SARS-CoV-2 mRNA Vaccination and Graves' Disease: A Report of 12 Cases and Review of the Literature.

CONTEXT AND OBJECTIVE: Thyroid autoimmunity has been reported to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the SARS-CoV-2 vaccination recently. We report a series of patients who presented with new onset or relapse of Graves' disease-related hyperthyroidism shortly after receiving the SARS-CoV-2 messenger RNA (mRNA) vaccine at a single tertiary institution in Singapore. METHODS AND RESULTS: We describe 12 patients who developed hyperthyroidism within a relatively short interval (median onset, 17 [range, 5-63] days) after receiving the SARS-CoV-2 mRNA vaccine. The majority were females (11/12) with median age of 35.5 (range, 22-74) years. Six patients had new-onset hyperthyroidism, whereas the other 6 had relapse of previously well-controlled Graves' disease. TSH receptor antibody concentrations ranged from 2.4 to 32 IU/L. The majority of the patients were able to go for the second dose of the vaccine without any further exacerbations. Literature review revealed 21 other similar cases reported from across the world. CONCLUSION: Our case series provides insight into the characteristics of individuals in whom Graves' disease was triggered by the SARS-CoV-2 vaccination. Clinicians need to be vigilant of precipitation or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the SARS-CoV-2 vaccination. Further epidemiological and mechanistic studies are required to elucidate the possible associations between the SARS-CoV-2 vaccines and the development of thyroid autoimmunity.

Clinical and economic outcomes of a multidisciplinary team approach in a lower extremity amputation prevention programme for diabetic foot ulcer care in an Asian population: A case-control study.

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m.

Metabolic effects of brown fat in transitioning from hyperthyroidism to euthyroidism.

OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.

Metastatic Malignant Struma Ovarii and Graves' Disease: A Rare Occurrence.

OBJECTIVE: Malignant struma ovarii (SO) is a rare condition. Although there have been a few reported cases of malignant SO with coexisting Graves' disease (GD), the exact incidence of metastasis in these cases is not known. We report a rare case of metastatic malignant SO coexisting with GD. METHODS: Clinical examination, pelvic ultrasound, and histopathology of the resected tumor were performed, followed by iodine-131 (I-131) and whole body scan. Antithyroglobulin titers were postoperatively followed. RESULTS: A 43-year-old woman with a history of left ovarian cystic teratoma with SO resected 8 years ago and recently diagnosed GD presented with lower abdominal fullness. Pelvis ultrasound showed a 13.8-cm left adnexal mass, and she underwent left salpingo- oophorectomy. Histology confirmed an intraovarian thyroid tissue housing a highly differentiated follicular thyroid carcinoma, with metastatic peritoneal deposits. She underwent completion surgery and total thyroidectomy. Histology showed no evidence of intrathyroidal malignancy. I-131 therapy was administered, and posttherapeutic I-131 whole body scan revealed a remnant disease. She was started on suppressive levothyroxine therapy and remained clinically well at her 1-year follow-up with downtrending antithyroglobulin titers. CONCLUSION: The coexistence of malignant SO and GD is very rare, and even rarer is the coexistence of metastasis malignant SO and GD. To the best of our knowledge, this is the first reported case of metastatic malignant SO in the setting of GD.

Diabetes Care During COVID-19 Pandemic in Singapore Using a Telehealth Strategy.

Singapore currently has one of highest number of confirmed COVID-19 cases in Southeast Asia. To curb the further spread of COVID-19, Singapore government announced a temporary nationwide lockdown (circuit breaker). In view of restrictions of patients' mobility and the enforcement of safe distancing measures, usual in-person visits were discouraged. Here we describe how diabetes care delivery was ad hoc redesigned applying a telehealth strategy. We describe a retrospective assessment of subjects with diabetes, with and without COVID-19 infection, during the circuit breaker period of 7th April to 1st June 2020 managed through Tan Tock Seng Hospital's telehealth platform. The virtual health applications consisted of telephone consultations, video telehealth visits via smartphones, and remote patient monitoring. The TTSH team intensively managed 298 diabetes patients using a telehealth strategy. The group comprised of (1) 84 inpatient COVID-19 patients with diabetes who received virtual diabetes education and blood glucose management during their hospitalisation and follow-up via phone calls after discharge and (2) 214 (n=192 non-COVID; n=22 COVID-positive) outpatient subjects with suboptimal glycaemic control who received intensive diabetes care through telehealth approaches. Remote continuous glucose monitoring was applied in 80 patients to facilitate treatment adjustment and hypoglycaemia prevention. The COVID-19 pandemic situation mooted an immediate disruptive transformation of healthcare processes. Virtual health applications were found to be safe, effective and efficient to replace current in-person visits.

Therapeutic plasma exchange for control of thyroid storm.

Therapeutic plasma exchange (TPE) for thyroid storm has recently been upgraded to a category II indication after decades though its recommendation level still remains at Grade 2C according to the American Society for Apheresis (ASFA). In the absence of prospective randomized controlled trials due to the rarity of thyroid storm, retrospective data from case series continue to elevate the clinical evidence supporting TPE as a life-saving modality for complicated thyroid storm patients. We report three cases of life-threatening thyroid storm from Graves' disease rescued by TPE via rapid reduction in circulating thyroid hormones. Each patient underwent TPE when it was judged that other thyroid storm treatment options were futile or unsafe. The first patient received 4 cycles of TPE while the second patient received 9 cycles of TPE, and the third patient received 2 cycles of TPE with satisfactory clinical improvement. Plasma FT4 and TSH receptor antibody levels of the first case declined by 41.3% and >50% respectively right after the first round of TPE; plasma FT4 of the second patient dropped by up to 31.6% during the course of TPE; plasma FT4 and TSH receptor antibody of the third patient declined by 66% and 56.2% respectively after the first cycle of TPE. This demonstrates the safety, efficacy, and feasibility of TPE in thyroid storm especially when other therapeutic interventions are contraindicated. TPE operates via the elimination of serum proteins-bound thyroid hormones, thyroid autoantibodies, cytokines, and catecholamines in addition to increasing unsaturated binding sites for thyroid hormones.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in thyroid cytology: Data from Singapore.

INTRODUCTION: The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. METHODS: We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. RESULTS: The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. CONCLUSION: Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies.

Agoitrous Graves' Hyperthyroidism with Markedly Elevated Thyroid Stimulating Immunoglobulin Titre displaying Rapid Response to Carbimazole with Discordant Thyroid Function.

We characterize the clinical and laboratory characteristics of 5 patients with Graves' thyrotoxicosis whose serum free thyroxine (fT4) concentration decreased unexpectedly to low levels on conventional doses of carbimazole (CMZ) therapy. The initial fT4 mean was 40.0 pM, range 25-69 pM. Thyroid volume by ultrasound measured as mean 11 ml, range 9.0-15.6 ml. Initial TSI levels measured 1487% to >4444%. Serum fT4 fell to low-normal or hypothyroid levels within 3.6 to 9.3 weeks of initiating CMZ 5 to 15 mg daily, and subsequently modulated by fine dosage adjustments. In one patient, serum fT4 fluctuated in a "yo-yo" pattern. There also emerged a pattern of low normal/low serum fT4 levels associated with discordant low/mid normal serum TSH levels respectively, at normal serum fT3 levels. The long-term daily-averaged CMZ maintenance dose ranged from 0.7 mg to 3.2 mg. Patients with newly diagnosed Graves' hyperthyroidism who have small thyroid glands and markedly elevated TSI titres appear to be "ATD dose sensitive." Their TFT on ATD therapy may display a "central hypothyroid" pattern. We suggest finer CMZ dose titration at closer follow-up intervals to achieve biochemical euthyroidism.

Epidemiology of Leptospira infection in livestock species in Saint Kitts.

This pilot study describes the prevalence of Leptospira infection and exposure in livestock species, cattle, pig, sheep, and goats in Saint Kitts in the Caribbean region. Serum and kidney samples were collected from cattle, pigs, sheep, and goats at a local abattoir between September 2016 and March 2017. Cattle had the highest seroprevalence (79.8%) followed by pigs (64.8%), sheep (39.4%), and goats (24.8%). Highest seroprevalence was observed to serovars, Mankarso in cattle, Bratislava in pigs, Hardjo in sheep, and goats. Leptospira DNA was amplified from kidney samples of 18/99 cattle (18.2%), 11/106 pigs (10.4%), 4/106 sheep (3.8%), and 2/105 goats (1.9%). Our findings warrant further studies to assess leptospirosis associated economic burden to subsistence farmers and public health impact.

High-sensitivity C-reactive protein concentrations among patients with and without diabetes in a multiethnic population of Singapore: CREDENCE Study.

OBJECTIVES: To determine whether high-sensitivity C-reactive protein (hs-CRP) concentrations differ between Chinese, Malays, and Indians with and without type 2 diabetes mellitus and to look for an association with demographic, metabolic and therapeutic variables. METHODS: Phase 1: We retrieved records of 50 Chinese, 51 Malay, and 67 Indian individuals who had routine health screening blood tests. Phase 2: We recruited 111 Chinese, 68 Malays, and 67 Indians with type 2 diabetes mellitus and measured their hs-CRP in addition to standard laboratory tests. RESULTS: Phase 1: The median hs-CRP was 0.6 mg/L (0.2-6.2) in Chinese, 1.2 mg/L (0.2-7.9) in Malays, and 1.9 mg/L (0.2-10.0) in Indians. The Indians had higher hs-CRP compared to Chinese (P < 0.05) when adjusted for age, sex, body mass index (BMI), lipids, blood pressure, and smoking, and a significant correlation was seen between female sex, smoking status, fasting glucose and triglyceride concentration, and hs-CRP in all three ethnicities. Phase 2: The median hs-CRP was 1.2 mg/L (0.2-9.9) in Chinese, 2.2 mg/L (0.2-9.0) in Malays, and 2.3 mg/L (0.2-9.8) in Indians. Indians had higher hs-CRP when compared to Chinese (P < 0.05) and a significant correlation was seen between BMI, female gender, diabetes, and the use of metformin and hs-CRP in all three ethnicities (P < 0.05) when adjusted for the above variables and use of aspirin, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB), statin, metformin, rosiglitazone, sulfonylurea, glinides, acarbose, and insulin. CONCLUSION: hs-CRP concentrations are significantly higher in Indians compared to the Chinese (in both the diabetic and nondiabetic individuals) after adjustment for the various demographic, metabolic, and therapeutic variables.