Incidence, recurrence and mortality among Filipinos with differentiated thyroid cancer: A systematic review / Journal of the ASEAN Federation of Endocrine Societies

Background@#The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality (DSM) of DTC among Filipinos residing in the Philippines and Filipino immigrants.@*Methodology@# In accordance with the 2020 PRISMA statement, we performed a systematic literature search in MEDLINE, Google Scholar, EBSCO, Cochrane and Clinicaltrials.gov for the period January 1, 1980 until January 27, 2022. Pooled incidence rate ratio and pooled proportions of disease extent, recurrence and DSM were determined.@*Results@#Literature search yielded 1,852 studies. Out of 26 articles retrieved, nine retrospective case controls and cohorts were included. Incidence of DTC was significantly higher in female Filipino immigrants compared with non-Hispanic whites (NHW). Distant metastases and recurrence were more common among Filipinos and Filipino immigrants compared with NHW. Limited data showed higher DSM in Filipino immigrants and NHW than Filipinos, which may be influenced by reporting bias.@*Conclusion@#This review supports the trend of increased incidence and recurrence of DTC among Filipinos, although case registries are essential to confirm these findings. In the setting of the newly released Philippine guidelines for DTC, prospective studies with active long-term follow-up will help detect any changes in the outcomes of DTC among Filipinos.

Genetic variants associated with poor responsiveness to sulfonylureas in Filipinos with type 2 diabetes mellitus / Journal of the ASEAN Federation of Endocrine Societies

Introduction@# Sulfonylureas (SUs) are commonly used drugs for type 2 diabetes mellitus (T2DM) in the Philippines. This study aimed to associate genetic variants with poor response to gliclazide and glimepiride among Filipinos.@*Methodology@#Two independent, dichotomous longitudinal substudies enrolled 139 and 113 participants in the gliclazide and glimepiride substudies, respectively. DNA from blood samples underwent customized genotyping for candidate genes using microarray. Allelic and genotypic features and clinical associations were determined using exact statistical methods.@*Results@#Three months after sulfonylurea monotherapy, 18 (13%) were found to be poorly responsive to gliclazide, while 7 (6%) had poor response to glimepiride. Seven genetic variants were nominally associated (p<0.05) with poor gliclazide response, while three variants were nominally associated with poor glimepiride response. For gliclazide response, carboxypeptidase-associated variants (rs319952 and rs393994 of AGBL4 and rs2229437 of PRCP) had the highest genotypic association; other variants include rs9806699, rs7119, rs6465084 and rs1234315. For glimepiride response, 2 variants were nominally associated: CLCN6-NPPA-MTHFR gene cluster – rs5063 and rs17367504 – and rs2299267 from the PON2 loci.@*Conclusion@#Genetic variants were found to have a nominal association with sulfonylurea response among Filipinos. These findings can guide for future study directions on pharmacotherapeutic applications for sulfonylurea treatment in this population.

Therapeutic plasma exchange in thyroid storm refractory to conventional treatment

@#<p style="text-align: justify;">Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves' disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01-19.05 pmol/L), FT3 23.91 (NV: 2.89-4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves' disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01-19.05 pmol/L), FT3 23.91 (NV: 2.89-4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.</p>

AFES A.S.-O.N.E.: ASEAN survey of needs in Endocrinologyin the time of the COVID-19 pandemic / Journal of the ASEAN Federation of Endocrine Societies

Objectives@#The COVID-19 pandemic has made a major impact on hospital services globally, including the care of persons with diabetes and endocrine disorders. The aim of this study is to describe the epidemiology of COVID-19 in the ASEAN Federation of Endocrine Societies (AFES) member countries; to describe challenges, changes and opportunities in caring for patients with endocrine diseases, as well as in fellowship training programs, and endocrine-related research in the AFES countries.@*Methodology@#The AFES ASEAN Survey Of Needs in Endocrinology (AFES A.S.-O.N.E.) was an open-ended questionnaire that was sent to the presidents and representatives of the AFES member countries by email. Responses from Societies were collated and synthesized to obtain perspectives on the emergent issues in endocrinology in the Southeast Asian region during this pandemic.@*Results@#The burden of COVID-19 cases varied widely across the AFES member countries, with the least number of cases in Vietnam and Myanmar, and the greatest number of cases in either the most populous countries (Indonesia and the Philippines), or a country with the highest capability for testing (Singapore). The case fatality rate was also the highest for Indonesia and the Philippines at around 6%, and lowest for Vietnam at no fatalities. The percentage with diabetes among patients with COVID-19 ranged from 5% in Indonesia to 20% in Singapore, approximating the reported percentages in China and the United States. The major challenges in managing patients with endocrine diseases involved inaccessibility of health care providers, clinics and hospitals due to the implementation of lockdowns, community quarantines or movement control among the member countries. This led to disruptions in the continuity of care, testing and monitoring, and for some, provision of both preventive care and active management including surgery for thyroid cancer or pituitary and adrenal tumors, and radioactive iodine therapy. Major disruptions in the endocrine fellowship training programs were also noted across the region, so that some countries have had to freeze hiring of new trainees or to revise both program requirements and approaches to training due to the closure of outpatient endocrine clinics. The same observations are seen for endocrine-related researches, as most research papers have focused on the pandemic. Finally, the report ends by describing innovative approaches to fill in the gap in training and in improving patient access to endocrine services by Telemedicine.@*Conclusion@#The burden of COVID-19 cases and its case fatality rate varies across the AFES member countries but its impact is almost uniform: it has disrupted the provision of care for patients with endocrine diseases, and has also disrupted endocrine fellowship training and endocrine-related research across the region. Telemedicine and innovations in training have been operationalized across the AFES countries in an attempt to cope with the disruptions from COVID-19, but its over-all impact on the practice of endocrinology across the region will only become apparent once we conquer this pandemic.

Clinical characterization of post-parathyroidectomy patients with primary hyperparathyroidism and the concordance of preoperative localization imaging with histopathology at a tertiary hospital in Manila, Philippines / Journal of the ASEAN Federation of Endocrine Societies

@#<strong>BACKGROUND:</strong> Philippine studies on primary hyperparathyroidism (PHPT) and preoperative localization are scarce, making improvements on detection and recognition particularly difficult.<strong>OBJECTIVE</strong>: Describe the clinical profile of post-parathyroidectomy PHPT patients at The Medical City (TMC) and  assess localization rates and concordance of neck ultrasound (UTZ) and 99mTc-sestamibi scan (MIBI) with surgical histopathologic findings.<strong>METHODOLOGY:</strong> Retrospective chart review of PHPT Filipino patients who underwent parathyroidectomy at The Medical City from January 2004 to August 2018. Clinical profile and presentations were described and compared with international data. Imaging results were compared with surgical histopathology findings and the level of agreement was determined.<strong>RESULTS:</strong> Thirty-five patients were analyzed with female predominance (63%) and an average age of 53 years. Our population had more overt manifestations including skeletal abnormalities (51%), renal calculi (49%) and musculoskeletal symptoms (43%) prior to surgery compared to western countries, where symptoms were noted in less than 20%. MIBI had higher rates of detection than UTZ (80% versus 58%) but had similar localization rates (96.4% versus94%). Whe n performed together, given a positive result from either test, a much higher yield (93.8%) was observed. The level of agreement between MIBI and surgery was 72.5% (?=0.54) while UTZ and surgery was 54.1% (?=0.38).<strong>CONCLUSION:</strong> Our Filipino subjects had predominantly overt symptomatic hyperparathyroidism upon diagnosis prior to surgery as opposed to more asymptomatic surgical patients in western countries. Combining UTZ and MIBI is a more successful preoperative localization approach in our setting than performing either imaging alone, especially in patients with nodular goiter.

T45G Adiponectin Gene Polymorphism and its association with Hyperglycemia in adult Filipinos seen at the Philippine General Hospital - A pilot study

Introduction@#Adiponectin is an adipocytokine known to have anti-inflammatory and anti-atherogenic effects. It appears to impact insulin resistance and the subsequent development of type 2 diabetes mellitus (T2D). The gene encoding adiponectin ADIPOQ, has single nucleotide polymorphisms (SNPs) that can be useful biomarkers to predict development of T2D; with the T/G polymorphism of SNP +45 in exon 2 being the most common. @*Objective@#This study was conducted to evaluate the association of T45G adiponectin gene polymorphism with hyperglycemia among adult Filipinos seen at the outpatient department of the Philippine General Hospital. @*Methods@#This is a matched case-control study, with duration of 12 months. DNA was extracted using the QIAGEN MIDI Blood Extraction Kit. The genomic DNA obtained was then subjected to real time PCR for SNP detection. @*Results@#One hundred (100) adults were enrolled; forty-three (43) had normoglycemia, while fifty seven (57) had hyperglycemia, after a 75-g oral glucose tolerance test. Hyperglycemic subjects were older (44±15.6 years vs. 52±8.3 years, p-value 0.002), and had lower HDL levels (58.5±16.0 mg/dLvs. 47.8+11.8 mg/dL, p-value 0.000). Among thirty-nine (39) participants found to have the T45G adiponectin gene polymorphism, 22 or 56.4% were hyperglycemic while 17 or 43.6% were normoglycemic. @*Conclusion@#There was no significant association observed between the T45G SNP and presence of hyperglycemia.

The Modified Ferriman-Gallwey Score and Hirsutism among Filipino Women

BACKGROUND: The modified Ferriman-Gallwey (mFG) score is the gold standard for the clinical evaluation of hirsutism. However, racial variations in terminal hair growth limit this tool. This study aimed to determine the mFG cut-off score among Filipino women and its association with biochemical hyperandrogenism.METHODS: A total of 128 Filipino women were included in this prospective cross-sectional study and were divided into two groups: a polycystic ovary syndrome (PCOS) group (n=28) and a non-PCOS group (n=100). The participants underwent mFG score determination, ovarian ultrasound conducted by a single sonographer, and hormone testing. The mFG cut-off score was determined based on the 95th percentile of the non-PCOS group. Logistic regression was used to analyze the relationship between mFG score and biochemical hyperandrogenism.RESULTS: Although the mFG score was generally low in both the PCOS and non-PCOS groups, the former exhibited a higher mean score than the latter (4.3±3.0 vs. 2.0±2.2, P<0.001). Normal values for the total mFG score ranged from 0 to 7. Using a cut-off score of 7, a higher proportion of hirsute women (mFG score ≥7) was observed in the PCOS group versus the non-PCOS group (17.9% vs. 5.0%, P=0.025). Elevated calculated free testosterone (FT) was also found to be significantly associated with hirsutism (odds ratio, 6.2; 95% confidence interval, 1.2 to 32.4 pmol/L; P=0.030).CONCLUSION: A score of 7 and above constitutes hirsutism in this population of Filipino women. Hirsute women are more likely than non-hirsute women to have elevated calculated FT.

Development and validation of a sunlight exposure questionnaire for urban adult Filipinos / 한국역학회지

OBJECTIVES: To develop and validate a self-reported sunlight exposure questionnaire (SEQ) for urban adult Filipinos. METHODS: The study included adults (19–76 years old) in Metro Manila, Philippines, well-versed in the Filipino (Tagalog) language and had resided in Metro Manila for at least 1 year. Exclusion criteria included pregnancy, active skin disorders, and immunocompromised states. An expert panel created a questionnaire in Likert-scale format based on a conceptual framework and 4 existing instruments. The study proceeded in 4 phases: questionnaire item development, translation and back-translation, pretesting, and construct validity and reliability testing using factor analysis, the Cronbach alpha coefficient, and the paired t-test. RESULTS: A 25-item, self-administered, Filipino (Tagalog) SEQ answerable using a 4-point Likert scale was created. The questionnaire was administered to 260 adult participants twice at a 2-week interval, with all participants completing both the first and second rounds of testing. All questionnaire items possessed adequate content validity indices of at least 0.86. After factor analysis, 3 questionnaire domains were identified: intensity of sunlight exposure, factors affecting sunlight exposure, and sun protection practices. Internal consistency was satisfactory for both the overall questionnaire (Cronbach alpha, 0.80) and for each of the domains (Cronbach alpha, 0.74, 0.71, and 0.72, respectively). No statistically significant differences were observed in the responses between the first and second rounds of testing, indicating good test-retest reliability. CONCLUSIONS: We developed a culturally-appropriate SEQ with sufficient content validity, construct validity, and reliability to assess sunlight exposure among urban adult Filipinos in Metro Manila, Philippines.

Attitudes, behaviors and beliefs of urban adult Filipinos on sunlight exposure: A qualitative study / Journal of the ASEAN Federation of Endocrine Societies

Objective@#To explore the attitudes, behaviors, and beliefs of urban adult Filipinos on sunlight exposure as an initial step in the development and validation of a culturally-appropriate questionnaire.@*Methodology@#Focus groups were conducted among urban Filipinos 19 years old and above (n=38). The transcribedresults underwent qualitative content and thematic analyses and were used to develop a conceptual framework.@*Results@#Qualitative analysis revealed four main themes of sunlight exposure: internal influences, external influences,perceived benefits, and perceived risks. Both internal and external influences lead to perceived risks and benefits.Consequently, the perceived benefits (or lack) of sunlight exposure influence an individual’s attitude towards vitamin D supplementation; whereas the perceived risks of sunlight exposure influence an individual’s attitude towards the needfor sun protection@*Conclusion@#The attitudes, behaviors and beliefs of urban adult Filipinos on sunlight exposure are influenced by bothinternal and external factors, that in turn lead to perceived risks and benefits. An increased awareness of these factorsis necessary to establish future recommendations on proper sunlight exposure in this population. The study results willbe used to develop and validate a culturally-appropriate sunlight exposure questionnaire.