Race/Ethnicity and the prevalence of thyrotoxicosis in young Americans.

BACKGROUND: Race/ethnicity may be a newly recognized risk factor for Graves' disease. OBJECTIVE: The aim of this study was to examine the prevalence of thyrotoxicosis by race/ethnicity in Americans aged 12-49 years using three National Health and Nutritional Examination Surveys (NHANES). METHODS: Data were analyzed from 17,939 participants in NHANES III (1988-1994), NHANES 1999-2002, and NHANES 2007-2010 with available thyroid function test results. Thyrotoxicosis was defined as a serum thyrotropin (TSH) of ≤0.1 mIU/L or subjects taking methimazole or propylthiouracil, and overt thyrotoxicosis was defined as high serum thyroxine and a serum TSH of ≤0.1 mIU/L. Logistic regression was performed accounting for the complex sampling design of NHANES, and the results from all three NHANES surveys were combined using a random-effects model. RESULTS: There were 75 study participants with point prevalent thyrotoxicosis, representing a pooled prevalence of 0.4% for Americans aged 12-49 years. Prevalent thyrotoxicosis was nearly three times more likely in non-Hispanic black subjects compared with non-Hispanic whites (OR=2.9 [CI 1.5-5.7]), while there was no difference between the prevalence of thyrotoxicosis in Mexican Americans compared to non-Hispanic whites (OR=1.2 [CI 0.6-2.4]; I2 for heterogeneity=0% for both). Among 27 patients with overt thyrotoxicosis, the odds ratio was 8.7 [CI 0.7-112.6] for non-Hispanic blacks and 4.6 [CI 0.4-59.3] for Mexican Americans compared with non-Hispanic whites. CONCLUSIONS: The results suggest there are race/ethnicity differences in the prevalence of thyrotoxicosis. Future studies should address whether these differences are due to heritable factors, environmental exposures, or a combination of both.

Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3.

Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.

A young man presenting with paralysis after vigorous exercise.

Thyrotoxic periodic paralysis (TPP) is a rare metabolic disorder characterised by muscular weakness and paralysis in predisposed thyrotoxic patients. Although patients with TPP are almost uniformly men of Asian descent, cases have been reported in Caucasian and other ethnic populations. The rapid increase in ethnic diversity in Western and European nations has led to increase in TPP reports, where it was once considered exceedingly rare. Correcting the hypokalaemic and hyperthyroid state tends to reverse the paralysis. However, failure to recognise the condition may lead to delay in diagnosis and serious consequences including respiratory failure and death. We describe a young man who was diagnosed with hyperthyroidism who presented with acute paralysis. The clinical characteristics, pathophysiology and management of TTP are reviewed.

Effects of sex steroid hormones, thyroid hormone levels, and insulin regulation on thyrotoxic periodic paralysis in Chinese men.

Our study is to determine the expression of thyroid hormone, sex hormone, insulin, and C-peptide in Chinese male patients with thyrotoxic periodic paralysis (TPP). This study covered 102 patients with hyperthyroidism from Xijing Hospital. According to whether occurrence of TPP or not, patients were divided into two groups (those that were hyperthyroid with and without TPP) that were, matched with age, blood pressure, urea, and creatinine. We found the body mass index (BMI) in patients with TPP was higher than that in pure hyperthyroidism patients. The levels of the total thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) were significantly lower in patients with TPP compared with pure hyperthyroidism patients, while serum testosterone levels were higher compared with pure hyperthyroidism patients. Moreover, after glucose administration, the concentration of insulin at 60, 120, and 180 min were significantly higher in patients with TPP than those in pure hyperthyroidism patients. The insulin area under the curve (AUC) was significantly increased in patients with TPP compared with pure hyperthyroidism patients. The levels of thyroid hormone, sex hormone, and insulin were different in Chinese male patients with TPP compared to those with only hyperthyroidism.

Thyrotoxic periodic paralysis in a Saudi patient complicated by life-threatening arrhythmia.

Thyrotoxic periodic paralysis (TPP) is rare in non-Orientals, and sporadic case reports were reported world-wide. Eight cases were reported in Arabs, including 3 Saudis. We present an additional case of TPP in a 38-year-old Saudi man, and review the literature on TPP in Arabs. Our patient presented with complete flaccid quadriplegia, 5 weeks after he was diagnosed with Graves' disease that was treated with carbimazole and propranolol. He was hyperthyroid, and his potassium was extremely low (1.5 mmol/L). During initial evaluation in the emergency room, he developed transient asystole manifested by syncope. He was resuscitated and his hypokalemia was corrected, and he had a full recovery. This case emphasizes the notion that TPP can occur in patients of any ethnic background. The development of serious cardiac complications in our patient underscores the importance of early and correct diagnosis of this potentially life-threatening complication of hyperthyroidism.

Thyrotoxic, hypokalaemic periodic paralysis: Polynesians, an ethnic group at risk.

BACKGROUND: Thyrotoxic, hypokalaemic periodic paralysis (TPP) is a reversible cause of severe muscle weakness that occurs in a small minority of thyrotoxic patients. Most cases to date have been reported in Asian men. AIMS: To evaluate the ethnic distribution of patients with TPP. METHODS: Retrospective analysis of all patients presenting with thyrotoxicosis and hypokalaemia with paralysis to two New Zealand hospitals. RESULTS: Seventy-one per cent of the 21 patients with TPP were of Polynesian ethnicity (Maori and Pacific Islander), 24% Asian and 5% European. Based on population demographics, these figures suggest a 37-fold overrepresentation for Polynesians and 159-fold for Asians compared with New Zealand Europeans. CONCLUSION: Polynesian, in addition to Asian people, are two ethnic groups at particular risk of TPP, and this condition must be considered in the differential diagnosis for patients presenting to the emergency department with severe hypokalaemia and weakness.

Thyrotoxicosis presenting as hypokalaemic paralysis and hyperlactataemia in an oriental man.

A 35-year-old Malaysian man presented with rapid onset of flaccid quadriparesis associated with nausea and vomiting. General blood tests revealed severe hypokalaemia (serum potassium 1.5 mmol/L) and hypophosphataemia (serum phosphate 0.29 mmol/L) as a potential cause of the flaccid paralysis. Arterial blood gases showed mixed acid base disturbance of respiratory alkalosis and metabolic acidosis with hyperlactataemia. Thyrotoxic periodic paralysis (TPP) was suspected as the underlying cause of this presentation and thyroid function tests showed severe hyperthyroid results (free T4 > 77.2 pmol/L, free T3 19.3 pmol/L, thyroid-stimulating hormone [TSH] < 0.05 mIU/L). Treatment with intravenous potassium and phosphate infusion and oral propranolol resulted in rapid resolution of his symptoms. A discussion of the clinical and pathophysiological features and treatment of TPP (a very rare encounter in UK clinical practice) is presented, and to our knowledge associated hyperlactataemia has not been previously described.

Thyrotoxic periodic paralysis in a Maori patient.

A case of thyrotoxic periodic paralysis (TPP) in a patient of Maori heritage is described. The epidemiology, aetiology and pathogenesis of TPP are discussed. The case demonstrates that neurological examination and biochemical findings may be normal between episodes of paralysis. Given that there is much racial variation in the prevalence of TPP, and the suggestion that non-thyrotoxic periodic paralysis may be more prevalent in Maori, the case highlights the need for more research into the prevalence and pathogenesis of TPP in Maori patients.

Thyrotoxic periodic paralysis: reports of seven patients presenting with weakness in an Asian emergency department.

OBJECTIVES: This study was done to describe the features of thyrotoxic periodic paralysis in young Asian men. METHODS: Seven male patients were enlisted who presented to the emergency department over a period of three years with weakness and paralysis in the morning. RESULTS: Initial electrolyte studies revealed hypokalaemia in these patients, and later thyroid function tests confirmed thyrotoxicosis for all. Only two of these patients had clinical symptoms and signs of thyrotoxicosis, the others being asymptomatic. CONCLUSIONS: Early morning paralysis can be the first manifestation of hyperthyroidism in Asian men, without the other more typical symptoms of weight loss, increased appetite, excitability, sweaty palms or goitre. Treatment to a euthyroid state will ameliorate the syndrome.

Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin.

OBJECTIVES: The prevalence of gestational transient thyrotoxicosis (GTT) in Europeans evaluated during the 8th to 14th weeks of pregnancy is 2-3%. However, there is evidence that GTT may be more common in some Asian populations. The aims of this study were to evaluate the prevalence of thyroid hormone abnormalities in Asian women in their 8th to 14th weeks of pregnancy using highly sensitive free T4 and TSH assays and to correlate these with total and free beta-hCG levels. DESIGN AND PATIENTS: One hundred and eighty-four consecutive unselected Asian (Singaporean) pregnant women seen at ante-natal clinics for the first time and who were in their 8th to 14th weeks of pregnancy were tested. MEASUREMENTS: Serum free T4, free T3, TSH, total beta-hCG and free beta-HCG levels were measured on the Vitros ECi system (Johnson & Johnson Ortho-Clinical Diagnostics, Amersham, UK) which employs chemiluminescent immunochemical technology. This free T4 assay is free of biases related to serum binding capacity. The TSH assay used was a third generation assay. Thyrotrophin-receptor antibody (TRAb) levels were measured using LUMItest TRAK (BRAHMS Diagnostica, Berlin, Germany). RESULTS: Two subjects (1.1%) were found to have Graves' disease. Elevated free T4, free T3, total T3 and suppressed TSH were seen in 14.8%, 3.3%, 26.4% and 33.0% of the remaining 182 pregnant women, respectively. Total and free beta-hCG correlated negatively with TSH (r = -0.30, P < 0.0001 and r = -0.29, P < 0.0001, respectively), positively with fT4 (r = 0.283, P < 0.001 and r = 0.253, P < 0.001) and fT3 (r = 0.273, P < 0.001 and r = 0.204, P < 0.01). 11.0% of cases had gestational thyrotoxicosis (GT) defined as elevated free T4 (> 19.1 pmol/l), suppressed TSH (< 0.36 mIU/l) and TRAb levels within the reference interval (0-0.9 U/l). The prevalence of GT was significantly higher in patients tested at 8-11 weeks compared to those evaluated at 12-14 weeks (14.4% vs. 4.7%, P < 0.05). Total beta-hCG (P = 0.0002), free beta-hCG (P < 0.0001) and free T4 (P = 0.02) levels were higher and TSH levels (P = 0.01) lower in patients tested at 8-11 weeks. Significant positive correlations between both total and free beta-hCG with free T4 were seen at 8-11 weeks but not in patients tested at 12 weeks or later. TT3 levels were similar in the two groups. CONCLUSIONS: Using sensitive assays, the prevalence of gestational thyrotoxicosis in Asian women was found to be 11.0% and was significantly higher in subjects at 8-11 weeks of gestation than at 12-14 weeks. The positive correlation between hCG and free T4 seen in patients tested at 8-11 weeks was absent in patients tested at later stages of the first trimester. Future studies investigating the entity of gestational thyrotoxicosis, at least in Asian patients, should focus on patients at earlier stages of gestation than currently practised.

Thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis is a thyroid-related disorder that is manifested as recurrent episodes of hypokalemia and muscle weakness lasting from hours to days. The periodic paralysis has been associated with thyrotoxicosis from various etiologies. Although the incidence of the disorder is relatively higher among Asians, it has been reported in many other ethnic groups. We review the literature and report the ninth and tenth cases of thyrotoxic periodic paralysis in black patients.

Thyrotoxic periodic paralysis in Mexican mestizo patients: a clinical, biochemical and HLA-serological study.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of a group of Mexican mestizo patients with TPP. METHODS: The sample was comprised of 14 men with TPP diagnosed since January 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available for HLA testing. RESULTS: Hyperthyroidism was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. CONCLUSIONS: TPP is more common than previously thought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications.

Thyrotoxic periodic paralysis in mexican mestizo patients: a clinical, biochemical and HLA-Serological study

Background. Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of group of Mexican mestizo patients with TPP. Methods. The sample was comprised of 14 men with TPP diagnosed since january 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available HLA testing. Results. Hyperthyroidsm was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. Conclusions. TPP is more common than previously thoought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications

Sudden periodic paralysis: rare manifestation of thyrotoxicosis.

Nonfamilial hypokalemic thyrotoxic periodic paralysis is rarely diagnosed among Caucasians and blacks in the western world but it is relatively common among Asiatics. Sudden paralysis occurring while at rest after a large carbohydrate meal or strenuous exercise in an undiagnosed mild thyrotoxic patient is a common presentation. A case illustrating such presentation is reported. Intracellular shifts of potassium triggered or facilitated by hyperthyroidism and hyperinsulinemia are the biochemical features. Correction of the thyrotoxic state is the definitive treatment for this disorder. Judicious administration of potassium is indicated during the hypokalemic episode to prevent life-threatening arrhythmias.

Thyrotoxic periodic paralysis in a Chinese population.

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium < or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.

Thyrotoxic hypokalemic periodic paralysis: report of four cases in black American males.

Thyrotoxic periodic paralysis (TPP) is an unusual complication of a fairly common disease affecting mostly Asian males. In the United States, there have been several reports of TPP in different ethnic populations and it appears that the incidence is approximately one-tenth of that found in Asian countries. Only six reports of TPP in African-Americans could be found in the literature; however, we are reporting four cases diagnosed within a 13-year period at our institution. We conclude that TPP may occur more often in Blacks than previously suspected and should be considered when patients present with unexplained hypokalemia, muscular weakness and rhabdomyolysis. The epidemiology, clinical manifestations, pathophysiology, and treatment of TPP are reviewed.