Thyrotoxicosis Abstracts 1

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A study of vitamin B 12 requirements in a patient with pernicious anemia and thyrotoxicosis: evidence of an increased need for vitamin B 12 in the presence of hyperthyroidism.
            (Alperin et al., 1970)  Download
The response to small doses of vitamin B12 was studied in a woman with pernicious anemia and thyrotoxicosis. No response to 1µg per day occurred, but she did respond to 10µg per day. The results of these studies provide evidence for increased vitamin B12 requirements in the presence of hyperthyroidism.

Lithium and iodine combination therapy for thyrotoxicosis.
            (Boehm et al., 1980)  Download
In order to compare the relative therapeutic efficacy of iodine (I) and lithium (Li) in thyrotoxicosis, investigate possible additive effects of these agents, and examine their effect upon thyroidal release, 17 thyrotoxic patients were assigned to groups given either I (n = 9) or Li (n = 8) alone during an initial treatment period, with the alternate drug added as combination treatment during a second treatment period. Half of the patients received methimazole (MMI). Three additional thyrotoxic patients received I during both treatment periods to evaluate the possibility of cumulative I effect upon thyroidal release during the second treatment period. A double isotope technique was utilized as an index of thyroidal release, employing 125I as an intrathyroidal label and [131I]T4 as a marker of T4 disposal. During the first treatment period either I or Li induced comparable, significant (P < 0.05) decreases in thyroidal release, as measured by slopes of ratios of serum PB125I:PB131I and by percentage inhibition of fractional T4 release rate. In response to Li, there was a 55% decrease in the slope of PB125I: PB131I with MMI and a 52% decrease without MMI. In response to I, there was a 70% decrease in the slope of PB125I : PB131I with MMI and a 57% decrease without MMI. Further significant (P < 0.05) decreases in the slopes of these ratios during the second, combined treatment period (I + Li) occurred only in those patients who had initially received I. No further decreases in the second treatment period were seen in patients receiving I during both treatment periods. Thus, I and Li together display additive inhibition of thyroidal release only if I is administered initially, but the combination, if Li is used first, does not appear to be more effective than Li alone.

Evaluating and managing patients with thyrotoxicosis.
            (Campbell and Doogue, 2012)  Download
BACKGROUND:  Thyrotoxicosis is common in the Australian community and is frequently encountered in general practice. Graves disease, toxic multinodular goitre, toxic adenoma and thyroiditis account for most presentations of thyrotoxicosis. OBJECTIVE:  This article outlines the clinical presentation and evaluation of a patient with thyrotoxicosis. Management of Graves disease, the most frequent cause of thyrotoxicosis, is discussed in further detail. DISCUSSION:  The classic clinical manifestations of thyrotoxicosis are often easily recognised by general practitioners. However, the presenting symptoms of thyrotoxicosis are varied, with atypical presentations common in the elderly. Following biochemical confirmation of thyrotoxicosis, a radionuclide thyroid scan is the most useful investigation in diagnosing the underlying cause. The selection of treatment differs according to the cause of thyrotoxicosis and the wishes of the individual patient. The preferred treatment for Graves disease is usually antithyroid drug therapy, almost always carbimazole. The primary treatment of a toxic multinodular goitre or toxic adenoma is usually radioactive iodine therapy. Specific therapy is usually not warranted in cases of thyroiditis, however, treatment directed at symptoms may be required. Referral to an endocrinologist is recommended if thyroiditis is unlikely or has been excluded.

Managing patients with acute thyrotoxicosis.
            (Dahlen, 2002)  Download
Acute thyrotoxicosis is a systemic syndrome that occurs as a result of excess production and release of the thyroid hormones triiodothyronine and thyroxine. The syndrome is characterized by a hypermetabolic state in which the tissues respond to an excess of circulating thyroid hormones by markedly increasing cellular function. Under normal circumstances, thyroid hormones control metabolic processes in body tissues by increasing the rate of protein, fat, and glucose metabolism. If left untreated, the sustained hypermetabolic state that occurs in acute thyrotoxicosis can lead to death.

Effect of estrogen replacement therapy upon bone mineral density in thyroxine-treated postmenopausal women with a past history of thyrotoxicosis.
            (Franklyn et al., 1995)  Download
We have shown that previous thyrotoxicosis and subsequent levothyroxine (L-T4) therapy are together associated with reduction in femoral and lumbar vertebral bone mineral density (BMD) in postmenopausal women. To determine whether estrogen replacement therapy exerts a beneficial effect upon bone loss in this situation, we performed a cross-sectional study comparing BMD measurements of the femur and lumbar spine in four groups of women (n = 15 in each group) matched for age and duration of menopause: (i) those with a previous history of thyrotoxicosis who were subsequently receiving both L-T4 and estrogen replacement therapy for at least 3 years (L-T4 + HRT group), (ii) previously thyrotoxic women matched to group (i) for L- dose and duration who had never used estrogen replacement (L-T4 alone group), (iii) those with no history of thyroid disease who had received estrogen replacement therapy for at least 3 years (HRT alone group), and (iv) those with no history of thyroid disease who had never received estrogen replacement therapy (control group). BMD measurements were higher at each site in the HRT alone group than in controls (6.0-13.6% increases in BMD, p < 0.05 for measurements at femoral neck, Ward's triangle, and trochanter) while measurements of BMD were lower at each site in the L-T4 alone group than in controls (3.3-6.1% reductions in BMD), although values did not reach statistical significance. Measurements at each site in the L-T4 + HRT group were higher than those from the L-T4 alone group (2.2-16.1% increases in BMD, p < 0.05 for measurements at lumbar spine), although lower than in the group receiving HRT alone (p < 0.05 for femoral neck and Ward's triangle) and similar to those in untreated controls. Our results indicate that estrogen replacement therapy abolishes reduction in femoral and vertebral BMD in postmenopausal women with previous thyrotoxicosis and subsequent L-T4 therapy. This potentially beneficial influence of estrogen replacement upon both BMD and fracture risk in postmenopausal women with a history of thyroid disease suggests that estrogen administration should be encouraged in this group.

Vitamin B12 and thyrotoxicosis: the administration of vitamin B12 to patients with hyperthyroidism, and the in vitro oxidation of iodide by vitamin B12.
            (George and Haan, 1963)  Download
We gave 1.0 mg of vitamin B12 daily intramuscularly for varying lengths of time to 7 thyrotoxic patients. Those patients who received the vitamin for protracted periods became less distressed than before, but the thryrotoxicosis did not abate. The thyroid uptake was increased in all patients except one. All subjcts showed a 0.4 to 0.7˚F fall in basal temperature after vitamin B12.

Effects of short-term potassium iodide treatment for thyrotoxicosis due to Graves disease in children and adolescents.
            (Jeong et al., 2014)  Download
PURPOSE:  Graves disease is the most common cause of hyperthyroidism in children. Inorganic iodide has been used in combination with antithyroid drugs for more effective normalization of thyroid hormones in some cases of severe thyrotoxicosis. This study aimed to investigate clinical characteristics of childhood thyrotoxicosis and effectiveness of inorganic iodide in the early phase of treatment. METHODS:  Sixty-seven pediatric patients (53 girls/14 boys, 11.1±3.4 years of age), with newly diagnosed thyrotoxicosis due to Graves disease were recruited. Forty-nine patients were treated with antithyroid drugs alone, while 18 patients were treated with combination of antithyroid drugs and potassium iodide. Initial thyroid function tests and levels of thyroid antibodies were recorded for all patients. Thyroid function tests were repeated 2 and 8 weeks after the initiation of treatment. Measurement thyroid antibodies were done 8 weeks after the initiation of treatment. RESULTS:  Mean triiodothyronine and free thyroxine levels were significantly lower (P<0.05) in the group receiving combined therapy of antithyroid drugs and potassium iodide after 2 weeks of treatment compared to the patients receiving antithyroid drugs alone. Eight weeks after the initiation of treatment, thyroid function tests in the two groups did not show significant differences. CONCLUSION:  The use of potassium iodide in combination with antithyroid drug is effective for more rapid normalization of thyroid hormones in the early phase treatment of childhood thyrotoxicosis, but larger studies with adequate power are needed in future.

Lithium as an Alternative Option in Graves Thyrotoxicosis.
            (Prakash et al., 2015)  Download
A 67-year-old woman was admitted with signs and symptoms of Graves thyrotoxicosis. Biochemistry results were as follows: TSH was undetectable; FT4 was >6.99 ng/dL (0.7-1.8); FT3 was 18 pg/mL (3-5); TSI was 658% (0-139). Thyroid uptake and scan showed diffusely increased tracer uptake in the thyroid gland. The patient was started on methimazole 40 mg BID, but her LFTs elevated precipitously with features of fulminant hepatitis. Methimazole was determined to be the cause and was stopped. After weighing pros and cons, lithium was initiated to treat her persistent thyrotoxicosis. Lithium 300 mg was given daily with a goal to maintain between 0.4 and 0.6. High dose Hydrocortisone and propranolol were also administered concomitantly. Free thyroid hormone levels decreased and the patient reached a biochemical and clinical euthyroid state in about 8 days. Though definitive RAI was planned, the patient has been maintained on lithium for more than a month to control her hyperthyroidism. Trial removal of lithium results in reemergence of thyrotoxicosis within 24 hours. Patient was maintained on low dose lithium treatment with lithium level just below therapeutic range which was sufficient to maintain euthyroid state for more than a month. There were no signs of lithium toxicity within this time period. Conclusion. Lithium has a unique physiologic profile and can be used to treat thyrotoxicosis when thionamides cannot be used while awaiting elective radioablation. Lithium levels need to be monitored; however, levels even at subtherapeutic range may be sufficient to treat thyrotoxicosis.

Benefit of short-term iodide supplementation to antithyroid drug treatment of thyrotoxicosis due to Graves' disease.
            (Takata et al., 2010)  Download
OBJECTIVE:  Combined treatment with anti-thyroid drugs (ATDs) and potassium iodide (KI) has been used only for severe thyrotoxicosis or as a pretreatment before urgent thyroidectomy in patients with Graves' disease. We compared methimazole (MMI) treatment with MMI + KI treatment in terms of rapid normalization of thyroid hormones during the early phase and examined the later induction of disease remission. DESIGN AND PATIENTS:  A total of 134 untreated patients with Graves' disease were randomly assigned to one of four regimens: Group 1, MMI 30 mg; Group 2, MMI 30 mg + KI; Group 3, MMI 15 mg and Group 4, MMI 15 mg + KI. For easy handling, KI tablets were used instead of saturated solution of KI. KI was discontinued when patients showed normal free thyroxine (FT4) levels but MMI was continued with a tapering dosage until remission. Remission rate was examined during a 4- to 5-year observation. MEASUREMENTS:  Serum FT4, FT3 and TSH were measured by chemiluminescent immunoassays. TSH receptor antibody (TRAb) was assayed with TRAb-ELISA. Goitre size was estimated by ultrasonography. RESULTS:  After 2 weeks of treatment, normal FT4 was observed in 29% of patients in Group 1 and 59% (P < 0.05) of patients in Group 2. Furthermore, normal FT4 after 2 weeks of treatment was observed in 27% of patients in Group 3 and 54% (P < 0.05) of patients in Group 4. Similarly, FT3 normalized more rapidly in Groups 2 and 4 than in Groups 1 and 3. None of the patients showed an increase in thyroid hormones or aggravation of disease during combined treatment with MMI and KI. The remission rates in Groups 1, 2, 3 and 4 were 34%, 44%, 33% and 51%, respectively, and were higher in the groups receiving combined therapy but differences among four groups did not reach significance. CONCLUSIONS:  Combined treatment with MMI and KI improved the short-term control of Graves' hyperthyroidism and was not associated with worsening hyperthyroidism or induction of thionamide resistance.

Effects of Lugol's solution on thyroid function in normals and patients with untreated thyrotoxicosis.
            (Tan et al., 1989)  Download
Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.

Vitamin D metabolism in thyrotoxicosis. Therapeutic aspects derived from an old observation.
            (Velentzas and Veletzas, 2009)  Download
In an article of 2007 about vitamin D deficiency, it was reported that low 25OH-vitD (25hydroxyvitaminD) plasma levels are found in thyrotoxicosis, with thyrotoxicosis being the last in the list of acquired causes of vita- min D deficiency (1). We first demonstrated low 25OH-vitD plasma levels in thyrotoxicosis (2), as well as the fact that the transformation of vitamin D into 25OH-vitD is 2.5 to eight times faster in thyrotoxic subjects in comparison to healthy controls

 


References

Alperin, JB, ME Haggard, and TP Haynie (1970), ‘A study of vitamin B 12 requirements in a patient with pernicious anemia and thyrotoxicosis: evidence of an increased need for vitamin B 12 in the presence of hyperthyroidism.’, Blood, 36 (5), 632-41. PubMed: 5473523
Boehm, TM, et al. (1980), ‘Lithium and iodine combination therapy for thyrotoxicosis.’, Acta Endocrinol (Copenh), 94 (2), 174-83. PubMed: 7415757
Campbell, K and M Doogue (2012), ‘Evaluating and managing patients with thyrotoxicosis.’, Aust Fam Physician, 41 (8), 564-72. PubMed: 23145395
Dahlen, R (2002), ‘Managing patients with acute thyrotoxicosis.’, Crit Care Nurse, 22 (1), 62-69. PubMed: 11852487
Franklyn, JA, et al. (1995), ‘Effect of estrogen replacement therapy upon bone mineral density in thyroxine-treated postmenopausal women with a past history of thyrotoxicosis.’, Thyroid, 5 359-63. PubMed: 8563472
George, WK and CL Haan (1963), ‘Vitamin B12 and thyrotoxicosis: the administration of vitamin B12 to patients with hyperthyroidism, and the in vitro oxidation of iodide by vitamin B12.’, Med Rec Ann, 56 149-50. PubMed: 13947229
Jeong, KU, HS Lee, and JS Hwang (2014), ‘Effects of short-term potassium iodide treatment for thyrotoxicosis due to Graves disease in children and adolescents.’, Ann Pediatr Endocrinol Metab, 19 (4), 197-201. PubMed: 25654065
Prakash, I, ES Nylen, and S Sen (2015), ‘Lithium as an Alternative Option in Graves Thyrotoxicosis.’, Case Rep Endocrinol, 2015 869343. PubMed: 26425375
Takata, K, et al. (2010), ‘Benefit of short-term iodide supplementation to antithyroid drug treatment of thyrotoxicosis due to Graves’ disease.’, Clin Endocrinol (Oxf), 72 (6), 845-50. PubMed: 19912243
Tan, TT, et al. (1989), ‘Effects of Lugol’s solution on thyroid function in normals and patients with untreated thyrotoxicosis.’, Clin Endocrinol (Oxf), 30 (6), 645-49. PubMed: 2591064
Velentzas, C and C Veletzas (2009), ‘Vitamin D metabolism in thyrotoxicosis. Therapeutic aspects derived from an old observation.’, Int J Clin Pract, 63 (8), 1265. PubMed: 19624794