Clinical Endocrinology (2008) 68, 143–152 doi: 10.1111/j.1365-2265.2007.03014.x
O R I G I N A L A R T I C L E
Blackwell Publishing Ltd
Thyrotoxic hypokalaemic periodic paralysis in a Turkish
population: three new case reports and analysis of the
case series
Mustafa Cesur*, Fahri Bayram†, Mehtap Akcil Temel‡, Mesut Ozkaya§, Abdulkadir Kocer¶, Melek Eda Ertorer**, Filiz Koc††, Ahmet Kaya‡‡ and Sevim Gullu§§
*Ufuk University, Faculty of Medicine, Department of Endocrinology and Metabolic Diseases, Ankara, †Erciyes University Medical School, Department of Endocrinology, Kayseri, ‡Baskent University Faculty of Science and Letters, Department of Statistics and Computer Science, Ankara, §Kahramanmaras Sutcu Imam University, Medical Faculty, Department of Internal Medicine, Division of Endocrinology and Metabolism, Kahramanmaras, ¶Duzce University, Duzce Medical Faculty, Neurology Department, Duzce, **Baskent University, Department of Internal Medicine, Division of Endocrinology and Metabolism, Adana, ††Cukurova University Medical School, Department of Neurology, Adana, ‡‡Selcuk University, Meram Medical Faculty, Division of Endocrinology, Konya and §§Ankara University School of Medicine, Department of Endocrinology and Metabolic Diseases, Ankara, Turkey
Summary
Objective Thyrotoxic hypokalaemic periodic paralysis (THPP) is an uncommon condition with intermittent episodes of muscle weakness and occasionally severe paralysis. THPP is a common complication of hyperthyroidism in Asian populations, and has also been reported in other ethnic groups including Caucasians. This study aimed to conduct an analysis of THPP in a Turkish population, and is to our knowledge the first analysis of a homogeneous Caucasian group.
Subjects Forty cases with THPP were identified in the Turkish population. Three out of the 40 were new cases and were assigned as index cases. Two cases were not included in the analysis because of lack of data.
Results THPP was diagnosed in 10 cases during the first attack and was observed to have a significant shorter complete recovery time statistically in this group (P < 0·01). The majority of cases were hypokalaemic, while there were two normokalaemic cases. Classifi-cation of the cases according to their potassium (K) levels revealed that the group with K levels < 2·5 mEq/l had a statistically longer amelioration time than the group with K levels ≥ 2·5 mEq/l. When the cases were classified according to intravenous or oral application of K, the mean amelioration time was 6·8 ± 3·6 h for the intravenous group and 13·1 ± 7·6 for the oral group. Mean complete recovery times of the groups were 29·4 ± 16·2 h and 52·8 ± 18·0 h, respect-ively. The intravenous group had a shorter amelioration time and
complete recovery time, and both were statistically significant
(P < 0·05 for each).
Conclusions THPP may be seen among Caucasians. Diagnosing THPP during the first attack might decrease the recovery time. The level of hypokalaemia seems to affect the recovery time and initial low K levels may lead to more deterioration in a patient’s health compared with mild or near-normal levels. Intravenous, rather than oral, application of K may be advantageous for shortening both the amelioration and complete recovery times.
(Received 15 March 2007; returned for revision 4 April 2007; finally revised 31 May 2007; accepted 11 July 2007)
Introduction
Thyrotoxic hypokalaemic periodic paralysis (THPP) is an uncommon condition associated with intermittent episodes of muscle weakness and occasionally with severe paralysis. Episodes are generally pre-cipitated by strenuous exercise or carbohydrate-rich meals. THPP is a common complication of hyperthyroidism in Asian populations, and has also been reported in some other ethnic groups, including Caucasians.1,2
Anatolia, part of the modern state of Turkey, is a peninsula bounded by the Black Sea to the north, the Aegean Sea to the west, the Mediterranean Sea to the south, and the Caucasus Mountains to the east.3 Most of the Turkish population are Caucasoid. The main subgroup is the Mediterranid race.4 Recently, cases of THPP have been reported increasingly for Turkish Caucasian populations. To date, six such cases have been reported in the English literature since 2004.5–10 However, there are other case reports in the Turkish liter-ature and in congress presentations, with the first reported case being published in 1968.11–30 There are also other cases originating from Correspondence: Mustafa Cesur, Ufuk University, Faculty of Medicine,
Department of Endocrinology and Metabolic Diseases, Mevlana Bulvari, 86–88, 06520 Ankara, Turkey. Tel.: + 90 312 204 41 87;
144 M. Cesur et al.
Anatolia and reported from Western European countries.31,32 The number of Turkish migrants in Europe has increased continuously and more than 3·5 million Turks are currently living in Europe.33 Thus, it is important to be aware of features of THPP in the Turkish population.
This study aimed to conduct an analysis of THPP in a Caucasian population, and to our knowledge this is the first analysis of a homo-geneous Caucasian group.
Materials and methods
Cases were identified through a Medline search of the English liter-ature using Pubmed and the following keywords in different settings: thyrotoxic hypokalemic periodic paralysis, hypokalemic periodic paralysis, periodic paralysis, Turkish, Caucasian, thyrotoxicosis, Graves’ disease, Graves. Then the same keywords were searched in English and in Turkish using Google and Yahoo databases. Turkish Medline was also searched using three different databases: Ulakbim Turk Tip Veri Tabani (ulakbim.gov.tr), Turkish Medline (www.turkishmedline.com) and Turk Medline (medline.pleksus.com.tr). Additionally, con-gress books of the Turkish National Concon-gress for Neurology and Endocrinology between 2000 and 2006 were searched. The planned study was announced at the 2006 Turkish National Congress of Endocrinology and Metabolic Diseases, and new cases were requested.
Forty Turkish cases with THPP were identified. Three of these were new cases and were assigned as index cases. All cases were checked for suitability for the analysis. If the information about a case was incomplete, we contacted the author by mail or telephone for more detailed information. Eventually two of the cases were not included in the analysis because of lack of data. The characteristics of the cases included in the study are given in Table 1.
SPSS for Windows version 13·0 (SPSS Inc., Chicago, IL) was used for statistical testing. The results are expressed as median, mean ± standard deviation (SD). The Mann–Whitney U-test and Wilcoxon’s matched pairs signed ranks test were used for statistical analysis. P-values < 0·05 were considered to be statistically significant.
Case 1
A 32-year-old Turkish man presented to the emergency department with the complaint of inability to move his legs after waking up at night following a heavy carbohydrate-rich meal. He mentioned that a similar but less severe episode had occurred 2 months ago and hypokalaemia had been detected and was treated with potassium chloride (KCl) infusion. After the first episode the patient had suffered from similar symptoms two more times, but had recovered spontaneously. Between the first and last attacks he had experienced weight loss of approximately 15 kg, constant muscle weakness and progressive tiredness while performing routine daily activities.
During physical examination he was conscious and well orientated but unable to walk. The thyroid gland was grade 2a diffuse palpable. An asymmetric paraplegia was noted in the lower extremities; muscle weakness was found (2/5) in the right and (3/5) in the left. Deep tendon reflexes were decreased but the other neurological examinations were normal.
Initial laboratory results revealed low serum potassium (K = 2·5 mEq/l; normal range 3·5–5·2), phosphorus (P = 1·2 mg/dl; normal range 2·5– 4·5) and magnesium (Mg = 0·9 mg/dl; normal range 1·7– 2·5) levels with a normal creatine phosphokinase (CPK = 116 UI/l; normal range 26–174) level. There was marked broadening and inverting in T waves with normal sinusal rhythm on electrocardio-graphic (ECG) evaluation. Serum K level was brought to normal and the symptoms improved and then disappeared within 6 h after a total of 80 mEq intravenous KCl replacement. The patient had recovered completely in 24 h. No rebound hyperkalaemia was seen. He was diagnosed with Graves’ disease with elevated serum free T3 (FT3 = 18·5 pmol/l; normal range 3·4 –7·2) and FT4 (5·8 ng/dl; normal range 0·89–1·8) and suppressed sensitive TSH (sTSH) level (0·03 mIU/l; normal range 0·35–5·5), with high anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody levels (anti-Tg) levels (179 and 311 IU/ml, respectively; normal range 0–40, for both antibodies). A thyroid ultrasound scan revealed diffuse heterogeneous enlargement of the thyroid gland. A thyroid Tc-99 m scan revealed hyperplasia of the thyroid gland with increased activity. 131I uptake was 61% at 4 h (normal 15–20%) and 65% at 24 h (normal 25–50%). No known family history of thyroid disease or periodic paralysis was present. Medication was started with propranolol (80 mg /day) and pro-pylthiouracil (300 mg/day) followed by radioactive iodine (10 mCi of 131I) for permanent treatment of hyperthyroidism. Clinical and biochemical changes were followed at monthly intervals. By the end of the second month, serum FT3 and FT4 were within normal levels and the patient was hypothyroid by the end of the third month of follow-up. Levothyroxine replacement was initiated and no hypo-kalaemic episode has been reported for the past 16 months.
Case 2
A 38-year-old Turkish man was admitted to the emergency department at midnight, suffering from the sudden development of muscle weakness after consuming some alcohol. The patient denied partic-ipating in a carbohydrate-rich meal or undertaking strenuous exercise. Bilateral proximal muscle weakness of the lower extremities had started 4 h ago, progressed rapidly and reached the upper extremities. The only complaint of the patient up until then was chronic fatigue. The first clinical observation was the patient’s inability to walk, and his muscle strength was found to be 2/5 in both lower extremities and 3/5 in upper extremities. The deep tendon reflexes were negative with-out a pathological reflex. The sense tests and biochemical laboratory analyses were within normal limits, except for a serum K level of 2·1 mEq/l (P = 3·2 mg /dl, Mg = 1·7 mg/dl, CPK = 143 UI/l). As the ECG showed a prominent ‘U’ wave with T-wave depression, KCl infusion was initiated. The paralysis and hypokalaemia resolved within 8 h after administration of 90 mEq KCl. By the end of 24 h, his neuro-logical status had recovered completely without rebound hyperkalaemia. Clinical and biochemical improvement was followed with an investigation for the aetiology of the attack. The patient had a grade 1a diffusely enlarged thyroid with abnormal thyroid function tests and high thyroid antibodies (FT3 = 11·5 pmol/l, FT4 = 3·1 ng/dl, TSH = 0·01 mIU/l, anti-Tg = 384 IU/ml, anti-TPO = 297 IU/ml). There was diffuse enlargement of the gland on thyroid sonography, and thyroid scanning showed diffusely increased activity of the
THPP in a Turkish population 145
gland. 131I thyroid uptake was 53% by the end of 4 h (normal range 15–25), and 66% by the end of 24 h (normal range 25–50). His family history was negative for periodic paralysis. Graves’ disease was diag-nosed, and he was started on propranolol (40 mg/day) and propylth-iouracil (300 mg/day). The medical treatment was completed with 8 mCi of 131I and no muscle weakness occurred in the following days.
Case 3
A 31-year-old Turkish man was admitted to the emergency department at 0400 h with a complaint of diffuse weakness of the extremities.
The condition was started after a carbohydrate-rich meal that consisted mainly of beverages and dessert. The patient declared that he had never experienced such a condition before, even though he is thyrotoxic, and had been taking propranolol (60 mg/day) and propylthiouracil (300 mg/day) for 2 months. He also mentioned that he had had an acute catarrhal infection of the upper respiratory tract a week ago but had recovered without any treatment.
Physical examination revealed that the patient was conscious, well orientated but unable to walk because of the flaccid paralysis of his extremities. Muscle strength was 2/5 in the lower extremities and 4/5 in the upper extremities. Total depression of the deep tendon Table 1. Some features of the cases included in the study
Case Age (years) Aetiology State of thyroid function Symptoms of TT Duration of periodic paralysis K (mEq/l) K supply method Amelioration time (h) Complete recovery time (h)
Aldemir et al.5 35 GD Overt TT Present First attack 1·5 IV 8 18
Erem6 28 GD Overt TT Present 2 months 1·5 IV 20 72
Akar et al.7 37 GD Overt TT Absent 10 years 2·6 WP 4 24
Cesur et al.8 38 GD Overt TT Present 2 years 2·5 IV 8 24
Ozdemirli et al.9 30 ST Overt TT Absent 3 months 1·5 IV 6 24
Cesur et al.10 29 GD Overt TT Present 1 month 2·2 IV 5 24
Ozdemir et al.11 41 GD NA Absent 10 years 4·0 O 4 36
Ozdemir et al.11 34 SAT NA Absent 2 months 3·8 O 3 24
Tataroglu and Baran12 54 ST Subclinical TT Absent 3 months 2·6 O 10 48
Kaya et al.13 23 GD Overt TT Absent 1 year 2·2 O 23 72
Kaya et al.13 35 GD Overt TT Absent 10 years 1·6 O 20 72
Kaya et al.13 37 GD Overt TT Present 4 months 1·8 O 10 48
Kaya et al.13 35 GD Overt TT Absent 1 year 2·3 O 15 50
Dokmetas et al.14 22 GD Overt TT Present 5 months 2·2 IV 1 8
Ataoglu et al.15 32 GD Overt TT Absent 3 years 2·0 IV 6 72
Gunel et al.16 33 TNG Overt TT Absent 5 months 3·4 WP 5 24
Kizkin et al.17 33 GD Overt TT Present 10 years 2·9 IV 4 24
Aluclu and Hamdanogullari18
45 GD Overt TT Present 1 month 2·7 IV 8 48
Guloglu et al.19 41 GD Overt TT Present 3 months 2·0 IV 8 48
Koc et al.20 32 TNG Euthyroid Absent 8 years 2·3 IV 10 24
Koc et al.20 42 GD Overt TT Present First attack 2·2 IV 7 23
Koc et al.20 29 TNG Overt TT Absent 7 months 2·1 IV 8 26
Koc et al.20 28 GD Overt TT Absent 5 years 1·8 IV 10 32
Koc et al.20 31 GD Overt TT Present 5 years 1·6 IV 10 34
Koc et al.20 38 TNG Overt TT Present 5 years 2·1 IV 8 25
Koc et al.20 48 GD Subclinical TT Absent First attack 2·8 IV 6 22
Aktaran et al.21 36 GD Overt TT Absent 1 month 1·9 IV 2 12
Akinci et al.22 49 TNG Overt TT Present First attack 1·6 IV 4 8
Eroglu et al.24 28 GD Overt TT Absent NA 1·2 O 20 72
Gencer25 30 GD Overt TT Present First attack 2·4 IV 8 48
Gokce et al.26 28 TNG Overt TT Absent First attack 3·2 IV 5 24
Yilmaz et al.28 35 GD Overt TT Present 2 months 3·0 IV 4 48
Demirdag et al.29 60 TNG Overt TT Absent 1 year 2·0 IV 4 24
Haydardedeoglu et al.30 26 GD Overt TT Present First attack 2·6 IV 3 10
Haydardedeoglu et al.30 29 GD Overt TT Absent First attack 2·2 IV 6 24
Case 1 38 GD Overt TT Present First attack 2·1 IV 8 24
Case 2 32 GD Overt TT Present 2 months 2·5 IV 6 24
Case 3 31 GD Overt TT Present First attack 1·7 IV 3 12
K, potassium; TT, thyrotoxicosis; GD, Graves’ disease; TNG, toxic nodular goitre; ST, silent thyroiditis; SAT, subacute thyroiditis; IV, intravenous; O, oral; WP, without potassium.
146 M. Cesur et al.
reflexes was present without any pathological reflexes. Sense tests were normal. Biochemical analysis showed a low serum K level (1·7 mEq/l) while other tests were within normal limits (P = 3·4 mg/dl, Mg = 1·8 mg/dl, CPK = 135 UI/l). As ECG confirmed hypokalaemia with prominent ‘U’ waves and sinusal tachycardia, KCl infusion was initiated. The generalized weakness started to resolve within 3 h from onset with a total of 50 mEq KCl. The patient made a complete clinical recovery after 12 h without any signs of rebound hyperkalaemia.
On further evaluation, elevated serum thyroid hormone and suppressed sTSH revealed an overt thyrotoxicosis (FT3 = 23·6 pmol/l, FT4 = 6·7 ng/dl, TSH = 0·005 mIU/l) even though the patient was receiving anti-thyroid medication. Thyroid antibody titres were concordant with an autoimmune thyroid disease (anti-Tg = 57 IU/ml, anti-TPO = 675 IU/ml). His family history of thyroid disease or periodic paralysis was negative. The finding of diffusely increased activity was observed on thyroid scanning. Thyroid sonography showed diffuse heterogeneous enlargement of the thyroid gland. 131I thyroid uptake was 51% at 4 h (normal range 15–25), and 61% at 24 h (normal range 25–50). Low compound muscle action potential amplitudes were present on electromyography (EMG) examination. The exercise test that was performed during normal muscle strength was positive. As the presence of Graves’ disease was confirmed, the dose of propylthiouracil was increased to 450 mg/day and additional propranolol (80 mg /day) was started.
Results
All cases reported from Turkey were male and family histories were negative for periodic paralysis. Mean and median ages of the cases were 35·1 ± 8·1 and 34 years, respectively. The amelioration times (resolving time of paralysis and hypokalaemia) were between 1 and 23 h (mean 7·9 ± 5·2, median 6·5) with complete recovery times (period of becoming completely well in neurological examination) between 8 and 72 h (mean 33·6 ± 19·1, median 24). The subjects were grouped according to their ages. The first age group comprised the cases between 22 and 34 years (total 20 cases, mean 29·4 ± 3·2, median 31) and the second age group comprised the cases between 35 and 60 years (total 18 cases, mean 41·3 ± 7·2, median 41). Com-parison of amelioration times and complete recovery times revealed no significant difference between the groups (P > 0·05).
The major aetiological factor was Graves’ disease (73·7%). Toxic nodular goitre was the second factor (18·4%) comprising four toxic adenomas and three toxic multinodular goitres. The other aetio-logical factors were silent thyroiditis (5·3%) and subacute thyroiditis (2·6%).
All cases were first admitted to the emergency department, 20 admissions were in the morning (54·1%), and 17 were at night (45·9%). Cases were reported mainly by neurologists (19 cases; 50·0%) and endocrinologists (15 cases; 39·5%), the rest were reported by a specialist of emergency medicine, a rheumatologist, a general surgeon and a physical medicine and rehabilitation (PMR) specialist separately (2·6% for each).
Most of the patients had a carbohydrate-rich meal and/or strenuous exercise as the precipitating factor (72·3%). Of the 37 cases, 10 had a carbohydrate-rich meal together with strenuous exercise (27·0%), 10 had had only a carbohydrate-rich meal (27·0%), and seven only
strenuous exercise (18·9%). Just 10 of the patients (27·0%) had different precipitating factors such as waking up in the middle of sleep (10·8%) or cold (8·1%) or other factors (Table 2).
In 10 cases THPP was diagnosed at the first attack (27·0%). There was delayed diagnosis in the remaining 27 cases (73·0%) of about 1 month to 10 years. When we grouped the subjects as cases diagnosed during the first attack and the others, mean amelioration times were 5·8 ± 2·0 h (median 6 h) and 8·4 ± 5·6 h (median 8 h), respectively, and mean complete recovery times were 21·3 ± 11·3 h (median 22·5 h) and 36·7 ± 18·7 h (median 26 h), respectively. No significant difference was observed between the groups for amelioration times (P > 0·05), but the first-attack group had a statistically significant shorter complete recovery time (P < 0·01). While most of the cases had overt thyrotoxicosis (92·1%), others were in subclinical thyrotoxic (5·3%) and euthyroid (2·6%) states. However, symptoms of thyro-toxicosis were reported only in 20 cases (52·6%) and the remaining 18 cases (47·4%) were asymptomatic. THPP had developed in four cases (10·5%) during the course of treatment for thyrotoxicosis. Furthermore, attacks relapsed in another three cases after THPP was diagnosed (7·9%).
The cardinal complaint of the patients was acute paralysis, which was usually apparent as quadriplegia (33 cases; 86·8%) and occa-sionally as paraplegia (five cases; 13·2%). Paralysis occurred bilateral symmetrically in most cases (35 cases; 92·1%) and asymmetrically in a few cases (three cases; 7·9%). Muscle weakness was more sig-nificant in the lower extremities in 19 cases (50·0%), while lower and upper extremities were both affected equally in 18 cases (47·4%), and in only one case were the upper extremities the major affected site (2·6%). Thirteen cases had information about the spread of paralysis. In 12 cases, paralysis started at the proximal muscles of the lower extremities and then spread to the distal and upper parts of the body, except for one case in which the muscle weakness started from the distal muscles and spread proximally. Depressed deep tendon reflexes were present in most cases (97·4%), with the exception of one case (2·6%). No abnormal sensory test was reported. EMG was performed in 17 cases and 10 of them were normal (58·8%), while the remaining seven (41·2%) had myogenic changes in the affected muscles, such as reduced amplitude and duration of the muscle action potential.
Hypokalaemia was screened in the majority of cases (38 cases; 94·7%), while there were two normokalaemic cases (5·3%). The cases were grouped according to K levels. The first group comprised Table 2. Precipitating factors in Turkish cases
Carbohydrate-rich meal Strenuous exercise
Waking up in the middle of sleep Cold exposure
Alcohol Glucocorticoid
Injection of diclofenac sodium Emotional stress
Upper respiratory tract infection Radioactive iodine treatment
THPP in a Turkish population 147
the cases whose K levels were under 2·5 mEq/l (25 subjects), while the second group consisted of those whose K levels were ≥ 2·5 mEq/l (13 subjects). Mean amelioration times were 9·2 ± 6·0 h (median 8 h) for the first group and 5·4 ± 2·1 (median 4·5 h) for the second group. Mean complete recovery time was 35·8 ± 21·8 h (median 24·5 h) for the first group and 29·2 ± 12·0 h (median 24 h) for the second. Comparison of the two groups revealed that the first group had a statistically longer amelioration time than the second (P < 0·05), while there was no statistical difference for the complete recovery times (P > 0·05). Blood phosphorus levels were obtained in 28 cases, and 23 of them (82·1%) were within normal limits, while hypo-phosphataemia was screened in five cases (17·9%). Out of 12 cases in whom serum magnesium levels were obtained, only one of them had a low level of magnesium (8·3%). Serum CPK levels were reported in 19 cases, with 12 cases demonstrating high (63·2%) and seven cases demonstrating normal CPK levels (36·8%).
ECG findings that were analysed in 33 cases revealed seven ECGs within normal limits (21·2%). The remaining 26 cases revealed some different ECG findings that were generally concordant with hypokalaemia (Table 3). Provocation tests were performed in five cases by loading glucose and/or doing exercise tests and all of them were positive.
With regard to treatment, 36 cases (94·7%) received K replace-ment by an intravenous (28 cases; 73·7%) or oral (eight cases; 21·0%) route and only two cases (5·3%) were treated without K. Information about rebound hyperkalaemia was given for 24 cases, and only three of them had rebound hyperkalaemia (12·5%). There was information about infused K amount in 17 cases. The mean of total infused K of the three cases with rebound hyperkalaemia was 223·3 ± 105·4 mEq, while the mean of the others was 95·9 ± 43·6 mEq. Beta blockers (propranolol in 29 cases, atenolol in one case) were used in 30 cases (78·9%). Furthermore, 26 cases (68·4%) received propylthiouracil; one received methimazole (2·6%) and one (2·7%) acetazolamide. Radioactive iodine (five cases) or surgery (two cases) was performed in seven cases (18·4%) for permanent therapy.
The cases were grouped according to whether they were using intravenous or oral K, and comparison was performed for the two groups with regard to amelioration time and complete recovery time. The mean amelioration time was 6·8 ± 3·6 h (median 6 h) for the
intravenous group and 13·1 ± 7·6 h (median 10 h) for the oral group. The mean complete recovery time was 29·4 ± 16·2 h (median 24 h) for the intravenous group and 52·8 ± 18·0 (median 48 h) for the oral group. When the two groups were compared, the intravenous group had a shorter amelioration time and a shorter complete recovery time than the oral group, which were statistically significant
(P < 0·05 for each). No statistical differences were found in both
amelioration time and complete recovery time for the cases who were either under beta-blocker coverage or not.
Discussion
The incidence of THPP in Asians, the most frequently affected popu-lation, is approximately 2%, while THPP is largely unknown in the West, although the number of reported cases in Western countries has increased recently in the literature.36 It is notable that most of the reported cases of European Whites are from the Mediterranean regions, and include Italian,37 Spanish,38 Portuguese,39 Greek,40 French,41 Croatian,42 Albanian43 and Bulgarian populations.44 Most of the Italian, Spanish, Portuguese, Greek and Bulgarian cases are of Mediterranid race. Moreover, some of the French, Croatian and Albanian cases are also of Mediterranid race.45 There are only three different THPP reports from other parts of Europe: from Germany,46 Belgium47 and Finland.48 All these reports and our 38 Turkish cases indicate the tendency to find THPP in the Mediterranid race other than the remaining Caucasoid subspecies.
All Turkish THPP patients were sporadic cases without a family history of THPP. This feature is important in differentiating THPP from familial periodic paralysis (FPP), which is common among Caucasians.2 Familial THPP has also been reported in the literature.49 Coexistence of THPP and FPP may be the reason for supposing the cases familial THPP, as Lane et al. suggested previously.50
Despite the higher incidence of thyrotoxicosis in females, THPP predominantly affects males, with a male/female ratio of 20 : 1.2 To date, only one Caucasian female with THPP has been reported in the literature.51 All of the Turkish cases were male. The youngest case was 22 years old and the oldest was 60. Most of the cases were between the third and fifth decades, as in previous reports, and two cases were in their sixth and seventh decades. No relationship between age of onset of the disease and amelioration time or com-plete recovery time was found in our study, in accordance with the study of Lu et al.52 However, Akinci et al. suggested that younger Turkish patients had a tendency to a longer recovery time.22 However, this suggestion was not supported with any definitive data.
Most of the aetiological factors for thyrotoxicosis might be associated with THPP. The leading factor was reported to be Graves’ disease in a large series,53,54 in parallel to our results. Of note, the rate of toxic nodular goitre, which comprises both toxic adenoma and toxic multinodular goitre, was relatively higher in the Turkish patients than in patients in other reports. This may be associated with iodine deficiency and the high prevalence of toxic nodular goitre in Turkey.55 Subacute thyroiditis and silent thyroiditis were the remaining aetio-logical factors in our study. Subacute thyroiditis was not reported in two important previous reviews.2,36 However, Kao et al. presented subacute thyroiditis as an underlying cause for THPP.56 Our report supports this presentation. Silent thyroiditis has also been reported Table 3. Possible ECG findings of patients with THPP
S–T segment depression and/or prominent U wave (found in 2/3 of the cases) T-wave deformation (found in 1/4 of the cases)
QT elongation (found in 1/4 of the cases) Sinus tachycardia (found in 1/5 of the cases) First-degree AV block (found in three cases) Extended QRS (found in two cases) Bradycardia (found in one case)
Right bundle-branch block (found in one case) Atrial fibrillation (found in one case)
Second degree AV block of the Wenckebach type34 Ventricular fibrillation35
148 M. Cesur et al.
as an aetiological factor.57 Other conditions, including TSH-secreting pituitary adenoma,58 ingestion of excessive thyroxine,59 and iodine-induced thyrotoxicosis with inadvertent use of iodine or with drugs containing iodine such as iodinate contrast agents or amiodarone,60–62 have also been implicated. One of the Turkish cases occurred as the first manifestation of interferon-alpha-induced Graves’ disease,8 while another occurred after radioactive iodine therapy, which led to the consideration of radiation thyroiditis.7
All of the Turkish patients with THPP had been admitted to the emergency department between late evening and early morning. This presentation period allowed the disease to be named historically as nocturnal paralysis or night palsy.63 Approximately three-quarters of the patients had a carbohydrate-rich meal and/or strenuous exercise as the precipitating factor. Paralysis usually occurs in a resting period after exercise, not during exercise, as seen in some Turkish cases.8,14,15,20–22,30 Awakening in the middle of sleep, cold, alcohol, glucocorticoids, injection of medicine, emotional stress, upper respiratory tract infection, and radioactive iodine treatment were other precipitating factors in the patients in our study. Moreover, menses, trauma, insulin and epinephrine may also trigger THPP attacks.2,64 We suggest that the emotional stress of a nightmare may be the reason for waking up with paralysis if the patient does not have another precipitating factor.
The pathophysiology of THPP is uncertain. Hypokalaemia is produced with a rapid shift in K from the extracellular compartment to the intracellular compartment, especially into the muscles. This may be related to increased sodium/potassium-adenosine triphos-phatase (Na/K-ATPase) pump activity, which may be stimulated by thyroid hormones, insulin and catecholamine. In THPP, the under-lying susceptibility may be manifest by excess thyroid hormone. It has been suggested that the direct effect of thyroid hormone in stimulating membrane Na/K-ATPase activity and/or the indirect effect of thyroid hormone in stimulating insulin hypersecretion may be involved in the intracellular K shift. Furthermore, thyroid hormones increase the sensitivity of beta-receptors, so catecholamine-mediated cellular K uptake is raised.10,36 These proposals may clarify why insulin and epinephrine induce paralytic attacks. In addition, carbohydrate-rich meals increase insulin release, and stress-related factors such as emotional stress, cold, trauma and infection increase epinephrine release. Exercise also releases K from the skeletal muscles, whereas rest promotes influx of K, so paralytic attacks may occur during recovery from exercise.65 Glucocorticoids reduce the K level due to its mineralocorticoid effect and may induce hypokalaemia. To prevent a thyrotoxic crisis in an uncontrolled thyrotoxicosis, adding methyl-prednisolone triggered THPP in one of our cases.30 Recently, Liu
et al. reported a glucocorticoid-induced THPP in the course of
thyrotoxicosis treatment66 and Miyashita et al. reported life-threatening hypokalaemia in a patient with glucocorticoid-induced THPP.35 Steroids are used in thyrotoxic states such as infiltrative ophthalmo-pathy and thyroid crisis, so doctors should be warned about the level of K when initiating and using them.
To reduce the severity of the disease, acting immediately is important in THPP. Despite its typical clinical features, diagnosis may be delayed, especially in Whites. Only one-quarter of the Turkish patients were recognized at the first attack while three-quarters of them were diagnosed with delay, up to 10 years after the initial manifestation.
In our study the mean amelioration time of the paralysis was found to be shorter arithmetically but not statistically significant in patients who were diagnosed at the first attack while the mean complete recovery time was much better statistically in this group. Doctors who work in the emergency department should therefore be aware of the characteristics of the disease. Most of the patients had been referred by neurologists or endocrinologists for further evaluation in our country after the first intervention. It seems that management after attendance at the emergency department is also important for relief of the patient’s symptoms.
The chief symptom was acute paralysis, manifested as symmetrical quadriplegia, and paraplegia and asymmetry were seen in only a few in our study. A known characteristic of the muscle weakness is that it usually starts in the proximal muscles of the lower extremities and then progresses to the distal and upper part of the body. Bulbar, respiratory and ocular muscles are usually spared.2,36 Our study confirms these observations. Only in one case has muscle weakness started from the distal and passed to the proximal.21 Muscle weakness was more significant in the lower extremities in approximately half of the cases and affected both lower and upper extremities equally in the remaining cases, except for one case with more weakness in the upper extremities.20 Depressed deep tendon reflexes, except in one case,12 normal sensory tests and normal cognitive functions were other characteristics. EMG may have a myopathic pattern during the attack of paralysis, and this may disappear during remission. Myopathic changes such as a decrease in duration of muscle action potentials, an increase in polyphasic potentials, a satisfactory interference pattern with reduced amplitude and reduced amplitude of the evoked muscle action potential on nerve stimulation may be noted.67 EMG had been performed in half of the Turkish cases and approximately two-thirds were normal.
The thyrotoxic state is accepted as a rule for induction of THPP. However, some studies have reported that acute paralysis had occurred in the euthyroid state after treatment for thyrotoxicosis.68,69 Most of the patients included in our study had overt thyrotoxicosis, while two had subclinical thyrotoxicosis. Furthermore, one case with a history of toxic nodular goitre and operated previously was euthyroid when he suffered from THPP. The reason for this may be a residual active adenoma, which was determined by thyroid scintigraphy. Half of the patients in the study had no symptoms of thyrotoxicosis, although they had high levels of thyroid hormones. Similar data have been reported previously.70,71 In addition, 10% of the patients had had the paralytic attack while on a course of treatment with antithyroid drugs. This feature has not been emphasized before and we suggest that doctors should consider THPP even if a patient is taking medicine for thyrotoxicosis.
Hypokalaemia is the cardinal laboratory finding in THPP despite some reports of normokalaemic thyrotoxic periodic paralysis.72,73 Normokalaemia may cause misdiagnosis, such as having Guillain– Barre syndrome or hysterical paralysis.73 Two of our patients who were normokalaemic during the attacks were diagnosed by pro-vocation tests.10 Provocation tests may be the glucose loading test,74 the glucose and insulin loading test37 and the exercise test.75 When we looked at the Turkish patients, these tests had been applied in only five cases: the glucose loading test was performed in three cases10,11 and the exercise test in two28 (one was our index case, case 3). The
THPP in a Turkish population 149 degree of hypokalaemia is important76 and may be one of the markers
of survey of the disease for its induction of fatal and life-threatening ventricular arrhythmias.77,78 Our study showed that the degree of hypokalaemia had a significant effect on the amelioration time of the disease, so a low K level at the initiation of the attack may lead to deterioration in a patient’s health much more than mild or near-normal levels. Hypophosphataemia and hypomagnesaemia have been reported to be common in THPP,53 while our results revealed the opposite view in that a minority of the patients manifested hypo-phosphataemia and hypomagnesaemia. This may be due to the ethnic variety and may be a characteristic of Caucasian patients. Lin et al. recently suggested using the urine calcium to phosphate ratio for early diagnosis of THPP,79 but we have no data on this topic. Serum CPK was found to be elevated in about two-thirds of our patients, as in other reports.32,53 Manoukian et al. suggested that hypo-kalaemia and hypophosphataemia were associated with an increase in serum CPK.53 However, only one patient among a series of Turkish patients was reported to have an elevated serum CPK level with a decreased phosphorus level.22 Rhabdomyolysis may be seen in severe THPP.80 Besides hypokalaemia81 and hypophosphataemia,82 hyper-thyroidism alone may cause rhabdomyolysis.83
ECG changes in THPP vary from nondiagnostic to those showing typical features of hypokalaemia.84 ECG manifestations may aid in early diagnosis of THPP. ECG changes associated with hypokalaemia and/or other ECG abnormalities may be seen.34,35,85,86 ECG findings were normal in some Turkish patients, but most of them were abnormal. Possible ECG findings are given in Table 3.
K and propranolol, given intravenously or orally or both, are the preferred treatment in the management of THPP, although some cases do improve spontaneously. If immediate amelioration is important, intravenous K may be a better method for the replace-ment therapy. When we compared intravenous and oral routes of administration, the intravenously treated group had shorter amel-ioration and complete recovery times than the orally treated group. Lu et al. reported a shorter amelioration time (6·3 h) in an intra-venous KCl group in comparison with a normal saline infusion group (13·5 h).52 In our study the mean amelioration time was 6·8 h in the intravenous K group, similar to the previous study, and 13·1 h in the oral K group. These results suggest that intravenous K infusion is the best choice in the initial treatment of THPP. No correlation was reported in a previous study between recovery time and administered KCl dose.53 For rebound hyperkalaemia, greater than 5·0 mmol/l was reported in approximately 30–40% of patients receiving KCl.52,53,87 However, the rate of rebound hyperkalaemia was found to be 12·5% in Turkish patients and resolved easily without any complication. There was insufficient evidence on the KCl dose administered to carry out an acceptable statistical analysis of the Turkish case reports. However, the mean of total infused K of the three cases with rebound hyperkalaemia was 223·3 ± 105·4 mEq while the mean of the others was 95·9 ± 43·6 mEq. A lower dose of KCl was suggested to be effi-cacious on reducing the patient’s risk of rebound hyperkalaemia.2 Manoukian et al. suggested intravenous KCl below 90 mEq/day.53 It is possible that the relatively low-dose KCl infusion prevented rebound hyperkalaemia in the Turkish cases from. Close monitoring of plasma K during treatment with intravenous KCl has been recommended for avoiding rebound hyperkalaemia.87 In addition, nonselective beta
blockers, especially oral propranolol, may be used as first-line therapy to terminate an acute attack of THPP without rebound hyperkalaemia.88 Most Turkish patients were receiving beta blockers. Oral propranolol, except atenolol in one case, was the drug of choice. Beta blockers were found to have no significant effect on amelioration and complete recovery times in our study, but a prospective study may provide a more accurate result other than our analysis. Acetazolamide was given to one Turkish case.18 Acetazolamide is effective in FPP, but has no effect in the prevention of the attacks of THPP and may even exacerbate them.1,89
Prompt action should be taken to treat thyrotoxicosis because THPP diminishes completely on curing of thyrotoxicosis. For high recurrence rates of long-term treatment with antithyroid drugs, early permanent therapy, especially with radioactive iodine, is recommended because surgical stress may further induce paralysis. However, surgical therapy with close monitoring can be performed if necessary.90,91 Furthermore, radioactive iodine treatment may lead to aggravate thyrotoxicosis after a few days of administration and may induce THPP, as seen in a Turkish case and a Latin-American case.7,89 A minority of the Turkish patients were given permanent therapy by radioactive iodine or surgery. Precipitating factors such as heavy carbohydrate intake, strenuous exercise, a high-salt diet and alcohol ingestion should be avoided until the thyrotoxicosis is well controlled. Relapse of the paralytic attacks may occur if the thyrotoxicosis is not controlled or relapses.92 Three of the Turkish patients were exposed to relapse of an episode after starting treatment for
thyrotoxico-sis.11,13,14 One of the reasons was strenuous exercise on the fifth day
of the medical treatment with propranolol and propylthiouracil, the other reason was early cessation of the drugs by the patient, while the reason for the third relapse is unknown.
In conclusion, THPP may be seen in the Turkish and also in the Caucasian populations, especially in the Mediterranid race. Diagno-sis may be delayed, especially in Whites, and recognizing the first attack may affect the recovery time positively. The characteristics of the Turkish Caucasian patients are usually similar to the patients of other races, but hypophosphataemia, hypomagnesaemia and rebound hyperkalaemia may be seen less often than in the others. Hypo-kalaemia and thyrotoxicosis are the major findings. The degree of hypokalaemia seems to have a significant effect on recovery time and an initial low K level may lead to deterioration in a patient’s health much more than mild or near normal levels. We suggest intravenous rather than oral K, with close monitoring, so that the amelioration and complete recovery times may be shortened. The cure of thyrotoxi-cosis usually leads to a decrease of the attacks, so permanent therapy, especially with radioactive iodine, should be performed.
References
1 Ahlawat, S.K. & Sachdev, A. (1997) Hypokalaemic paralysis. Post-graduate Medical Journal, 75, 193 –197.
2 Lin, S.H. (2005) Thyrotoxic periodic paralysis. Mayo Clinic Proceedings, 80, 99–105.
3 Department of Ancient Near Eastern Art (2001) Geography of Ana-tolia and the Caucasus. In: Timeline of Art History. The Metropolitan Museum of Art, New York. Available online at: www.metmuseum.org/ toah/hd/m_waa/hd_m_waa.htm.
150 M. Cesur et al.
4 McCulloch, R. The Races of Humanity. Available online at: www.racialcompact.com.
5 Aldemir, M., Guloglu, C., Balakan, O., Suner, A. & Kaya, Z. (2004) Thyrotoxic periodic paralysis: a case report and review of the liter-ature. European Journal of General Medicine, 1, 48 –51.
6 Erem, C. (2005) Thyrotoxic hypokalemic periodic paralysis in a Turkish male with Graves’ disease: a rare case report and review of the literature. Endocrine, 27, 63–65.
7 Akar, S., Comlekci, A., Birlik, M., Onen, F., Sari, I., Gurler, O., Bekis, R. & Akkoc, N. (2005) Thyrotoxic periodic paralysis in a Turkish male; the recurrence of the attack after radioiodine treatment. Endocrine Journal, 52, 149–151.
8 Cesur, M., Gursoy, A., Avcioglu, U., Erdogan, M.F., Corapcioglu, D. & Kamel, N. (2006) Thyrotoxic hypokalemic periodic paralysis as the first manifestation of interferon-alpha-induced Graves’ disease. Journal of Clinical Gastroenterology, 40, 864 –865.
9 Ozdemirli, B., Kocer, A., Onder, E. & Gunes, M. (2007) Hypokalaemic periodic paralysis related to thyroiditis (A case report and review of the pathology). Case Reports and Clinical Practice Review, 8, 16–18. 10 Cesur, M., Ilgin, S.D., Baskal, N. & Gullu, S. Hypokalemic paralysis is not just a hypokalemic paralysis. European Journal of Emergency Medicine, in press.
11 Ozdemir, C., Gogusgeren, I. & Hatemi, H. (1968) Hypokalemic periodic paralysis. (Report of 2 cases) [in Turkish]. Tip Fakültesi Mecmuasi, 31, 503–521.
12 Tataroglu, C. & Lutfi, B. (2001) Thyrotoxic hypokalemic periodic paralysis: a case report [in Turkish]. Anadolu Tıp Dergisi, 2, 230 –233. 13 Kaya, A, Akpınar, Z. & Karakose, Z. (2001) Thyrotoxic periodic paralysis: report of four cases. Turkish Journal of Endocrinology and Metabolism, 5, 123 –126.
14 Dokmetas, H.S., Yuksel, I. & Yonem, O. (2001) Hypokalemic thyrotoxic periodic paralysis. Turkish Journal of Endocrinology and Metabolism, 5, 127–129.
15 Ataoglu, S. (2001) Thyrotoxic hypokalemic periodic paralysis a case report [in Turkish]. Türkiye Fiziksel Tıp ve Rehabilitasyon Dergisi, 47, 40 – 44.
16 Gunel, G., Cabalar, M., Canoz, M.B., Aslan, H., Yagiz, O., Sacak, S. & Tuna, S. (2002) Hypokalemic periodic paralysis and hyperthy-roidism: case report [in Turkish]. Kartal Devlet Hastanesi Tip Dergisi, 13, 134 –136.
17 Kizkin, S., Ozisik, H.I., Caliskan, O. & Ozcan, C. (2002) A case report with hypokalemic periodic paralysis [in Turkish]. Inonu Universitesi Tip Fakultesi Dergisi, 9, 267 –271.
18 Aluclu, U. & Hamdanogullari, D. (2004) Thyrotoxic periodic paralysis: case report [in Turkish]. Dicle Tip Dergisi, 31, 62 – 64.
19 Guloglu, C., Aldemir, M., Sogut, O. & Al, B. (2004) Thyrotoxic peri-odic paralysis: our experience with two cases [in Turkish]. Sendrom Aylik Aktuel Tip Dergisi, 16, 92 – 95.
20 Koc, F., Bozdemir, H., Over, F. & Sarica, Y. (2004) Thyrotoxic hypokalemic periodic paralysis: analysis of 7 cases and review of the literature [in Turkish]. Gulhane Tip Dergisi, 46, 59 –65.
21 Aktaran, S., Akarsu, S. & Altunoren. O. (2005) Hypokalemic and hypophosphatemic periodic paralysis in Graves’ disease [in Turkish]. Endokrinolojide Yonelisler, 14, 48 –50.
22 Akinci, B., Demir, T., Saklamaz, A., Kebapcilar, L. & Comlekci, A. (2005) Thyrotoxic hypokalaemic periodic paralysis (THPP) in Turkey: report of a case and review of the literature. Turkish Journal of Endocrinology and Metabolism, 9, 73 –79.
23 Tuncbay, T. & Bolukoglu, S. (1977) Periodic paralysis associated with thyroid dysfunction [in Turkish]: 13. Ulusal Psikiyatri ve Norolojik Bilimler Kongresi, Ankara, Turkey. Kongre Ozet Kitabi, 16.
24 Eroglu, E., Demirkaya, S., Ulas, U.H., Odabasi, Z., Onal, M.Z. & Okay, V. (2000) Nonfamilial hypokalemic periodic paralysis and thyrotoxicosis: a case report. 5th Congress of the European Federation of Neurological Societies, Copenhagen, Denmark. European Journal of Neurology, 7 (Suppl. 3), 52.
25 Gencer, A. (2001) Thyrotoxic periodic paralysis [in Turkish]: 18. Ulusal Norofizyoloji EEG-EMG Kongresi, Antalya, Turkey. Kongre Ozet Kitabi, 14.
26 Gokce, C., Bayram, F., Sakrak, O., Atmaca, H., Unluhizarci, K. & Kelestimur, F. (2004) Thyrotoxic periodic paralysis together with toxic nodular goitre: case report [in Turkish]. Turkish Journal of Endocrinology and Metabolism, 8 (Suppl. 2), 44.
27 Domac, F.M., Misirli, H., Mataraci, C., Ozer, B. & Erenoglu, N. (2004) Hypokalemic periodic paralysis: 5 case reports [in Turkish]: 40. Ulusal Noroloji Kongresi, Antalya, Turkey. Konusma Metinleri ve Ozet Kitabi, 343.
28 Yilmaz, N., Ergin, O., Isikay, C.T. & Mutluer, N. (2005) A case of hypokalemic periodic paralysis associated with thyrotoxicosis [in Turkish]: 41. Ulusal Noroloji Kongresi, Istanbul, Turkey. Turk Noroloji Dergisi, 11 (Suppl. 2), 209.
29 Demirdag, B., Tuncel, D. & Cetinkaya, A. (2006) Thyrotoxic hypo-kalemic periodic paralysis: case report [in Turkish]. 42. Ulusal Noroloji Kongresi, Antalya, Turkey. Kongre Ozet Kitabi, 51.
30 Haydardedeoglu, F.E., Bakiner, O., Ertorer, M.E., Tutuncu, N.B. & Demirag, N.G. (2006) Thyrotoxic periodic paralysis: two case reports [in Turkish]: 29. Ulusal Endokrinoloji ve Metabolizma Hastaliklari Kongresi; Istanbul, Turkey. Bildiri ve Konusma Ozet Kitabi, 97. 31 Gamper, G., Stulnig, T. & Weissel, M. (1998) Thyrotoxic
hypokale-mic periodic paralysis in a male Kurd. Acta Medica Austriaca, 25, 106 –108.
32 Sabau, I. & Canonica, A. (2000) Hypokalaemic periodic paralysis associated with controlled thyrotoxicosis. Schweizerische Medizinische Wochenschrift, 130, 1689–1691.
33 Icduygu, A. (2004) Turkey and International Migration. SOPEMI Report for Turkey. Available online at: www.mirekoc.com/docs/2004-sopemi.doc.
34 Chia, B.L., Lee, K.H. & Cheah, J.S. (1995) Sino-atrial Wenckebach conduction in thyrotoxic periodic paralysis: a case report. Inter-national Journal of Cardiology, 47, 285 –289.
35 Miyashita, Y., Monden, T., Yamamoto, K., Matsumura, M., Kawagoe, N., Iwata, C., Banba, N., Hattori, Y. & Kasai, K. (2006) Ventricular fibril-lation due to severe hypokalemia induced by steroid treatment in a patient with thyrotoxic periodic paralysis. Internal Medicine, 45, 11–13. 36 Kung, A.W. (2006) Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. Journal of Clinical Endocrinology and Metabo-lism, 91, 2490–2495.
37 Didonna, D., D’Alessandro, G., De Michele, A., Conte, M., Storelli, A., Totaro, M. & Altomare, E. (2000) Thyrotoxic periodic paralysis in a Caucasian man in treatment for Graves’ disease. Panminerva Medica, 42, 293 –294.
38 Lasterra Sanchez, M., Perez Perez, M., Martinez Conde, S.C., Gavilan Villarejo, I. & Aguilar Diosdado, M. (1995) Thyrotoxic periodic paralysis: an exceptional case report in a Spanish population [in Spanish]. Anales de Medicina Interna, 12, 603 – 605.
39 Vale, J., Canas, N., Leal, A. & Vilar, H. (2005) Thyrotoxic periodic paralysis: a case report [in Portuguese]. Acta Medica Portuguesa, 18, 399 – 402.
40 Michail, S., Dagounaki, P., Stamatiadis, D., Vaiopoulos, G., Stathakis, C. & Vosnides, G. (1996) A case of thyrotoxic hypokalaemic periodic paralysis in a Greek man. Nephrology, Dialysis, Transplantation, 11, 1634 –1636.
THPP in a Turkish population 151 41 Pili, S., Deveze, A., Iacobone, M., Guibout, M. & Henry, J.F. (2002)
Thyrotoxic hypokalemic periodic paralysis. Report of three cases [in French]. Annales de Chirurgie, 127, 297–299.
42 Morovic, J.V., Ostricki, B., Galesic, K., Skoro, M. & Zelenika, D. (2002) Thyrotoxic periodic paralysis: a case report. Acta Clinica Croatica, 41, 99–102.
43 Barbullushi, M. & Idrizi, A. (2002) Thyrotoxic hypokalemic periodic paralysis in an Albanian man. Hippokratia, 6, 81–82.
44 Kalburova, F., Petrov, D., Ilieva, K. & Belovezhdov, N. (1989) Hypokalemic periodic paralysis in thyrotoxicosis. Vuˇtreshni Bolesti, 28, 73–76.
45 McCulloch, R. The Nordish Race. Available online at: www.racialcompact.com.
46 Gaul, C., Leonhardt, G., Spens, A., Schneyer, U. & Zierz, S. (2005) Hypokalemic thyrotoxic periodic paralysis (HTPP). Rare differential diagnosis in case of acute tetraparesis in Europe. Medizinische Klinik (Munich), 100, 583 –586.
47 Vandergheynst, F., Vandergheynst, A., Leleux, A. & Ducobu, J. (2002) Hypokalemic thyrotoxic periodic paralysis: a case report. Acta Clinica Belgica, 57, 19 –22.
48 Schalin-Jantti, C., Laine, T., Valli-Jaakola, K., Lonnqvist, T., Kontula, K. & Valimaki, M.J. (2005) Manifestation, management and molecular analysis of candidate genes in two rare cases of thyrotoxic hypokalemic periodic paralysis. Hormone Research, 63, 139 –144.
49 Kufs, W.M., McBiles, M. & Jurney, T. (1989) Familial thyrotoxic periodic paralysis. Western Journal of Medicine, 150, 461– 463. 50 Lane, A.H., Markarian, K. & Braziunene, I. (2004) Thyrotoxic
periodic paralysis associated with a mutation in the sodium channel gene SCN4A. Journal of Pediatric Endocrinology and Metabolism, 17, 1679 –1682.
51 Dixon, A.N. & Jones, R. (2002) Thyrotoxic periodic paralysis in a white woman. Postgraduate Medical Journal, 78, 687– 688. 52 Lu, K.C., Hsu, Y.J., Chiu, J.S., Hsu, Y.D. & Lin, S.H. (2004) Effects
of potassium supplementation on the recovery of thyrotoxic periodic paralysis. American Journal of Emergency Medicine, 22, 544 –547. 53 Manoukian, M.A., Foote, J.A. & Crapo, L.M. (1999) Clinical and
metabolic features of thyrotoxic periodic paralysis in 24 episodes. Archives of Internal Medicine, 159, 601– 606.
54 Silva, M.R., Chiamolera, M.I., Kasamatsu, T.S., Cerutti, J.M. & Maciel, R.M. (2004) Thyrotoxic hypokalemic periodic paralysis, an endocrine emergency: clinical and genetic features in 25 patients. Arquivos Brasileiros de Endocrinologia e Metabologia, 48, 196 –215. 55 Ozbakir, O., Dogukan, A. & Kelestimur, F. (1995) The prevalence of
thyroid dysfunction among elderly subjects in an endemic goiter area of Central Anatolia. Endocrine Journal, 42, 713 –716.
56 Kao, C.L., Tu, S.T. & Su, S.L. (2002) Thyrotoxic periodic paralysis: analysis of 13 cases. Journal of Internal Medicine Taiwan, 13, 22 – 26. 57 Nakamura, S., Sugimoto, M., Kosaka, J., Watanabe, H., Shima, H. & Kawahira, S. (1990) Silent thyroiditis with thyroid-stimulation-blocking antibodies (TSBAb). Japanese Journal of Medicine, 29, 623 – 627.
58 Alings, A.M., Fliers, E., de Herder, W.W., Hofland, L.J., Sluiter, H.E., Links, T.P., van der Hoeven, J.H. & Wiersinga, W.M. (1998) A thyrotropin-secreting pituitary adenoma as a cause of thyrotoxic periodic paralysis. Journal of Endocrinological Investigation, 21, 703 –706. 59 Chen, Y.C., Fang, J.T., Chang, C.T. & Chou, H.H. (2001) Thyrotoxic
periodic paralysis in a patient abusing thyroxine for weight reduction. Renal Failure, 23, 139–142.
60 Tran, H.A. (2005) Inadvertent iodine excess causing thyrotoxic hypokalemic periodic paralysis. Archives of Internal Medicine, 165, 2536.
61 Kane, M.P. & Busch, R.S. (2006) Drug-induced thyrotoxic periodic paralysis. Annals of Pharmacotherapy, 40, 778 –781.
62 Laroia, S.T., Zaw, K.M., Ganti, A.K., Newman, W. & Akinwande, A.O. (2002) Amiodarone-induced thyrotoxicosis presenting as hypokalemic periodic paralysis. Southern Medical Journal, 95, 1326 –1328. 63 Talbott, J.H. (1941) Periodic paralysis: a clinical syndrome. Medicine,
20, 85 –143.
64 Mellgren, G., Bleskestad, I.H., Aanderud, S. & Bindoff, L. (2002) Thyrotoxicosis and paraparesis in a young woman. case report and review of the literature. Thyroid, 12, 77– 80.
65 Ober, K.P. (1992) Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of the literature. Medicine, 71, 109 – 120.
66 Liu, Z., Braverman, L.E. & Malabanan, A. (2006) Thyrotoxic periodic paralysis in a Hispanic man after the administration of prednisone. Endocrine Practice, 12, 427 – 431.
67 Puvanendran, K., Cheah, J.S. & Wong, P.K. (1977) Electro-myographic (EMG) study in thyrotoxic periodic paralysis. Australian and New Zealand Journal of Medicine, 7, 507 – 510.
68 Rone, J.K. & Brietzke, S.A. (1991) Euthyroid thyrotoxic periodic paralysis. Military Medicine, 156, 434 – 436.
69 Coates, J.T., Mirick, M.J. & Rubino, F.J. (1987) Thyrotoxic periodic paralysis with relapse during the euthyroid state. Wisconsin Medical Journal, 86, 20 –22.
70 Kelley, D.E., Gharib, H., Kennedy, F.P., Duda, R.J. Jr & McManis, P.G. (1989) Thyrotoxic periodic paralysis. Report of 10 cases and review of electromyographic findings. Archives of Internal Medicine, 149, 2597– 2600.
71 Goh, S.H. (2002) Thyrotoxic periodic paralysis: reports of seven patients presenting with weakness in an Asian emergency department. Emergency Medicine Journal, 19, 78–79.
72 Gonzalez-Trevino, O. & Rosas-Guzman, J. (1999) Normokalemic thyrotoxic periodic paralysis: a new therapeutic strategy. Thyroid, 9, 61– 63.
73 Wu, C.C., Chau, T., Chang, C.J. & Lin, S.H. (2003) An unrecognized cause of paralysis in ED: thyrotoxic normokalemic periodic paralysis. American Journal of Emergency Medicine, 21, 71–73.
74 Hamada, N., Ishii, T., Hasegawa, M., Ishikawa, N., Tabata, T., Okuno, Y., Ito, K., Matsuura, S., Morii, H. & Wada, M. (1985) Transient glucose intolerance during attacks of thyrotoxic periodic paralysis. Hormone and Metabolic Research, 17, 301–305.
75 Tengan, C.H., Antunes, A.C., Gabbai, A.A. & Manzano, G.M. (2004) The exercise test as a monitor of disease status in hypokalaemic periodic paralysis. Journal of Neurology, Neurosurgery, and Psychiatry, 75, 497– 499.
76 Stedwell, R.E., Allen, K.M. & Binder, L.S. (1992) Hypokalemic para-lyses: a review of the etiologies, pathophysiology, presentation, and therapy. American Journal of Emergency Medicine, 10, 143–148. 77 Randall, B.B. (1992) Fatal hypokalemic thyrotoxic periodic paralysis
presenting as the sudden, unexplained death of a Cambodian refugee. American Journal of Forensic Medicine and Pathology, 13, 204 –206.
78 Loh, K.C., Pinheiro, L. & Ng, K.S. (2005) Thyrotoxic periodic para-lysis complicated by near-fatal ventricular arrhythmias. Singapore Medical Journal, 46, 88 – 89.
79 Lin, S.H., Chu, P., Cheng, C.J., Chu, S.J., Hung, Y.J. & Lin, Y.F. (2006) Early diagnosis of thyrotoxic periodic paralysis: spot urine calcium to phosphate ratio. Critical Care Medicine, 34, 2984 –2989. 80 Kilpatrick, R.E., Seiler-Smith, S. & Levine, S.N. (1994) Thyrotoxic
hypokalemic periodic paralysis: report of four cases in black American males. Thyroid, 4, 441– 445.
152 M. Cesur et al.
81 Singhal, P.C., Abramovici, M., Venkatesan, J. & Mattana, J. (1991) Hypokalemia and rhabdomyolysis. Mineral and Electrolyte Metabo-lism, 17, 335 – 339.
82 Amanzadeh, J. & Reilly, R.F. Jr (2006) Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nature Clinic Practice. Nephrology, 2, 136 –148.
83 Lichtstein, D.M. & Arteaga, R.B. (2006) Rhabdomyolysis associated with hyperthyroidism. American Journal of Medical Science, 332, 103 –105.
84 Ee, B. & Cheah, J.S. (1979) Electrocardiographic changes in thyro-toxic periodic paralysis. Journal of Electrocardiology, 12, 263 –279. 85 Ngo, A., Lim, S.H., Charles, R.A. & Goh, S.H. (2005)
Electrocardio-graphical case. Young man with generalised myalgia. Singapore Medical Journal, 46, 38 – 40.
86 Hsu, Y.J., Lin, Y.F., Chau, T., Liou, J.T., Kuo, S.W. & Lin, S.H. (2003) Electrocardiographic manifestations in patients with thyrotoxic periodic paralysis. American Journal of Medical Science, 326, 128 –132.
87 Ko, G.T., Chow, C.C., Yeung, V.T., Chan, H.H., Li, J.K. & Cockram, C.S. (1996) Thyrotoxic periodic paralysis in a Chinese population. Quarterly Journal of Medicine, 89, 463 – 468.
88 Huang, T.Y. & Lin, S.H. (2001) Thyrotoxic hypokalemic periodic paralysis reversed by propranolol without rebound hyperkalemia. Annals of Emergency Medicine, 37, 415–416.
89 Shulkin, D., Olson, B.R. & Levey, G.S. (1989) Thyrotoxic periodic paralysis in a Latin-American taking acetazolamide. American Journal of Medical Science, 297, 337–338.
90 Hochberg, D.A., Vassolo, M. & Paniagua, D. (1996) Thyrotoxic peri-odic paralysis in a black man. South Medical Journal, 89, 735–737. 91 Maeda, S., Ahmad, T.A., Minami, S., Furui, J. & Kanematsu, T.
(2001) Video-assisted total thyroidectomy. International Surgery, 86, 195 –197.
92 Papadopoulos, K.I., Diep, T., Cleland, B. & Lunn, N.W. (1997) Thyrotoxic period paralysis: report of three cases and review of the literature. Journal of Internal Medicine, 241, 521– 524.
