Displaying publications 1 - 20 of 57 in total

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  1. Mohd Said MS, Bin Shudim SS, Mohamad K, Shaharir SS, Kong NCT, Ali RA
    Egyptian Rheumatologist, 2016;38:189-194.
    DOI: 10.1016/j.ejr.2015.12.001
    Aim of the work This work aimed to determine the frequency of subclinical memory dysfunction in a group of Malaysian systemic lupus erythematosus (SLE) patients and to study its relation to clinical characteristics, laboratory investigations and disease activity. Patients and methods Fifteen SLE patients attending the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and not known to have neuropsychiatric lupus were recruited. These patients were assessed using the Wechsler Memory Scale. Disease activity was assessed using the SLE disease activity index 2000 (SLEDAI-2K). Results The median age of the patients was 28 years (25–37 years) and they were 14 females and one male. Their median disease duration was 9.3 years (4.8–10 years). Their median SLEDAI-2K was 4 (0–6). Memory dysfunction was identified in 7/15 (46.7%) SLE patients and was significantly associated with lower serum thyroxine levels (median 12.27; 11.8–13.3 μg/dl) (p = 0.027) compared to those without memory impairment (15.48; 14.39–16.56 μg/dl). Auditory memory impairment was associated with the education level as the auditory memory index was significantly lower in patients with secondary education (n = 7, median 88; 86.5–91.5) compared to those who received tertiary education (n = 8, median 103; 97.5–119.5) (p = 0.025) while visual memory was influenced by disease duration (p = 0.016). There was no association between overall memory dysfunction and disease duration, number of relapses, clinical manifestations and SLEDAI-2K scores. Conclusion There is a high frequency of subclinical memory dysfunction among SLE patients. A remarkable association is present with lower thyroxine. Auditory memory impairment is related to the level of education and visual memory to disease duration. © 2015 The Authors
    Matched MeSH terms: Hypothyroidism
  2. Wan Muhammad Hatta SF, Kandaswamy L, Gherman-Ciolac C, Mann J, Buch HN
    PMID: 30087779 DOI: 10.1530/EDM-18-0074
    Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing's syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test.

    Learning points: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.

    Matched MeSH terms: Hypothyroidism
  3. Zaini A, Ngan A, Paramsothy M, Khoo BH, Ch'ng SL
    Med J Malaysia, 1983 Dec;38(4):331-3.
    PMID: 6599994
    Matched MeSH terms: Hypothyroidism/etiology*
  4. Ratnasingam J, Karim N, Paramasivam SS, Ibrahim L, Lim LL, Tan AT, et al.
    Pituitary, 2015 Aug;18(4):448-55.
    PMID: 25134488 DOI: 10.1007/s11102-014-0593-6
    PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors.

    METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.

    RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.

    CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.

    Matched MeSH terms: Hypothyroidism/blood; Hypothyroidism/epidemiology
  5. Ho CL, Cheah JS
    Med J Malaysia, 1982 Mar;37(1):70-1.
    PMID: 7121352
    The serum alpha-1 acid glycoprotein of 9 euthyroid subjects, 14 hypothyroid patients and 21 hyperthyroid patients was determined by radial immunodiffussion in agar plates. The serum alpha1 acid glycoprotein level in both the hypothyroid and hyperthyroid patients were significantly lowered when compared to the euthyroid subjects. There was no significant correlation between the alpha-1 acid glycoprotein level mid the Liothyronine resin uptake (T3 resin. uptake) and the serum total Thyroxine Iodide (T4I) level.
    Matched MeSH terms: Hypothyroidism/blood
  6. Ong SG, Choy CH
    Lupus, 2016 Jan;25(1):67-74.
    PMID: 26113361 DOI: 10.1177/0961203315593164
    Autoimmune thyroid disease (ATD) has been associated with other systemic autoimmune diseases. To date, there is limited data on thyroid disorders and autoimmune thyroid disease in Malaysia. The frequency of ATD among 189 systemic lupus erythematosus (SLE) patients was 6.3%, with 2.6% in the hyperthyroid group and 3.7% in the hypothyroid group. Hypothyroidism developed at a much younger mean age (24.3 years), suggesting that SLE might be a predisposing factor for the development of Hashimoto's thyroiditis. There was a higher rate of thyroid peroxidase antibody (TPO) positivity compared with anti-thyroglobulin antibody (Tg) in the hyperthyroid subgroup. This study also demonstrated a greater proportion of ATD patients who demonstrated high titres (≥ 1:6400) of TPO compared with high titres of Tg. Although there was an association between ATD and the presence of anti-Ro/SSA and/or anti-La/SSB antibodies, the absence of sicca symptoms and negative Schirmer's tests suggest a lack of association with secondary Sjogren's syndrome. A novel association between ATD and antiphospholipid syndrome (APS) was detected in our cohort. Hence we propose that patients affected by APS be routinely screened for ATD.
    Matched MeSH terms: Hypothyroidism
  7. Wan Mohamed WMI, Sayuti SC, Draman N
    J Taibah Univ Med Sci, 2018 Oct;13(5):432-437.
    PMID: 31435358 DOI: 10.1016/j.jtumed.2018.06.004
    Objectives: The aim of this study was to determine the incidence of hypothyroidism and its associated factors within one-year post radioactive iodine (RAI) therapy.

    Methods: A retrospective study was conducted among patients with hyperthyroidism who received RAI therapy at Nuclear Medicine Clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan. Data regarding patients' demographics, gender, aetiology of hyperthyroidism, presence of autoantibodies, dose of RAI used and usage of antithyroid drug post RAI therapy were included in the analysis.

    Results: Of a total of 167 screened patients, 137 subjects were eligible for this study. The incidence of hypothyroidism within one year of RAI therapy was 32.9%. Women were found to be less likely to develop hypothyroidism post RAI therapy (adjusted odds ratio, 0.406; 95% confidence interval: 0.181-0.908; p = 0.028). The usage of antithyroid drug post RAI was significantly associated with a lower incidence of hypothyroidism post RAI therapy (adjusted odds ratio, 0.188; 95% confidence interval: 0.081-0.438; p<0.001).

    Conclusion: This study showed a high incidence of hypothyroidism within one-year post RAI therapy. Gender and usage of antithyroid drug post RAI therapy are significantly associated with the development of hypothyroidism.

    Matched MeSH terms: Hypothyroidism
  8. Maberly GF, Eastman CJ
    PMID: 1030847
    A comparative epidemiological and anthropometric survey was conducted among Ibans, the largest indigenous ethnic group in Sarawak, in three regions where the endemicity of goitre exhibited marked differences , to assess the effect of endemic goitre on somatic growth. In the Ai river region the prevalence of goitre was 99.5%; 35% having grade 3 goitres, 55% grade 2 goitres and 9.5% grade 1 goitres. At Rubu the prevalence of endemic goitre was 74%; 3% having grade 3 goitre, 16% grade 2 goitre and 55% grade 1 goitre. In the Bajong region relatively few people were detected with goitre and most of these had migrated from other regions. Neurological cretinism was estimated at 3.6% in the severely goitrous Ai river population but was not detected in the other regions. Anthropometric data obtained from the three adult populations did not reveal any statistically significant differences in the following parameters: weight, height, weight/height ratio, height/sitting height ratios, head circumference, scapular skinfold thickness and left mid arm muscle circumference. The haemoglobin, serum total protein and serum albumin concentrations were similar in the three populations. It is concluded that endemic goitre occurs with a frequency of close to 100% in certain Iban populations which represents one of the highest incidences of endemic goitre in the world. Neurological cretinism is common in this population. Our observations suggest that body proportions and somatic growth do not vary among similar ethnic populations exhibiting greatly different endemicity of goitre. Although no iodine balance studies were performed, assessment of diets suggested that iodine deficiency is a significant contributory factor in the development of endemic goitre in Sarawak. Urgent attention to iodine supplementation is indicated to prevent the development of endemic goitre and neurological cretinism.
    Matched MeSH terms: Congenital Hypothyroidism/epidemiology
  9. Jaafar AS, Mohd Shokri SS, Paramasvaran S, Palaniandy K, Fadzil F
    Cureus, 2020 Jul 14;12(7):e9174.
    PMID: 32802610 DOI: 10.7759/cureus.9174
    Spontaneous regression of pituitary tumours are rare and can be due to tumour ischaemia, pituitary apoplexy, or lymphocytic hypophysitis. We report a case of a 32-year-old female, who presented with symptoms and signs of extrasellar pituitary enlargement and hypothyroidism. MRI revealed a pituitary mass that spontaneously regressed after a month, with complete resolution of symptoms. Not all pituitary tumours require surgical intervention especially in the case of autoimmune lymphocytic hypophysitis.
    Matched MeSH terms: Hypothyroidism
  10. Darrat M, Flaherty GT
    PMID: 31548898 DOI: 10.1186/s40794-019-0094-8
    Background: Older people represent a significant proportion of overseas travellers. The epidemiology of older international travellers is not well described in the literature. This study aims to identify demographics, travel characteristics and the medical profile of older travellers seeking pre-travel health advice in a specialist travel medicine clinic.

    Methods: Records of travellers aged 60 years and older attending the Tropical Medical Bureau clinic in Galway, Ireland between 2014 and 2018 were examined. Descriptive and inferential.analysis of data was performed.

    Results: A total of 337 older travellers sought pre-travel health advice during the study period. The mean age of the cohort was 65.42 (±10) years. Most of the travellers (n = 267, 80%) had at least one travelling companion. Nearly half of older travellers (n = 155, 46.8%) were travelling with a single companion. Tourism was the main reason for travel for the majority (n = 260, 77.6%), followed by visiting friends and relatives (VFR) (n = 23, 6.9%) travellers. The mean interval remaining before the planned trip was 4.36 (±2) weeks, and the mean duration of travel was 3.16 (±1) weeks. The most popular single country of destination was India with 33 (9.8%) visitors, and South East Asia was the most popular region with 132 (39.2%) older travellers. The majority of travellers (n = 267, 79.2%) had a documented pre-existing medical condition. The most commonly reported medical conditions were hypertension (n = 26, 7.7%), dyslipidaemia (n = 18, 5.3%), diabetes mellitus (n = 12, 3.5%), insect bite sensitivity (n = 11, 3.3%), and hypothyroidism (n = 9, 2.6%). Antihypertensive agents (n = 32, 9.4%) and statins (n = 24, 7.1%) were the most frequently used medications. Typhoid (n = 112, 33.2%) and hepatitis A (n = 84, 24.9%) were the most common vaccinations administered to older travellers at the clinic.

    Conclusions: This study provides an insight into the demographics, travel characteristics, and medical profile of elderly travellers seeking advice at a large travel clinic in Ireland. A wide range of travel destinations, diseases and medication use was reported among this group of travellers, which may enable travel medicine physicians to provide more tailored advice and to more appropriately counsel older travellers.

    Matched MeSH terms: Hypothyroidism
  11. Lee KT, Lim SL, Goh AS
    Med J Malaysia, 2020 01;75(1):33-37.
    PMID: 32008017
    INTRODUCTION: Frequent blood transfusions results in iron overload and lead to multiple endocrine complications. In spite of improvements in iron chelation therapy, a significant number of transfusion dependent thalassaemia (TDT) patients still develop endocrine complications. The aim of this study is to evaluate the prevalence of various endocrine complications in our adult TDT patients and to study the correlation with serum ferritin and liver iron concentration (LIC).

    METHODS: A retrospective review of all TDT patients treated in Haematology Unit, Hospital Pulau Pinang (HPP) was conducted.

    RESULTS: Of the 45 adult TDT patients, 22 were males and 23 were females with mean age of 28.8±6.9 years old. Majority of TDT in HPP were beta thalassemia major (71.1%), followed by E-Beta thalassemia (24.4%) and HbH-Constant Spring (4.4%). Frequency of transfusion was 3-4 weekly. 40.0% of adult TDT suffered from at least one endocrine complication. Among the adult TDT patients with endocrine complication, 50% have one endocrinopathy, 38.9% with two types of endocrinopathies and 11.1% of them have three or more types of endocrinopathies. Hypogonadism (22.2%) was the commonest endocrine complication, followed by osteoporosis (20%), hypothyroidism (13.3%), diabetes mellitus (6.7%) and hypocortisolism (4.4%). Patients with endocrine complications were significantly older. Mean serum ferritin level and LIC was higher among patients with endocrine complications but both were not statistically significant.

    CONCLUSION: Endocrinopathy is still prevalent in 40% of adult TDT patients. This leads to higher health-care resource utilization, cost and significant morbidities among patients with TDT. Therefore, regular monitoring and early detection with intensification of chelation therapy is essential.

    Matched MeSH terms: Hypothyroidism/etiology
  12. Tan HT, Tan CY, Teong CS, Ratnasingam J, Goh KJ
    J Clin Neurophysiol, 2020 Aug 05.
    PMID: 32773648 DOI: 10.1097/WNP.0000000000000766
    PURPOSE: Thyrotoxic periodic paralysis is characterized by recurrent episodes of reversible, severe proximal muscle weakness associated with hypokalemia and hyperthyroidism. Prolonged exercise test is an easy, noninvasive method of demonstrating abnormal muscle membrane excitability in periodic paralyses. Although abnormal in thyrotoxic periodic paralysis patients, the effects thyroid hormone levels in non-thyrotoxic periodic paralysis thyrotoxicosis patients have not been well studied. The study aims to evaluate thyrotoxicosis patients (regardless of thyrotoxic periodic paralysis history) with prolonged exercise test and correlate it with their thyroid status.

    METHODS: This is a prospective, cross-sectional study of consecutive thyrotoxicosis patients seen at the endocrine clinic of a tertiary medical center. Thyroid status was determined biochemically before prolonged exercise test. Compound muscle action potential (CMAP) amplitudes postexercise were compared against pre-exercise amplitudes and recorded as percentage of mean baseline CMAP amplitude. Comparisons of time-dependent postexercise CMAP amplitudes and mean CMAP amplitude decrement were made between hyperthyroid and nonhyperthyroid groups.

    RESULTS: Seventy-four patients were recruited, 23 (31%) men, 30 (41%) Chinese, and the mean age was 48.5 ± 16.8 years. Of 74 patients, 32 (43%) were hyperthyroid and 42 (57%) were nonhyperthyroid viz. euthyroid and hypothyroid. Time-dependent CMAP amplitudes from 10 to 45 minutes after exercise were significantly lower in hyperthyroid patients compared with nonhyperthyroid patients (P < 0.01). Mean CMAP amplitude decrement postexercise was significantly greater in hyperthyroid than nonhyperthyroid patients (23.4% ± 11.4% vs. 17.3% ± 10.5%; P = 0.02).

    CONCLUSIONS: Compound muscle action potential amplitude declines on prolonged exercise test were significantly greater in hyperthyroid patients compared with nonhyperthyroid patients. Muscle membrane excitability is highly influenced by thyroid hormone level. Thyrotoxic periodic paralysis occurs from increased levels of thyroid hormone activity in susceptible patients.

    Matched MeSH terms: Hypothyroidism
  13. Zhang Y, Kim BK, Chang Y, Ryu S, Cho J, Lee WY, et al.
    Arterioscler Thromb Vasc Biol, 2014 Sep;34(9):2128-34.
    PMID: 25060795 DOI: 10.1161/ATVBAHA.114.303889
    OBJECTIVE: Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).
    APPROACH AND RESULTS: We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone.
    CONCLUSIONS: In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.
    KEYWORDS: thyroid hormones; thyrotropin; thyroxine; triiodothyronine
    Matched MeSH terms: Hypothyroidism/blood*; Hypothyroidism/epidemiology
  14. Harun, F.
    MyJurnal
    Thyroid hormones mediate the biological activities of almost all organ systems in the body. Patients with a deficiency of these hormones may present with a wide spectrum of clinical symptomatology. This report is of an infant who presented with chronic anaemia which was found to be secondary to hypothyroidism associated with a hypoplastic lingual thyroid gland. Physicians need to be alert to the varied manifestations of hypothyroidism so as to avoid delay in diagnosis and treatment.
    Matched MeSH terms: Hypothyroidism
  15. Yong PH, Junit SM, Harun F, Hashim OH
    Clin Biochem, 2006 Feb;39(2):126-32.
    PMID: 16412408
    To compare the plasma protein profiles of treated and untreated congenital hypothyroidism (CH) patients with those of normal control infants.
    Matched MeSH terms: Congenital Hypothyroidism/blood*; Congenital Hypothyroidism/drug therapy
  16. West R, Hong J, Derraik JGB, Webster D, Heather NL, Hofman PL
    J Clin Endocrinol Metab, 2020 09 01;105(9).
    PMID: 32598474 DOI: 10.1210/clinem/dgaa415
    BACKGROUND: It is unclear whether newborns with mild thyrotropin elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings.

    METHODS: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.

    RESULTS: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores.

    CONCLUSIONS: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected.

    Matched MeSH terms: Congenital Hypothyroidism/blood; Congenital Hypothyroidism/complications; Congenital Hypothyroidism/diagnosis*; Congenital Hypothyroidism/epidemiology
  17. Chong SS, Hoh SY, Huang SM
    Asian J Surg, 2019 Nov;42(11):957-962.
    PMID: 30987945 DOI: 10.1016/j.asjsur.2019.01.015
    BACKGROUND: Hemithyroidectomy has a known but less predictable sequelae of hypothyroidism. Presence of anti-thyroid antibody is known, well studied risk factor. Other postulated risk factors include higher pre-operative TSH level and lower ratio of post-operative thyroid remnant to the patient's weight. We reviewed our data to address the above mentioned risk factors.

    METHOD: This was a retrospective study done in National Cheng Kung University Hospital, Taiwan from 2015 to 2017. 125 patients underwent hemithyroidectomy, but 24 patients were excluded due to autoimmune thyroiditis, which was determined as the exclusion criteria. Standard panel of blood investigations were taken in each clinic visit before and after operation. A neck ultrasound was done 2 months post-operatively to assess the thyroid remnant. Chi-square test was used for categorical data analysis. Independent student t-test was used for continuous data with parametric distribution and Mann-Whitney U test for non parametric data. p 2.0 uIU/mL was a risk factor as Chi square test showed p 

    Matched MeSH terms: Hypothyroidism/etiology*; Hypothyroidism/epidemiology
  18. Nor Azlin MI, Bakin YD, Mustafa N, Wahab NA, Johari MJ, Kamarudin NA, et al.
    J Obstet Gynaecol, 2010;30(7):675-8.
    PMID: 20925608 DOI: 10.3109/01443615.2010.503908
    This study was undertaken to determine the presence of thyroid autoantibodies and associated pregnancy complications from 49 pregnant women with thyroid disease. There were 31 (63%) women with Graves' disease (GD) and 18 (37%) with primary hypothyroidism (PHT). A total of 26 (53.1%) women, 19 (61%) with GD and seven (39%) with PHT, had positive antibodies. Six had thyroid peroxidase antibodies (TPO), one with thyroglobulin antibody (TG) and eight had TSH receptor antibodies (TR). Two had a mixture of antibodies involving TG/TPO (one GD vs one PHT), four with TG/TPO/TR (all had GD) and five with TPO/TR (four with GD vs one with PHT). There were associations in women with positive thyroid antibodies and pre-eclampsia (15.4%), abruptio placenta (4%), caesarean deliveries (31%), postpartum thyroiditis (19.2%) and abnormal neonatal thyroid function (15.4%). Women with positive thyroid antibodies in pregnancy need close care during and after pregnancy, as they can develop complications affecting both mother and fetus.
    Matched MeSH terms: Hypothyroidism/immunology*; Hypothyroidism/epidemiology
  19. Lee CC, Harun F, Jalaludin MY, Heh CH, Othman R, Junit SM
    BMJ Open, 2015 Jan 05;5(1):e006121.
    PMID: 25564141 DOI: 10.1136/bmjopen-2014-006121
    OBJECTIVES: The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian-Chinese and its possible phenotypic effects.

    SETTING: Cohort study.

    PARTICIPANTS: Twelve biologically unrelated Malaysian-Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland.

    PRIMARY OUTCOME MEASURE: Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR-direct DNA sequencing method.

    SECONDARY OUTCOME MEASURE: Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation.

    RESULTS: The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein.

    CONCLUSIONS: The c.2268dup mutation was detected in approximately one-third of the Malaysian-Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis.

    Matched MeSH terms: Congenital Hypothyroidism/enzymology*; Congenital Hypothyroidism/genetics*; Congenital Hypothyroidism/epidemiology
  20. Kang IN, Musa M, Harun F, Junit SM
    Biochem Genet, 2010 Feb;48(1-2):141-51.
    PMID: 20094846 DOI: 10.1007/s10528-009-9306-7
    The FOXE1 gene was screened for mutations in a cohort of 34 unrelated patients with congenital hypothyroidism, 14 of whom had thyroid dysgenesis and 18 were normal (the thyroid status for 2 patients was unknown). The entire coding region of the FOXE1 gene was PCR-amplified, then analyzed using single-stranded conformational polymorphism, followed by confirmation by direct DNA sequencing. DNA sequencing analysis revealed a heterozygous A>G transition at nucleotide position 394 in one of the patients. The nucleotide transition changed asparagine to aspartate at codon 132 in the highly conserved region of the forkhead DNA binding domain of the FOXE1 gene. This mutation was not detected in a total of 104 normal healthy individuals screened. The binding ability of the mutant FOXE1 protein to the human thyroperoxidase (TPO) promoter was slightly reduced compared with the wild-type FOXE1. The mutation also caused a 5% loss of TPO transcriptional activity.
    Matched MeSH terms: Hypothyroidism/genetics*; Hypothyroidism/metabolism
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