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Zymosan-induced luminol-amplified chemiluminescence of whole blood phagocytes in experimental and human hyperthyroidism.

Luminol-amplified CL of whole blood phagocytes was studied in rats given 3 consecutive doses of 0.1 mg L-triiodothyronine T3/kg or in hyperthyroid patients, after stimulation by zymosan. In both cases, CL was significantly increased, an effect which was produced independently of the opsonization of the zymosan particles and markedly inhibited by azide. The in vitro addition of T3 or L-thyroxine (T4) to whole blood phagocytes from normal rats did not modify the opsonized zymosan-dependent CL, when assayed at the concentrations found in euthyroid subjects or in hyperthyroid patients. Administration of propylthiouracil (400 mg/day for 2-3 months) to hyperthyroid patients reduced the CL response observed prior to treatment, to values comparable to those found in the euthyroid group. These data indicate that hyperthyroidism elicits an enhanced respiratory burst activity of whole blood phagocytes, probably related to adaptive changes induced by thyroid hormone on the mieloperoxidase-H2O2 system, rather than to direct actions of the hormone molecule or changes in the opsonic capacity of plasma.

Adult↗

A case report of neonatal thyrotoxicosis due to maternal autoimmune hyperthyroidism.

A case of neonatal thyrotoxicosis secondary to maternal autoimmune hyperthyroidism is reported in an infant born at 34 weeks gestation who presented with tachycardia, jitteriness, diarrhea, and a small goiter. Propranolol and oxygen were used to treat high-output cardiac failure and transient persistent pulmonary hypertension. The infant's response to propylthiouracil therapy, gradual resolution of cardiac and systemic symptoms, and normaliziation of thyroid studies are described. Thyroid physiology and function and the special considerations in a premature infant are reviewed. An overview of maternal autoimmune hyperthyroidism and the implications for the developing fetus and neonate are presented. The risk factors for, and clinical presentation of, hyperthyroidism are outlined and treatment strategies highlighted. The nursing care of infants with hyperthyroidism is carefully described with an emphasis on the surveillance for and management of multisystem manifestations.

Autoimmune Diseases↗

Resistance training improves muscle function and body composition in patients with hyperthyroidism.

OBJECTIVE: To evaluate the effect of resistance training on skeletal muscle performance and body composition in patients with medically treated hyperthyroidism. DESIGN: Nonrandomized controlled trial. SETTING: Large public tertiary hospital. PARTICIPANTS: Sixteen sedentary patients with recent clinical diagnosis and laboratory confirmation of hyperthyroidism (7 men, 9 women; age, 38+/-11 y; weight, 58.4+/-2.6 kg; height, 1.6+/-0.3m) were assigned to the control group (medical therapy; n=9) or training group (medical therapy associated with resistance training; n=7). An age- and sex-matched healthy group served as controls (3 men, 5 women; age, 40+/-3 y; weight, 68.4+/-4.3 kg; height, 1.6+/-0.3m). INTERVENTION: Resistance training twice a week for 16 weeks. MAIN OUTCOME MEASURES: Peak muscular strength (by dynamometry and 1 repetition maximum method) and endurance (30% of peak force) for 7 movements and anthropometric measurements. RESULTS: The hyperthyroid patients as a group had lower baseline overall strength values when compared with healthy subjects (200.3+/-16.0 kg vs 274.9+/-21.8 kg, respectively; P=.006). Overall absolute increases in strength (49 kg vs 91 kg, P<.05) and endurance (78.5x10(2)kg/s vs 176.9x10(2)kg/s, P<.05) were higher in the training group compared with the control group. Body weight increased in both groups, but the sum of muscular circumference increased only in the training group (training group, 92.6+/-3.3 cm vs 97.1+/-3.8 cm; control group, 94.6+/-2.2 cm vs 94.4+/-2.1cm; P<.05), with no change in the sum of skinfolds. CONCLUSIONS: Resistance training accelerates the recovery of skeletal muscle function and promotes weight gain based on muscle mass improvement in patients with medically treated hyperthyroidism.

Adult↗

Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine.

A raised concentration of serum cardiac troponin I (cTnI) is a sensitive marker of cardiac myocyte injury in the cat and assays developed for its measurement in human patients have been validated in the cat. Raised levels have been associated with a number of cardiac insults including hypertrophic cardiomyopathy and trauma. Hyperthyroidism is a common disease of older cats and excess thyroid hormone is known to produce significant cardiovascular effects in this species. This study evaluated the effect of treatment for hyperthyroidism with radioactive iodine on cTnI concentration, assessed the association between thyroxin levels and glomerular filtration rate (GFR) and cTnI concentration in cats treated for hyperthyroidism and described changes in echocardiographic parameters following treatment. Prior to the treatment serum cTnI was measured and echocardiography performed, thyroxin, cTnI, and echocardiography were then repeated at various time points following radioisotope therapy. The results show that higher thyroxin levels were significantly (P=0.002) associated with a higher likelihood of the cat presenting with detectable levels of cTnI. No significant association was found between GFR and presence of detectable levels of cTnI. Furthermore the results indicate that the effects of hyperthyroidism on echocardiographic parameters appear considerably less in this study than in previous studies and that the main outcome of treatment on these parameters is a significant reduction in fractional shortening (P=0.006). These results suggest that chronic exposure to excess thyroid hormone may induce myocyte damage of sufficient severity to raise serum cTnI concentration in a proportion of cats that resolves following establishment of a euthyroid state.

Animals↗

Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats.

Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations. Lycopus extract was tested in thyroxine treated hyperthyroid rats (0.7 mg/kg BW i.p.). Co-treatment with an hydroethanolic extract from L. europaeus L. started one week later than T4-application and lasted 5.5 weeks. As reference substance atenolol was used. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and the increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed. Lycopus extract and atenolol reduced the increased heart rate and blood pressure. The cardiac hypertrophy was alleviated significantly by both treatment regimes. beta-Adrenoceptor density in heart tissue was significantly reduced by the Lycopus extract or the beta-blocking agent showing an almost equal efficacy. Although the mode of action remains unclear, these organo-specific anti-T4-effects seem to be of practical interest, for example in patients with latent hyperthyroidism.

Adrenergic beta-Antagonists↗

Myocardial antioxidant enzyme activities and concentration and glutathione metabolism in experimental hyperthyroidism.

Hyperthyroidism was induced in rats by l-thyroxine administration (12 mg/L in drinking water, 4 weeks). Animals were assessed hemodynamically, and heart, lung, and liver morphometry were performed. Lipid peroxidation (LPO) and protein oxidation (carbonyls) were measured in heart homogenates. It was quantified glutathione (GSH) metabolism, and antioxidant enzyme activities its and protein expression (by Western blot). At the end of treatment, it was observed cardiac hypertrophy, elevation of left ventricular systolic and end diastolic pressures, lung and liver congestion. LPO and carbonyls were increased in the hyperthyroid group, and GSH was decreased by 46% in the fourth week. Myocardial oxidative stress time course analysis revealed that it was increased in the second week of treatment. Antioxidant enzyme activities elevation was accompanied by protein expression induction in the hyperthyroid group in the fourth week. These results imply that hyperthyroidism generates myocardial dysfunction associated with oxidative stress inducing antioxidant enzyme activities and protein expression.

Animals↗

Hypo-and hyperthyroidism affect the ATP, ADP and AMP hydrolysis in rat hippocampal and cortical slices.

The presence of severe neurological symptoms in thyroid diseases has highlighted the importance of thyroid hormones in the normal functioning of the mature brain. Since, ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters release in the central nervous system (CNS), the ectonucleotidase cascade that hydrolyzes ATP to adenosine, is also involved in the control of brain functions. Thus, we investigated the influence of hyper-and hypothyroidism on the ATP, ADP and AMP hydrolysis in hippocampal and cortical slices from adult rats. Hyperthyroidism was induced by daily injections of l-thyroxine (T4) 25 microg/100 g body weight, for 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water for 14 days. Hypothyroid rats were hormonally replaced by daily injections of T4 (5 microg/100 g body weight, i.p.) for 5 days. Hyperthyroidism significantly inhibited the ATP, ADP and AMP hydrolysis in hippocampal slices. In brain cortical slices, hyperthyroidism inhibited the AMP hydrolysis. In contrast, hypothyroidism increased the ATP, ADP and AMP hydrolysis in both hippocampal and cortical slices and these effects were reverted by T4 replacement. Furthermore, hypothyroidism increased the expression of NTPDase1 and 5'-nucleotidase, whereas hyperthyroidism decreased the expression of 5'-nucleotidase in hippocampus of adult rats. These findings demonstrate that thyroid disorders may influence the enzymes involved in the complete degradation of ATP to adenosine and possibly affects the responses mediated by adenine nucleotides in the CNS of adult rats.

5'-Nucleotidase↗

Signal-averaged P-wave duration and risk of paroxysmal atrial fibrillation in hyperthyroidism.

The onset of atrial fibrillation (AF) in hyperthyroid patients constitutes an unfavorable clinical event associated with high risk of cardiovascular complications, occurring in approximately one fifth of patients. Therefore, it is advantageous to define noninvasive markers that may identify patients at risk. The high-resolution, signal-averaged electrocardiogram was used to evaluate the relation between P-wave duration and occurrence of paroxysmal AF in a group of 50 patients with hyperthyroidism, of whom 24 had a history of paroxysmal AF and 26 did not. Filtered signal-averaged P-wave duration was measured over an average of 300 beats/patient while in sinus rhythm, both at the time of first diagnosis of hyperthyroidism and after restoration of euthyroidism by medical treatment. The 24 patients with paroxysmal AF had significantly greater P-wave duration than the 26 patients without it (135 +/- 7 vs 124 +/- 9 ms; p = 0.001). A P-wave duration cut-off value of 130 ms held specificity, sensitivity, and positive predictive accuracy values of 79%, 85%, and 83%, respectively. Of several variables, multivariate analysis showed P-wave duration to be the only independent variable significantly associated with the occurrence of paroxysmal AF. Thus, the high-resolution signal-averaged electrocardiogram may be a useful noninvasive clinical tool for the identification of electrical instability associated with paroxysmal AF in hyperthyroid patients.

Adult↗

[Severe neonatal hyperthyroidism which reveals a maternal Graves' disease].

Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.). Due to transfer into the fetal compartment of maternal antibodies which stimulate the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1% of children born to these mothers are described as having hyperthyroidism. Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies; clinical signs usually disappear during the first four Months of life. The most frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter, hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid retraction. Diagnosis is based on determination of the blood level of triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The kinetics of TSI provides a guide for therapeutic adaptation and disappearance of TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism have been shown to be caused by germline mutation of the thyrotropin receptor. We report a case of severe neonatal hyperthyroidism which led to the diagnosis of maternal Graves' disease.

Antithyroid Agents↗

Disturbances of calcium and magnesium metabolism occur in most hyperthyroid patients.

The concentrations in serum of total and ionised calcium, phosphate, magnesium, albumin and alkaline phosphatase activity were measured in patients when hyperthyroid and again when euthyroid. Significant declines in the mean values of ionised calcium, phosphate and alkaline phosphatase activity and significant increases in the mean concentrations of magnesium and albumin were observed. Similar changes were observed in most individual patients. Levels of ionised calcium greater than two standard deviations (representing between batch imprecision) above the upper limit of the reference range were present in 15.6% of hyperthyroid patients. The hyperthyroid levels of calcium, ionised calcium and alkaline phosphatase activity were highest in patients with the most severe thyrotoxicosis. Disturbances of calcium and magnesium metabolism are frequent in hyperthyroid patients.

Adolescent↗

Contribution of the autonomic nervous system to blood pressure and heart rate variability changes in early experimental hyperthyroidism.

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous system activity and thyroid hormones in the control of heart rate and blood pressure. We now report on thyrotoxicosis produced by daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt. in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvent. In order to estimate the degree of autonomic activation in hyperthyroidism, specific blockers were administered intravenously: atropine (0.5 mg/kg), prazosin (1 mg/kg), atenolol (1 mg/kg) or the combination of atenolol and atropine. A jet of air was administered in other animals to induce sympathoactivation. Eight animals were studied in each group. The dose and duration of L-thyroxine treatment was sufficient to induce a significant degree of hyperthyroidism with accompanying tachycardia, systolic blood pressure elevation, increased pulse pressure, cardiac hypertrophy, weight loss, tachypnea and hyperthermia. In addition, the intrinsic heart period observed after double blockade (atenolol + atropine) was markedly decreased after treatment with L-thyroxine (121.5+/-3.6 ms vs. 141.2+/-3.7 ms, P < 0.01). Of the autonomic indices, vagal tone (difference between heart period obtained after atenolol and intrinsic heart period) was negatively linearly related to intrinsic heart period (r = 0.71, P < 0.05). Atenolol modified neither the heart period nor blood pressure variability in rats with hyperthyroidism and in these rats the jet of air did not significantly affect the heart period level. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of blood pressure variability (analyses on 102.4 s segments, modulus 1.10+/-0.07 vs. 1.41+/-0.06 mm Hg, P < 0.01) and prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic heart rate could be the main determinant of tachycardia. The blood pressure elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Adrenergic alpha-Antagonists↗

Constitutively active germline mutation of the thyrotropin receptor gene as a cause of congenital hyperthyroidism.

Congenital hyperthyroidism is a rare, transient disease usually caused by transmission of thyrotropin receptor autoantibodies from the mother with Graves' disease to her child. We report a German women and her two sons who had congenital, but persistent hyperthyroidism without any signs of autoimmunity. Direct sequencing of the polymerase chain reaction-amplified exon 10 of the thyrotropin receptor genomic DNA revealed in the mother and both sons a transition of GCC to GTC, resulting in an exchange of alanine 623 to valine. This germline mutation in a highly conserved region of the thyrotropin receptor resulted in a constitutive activation of the cyclic adenosine monophosphate-generating cascade with resulting hyperthyroidism. Analysis of the family for a corresponding BstXI restriction-site polymorphism revealed heterozygosity for this mutation in the affected family members, but not in the father or other relatives. We conclude that whenever congenital hyperthyroidism is persistent and parameters of autoimmunity are absent, a constitutively active thyrotropin receptor mutation should be considered. Treatment appears to require aggressive means such as total thyroidectomy or ablation by 131iodine because two subtotal thyroidectomies in the mother were insufficient to control the disease.

Adult↗

The development of aversive responses to quinine in hyperthyroid rats.

Normal and hyperthyroid rat pups received intraoral infusions of 0.25% quinine hydrochloride at 8, 10, 12, 14, or 16 days of age. Chin scraping and paw treading, aversive behaviors that adult rats show to quinine, emerged at 12 to 14 days in normal animals and were accelerated in hyperthyroid animals. Once these behaviors emerged, the hyperthyroid pups showed levels of both paw treading and chin scraping that were typical of controls several days older. Hyperthyroid and control pups did not differ in their intake of quinine at ages at which there were marked differences in chin scraping and paw treading. Other types of responses that pups show to aversive stimuli, such as paw treading. Other types of responses were not affected by the thyroid treatment. These findings suggest that the appearance of chin scraping and paw treading at 12-14 days of age in normal animals results from maturation of motor systems underlying these behaviors, and that this maturation can be accelerated by treatment with thyroid hormones.

Administration, Oral↗

Thyroid hormones and the hepatic handling of bilirubin. II. Effects of hypothyroidism and hyperthyroidism on the apparent maximal biliary secretion of bilirubin in the Wistar rat.

This study was undertaken in the Wistar R/A Pfd rat to investigate the effects of hypothyroidism and of hyperthyroidism on the maximal biliary excretion (Tm) of bilirubin and on the concentration and composition of bilirubin in liver and plasma at the end of a bilirubin load. Hypothyroidism caused a cholestatic condition with a 50% decrease in bile flow and in bilirubin Tm, and with an increased proportion of conjugated bilirubin in liver and plasma. This was associated with an increased ratio of bilirubin diconjugates to monoconjugates in bile, liver, and plasma, which can be ascribed to the increased hepatic conjugation activity towards bilirubin and/or to the prolonged retention of bile pigments in the hepatocytes with increased conversion of monoconjugates to diconjugates. Cholestasis induced by hypothyroidism was further characterized by a decreased biliary output of unconjugated bilirubin. The latter phenomenon might represent an indirect effect related to a decreased output of bilirubin monoconjugates with impaired hydrolysis to unconjugated bilirubin; it might also reflect the cholestatic condition with decreased excretion of the unesterified bile pigment as such. Hyperthyroidism resulted in a 1.3-1.4-fold increase in bile flow. The maximal bilirubin concentration in bile decreased 1.3-1.4-fold, so that the apparent maximal bilirubin excretion rate remained unchanged at 115 nmol.min-1.100 g-1, as observed in untreated rats. Hyperthyroidism lowered the bilirubin UDP-glucuronosyltransferase activity, produced a decreased ratio of bilirubin di- to monoconjugates in bile and plasma, and a decreased ratio of conjugated to total bile pigment concentration in liver and in plasma. Similar findings are present in the heterozygous Gunn rat strain and in patients with hepatic bilirubin UDP-glucuronosyltransferase deficiency. We therefore propose the hyperthyroid rat as an experimental animal model of Gilbert's syndrome.

Animals↗

[Hyperthyroidism in people over 50 years of age in Senegal. Study of 31 cases observed over a 14-year period].

PURPOSE: Though common in elderly, with poor and masked symptomatology, hyperthyroidism has never been studied in people older than 50 years of age in African countries. METHODS: Of the 300 cases of hyperthyroidism that were observed during this study, 31 belonged to this category. We analyzed the frequency of various parameters, demographic characteristics, motivation for consulting, thyrotoxic syndrome, non thyrotoxic signs, cardiac manifestations, hormonal and scintigraphic characteristics, etiology and etiologic factors, and treatment. RESULTS: The frequency of hyperthyroidism in this population was 10%. Housewives were more numerous, with 20 cases observed in the 31 patients. The main group (13/31) was of rural origin. Signs that predominantly led to consultation were weight loss (23/31), cervical tumor (17/31), and palpitations (12/31). Three major signs were associated with the thyrotoxic syndrome: weight loss (29 cases), tachycardia (27/31), and the existence of tremors in the extremities (22/31). Hormone assays showed that thyroxine (T4) was about 265 +/- 74 nmol/L and triiodothyronine (T3) about 6 +/- 2 nmol/L, at immunoradiometric assay; thyroid-stimulating hormone (TSH) was about 0.17 +/- 0.23 muIU/mL. Eye protrusion predominated in the nonthyrotoxic syndrome, with 25 cases in the 31 patients. Etiologic forms of the disease were composed of 25 Grave's disease, with 22 typical cases. Etiologic factors were various, however without any case of neoplasia. Cardiac complications included two cases of atrial fibrillation. No iatrogenic form of the disease was observed. Mean initial carbimazole dosage was about 34 +/- 8 mg/d. Of the 23 patients, 15 had a favourable outcome. CONCLUSIONS: In this series, the high number of housewives and the patients' rural origin were less characteristic of hyperthyroidism than the Grave's disease etiology. This might be due to the young age of this African population.

Age Factors↗

Diagnosis of hyperthyroidism: the newer biochemical tests.

Investigation of suspected hyperthyroidism is conventionally based on measurement of total or free T4 as the initial test, followed in equivocal cases by total or free T3, and the TRH test. Recent developments in techniques for measuring free hormones and TSH promise to change this approach. Free T4 and free T3 can now be rapidly and simply quantitated in whole serum using labelled analogue radioimmunoassays. Specific and highly sensitive assays using labelled monoclonal antibodies are now available for serum TSH that permit the suppressed levels found in most cases of hyperthyroidism to be distinguished from euthyroid levels. These newer assays are available at a cost per test that is often similar to that of the more established tests. Available evidence indicates that measurement of basal serum TSH by a sensitive labelled antibody method can serve as a first line test, at least in uncomplicated cases of suspected hyperthyroidism. In patients with a suppressed TSH, a serum free T4, and in equivocal cases free T3, will distinguish the clinical and subclinical forms of hyperthyroidism. Such an approach would obviate the need for the TRH test. It must be emphasized, however, that experience with this new approach is limited. Caution is advised in the interpretation of low TSH and free hormone levels when there are associated complicating features, such as severe non-thyroidal illness, or pregnancy. These developments mark a trend in thyroid function testing away from measurement of circulating total hormone levels. The newer tests provide an assessment of end organ (thyrotroph) response, and an assessment of biologically active (free) hormone to which the tissues are exposed. These complementary approaches have the potential to identify relatively minor degrees of thyroid dysfunction.

Diagnosis, Differential↗

Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism.

The issue of residual complaints after treatment for hyperthyroidism in current euthyroid patients was investigated by means of a survey. Patients treated for hyperthyroidism were selected from medical records of the previous 6 years in two Dutch University Clinics. After the exclusion of patients with comorbidity, 303 one-time hyperthyroid respondents were included in the analysis. A total of 77% of these patients had been diagnosed with Graves' Disease. The newly developed Hyperthyroidism Complaint Questionnaire (HCQ), was used to quantify problems of somatic and mental functioning. The SymptomsCheckList-90 (SCL-90) was used to assess self-reported psychopathological symptoms, the Nottingham Health Profile was used to measure perceived health/quality of life. Dysthyroid patients (n = 20) had a mean HCQ-score of 14.5 (+/- 8.1) complaints; patients who reported euthyroidism for less than 12 months (n = 171) had a mean of 9.3 (+/- 7.6) residual complaints; patients who reported euthyroidism for more than 12 months (n = 54) a mean of 6.6 (+/- 6.8) residual complaints. On each dimension of psychopathology covered by the SCL-90, including depression and anxiety, approximately one third of the total sample had a score exceeding 80% of adult females. According to the NHP lack of energy was evident in 53% of all respondents. Over one third of patients with a full-time job were unable to resume the same work after treatment. It appears that many of these patients are in need of psychological support.

Adolescent↗

A case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia in childhood.

We report here a case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia. The patient was a 13-year-old girl with struma and hyperthyroidism which began at age 12. Two weeks following the initiation of treatment against hyperthyroidism she developed left blepharoptosis, diplopia, and dysphagia, which responded promptly to edrophonium administration. An increase of the anti-acetylcholine receptor antibody was found in the serum. A chest CT showed a large soft tissue mass in front of the ascending aorta, which was proven histopathologically as thymic hyperplasia. The patient underwent an extensive thymectomy and was placed on combination therapy with an anti-thyroid drug, glucocorticosteroid, and an anti-cholinesterase drug. Her symptoms and signs have been well controlled by this treatment. Coexistence of myasthenia gravis, hyperthyroidism, and thymic hyperplasia in childhood have never been documented in literature.

Adolescent↗