Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia.

CONTEXT: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited health care access. OBJECTIVE: We aimed to assess the availability and affordability of health care resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. METHODS: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries. RESULTS: Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin ratio is performed in all countries, confirmatory testing is routinely performed in only 6 countries due to lack of facilities and local assays, and cost constraint. Assays are locally available in only 4 countries, and some centers have a test turnaround time exceeding 3 weeks. In 7 countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In 6 countries, the cost of AVS and adrenalectomy combined is more than 30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable. CONCLUSION: Large populations currently do not have access to the health care resources required for the optimal management of PA. Greater efforts are required to improve health care access and affordability. Future guideline revisions for PA may need to consider these limitations.

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.

Patients with germline SDHD pathogenic variants (encoding succinate dehydrogenase subunit D; ie, paraganglioma 1 syndrome) are predominantly affected by head and neck paragangliomas, which, in almost 20% of patients, might coexist with paragangliomas arising from other locations (eg, adrenal medulla, para-aortic, cardiac or thoracic, and pelvic). Given the higher risk of tumour multifocality and bilaterality for phaeochromocytomas and paragangliomas (PPGLs) because of SDHD pathogenic variants than for their sporadic and other genotypic counterparts, the management of patients with SDHD PPGLs is clinically complex in terms of imaging, treatment, and management options. Furthermore, locally aggressive disease can be discovered at a young age or late in the disease course, which presents challenges in balancing surgical intervention with various medical and radiotherapeutic approaches. The axiom-first, do no harm-should always be considered and an initial period of observation (ie, watchful waiting) is often appropriate to characterise tumour behaviour in patients with these pathogenic variants. These patients should be referred to specialised high-volume medical centres. This consensus guideline aims to help physicians with the clinical decision-making process when caring for patients with SDHD PPGLs.

Socioeconomic impact and burden of hypertension in the Philippines projected in 2050.

Hypertension has remained the number one cause of cardiovascular death in the Philippines for over three (3) decades. Despite this finding, the burden accounted for by hypertension is investigated to a lesser extent. We performed this study to determine the socioeconomic impact of hypertension in the Philippines, and it was projected in the next 30 years. We gathered primary data through interviews, Labor Force Survey (N = 806), and secondary data from various government published reports. The cost of illness (COI) was calculated using the direct morbidity and mortality costs. The impact (% of respondents) of uncontrolled hypertension on productivity at work showed the following; four (4) days missing work (72%) and ten (10) days lost of productivity (63%). The impact (% of respondents) of uncontrolled hypertension on productivity at home showed the following: six (6) days of household suspended (66%), eleven (11) days reduced household work (78%), and five (5) days affected social activity (60%). The productivity loss of premature mortality accounts for 17% of the total economic burden in 2020 and will increase to 20% by 2050. In 2020, 70% of the total economic burden was accounted for direct & indirect care. At its present value, the economic cost of hypertension is expected to increase from US$1 billion in 2020 to US$1.9 billion by 2050. The socioeconomic impact of uncontrolled hypertension in the Philippines was enormous, challenging, and overwhelming for the next 30 years.

May Measurement Month 2019: an analysis of blood pressure screening results in the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2019 (MMM19) blood pressure (BP) measurement campaign to raise awareness of hypertension especially in those who are not aware of their condition. The MMM19 standard protocol designed by the International Society of Hypertension was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken two to three times, using an automated BP apparatus and were inputted either in the MMM19 app or data were recorded in paper form and manually transferred to Excel spreadsheets by encoders supervised by the PSH. A total of 89 941 participated through opportunistic convenience sampling. After multiple imputation, a total of 47 925 (53.3%) participants had hypertension (≥140/90 mmHg or on antihypertensive medication). Of this number, 31 151 (65%) were aware that they had high BP and 30 120 (62.8%) were on antihypertensive medications. Of the 30 120 participants on antihypertensive medications, only 18 373 (61.1%) had controlled BP (<140/90 mmHg). Being overweight or obese were significant predictors of high BP. Other predictors of high systolic BP and diastolic BP were alcohol intake, smoking, and a previous history of hypertension in pregnancy, while pregnant participants had significantly lower BP. The MMM19 campaign succeeded in raising awareness of high BP in our country, and the opportunistic sampling enhanced a sense of people empowerment by their knowing how easy it is to detect high BP and thereby enabling the prevention of long-term health complications. The higher BP control in the MMM19 hypertensive individuals possibly attests to the success of the previous MMM17 and MMM18 campaigns.

Executive summary of the 2020 clinical practice guidelines for the management of hypertension in the Philippines.

Hypertension is the most common cause of death and disability worldwide with its prevalence rising in low to middle income countries. It remains to be an important cause of morbidity and mortality in the Philippines with poor BP control as one of the main causes. Different societies and groups worked and collaborated together to develop the 2020 Philippine Clinical Practice Guidelines of hypertension arising for the need to come up with a comprehensive local practice guideline for the diagnosis, treatment, and follow up of persons with hypertension. A technical working group was organized into six clusters that analyzed the 30 clinical questions commonly asked in practice, looking into the definition of hypertension, treatment thresholds, blood pressure targets, and appropriate medications to reach targets. This guideline also includes recommendations for the specific management of hypertension among individuals with uncomplicated hypertension, hypertension among those with diabetes, stroke, chronic kidney disease, as well as hypertension among pregnant women and pediatric populations. It also looked into the appropriate screening and monitoring of patients when managing hypertension, and identification of groups who are at high risk for cardiovascular (CV) events. The ADAPTE process was used in developing the statements and recommendations which were then presented to a panel of experts for discussion and approval to come up with the final statements. This guideline aims to aid Filipino healthcare professionals to provide evidence-based care for persons with hypertension and help those with hypertension adequately control their blood pressure and reduce their CV risk.

Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

May Measurement Month 2018: an analysis of blood pressure screening in the Philippines.

Building on the gains of May Measurement Month 2017 (MMM17), the Philippine Society of Hypertension once again took part in MMM18 to raise awareness of high blood pressure (BP) in the country and to harness opportunistic BP screening in detecting unaware hypertensive individuals and referring them for treatment. We followed the standard MMM18 protocol designed by the International Society of Hypertension, utilizing convenience sampling with volunteer investigators, taking three sitting BP measurements of volunteer adults (≥18 years). Basic data on demographic, lifestyle, and environmental factors were also taken. We analysed 177 176 screened individuals from the Philippines. Of these, 29.1% (51 527) had also participated in MMM17, whereas 68.8% (121 893) were new screenees; and 14.2% (25 232) had their BP taken for the first time ever. After multiple imputation, 39.0% (69 126) were hypertensive. Of these, 50.3% (34 795) were aware they were hypertensive. 49.9% (34 491) were on antihypertensive medication, 58.0% (20 010) of whom had controlled BP <140/90 mmHg. Only 28.9% of all participants with hypertension had controlled BP. Systolic BPs and diastolic BPs were significantly higher in the overweight and obese, in those receiving antihypertensive medications, in patients with diabetes, and significantly lower in pregnant women. MMM18 has again shown that opportunistic BP screening, harnessing volunteers, is a pragmatic public health measure to improve awareness and treatment rates of raised BP.

Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents.

PURPOSE: Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare in children with only a few SDHB mutation-related cases. Previous studies on children were conducted in small cohorts. This large set of pediatric patients provides robust data in the evaluation of clinical outcomes. METHODS: Sixty-four pediatric PHEO/PGL patients with SDHB germline mutations were included in the present study. The clinical presentation, disease course, and survival rate were evaluated. RESULTS: Thirty-eight males and 26 females were diagnosed with PHEO/PGL at a median age of 13 years. The majority of patients displayed norepinephrine hypersecretion and 73.44% initially presented with a solitary tumor. Metastases developed in 70% of patients at the median age of 16 years and were mostly diagnosed first 2 years and in years 12-18 post-diagnosis. The presence of metastases at the time of diagnosis had a strong negative impact on survival in males but not in females. The estimated 5-, 10-, and 20-year survival rates were 100%, 97.14%, and 77.71%, respectively. CONCLUSION: The present report has highlighted several important aspects in the management of pediatric patients with SDHB mutations associated-PHEO/PGL. Initial diagnostic evaluation of SDHB mutation carriers should be started at age of 5-6 years with initial work-up focusing on abdominal region. Thorough follow-up is crucial first 2 years post-diagnosis and more frequent follow-ups are needed in years 10-20 post-diagnosis due to the increased risk of metastases. Although this age group developed metastasis as early as 5 years from diagnosis, we have shown that the overall 20-year prognosis and survival are good.

May Measurement Month 2017: an analysis of blood pressure screening in the Philippines-South-East Asia and Australasia.

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population.

Correction to: Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region.

In this article the name of the sixth author, E. Michael Lewiecki was rendered incorrectly. The publisher regrets this error and apologizes for the inconvenience caused.

Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region.

The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. PURPOSE: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. METHODS: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. RESULTS: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. CONCLUSIONS: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

PHEOCHROMOCYTOMA: A GENETIC AND DIAGNOSTIC UPDATE.

OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathologic studies are performed to prove, localize, treat, and monitor disease progression. Improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (<1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment. METHODS: This review outlines the most updated approach to PPGL patients and presents a new diagnostic protocol for physicians to increase earlier tumor identification and accurately assess metastatic behavior. CONCLUSION: We present the most recent advances in genetics, epigenetics, metabolomics, biochemical, and imaging diagnoses of this rare tumor to properly assess disease, decide treatment options, and manage follow-up. We also elaborate on new therapeutic perspectives in these very rare neoplastic entities. ABBREVIATIONS: ATRX = ATRX chromatin remodeler; ccRCC = clear cell renal cell carcinoma; c-MYC = MYC proto oncognene; CT = computed tomography; DOTATATE = DOTA-octreotate; EGLN1/2 = egl-9 family hypoxia inducible factor 1/2; EGLN2/PHD1 = egl-9 family hypoxia inducible factor 2; EPAS1/HIF2A = endothelial PAS domain protein 2/hypoxia-inducible factor 2α; ERK = extracellular signal-regulated kinase; HIFs = hypoxia-inducible factors; HIF-α = hypoxia-inducible factor alpha; HNPGLs = head and neck paragangliomas; 177Lu-DOTATATE = lutetium octreotate; MAX = myc-associated factor X; MDH2 = malate dehydrogenase; MIBG = metaiodobenzylguanidine; MN = metanephrine; MRI = magnetic resonance imaging; mTOR = mammalian target of rapamycin; NETs = neuroendocrine tumors; NF1 = neurofibromin 1; NMN = normetanephrine; PHD = prolyl hydroxylase domain protein; PI3K = phosphoinositide 3-kinase; PPGLs = pheochromocytoma and paragangliomas; PRRT = peptide receptor radionuclide therapy; Pvhl = von Hippel-Lindau protein; RAS = rat sarcoma oncogene; RET = rearranged during transfection proto-oncogene; SDH = succinate dehydrogenase; SDHA, -B, -C, -D = succinate dehydrogenase subunits A, B, C, D; SDHAF2 = succinate dehydrogenase complex assembly factor 2; SDHB, C, D = succinate dehydrogenase subunits B, C, D; SDHx = succinate dehydrogenase subunits; SSTRs = somatostatin receptors; VHL = von Hippel-Lindau.

Osteoporosis and Prevalent Fractures among Adult Filipino Men Screened for Bone Mineral Density in a Tertiary Hospital.

BACKGROUND: Osteoporosis in men is markedly underdiagnosed and undertreated despite higher morbidity and mortality associated with fractures. This study aimed to characterize adult Filipino men with osteopenia, osteoporosis and prevalent fractures. METHODS: A cross-sectional study of 184 Filipino men ≥50 years screened for bone mineral density was performed. Age, weight, body mass index (BMI), Osteoporosis Self-Assessment Tool for Asians (OSTA) score, smoking status, family history of fracture, diabetes mellitus, physical inactivity, and T-score were considered. RESULTS: Of the 184 patients, 40.2% and 29.9% have osteopenia and osteoporosis. Sixteen (21.6%) and 18 (32.1%) osteopenic and osteoporotic men have fragility hip, spine, or forearm fractures. Men aged 50 to 69 years have the same risk of osteoporosis and fractures as those ≥70 years. While hip fractures are higher in osteoporotic men, vertebral fractures are increased in both osteopenic and osteoporotic men. Mere osteopenia predicts the presence of prevalent fractures. A high risk OSTA score can predict fracture. A BMI <21 kg/m² (P<0.05) and current smoking are associated with osteoporosis. CONCLUSION: A significant fraction of Filipino men with osteopenia and osteoporosis have prevalent fractures. Our data suggest that fractures occur in men <70 years even before osteoporosis sets in. Low BMI, high OSTA score, and smoking are significant risk factors of osteoporosis.

False-negative ¹²³I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease.

The purpose of this study was to present the characteristics and outcome of patients with proven pheochromocytoma or paraganglioma who had false-negative iodine-123 metaiodobenzylguanidine single photon emission computed tomography ((123)I-MIBG SPECT). Twenty-one patients with false-negative (123)I-MIBG SPECT (7 males, 14 females), aged 13-55 years (mean: 41.40 years), were included. We classified them as nonmetastatic or metastatic according to the stage of the disease at the time of false-negative (123)I-MIBG SPECT study, the location and size of the tumor, plasma and urinary catecholamine and metanephrine levels, genetic mutations, and outcome in terms of occurrence and progression of metastases and death. Thirteen patients were evaluated for metastatic tumors, while the remaining eight were seen for nonmetastatic disease. All primary tumors and multiple metastatic foci did not show avid (123)I-MIBG uptake regardless of the tumor diameter. The majority of patients had extraadrenal tumors with hypersecretion of normetanephrine or norepinephrine. SDHB mutations were present in 52% (n=11) of cases, RET mutation in 4% (n=1), and the rest were apparently sporadic. Twenty-four percent (n=5) had metastatic disease on initial presentation. Fourteen patients were followed for 3-7 years. Of them, 71% (n=10) had metastatic disease and the majority had SDHB mutations. Nine are still alive, while five (four with SDHB) died due to metastatic disease. We concluded that false-negative (123)I-MIBG SPECT is frequently related to metastatic tumors and usually due to SDHB mutations with unfavorable prognosis. We therefore recommend that patients with false-negative (123)I-MIBG SPECT be tested for SDHB mutations and undergo more regular and close follow-up.

Postprandial effect of orlistat on the peaking of lipid level after sequential high fat meals.

BACKGROUND: Postprandial lipemia has been found to be strongly associated with atherosclerosis due to its atherogenic and thrombogenic lipoprotein changes. This phenomenon occurs even in normal subjects especially after high fat meals. Orlistat, an anti- obesity drug, has been shown to address postprandial lipemia after a single high fat meal. OBJECTIVES: To compare the effects of orlistat and placebo on the postprandial lipid levels after sequential high-fat meals in healthy individuals with normal fasting lipid levels. PATIENTS AND METHODS: Thirty-one healthy adult volunteers with normal fasting lipid levels were fed 50% fat meals (3 meals and 2 snacks of pre-weighted butter and bread). The subjects were blindly randomized to receive either placebo or orlistat 120 mg before each main meal. The outcome parameters were total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol levels measured at fasting (0 h) and every 2 h thereafter, until the sixteenth hour. Additionally, we estimated the lipid levels at the fifth and ninth hour. RESULTS: The non-orlistat group showed a significant postprandial rise in the levels of TG and VLDL, which began 4 h after breakfast (P < 0.05); this rise in levels was sustained until 9 h after breakfast for TG and up to 10 h after breakfast for VLDL. In contrast, only one significant rise in both TG and VLDL levels (at 4 h after breakfast) was noted in the orlistat group. The maximum mean difference from the baseline TG level for the orlistat group was lower than that for the non-orlistat group (0.22 mmol/L vs. 0.756 mmol/L, respectively). Similarly, the maximum mean difference from the baseline VLDL level from baseline in the orlistat group was only 0.099 mmol/L, which was lower than that in the non-orlistat group (0.588 mmol/L). LDL levels rose to a lesser extent in the orlistat group than in the non-orlistat group (0.268 vs. 0.362 mmol/L). The TC levels did not show a postprandial rise; instead, the levels reduced in both groups, with the orlistat group showing a higher reduction than the non-orlistat group (-0.288 vs. -0.188 mmol/L). The orlistat group did not show any significant differences in the HDL measurements. CONCLUSIONS: Administration of orlistat abolished the significantly sustained postprandial rise of TG and VLDL levels in healthy individuals who were fed sequential 50% fat meals.

Postprandial Peaking and Plateauing of Triglycerides and VLDL in Patients with Underlying Cardiovascular Diseases Despite Treatment.

BACKGROUND: Dyslipidemia is associated with cardiovascular morbidities and mortality. Currently, fasting lipid profile determination is used to monitor treatment response. Recently, postprandial lipemia is of increasing interest because of its atherogenic and thrombogenic potential and also was found to be more predictive for cardiovascular diseases. OBJECTIVES: To demonstrate postprandial lipemia among patients with cardiovascular diseases despite low fat diet, normal fasting lipid profile and even statin regimen. PATIENTS AND METHODS: Patients aged 40-80 years old with cardiovascular diseases (i.e. coronary artery disease and cerebrovascular disease) more than 6 months, on statin treatment for more than 6 months and normal fasting lipid profile (according to NCEP ATP III guidelines) were included. Study exclusion criteria were pregnancy, acute cardiovascular events < 6 months, hepatic or renal failure. Finally, twelve patients were included. RESULTS: The triglyceride level showed a significant rise from fasting to 2 hours after breakfast with a mean difference of 23.86 mg/dL (P =0.012). The level peaked at 4 hours after breakfast with a mean difference (MD) of 72.02 mg/dL (P =0.002). Subsequent triglyceride levels plateaued and were significantly higher than the baseline (P <0.05) until the 12th hour of observation. VLDL levels showed a similar pattern. Levels increased significantly from fasting to 2h after breakfast (mean difference: 4.49 mg/dL, P = 0.007), then plateaued and further increased 4 hours after breakfast (MD: 14.01 mg/dL, P = 0.002). VLDL levels were significantly higher than fasting (P < 0.05) and did not return to baseline until the 12th hour of observation. In contrast, the levels of total cholesterol, HDL and LDL decreased postprandially. CONCLUSIONS: Triglyceride and VLDL peaking and plateauing were observed in patients with cardiovascular diseases despite low fat diet, normal fasting lipid profile and statin regimen. These findings may raise more attentions in monitoring and management of dyslipidemia in patients with cardiovascular and cerebrovascular events.

Recombinant TSH and Lithium Overcomes Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female.

INTRODUCTION: Recombinant human thyroid-stimulating hormone(rhTSH) increases radioactive iodine uptake(RAIU) in selected populations, while lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves' disease with low RAIU. In this report, both drugs used in combination, overcame low iodine-131 uptake in a Graves' patient. CLINICAL CASE: A 39-year old female with Graves' disease, acquired thionamide-induced agranulocytosis, and severe hypokalemia, subsequently went into cardiorespiratory arrest. On resuscitation, she had ventricular tachyarrhythmias which were cardioverted using amiodarone. She was subsequently placed on IV hydrocortisone amiodarone and propranolol. On admission, she was normotensive, tachycardic, and afebrile. She had fine tremors, hyper reflexia, and diffuse, non-tender thyromegaly. Initial investigations showed normal complete blood count, hypokalemia and elevated alanine transaminase levels. Levels of thyroid stimulating hormone were low (0.03 uIU/L, N = 0.27-3.75). Thyroid ultrasound showed diffuse thyromegaly with uniform echopattern and normal color flow Doppler, radioiodine uptake showed low uptake at 0400h and 2400h (6% and 7%, respectively). In preparation for RAI therapy, she was given lithium 900mg/day for 12 days to increase RAI retention. To increase iodine-131 uptake, two doses of 0.9mg rhTSH were injected intramuscular, 24 hours apart, before RAI therapy. Repeat RAIU after the second dose of rhTSH showed more than a 5-fold increase in 0400h uptake compared with the baseline (32% vs. 6%). Exactly 24 hours after the second dose of rhTSH, she was given 25mCi of iodine-131. Thereafter, the patient's clinical and biochemical markers continued to improve. She became hypothyroid and is currently on levothyroxine replacement therapy. CONCLUSIONS: This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves' disease.