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Introduction:acromegaly, an overproduction of growth hormone (GH), is associated with high rate of morbidity and mortality particularly in case of delayed in diagnosis and treatment. A wide variation of clinical presentations, treatment outcomes and morbidities have been reported. Methods:a retrospective study was conducted to review clinical characteristics and treatment outcomes of patients with acromegaly treated in King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 2006 and 2018. Results:eighty-four patients (31 males and 53 females) were reviewed, mean age at diagnosis was 45.7 ± 12.6 years (±SD), mean time of disease onset was 7.6 ± 6.4 years and mean follow-up period was 7.8 ± 5.3 years. The most common presenting symptoms were maxillofacial change (96.8%) and acral enlargement (94.7%). Hypertension (39.3%), diabetes mellitus (28.6%) and dyslipidemia (23.8%) were prevalent co-existing conditions. Four patients were identified having cancer at presentation; however, no additional malignancy was reported during the follow up. Most patients harbored macroadenomas, only 10 were found to have microadenomas. The outcomes of treatment were controlled disease in 70% of microadenoma and 64.9% of macroadenoma. Permanent loss of pituitary function was found in about 21.3% and there was one case reported of mortality. The logistic regression analysis for controlled disease outcome showed the IGF-I index after surgery was associated with controlled disease outcome with statistically significant result (P-value=0.006).==Replace this with the results section of the abstract== Conclusion:our study offers descriptive clinical data of case series of acromegalic patients, which had favorable outcomes comparable with previous reports. In addition, IGF-I index after surgery is a predictive parameter for outcome of treatment.

Background Adrenal histoplasmosis and tuberculosis (TB) are the most common adrenal infections. These conditions are widely reported in developing countries. Methods We performed a retrospective study of patients with adrenal histoplasmosis and TB at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from 2005 to 2020, and evaluated clinical characteristics, treatment, and outcomes. The diagnosis was made by proven microbiologic evidence of infection and morphologic adrenal abnormalities by cross-sectional imaging. Results Of all 27 patients, 20 had adrenal histoplasmosis, 6 had adrenal TB, and 1 had coinfection with both pathogens. The majority of the patients had bilateral adrenal involvement (93%). Most patients were males (81%), and the mean age was 62 years. Ninety-six percent of patients did not have HIV infection. The most frequent comorbidities were hypertension (50%) and diabetes mellitus (23%). Common presentations were weight loss and anorexia (77%), and fever (65%), in which the median time from the presentation to diagnosis was 3.5 months. The prevalence of adrenal insufficiency was 67%. All patients with adrenal insufficiency received steroid replacement, yet 17% had an adrenal crisis during the treatment course. Ninety-six percent of patients received medical treatment (antituberculosis or antifungal agents), while almost half needed additional surgery (44%). During a median follow-up period of 20.5 months, the mortality rates were 28.5%, in which all death was from patients with adrenal histoplasmosis or coinfection with histoplasmosis and TB. Conclusion There were high rates of adrenal insufficiency in patients with adrenal histoplasmosis and TB. High mortality rates were also observed, particularly in adrenal histoplasmosis. Appropriate management of these conditions is required from both infectious and hormonal perspectives. Presentation: No date and time listed

Background: Cushing’s syndrome (CS) in pregnancy is a rare condition. Accurate diagnosis and appropriate treatment are necessary due to increased morbidity and mortality in the fetus and mother with active CS. However, hormonal changes during pregnancy and limitations in terms of teratogenicity complicates the diagnosis of CS. Clinical case: A 27-year-old female presented at gestational age (GA) of 8 weeks with a 2-month history of proximal muscle weakness. She had 20-kg weight gain in 2 years before hypertension, prediabetes and pulmonary tuberculosis developed at the age of 25. On physical examination, her blood pressure was 160/100 mmHg. She had moon face, buffalo hump, wide purplish striae and hirsutism without signs of virilization. At GA 9 weeks, her morning cortisol was 32 μ;g/dL (883 nmol/L). Her salivary cortisol was 0.7 μ;g/dL (19 nmol/L) and a mean 24-hour urinary free cortisol was 237 μ;g/d (654 nmol/d), which were above reference ranges. Adrenocorticotropic hormone (ACTH) were 48 pg/mL (11 pmol/L) and 40 pg/mL (9 pmol/L). Dehydroepiandrosterone sulphate was 378 μ;g/dL (10 nmol/L). A non-gadolinium enhanced magnetic resonance imaging (MRI) at GA 12 weeks did not reveal a pituitary mass. Desmopressin stimulation test was carried out at GA 14 weeks. Her baseline cortisol was 31 μ;g/dL (855 nmol/L) and ACTH was 35 pg/mL (8 pmol/L). Her ACTH increased 70% at 15 minutes after desmopressin stimulation, with an absolute difference between basal and peak ACTH of 24 pg/mL (5 pmol/L). MRI pituitary gland with gadolinium at GA 14 weeks revealed an 8-mm adenoma at right inferolateral aspect of pituitary gland. Transsphenoidal surgery with selective adenomectomy was done at GA 18 weeks without immediate complications. Pathological findings showed a segment of pituitary adenoma with ACTH positive cells. After surgery, her morning cortisol was 6 μ;g/dL (166 nmol/L). Hydrocortisone supplement was given and had been continued throughout pregnancy. She successfully gave birth to a term 2300-gram male infant. One year after delivery, she had spontaneous pregnancy and also delivered a term 3300-gram male infant. Cushing’s syndrome had been in remission for 2 years of follow-up. Conclusion: Hormonal changes during pregnancy lead to an increased in ACTH after 7 weeks of gestation. Desmopressin test can be a safe and reliable test to differentiate between ACTH-dependent and ACTH-independent CS. Because a non-gadolinium enhanced MRI may not always detect pituitary microadenoma, this raises the necessity of the use of MRI with gadolinium as an initial imaging in pregnant patients with ACTH-dependent CS. References: Brue T, Amodru V, Castinetti F. Management of Cushing’s syndrome during pregnancy: solved and unsolved questions. Eur J Endocrinol. 2018;178(6):R259-266.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p

Somatic KCNJ5 mutations result in excess aldosterone production and are reported to be more common in Asia than elsewhere. To assess the prevalence of somatic KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed the clinical characteristics, treatment outcomes, and biochemistry and histologic differences among patients with and without somatic KCNJ5 mutations. Of the 96 patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient with p.W126R. All patients presented with hypertension. Hypokalemia was documented in 98% of patients. The hypertension cure rate at 1 year after surgery was 35%. Patients with somatic KCNJ5 mutations required more potassium supplementation and had adrenal histology compatible with zona fasciculata-like cells compared with patients without the mutations (all P < 0.05). There were no significant differences in preoperative plasma aldosterone concentration (PAC), plasma renin activity, aldosterone/renin ratio, potassium level, treatment of hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5-mutant and nonmutant groups. In a multivariate analysis, a higher PAC was associated with the presence of somatic KCNJ5 mutations. In summary, the prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand, an Asian country with residents of different ethnic backgrounds, is comparable to previous reports in Asia.

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.

Somatic KCNJ5 mutations result in excess aldosterone production and are reported to be more common in Asia than elsewhere. To assess the prevalence of somatic KCNJ5 mutations in Thai patients with aldosterone-producing adrenal adenomas (APAs) in a single tertiary center, we analyzed the paraffin-embedded tissue of KCNJ5 mutations from 96 patients with sporadic APAs who underwent unilateral laparoscopic adrenalectomy at our center during 2007 to 2016. We also assessed the clinical characteristics, treatment outcomes, and biochemistry and histologic differences among patients with and without somatic KCNJ5 mutations. Of the 96 patients with APA, 67 (70%) had somatic mutations of the KCNJ5 gene: 39 patients with p.G151R, 26 patients with p.L168R, one patient with p.T158A, and one patient with p.W126R. All patients presented with hypertension. Hypokalemia was documented in 98% of patients. The hypertension cure rate at 1 year after surgery was 35%. Patients with somatic KCNJ5 mutations required more potassium supplementation and had adrenal histology compatible with zona fasciculata–like cells compared with patients without the mutations (all P < 0.05). There were no significant differences in preoperative plasma aldosterone concentration (PAC), plasma renin activity, aldosterone/renin ratio, potassium level, treatment of hypertension, tumor size, and hypertension cure rate among patients in the KCNJ5-mutant and nonmutant groups. In a multivariate analysis, a higher PAC was associated with the presence of somatic KCNJ5 mutations. In summary, the prevalence of somatic KCNJ5 mutations in patients with sporadic APAs in Thailand, an Asian country with residents of different ethnic backgrounds, is comparable to previous reports in Asia.

Patients with long-standing hypothyroid are, in some cases, reported to develop pituitary gland hyperplasia due to loss of feedback inhibition of thyroxine in hypothalamus—the condition of which typically regresses after thyroxine replacement. Herein, a 15-year-old girl—with long-standing untreated lingual hypothyroid—presents with a pathologically proven TSH pituitary macroadenoma and bilateral large ovarian cysts. Although MR imaging may differentiate between hyperplasia and macroadenoma of the pituitary gland, pathological examination is still a cornerstone to correct diagnosis.

Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes.We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900TC, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously.MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.

Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

Thirty-three patients with mild-to-moderate essential hypertension received either placebo or fenoldopam, a selective dopamine-1 agonist, by intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 μg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h drug infusion. Plasma concentrations of racemic fenoldopam were measured at frequent intervals during and for 24 h after fenoldopam infusion. In the 26 patients who received fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied ( − 9 and − 9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 μg/kg/min, P .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving fenoldopam at 0.8 μg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the drug developed slowly during the 48 h of drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate hypertension at doses as low as 0.04 μg/kg/min, is well tolerated at doses up to 0.8 μg/kg/min, maintains most of its antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound hypertension when discontinued. The pharmacodynamic effects of the drug are best predicted by pharmacokinetics of racemic and R-fenoldopam.

A retrospective review was conducted of medical records of newly diagnosed diabetes in adults who presented with DKA between 2003 and 2007. The majority of DKA in Thailand could not be classified as classical type 1 diabetes. Some newly diagnosed people presenting with DKA could be safely withdrawn from insulin treatment.

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.

Serum insulin-like growth factor (IGF)-I level is growth hormone (GH) dependent and reflects GH secretion. Analysis of IGF-I is a component in the diagnosis of GH-related disorders and is going to be of interest in determining the risk of many disorders such as cancer or atherosclerosis. The diagnosis value of IGF-I is dependent on the establishment of an accurate reference ranges, which can be affected by parameters such as age, gender, ethnicity, medications, chronic illness, or assay methodologies.To determine reference ranges of IGF-I for healthy Thai adults.Eight hundred sixteen healthy Thai adults aged between 21-70 years were recruited in the present study. Serum IGF-I was measured by using immunochemiluminescent (ICMA; Roche, USA). Subjects were recorded by their age and gender groups. Data were presented in mean and +/- 2 standard deviation (SD). Correlation analysis between serum IGF-I and physical parameters including sex, age, weight, height, and body mass index (BMI) was also made.The present study demonstrated normal reference range of serum IGF-I by using mean +/- 2 SD value. The well-known age dependency of serum IGF-I levels was also revealed. Levels decreased with increasing age in both genders. The mean value of serum IGF-I was slightly higher in women at the age of 30-40 years compared with men in the same age group, but not statistically insignificant. In addition, serum IGF-I was found to correlate directly with the height and negatively with BMI. However, age-adjusted IGF-I level did not show correlation with these physical parameters.This reference range will be beneficial for using IGF-I assay as a tool in the diagnosis of GH function abnormalities in Thai subjects.

The most common endocrine disorder in patients with human immunodeficiency virus (HIV) is adrenocortical dysfunction. The prevalence of adrenal insufficiency in patients with AIDS is unclear; partly due to different tests, doses of adrenocorticotrophic hormone (ACTH), and criteria used. In addition, there is controversy regarding the assessment of adrenal insufficiency in patients with and without critical illness.To help clarify the prevalence of adrenal insufficiency in patients with AIDS both in critical and non-critical illness, the authors compared the prevalence based on the high-dose ACTH stimulation test.There were 26 patients with AIDS (19 males and 7 females) with a mean age of 33.6 years (range: 22-46 years). Twelve and 14 patients were in critical and non-critical illness, respectively.Overall, the prevalence of adrenal insufficiency was 19.2% (5 of 26) and 30.8% (8 of 26) when a peak stimulated cortisol level of18 microg/dL and25 microg/dL was defined, respectively. The prevalence was 8.3% and 28.6% in critically and non-critically ill patients; respectively, when a peak stimulated cortisol level of18 microg/dL was defined. Finally, when a peak stimulated cortisol level of25 microg/dL was defined, the prevalence was 16.7% and 42.9% in critically and non-critically ill patients, respectively.Adrenal insufficiency in patients with AIDS is more prevalent than those without HIV infection, no matter what criteria of cortisol response after ACTH test are defined An adrenal testing should be performed in all hospitalized patients with AIDS, both in critical and non-critical illness.

Fibrocalculous pancreatitis diabetes (FCPD), a late stage of tropical chronic pancreatitis (TCP), is classified as a secondary cause of diabetes mellitus resulting from pancreatic exocrine dysfunction. The distinctive features of FCPD and TCP are young age at onset, presence of large intraductal pancreatic calculi, and reported mainly in tropical developing countries. Their etiology is still obscure, but the autodigestion due to aberrant intraductal activation of zymogens by trypsin is thought to be a primary common event. Recently, mutations in SPINKI gene encoding a pancreatic secretory trypsin inhibitor have been reported in association with an increased risk of pancreatitis. We describe a heterozygous mutation, IVS3+2 TC, of SPINK1 gene in a young Thai female patient with typical presentation of FCPD. To our knowledge, this is the first report of the SPINK1 gene mutation in a FCPD patient in Southeast Asia.

Thyroid function test is an essential tool in the diagnosis of thyroid dysfunction. To date, it is still controversial which diagnostic algorithm is best applicable to clinically hyperthyroidism patients.To compare various algorithms of thyroid function tests in the diagnosis of hyperthyroidism.Patients from the endocrine clinic, King Chulalongkorn Memorial Hospital were investigated for thyroid function tests (T3, T4, FT3, FT4 and TSH). Hyperthyroidism was defined as an elevated either FT3 or FT4 with suppressed TSH. The authors compared the effectiveness in hyperthyroidism diagnosis among algorithms by using sensitivity, specificity, positive predictive value and negative predictive value.Of all 452 patients in the present study, 94.24 percent were women. There were 206 hyperthyroidism, 30 subclinical hyperthyroidism, 1 subclinical hypothyroidism, 8 primary hypothyroidism and 207 normal subjects. The incidence of T3 toxicosis was 16.02% while that of T4 toxicosis was 2.16%. After the effectiveness analysis of these algorithms, FT3 and TSH is the most optimal test with 97.57% sensitivity and 100% specificity. Compared to FT4 and TSH, it gave 83.98% sensitivity and 100% specificity.According to the high incidence of T3 toxicosis in the present study, FT3 and TSH should be the initial test for diagnosis of hyperthyroid patients in an outpatient setting and FT4 should be measured subsequently in case of suspected T4 toxicosis.

Tight blood pressure control among diabetic and nondiabetic patients with hypertension is perhaps the single most effective intervention used to delay progression to end-stage renal disease (ESRD). The renoprotective actions of angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic and hypertensive nephropathy is well established. Drugs of this class fairly uniformly reduce glomerulosclerosis, delay the deterioration in renal function, and improve proteinuria, a predictive surrogate marker for renal injury. Calcium- channel blockers (CCBs) in the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) classes also improve proteinuria and delay the progression of renal disease in diabetic and nondiabetic hypertensive nephropathy beyond that attributable to blood pressure control. The short-acting dihydropyridine CCBs worsen proteinuria and accelerate renal injury in both animal models and humans with hypertension or diabetes. A very limited number of studies in animals or humans with hypertension or diabetes have demonstrated at least an additive renoprotective effect when the combination of ACE inhibitors and nondihydropyridine CCBs has been compared with each agent administered as monotherapy. Because patients with impaired renal function and either hypertension or diabetes appear to benefit from aggressive blood pressure reduction, many of these patients will require two or more drugs to achieve the currently recommended blood pressure goals. Combinations of ACE inhibitor and CCB are attractive because they may provide better blood pressure control, appear to be better tolerated with fewer side effects than either drug alone, and may exert a greater renoprotective effect in patients at risk for renal failure than either an ACE inhibitor or a CCB.

The coexistence of pheochromocytoma and renal artery stenosis had been reported occasionally from the possible mechanism of catecholoamine-induced vasospasm and extrinsic compression of renal artery in some reported cases. However, renal infarction caused by pheochromocytoma is an uncommon phenomenon. Herein, we report an interesting case of adrenal pheochromocytoma associated with renal artery thrombosis, which should be included in the differential diagnosis of pheochromocytoma patients who present with abdominal pain.

We describe a case of bacterial aortitis caused by Burkholderia pseudomallei. This patient presented with prolonged fever and hoarseness of voice. Aneurysm removal with Dacron graft replacement was performed, followed by a prolonged course of antibiotics. The patient has progressed satisfactorily without recurrence of symptoms. Previous case reports are summarized.

Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS gene. Most published mutation studies of Pendred syndrome have dealt with Western populations. In this study, we examined clinical and molecular characteristics of 16 affected individuals in 6 unrelated Thai families. Of all the affected, 100% (16/16) had bilateral deafness, 68.8% (11/16) goiters, and 25% (4/16) hypothyroidism. Follicular thyroid carcinoma and Hurthle cell adenoma were found in affected members of a family, raising the possibility of an increased risk of thyroid carcinoma in Pendred syndrome patients. Sequence analysis of the entire coding region of the PDS gene successfully identified all 12 mutant alleles in these 6 families. The 12 identified mutant alleles constituted 6 distinct mutations including 3 splice site mutations (IVS4-1G>A, IVS7-2A>G, IVS9-1G>A), one frame shift mutation (1548insC) and 2 missense mutations (T67S, H723R). Eight mutations out of 12 were constituted by IVS7-2A>G and 1548insC, each one being present in 4 distinct alleles in our studied group. The identification of these two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome in Thai populations. In addition, three newly identified mutations, T67S, IVS4-1G>A, and IVS9-1G>A, were not observed in 50 unrelated healthy Thai controls.