Thyrotoxic hypokalemic periodic paralysis: a life-threatening disorder in Asian men.

Thyrotoxicosis can present as a sporadic form of hypokalaemic periodic paralysis. The condition is associated with massive intracellular shift of potassium, mainly in skeletal muscles. As the total body stores of potassium remain normal, overzealous potassium supplementation targeting serum potassium level results in a poor outcome. We present a fatal case of thyrotoxic hypokalaemic periodic paralysis.

Investigational drugs in early stage clinical trials for thyrotoxicosis with hyperthyroidism.

INTRODUCTION: Thyrotoxicosis with hyperthyroidism is treated with these classical approaches (i) antithyroid drugs to blockade thyroid hormone release and normalize thyroid hormone production and (ii) destruction of the thyroid using radioiodine or surgical removal of the thyroid. The optimal medical therapy, especially for Graves´ disease, remains a subject of debate and there has been little progress in Graves' disease therapeutics over the last decade. AREAS COVERED: Novel treatments of thyrotoxicosis with hyperthyroidism. This includes (i) small molecules such as synthetic thyroid hormone receptor antagonists and environmental molecules and (ii) molecules with interaction between thyroid stimulating hormone (TSH) receptor and TSH receptor antibodies such as M22, ANTAG3, org274179-0, 5C9, and K1-70. Other approaches to Graves´ disease treatment includes immunosuppressive treatment, glucocorticosteroids, rituximab, and intrathyroid injection of dexamethasone. Optimal iodine and selenium supplementation can also be considered. EXPERT OPINION: Clinical trials results suggest that novel thyroid treatments involving small molecule therapy, may predict a good future in Graves' disease treatment; however, a greater understanding of these antagonists is needed. Other treatments comprising immunosuppressives have demonstrated a significant reduction of relapse of the disease, but are not recommended by international guidelines.

Over-the-counter-drug-induced thyroid disorders.

OBJECTIVE: Excessive iodine ingestion may cause thyroid dysfunction. In this case series, we report four patients who developed significant thyroid dysfunction after ingesting over-the-counter (OTC) drugs containing large concentrations of iodine. METHODS: Four patients from a tertiary medical center are reported. RESULTS: Case 1 involved acute exacerbation of thyrotoxicosis induced by taking OTC Tri-iodine™ in a 35-year-old woman while still on methimazole therapy. Case 2 involved thyroid-extract-induced thyrotoxicosis following ingestion of Thyromine™, and was confirmed by laboratory studies and ¹³¹I thyroid uptake. Cases 3 and 4 involved severe, symptomatic hypothyroidism induced in 2 patients with underlying autoimmune thyroiditis (Hashimoto's disease) following ingestion of Iodoral™. In all cases, thyroid dysfunction resolved with appropriate management and discontinuation of the OTC drugs. CONCLUSION: These case reports demonstrate the significant risks associated with OTC preparations containing iodine in patients predisposed to thyroid dysfunction. There is no valid reason for taking high-dose OTC iodine supplements, which have been shown to cause harm and have no known benefit.

Peak systolic velocity of superior thyroid artery for the differential diagnosis of thyrotoxicosis.

AIM: The differentiation of destruction-induced thyrotoxicosis and Graves' disease (GD) is of great importance for selection of proper therapy. Radioactive iodine uptake (RAIU) is the gold standard for differentiating these two conditions but its application has remained somewhat limited. Thyroid color Doppler flow sonography (CDFS) is a potential alternative of RAIU but more supporting evidence is warranted. In the present study, a standard operative procedure was developed to measure the mean peak systolic velocity of superior thyroid artery (STA-PSV) and evaluate its role in the differential diagnosis of thyrotoxicosis. METHODS: A total of 135 patients with untreated thyrotoxicosis were enrolled into one retrospective study (GD, n = 103; thyroiditis, n = 32) and another prospective study recruited 169 patients (GD, n = 118; thyroiditis, n = 51). Thirty normal controls were also enrolled. Thyroid function, anti-TSH-receptor antibody (TRAb), RAIU, CFDS of thyroid and STA-PSV were performed for each patient. Receiver operator curve (ROC) was used to evaluate the diagnostic value of STA-PSV in a retrospective study so as to seek the optimal cutoff point. Then the cutoff point value was used to validate its diagnostic value in a prospective study and in another thyrotoxicosis population. RESULTS: STA-PSV of GD was significantly higher than that of thyroiditis in both retrospective and prospective studies. The area under the ROC curve of mean STA-PSV was 0.8799 and 0.9447 in the retrospective and prospective studies respectively. If a mean STA-PSV cutoff point of 50.5 cm/s was set from the retrospective analysis for the prospective study, the sensitivity and specificity in distinguishing GD from thyroiditis were 81.04% and 96.08% respectively. Mean STA-PSV and TRAb had similar area under ROC. The coefficients of variation in STA-PSV measurement were lower than 10% for the euthyroid, thyroiditis and GD groups. CONCLUSIONS: STA-PSV is a feasible supplement alternative of RAIU for differentiating the causes of thyrotoxicosis.

Novel etiopathophysiological aspects of thyrotoxic periodic paralysis.

Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and is the most common cause of acquired periodic paralysis. Typically, paralytic attacks cease when hyperthyroidism is abolished, and recur if hyperthyroidism returns. TPP is often underdiagnosed, as it has diverse periodicity, duration and intensity. The age at which patients develop TPP closely follows the age at which thyrotoxicosis occurs. All ethnicities can be affected, but TPP is most prevalent in people of Asian and, secondly, Latin American descent. TPP is characterized by hypokalemia, suppressed TSH levels and increased levels of thyroid hormones. Nonselective ß adrenergic blockers, such as propranolol, are an efficient adjuvant to antithyroid drugs to prevent paralysis; however, an early and definitive treatment should always be pursued. Evidence indicates that TPP results from the combination of genetic susceptibility, thyrotoxicosis and environmental factors (such as a high-carbohydrate diet). We believe that excess T(3) modifies the insulin sensitivity of skeletal muscle and pancreatic ß cells and thus alters potassium homeostasis, but only leads to a depolarization-induced acute loss of muscle excitability in patients with inherited ion channel mutations. An integrated etiopathophysiological model is proposed based on molecular findings and knowledge gained from long-term follow-up of patients with TPP.

Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illness.

INTRODUCTION: Prolonged critically ill patients reveal low circulating thyroid hormone levels without a rise in thyroid stimulating hormone (TSH). This condition is labeled "low 3,5,3'-tri-iodothyronine (T3) syndrome" or "nonthyroidal illness syndrome (NTI)" or "euthyroid sick syndrome". Despite the low circulating and peripheral tissue thyroid hormone levels, thyrotropin releasing hormone (TRH) expression in the hypothalamus is reduced and it remains unclear which mechanism is responsible. We set out to study whether increased hypothalamic T3 availability could reflect local thyrotoxicosis and explain feedback inhibition-induced suppression of the TRH gene in the context of the low T3 syndrome in prolonged critical illness. METHODS: Healthy rabbits were compared with prolonged critically ill, parenterally fed animals. We visualized TRH mRNA in the hypothalamus by in situ-hybridization and measured mRNA levels for the type II iodothyronine diodinase (D2), the thyroid hormone transporters monocarboxylate transporter (MCT) 8, MCT10 and organic anion co-transporting polypeptide 1C1 (OATP1C1) and the thyroid hormone receptors alpha (TRalpha) and beta (TRbeta) in the hypothalamus. We also measured the activity of the D2 and type III iodothyronine deiodinase (D3) enzymes. RESULTS: In the hypothalamus of prolonged critically ill rabbits with low circulating T3 and TSH, we observed decreased TRH mRNA, increased D2 mRNA and increased MCT10 and OATP1C1 mRNA while MCT8 gene expression was unaltered as compared with healthy controls. This coincided with low hypothalamic thyroxine (T4) and low-normal T3 concentrations, without a change at the thyroid hormone receptor level. CONCLUSIONS: Although expression of D2 and of the thyroid hormone transporters MCT10 and OATP1C1 were increased in the hypothalamus of prolonged critical ill animals, hypothalamic T4 and T3 content or thyroid hormone receptor expression were not elevated. Hence, decreased TRH gene expression, and hereby low TSH and T3 during prolonged critical illness, is not exclusively brought about by hypothalamic thyrotoxicosis, and infer other TRH suppressing factors to play a role.

[Thyrotoxic hypokalaemic periodic paralysis in a Caucasian male]. / Paralysie périodique hypokaliémique thyréotoxique chez un Caucasien.

We report the case of a caucasian patient with a presentation of a periodic paralysis associated with hypokalaemia disclosing Graves' disease. Major pathophysiologics hypothesis are discused in order to explain relationships between hyperthyroidism and paralysis through a disturbance of the excitability of the muscle fibres. A genetic predisposition explain the high incidence of this affection in asiatic population while it is uncommon in caucasian race. Potassium supplementation is not needed in order to correct hypokalaemia except in case of cardiac disturbances. Treatment by beta-blockers is advisable with the specific treatment of hyperthyroidism.

Neonatal thyroid disorders.

Hypothyroxinaemia, which is common in the preterm infant, and thyrotoxicosis, which is rare, are important neonatal thyroid disorders. Their causes and treatment are discussed.

[Neurohumoral regulation during balneotherapy of children with diffuse thyroid enlargement]. / Osobennosti neirogumoral'noi reguliatsii organizma v protesesse bal'neolecheniia detei s diffuznym uvelicheniem shchitovidnoi zhelezy.

Spectral analysis of cardiac rhythm registered neurohumoral rearrangements which indicated differences in activity of regulatory mechanisms in children with diffuse enlargement of the thyroid. This activity varied with the size of the thyroid, age of patients, special effects of sodium-chloride (mineralization 20 and 40 g/l) and iodobromine baths. Indications and contraindications are specified to administration of these factors in diffuse thyroid enlargement of the first and second degree.

Thyrotoxicosis in children: thirty years' experience.

Optimal treatment for thyrotoxicosis remains controversial in adults, but more so in paediatric practice. We have conducted a retrospective review of the records of 76 paediatric patients seen between 1965 and 1995 to determine management practice and outcome of therapeutic interventions. Seventeen are currently on antithyroid drug (ATD) treatment, while four have had their care transferred. Of the remaining 55, 21 (38%) achieved long-term remission with ATD alone following a mean treatment duration of 3.3 y (range 0.5-7 y). Block-replacement (high dose of ATD with thyroxine replacement) was more convenient than the titration regimen (3.4+/-0.3 visits to hospital per year versus 6.1+/-0.4, p<0.001). Surgery (subtotal/total thyroidectomy) was carried out in 27 patients, of whom 24 subsequently became hypothyroid and were treated with thyroxine. I131 was used successfully in six patients, two following surgery. ATD should remain the first-line therapy; a block-replacement regimen is more convenient. Surgery in a specialized centre carries a low risk. Caution should still be exercised in the use of I131 in young children.

Effect of propranolol on calcium, phosphorus, and magnesium metabolic disorders in Graves' disease.

The purpose of this study was to determine whether propranolol alone can improve mineral metabolic disorders in thyrotoxicosis. Ten Graves' disease patients and 11 normal age- and sex-matched controls participated in the study. In the untreated Graves' patients, serum levels of calcium (Ca), calcium x phosphorus product (Ca x P), urinary Ca, phosphorus (P), magnesium (Mg), and hydroxyproline (Hp) were higher than in control subjects (P less than .05), intestinal Ca absorption was lower than in control subjects (P less than .05), and Ca, P, and Mg balance were negative (P less than .05). After 40 mg propranolol four times per day (qid) for 28 days, serum triiodothyronine (T3) had decreased (P less than .05), serum reverse triiodothyronine (rT3) increased (P less than .05), serum thyroxine (T4) remained unchanged (P greater than .05), serum Ca and urine Ca and Mg decreased (P less than .05), intestinal Ca absorption increased, Ca balance was corrected, and P and Mg balance was improved (P less than .05). Our results indicate that propranolol can improve the metabolic disorders in addition to the symptomatic manifestations of Graves' disease. The mechanism responsible for the improved mineral balance is unclear, but may be related to beta-adrenergic blockade, increased membrane stability, or a decrease in the thyrotoxic state caused by the therapeutically induced decrease in serum T3.