: T2DM who had HbA1c >8% during treatment with a combination of maximum dosages of metformin and SU were studied. After enrollment, the patients were assigned to continue maximum dosages of SU and metformin for 2 weeks and then underwent the first oral glucose tolerance test (OGTT), the Max-SU OGTT. After the Max-SU OGTT, SUs were discontinued for 4 weeks and the second OGTT, the Discont-SU OGTT, was performed. After the Discont-SU OGTT, the same SU was restarted at 25% of the maximum dosage (25%Max-SU). After taking 25%Max-SU for 4 weeks, the third OGTT, the 25%Max-SU OGTT, was performed. Metformin at the same dosage was continued throughout the study. Normal OGTT (NGT) subjects, matched for age and body mass index (BMI), were also studied.Results: There were 25 T2DM and 28 NGT subjects. There was no difference in age and BMI between the two groups. The beta-cell function during Max-SU was 0.1, which was higher than 0.06 during Discont-SU (p<0.001) and also higher than 0.09 during 25%Max-SU (p=0.269). The beta-cell function during 25%Max-SU was higher than during Discont-SU (p<0.001). The beta-cell function of the NGT group was 0.34 and higher than during Max-SU (p<0.001). Fasting capillary blood glucose (FCBG) levels during Discont-SU (14.2±3.7 mmol/L) were higher than during 25%Max-SU (12.3±3.4 mmol/L) and during Max-SU (10.3±2.4 mmol/L) (p<0.05). In addition, the FCBG during Discont-SU was higher than that during 25%Max-SU (p<0.05).Conclusion: In T2DM patients who failed to achieve glycemic control with a combination of maximum dosages of metformin and SU, the beta-cell function declined compared to NGT subjects. However, the beta-cells were still responsive to SUs, which play a significant role in glycemic control.Keywords: beta-cell function, sulfonylureas, sulfonylurea failure, type 2 diabetes mellitu

Spontaneous Large Serous Retinal Pigment Epithelial Tear

Purpose: To report cases of spontaneous retinal pigment epithelial (RPE) tear complicating serous pigment epithelial detachment (PED). Methods: The records of 3 Asian patients with spontaneous giant RPE tear were reviewed retrospectively by including clinical presentation, angiography, optical coherence tomography, fundus autofluorescence imaging, and visual outcome. Results: Three patients (4 eyes) were included in this study, with a mean age of 48.3 (42–56) years, and a mean follow-up period of 7.75 (4–18) months. Fundus examination in all patients showed giant RPE tear associated with bullous PED. Two cases had a history of prior corticosteroid use, and 1 had no history of medication use. All 3 patients developed spontaneous resolution of subretinal fluid with no treatment. However, in patients who used corticosteroids, initial progression of the tear and subretinal fluid were observed despite ceasing medication. On subsequent follow-up, an incomplete RPE regeneration was demonstrated by fundus autofluorescence imaging, and choroidal neovascularization developed in 1 patient. Conclusion: Large PED with RPE tear is a rare manifestation. When the fovea is spared, visual prognosis is favorable. No specific treatment is required, but careful choroidal neovascularization monitoring should be performed

HLA‐B27‐associated acute anterior uveitis in the University Referral Centre in North Thailand: clinical presentation and visual prognosis

BACKGROUND: Acute anterior uveitis (AAU) is the most frequent type of uveitis encountered in the west. Although human leucocyte antigen (HLA)‐B27‐associated ankylosing spondylitis was reported in South East Asia, it is not known whether HLA‐B27‐associated ocular disease is prevalent in Thailand. METHODS: A prospective study of 100 unrelated blood donors and 121 consecutive patients with AAU was carried out. All people underwent HLA‐B27 typing and full ocular examination. Radiological examination of the sacroiliac joints was conducted in patients with low back pain or arthralgias. RESULTS: The prevalence of HLA‐B27 was 10% among the blood donors in contrast with 44% in the AAU group (p<0.001). The clinical characteristics of HLA‐B27‐associated AAU were similar to those published throughout the world (unilaterality in 74%, hypopyon in 31%, recurrent AAU in 64%). However, the increased intraocular pressure (IOP) was more common in the HLA‐B‐27‐negative group (p = 0.03) than in their HLA‐B27‐positive counterparts. At least 15% of the HLA B27‐positive group had radiological signs of ankylosing spondylitis. CONCLUSION: The prevalence of HLA‐B27 in the population without uveitis in Thailand is about 10% and clinical characteristics of HLA‐B27‐positive AAU are similar to those reported in the west. In contrast with earlier reports, HLA‐B27‐negative AAU in Thailand was associated with increased IOP and should be further studied