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The thyroid gland is the biggest gland in the neck. It is situated in the anterior part of the neck below the skin and muscle layers. The thyroid gland takes the shape of a butterfly with the two wings being represented by the left and right thyroid lobes which wrap around the trachea. The sole function of the thyroid is to make thyroid hormone. This hormone has an effect on nearly all tissues of the body where it increases cellular activity. The function of the thyroid, therefore, is to regulate the body's metabolism

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  1. 1. UNDERSTANDING ANTI THYROID DRUGS Bv Dr Bashir Ahmed Dar Associate Professor Medicine Chinkipora Sopore Kashmir Email: drbashir123@gmail. com
  2. 2. _ . E , _
  3. 3. A The presentation on thyroid is divided into A three parts Part one deals with thyroid basics Part two on anti thyroid drugs and part three is on thyroid disorders A It therefore becomes important to read all the three parts to have better understanding of thyroid diseases and their management. Most of these slides are on, ~,y slideshare and other websites ‘ Jr; : V ‘i’
  4. 4. ° The whole presentation deals in explaining Diagram 555.| fyou understand this diagram then no need to read all presentation. But if you feel difficulty in understandingthen better read all of this presentation including Part-1 of ° this presentation. All on slideshare and other websites.
  5. 5. | . l, '%V‘-, -’ I &. _j Following drugs inhibit Iodide symporter ’ 1 Potassium Perchlorate 200—2000mg/ day _ - . _— . . . Na+ Thiocyanates Followingdrugs inhibit thyroid peroxidase 0 Potassium Iodide iaomglday Carbimazole 15-60 mg. /day K’ —- — - SSKI 2-3drops/ day equalant to tablet 130/day -Methimazole ‘l5—60mg/ day Propylthiouracil 150-300mg/ day PTU also inhibits conversion of T4 to T3 . - *- CI‘ . h_E_h_F’_e. r1<1rI_n_(, )_______ '2 ‘ , _. . H202 Thyroglobulin ‘Pe'°x'daSe precurspr (TG) + Iodination -~~ —— -7 -- TG and Peroxidase I coupling _ T -/ l MIT. DIT MIT F DIT R73 Secretion T3 I I , - T3 8 " S’ if T T ' "TO Pinoc tosis 3 T4 “ Proteases Colloid V T, droplet Radioactive iodine usually single dose orally maximum 3 doses Kills thyroid cells by emiting beta radiation to thyroid cells
  7. 7. ‘I Perchlorate is an inorganic anion that is a potent competitive inhibitor of the sodium- iodide symporter. Perchlorate decreases the active transport of iodide into the thyroid ° Most perchlorates are colorless solids that are soluble in water I»-‘ ‘~ If ‘s'/ v
  8. 8. Perch Iorates/ Dose ° Potassium perchlorate 200-2000mg per day for many weeks or months around 2 weeks to 5 months were used in hyperthyroidism
  9. 9. Perch | orates/ Dose ° 1000mg per day can be given to hyperthyroid patients try to bring it to 100 mg over 12 months the patients can then receive 40- 120mg , sometimes to 200 mg/ day as maintenance therapy with good control of symptoms
  10. 10. ‘I A lady was rendered euthyroid with potassium perchlorate, one g/ day by mouth for one month. then was put on maintenance therapy of 200 mg/ a day to maintain euthyroidism over a period of 22 years. I»-‘ ‘~ If ‘s'/ v
  11. 11. Perchlorates ° The treatment was stopped in between she became hyperthyroid so treatment started again in these 22 years. ° The temporal relationship between withdrawal of perchlorate and recurrence of thyrotoxicosis suggests that perchlorate was responsible for the maintenance of uthyroidism
  12. 12. ii Hyperthyroidism induced by amiodarone may be treated with potassium perchlorate and methimazole given simultaneously while treatment with amiodarone is continued. ‘. is 3.” t_ . A ‘~ vii E? V
  13. 13. ii Patients with amiodarone induced thyrotoxicosis were given simultaneously 1 g potassium perchlorate a day for 40 days and a starting dose of 40 mg methimazole a day while they continued to take amiodarone. I»-i ‘~ vii %'/ v
  14. 14. Perchlorates ° When 400 mg/ day was discovered not to control thyrotoxicosis in all subjects then 400 mg of potassium perchlorate divided into four or five daily doses was used and found effective
  15. 15. Perch | orates/ Dose ° Current regimens for treatment of thyrotoxicosis (including Graves‘ disease), commonly include 500 mg potassium perchlorate twice per day for 20-40 days ° Taper the dose and put on maintenance dose after 20-40days
  16. 16. Perchlorates ° To completely block the uptake of Iodine-131 perchlorate ions would need to continue for no less than 80-90 days. ° After 80-90 days had passed released radioactive iodine-131 would have decayed to less than 0.1% of its initial quantity at which time the danger from biouptake of iodine-131 ' essentially over.
  17. 17. Perchlorates ° Perchlorate is produced by natural atmospheric processes and has been measured in rainwater, snow and groundwater.
  18. 18. Perchlorates ° Solid rocket fuel for rocket propulsion, road flares, fireworks, matches, and airbag inflation systems cause environmental impact of percholarate due to its presence in them
  19. 19. is High levels of perchlorate can also be found in some crop fertilisers / “ ii‘ v v ii. .i. ~. v_ ‘er y"
  20. 20. ii Therefore low levels of perchlorate have been detected in various sources. In the U. S., it has been found in many substances, including tobacco, alfalfa, tomato, cow's milk, cucumber, lettuce, soybeans, eggs and vitamins, dairy milk, variety of fruits and vegetables, milk, tap and bottled water, wine , «—. and beer products ‘*9
  21. 21. ii They may be in such low levels that don't cause any disturbance in thyroid function. Most coming from fertilisers , rocket fuel, road flares, fireworks, matches, and get deposited in soil and on crop I»-i ‘~ vii %'/ v
  22. 22. Perchlorates ° Use of perchlorate diminished after several cases of aplastic anaemia were observed
  23. 23. Perchlorates ° Although still in use in Europe and other regions, medicinal perchlorate is no longer readily available in the U. S. since the producer discontinued production owing to limited demand.
  24. 24. ii Lower doses have been used safely and effectively in the treatment of Graves’ disease and iodine-induced hyperthyroidism and in cases of amidarone induced thyroid problems I V is 3." I» -i “ "i1 E? V
  25. 25. Perchlorates ° Perchlorate may be valuable as a second-line agent in patients who are intolerant of thionamide therapy
  26. 26. ‘I Are also potent competitive inhibitor of the sodium-iodide symporter. * Thiocynates like perchlorates decreases the active transport of iodide into the thyroid * Potassium thiocyanate is rarely used now I»-i ‘~ vii %'/ v
  27. 27. Thiocyanates ° Thiocyanates ( lsothiocyanates) are made from phytonutrients known as glucosinolates, which are found in abundance in cruciferous vegetables like broccoli which may interfere with iodide absorption and be linked to certain types of thyroid dysfunction.
  28. 28. ii Broccoli is actually full of beneficial substances which have been shown to reduce the risk of certain cancers like colorectal, lung, prostate and breast cancers. If you have normal thyroid l function, the goitrogenic substances found in I broccoli are probably out weighed by all the other health benefits found in cruciferous . vegetables iii ii . is ~. v_ *9 y"
  29. 29. ii Experts agree that cooking eliminates at least some of the goitrogenic substances in broccoli. Cruciferous vegetables therefore need to be boiled atleast for 30 minutes I»-i ‘~ vii %'/ v
  30. 30. Major Applications of Thiocyanates ° Thiocyanates can be used in different applications in the textile and fibre industry, printing, dyeing and finishing operations; in agriculture (As Ammonium Thiocyanate to stabilize various herbicides), in metal and steel industry for silver and tin plating, in construction industry as a hardening accelerator for cement and concrete mixes. nd each thiocyanate has its own specific plications
  31. 31. Major Applications of Thiocyanates ° In a number of applications either ammonium, sodium or potassium thiocyanate can be used. Among them are: ° In agriculture, as raw material for the production of a number of herbicides and fungicides
  32. 32. Major Applications of Thiocyanates ° in the oil field industry, as a tracer of chemicals (? ), because of the intense red colour of the ferric-thiocyanate complex
  33. 33. Major Applications of Thiocyanates ° Further uses ° in the production of solid-cell batteries; ° in the production of ink for ink—jet printers; ° in hair dying, to reduce the duration of treatment; ° As a natural preservative. used also in the synthesis of antibiotics and other pharmaceutical products
  34. 34. Goitrogens Consumption of naturally occurring goitrogens, certain environmental toxins and cigarette smoke can significantly increase SCN- concentrations to levels potentially capable of l affecting the thyroid gland
  35. 35. ii "Goitrogen" is a term used to describe any substance that can cause enlargement of the thyroid gland I»-i ‘~ vii %'/ v
  36. 36. ii The term "goitrogenic food" makes it sound as if something is wrong with the food, but that is simply not the case. I»-i ‘~ vii %'/ v
  37. 37. i What causes problems for certain individuals is not the food itself but the mismatched nature of certain substances within the food that cause thyroid problems in some people in normal people so is related to their unique health circumstances I»-i ‘~ vii %'/ v with already having thyroid problems and not 1
  38. 38. Goitrogenic foods ° Goitrogenic foods ° Cassava, when crushed and not detoxified by soaking ° Soybeans (and soybean products such as tofu, soybean oil, soy flour, soy lecithin) - Pine nuts Peanuts
  39. 39. ii Flax seed, flax seed contains cyanide which transforms into thiocyanate inside the body leading to hypothyroid syndrome I»-i ‘~ vii %'/ v
  40. 40. Goitrogenic Foods ° Millet ° Strawberries ° Pears ° Peaches Spinach Bamboo shoots Sweet potatoes Vegetables in the genus Brassica
  41. 41. Goitrogenic Foods ° Broccoli ° Broccolini (Asparations) Brussels sprouts Cabbage Canola Cauliflower hinese cabbage
  42. 42. Goitrogenic Foods ° Choy sum Collard greens Horseradish Kai-Ian (Chinese broccoli) Kale Kohlrabi Mizuna Mustard greens
  43. 43. Goitrogenic Foods ° Radishes Rapeseed (yu choy) Rapini Rutabagas (swedes) Tatsoi Turnips
  44. 44. Goitrogenic Foods ° Others Soy-Based Infant Formulas Soy based tofu Lithium Phenylbutazone Amidarone
  45. 45. Goitrogenic Foods ° In parts of Central Africa where cassava root and cassava flour may be relied on for too great a percentage of total carbohydrates — risk to thyroid function has been documented, especially when accompanied by deficiency of dietary selenium
  46. 46. Goitrogenic Foods ° Small dose of potassium thiocyanate significantly lowers the thyroid iodide within 15 minutes ,100mg practically empties the iodide compartment
  47. 47. Goitrogenic Foods ° Broccoli and other cruciferous vegetables like cauliflower, kale and cabbage are not inherently ”bad” for the thyroid in normal people— but they may need to be limited — or at least thoroughly cooked — by people with goiter or hypothyroidism
  48. 48. 4* Lethal dose 200-300mg KCN potassium cyanide * Thiocyanates are rarely used now / ‘ . i*‘i‘ v it . is ~. v_ *9 y"
  49. 49. Potassium iodide ° Like perchlorates and thiocyanates Potassium iodide in high doses is inhibitor of sodium iodide symporter ° Thus used before thyroid surgery to reduce size of thyroid gland and its vascularity
  50. 50. Potassium iodide ° Potassium iodide is an inorganic compound with the chemical formula Kl. ° This is white salt most commercially used. It is less hygroscopic (absorbs water less readily) than sodium iodide, making it easier to work with
  51. 51. Potassium iodide ° Potassium iodide is medicinally used for thyroid blockade, thyroid storm and also as an expectorant. Potassium iodide is ionic, K+| —
  52. 52. Applications of Potassium Iodide ° Industry ° Kl is used with silver nitrate to make silver iodide (Agl) an important chemical in film photography also used as a fluorescence agent in biomedical research
  53. 53. Applications of Potassium Iodide ° Nutrition ° The major uses of Kl include use as a nutritional supplement in animal feeds and also the human diet. For the latter, it is the most common additive used to "iodize" table salt (a public health measure to prevent iodine deficiency in populations which get little eafood)
  54. 54. Applications of Potassium Iodide ° The oxidation of iodide causes slow loss of iodine content from iodised salts when it is exposed to excess air. Potassium iodate is used to add iodine to some salts so that the iodine is not lost by oxidation.
  55. 55. Applications of Potassium Iodide ° Dextrose or sodium thiosulfate are often added to iodized table salt to stabilize potassium iodide thus reducing loss of the volatile chemical
  56. 56. Applications of Potassium Iodide - If you are exposed to nuclear fission reactions ° You may get Radio active iodine 131 RAI deposited in your thyroid gland since one of the products these explosions release is radio active iodine ° To block uptake of radio active iodine you can take potassium iodide so that it is taken up by thyroid and blocks taking up of RAI. ° For this you may take tablet or saturated solution of potassium iodide
  57. 57. Applications of Potassium Iodide ° For reasons noted above, therapeutic drops of SSKI, or 130 mg tablets of Kl as used for nuclearfission accidents, since an SSKI drop or nuclear-emergency tablet provides 300 to 700 times more iodine than the daily adult nutritional requirement
  58. 58. Potassium Iodide ° Nutritional iodide tablets containing 0.15 mg (150 microgram or mcg) of iodide, are not to be confused with the much higher pharmaceutical dose preparations.
  59. 59. Pharmaceutical applications ° Tablet ° Potassium iodide is medicinally supplied in 130 mg tablet to be taken every day (each containing 100 mg iodine as iodide and 30 mg potassium) for emergency purposes to block uptake of radio active iodine , a common form of radiation poisoning due to environmental nuclear explosions or fission reactions that release product iodine—131.
  60. 60. Potassium Iodide ° This radio active iodine 131 after such exposure gets deposited in thyroid cells where it emits beta radiations and damages thyroid cells even can cause cancer in them ° Potassium iodide is also used for thyroid storm-severe form of hyperthyroidism or flare ups or you can call it thyroid crises
  61. 61. Potassium iodide ° SSKI 0 Potassium iodide (Kl) can be conveniently prepared as a saturated solution, abbreviated SSKI
  62. 62. Potassium Iodide ° Saturated solutions of potassium iodide can also be used as an emergency treatment to decrease the thyroxine levels quickly
  63. 63. Potassium Iodide ° Due to its high potassium content, SSKI is extremely bitter, and if possible it is administered in a sugar cube or small ball of bread. It may also be mixed into much larger volumes ofjuices
  64. 64. Potassium Iodide ° Neither SSKI or Kl tablets are used as nutritional supplements, since the nutritional requirement for iodine is only 150 micrograms or 0.15 mg of iodide per day.
  65. 65. Potassium Iodide ° Thus, a drop of SSKI provides 50/0.15 = 333 times the daily iodine requirement, and a standard Kl tablet provides twice this much.
  66. 66. Potassium Iodide ° Also by saturating the body with stable potassium iodide prior to exposure, inhaled or ingested radio active iodine131 prevents radioiodine uptake by the thyroid
  67. 67. Potassium Iodide ° The protective effect of Kl lasts approximately 24 hours. For optimal prophylaxis, Kl must be dosed daily until a risk of significant exposure to radioiodine by either inhalation or ingestion no longer exists
  68. 68. Potassium Iodide ° Potassium iodide cannot protect against any other causes of radiation poisoning, nor can it provide any degree of protection against dirty bombs that produce radionuclides other than radionuclides of iodine. The potassium iodide in iodized salt is insufficient for this use so higher doses are to be given
  69. 69. Potassium Iodide ° SSKI ''blocks'' the thyroid's uptake of radioiodine, at a dose of two to three drops of SSKI per day equaling to that of 130 mg tablet of Kl
  70. 70. Potassium Iodide ° For protection of the thyroid against radioiodine(iodine-131) contamination, the convenient standard 130 mg Kl pill is used, if available. As noted, the equivalent two or three drops of SSKI (equaling the dose of one Kl pill) may be used for this purpose, if the pills are not available
  71. 71. Adverse reactions and alternatives Potassium Iodide ° lod-Basedow phenomena, and the Wolff- Chaikoff effect, trigger and/ or worsen hyperthyroidism and hypothyroidism, and then cause temporary or even permanent thyroid conditions
  72. 72. Adverse reactions and alternatives Potassium Iodide ° It can also cause sialadenitis (an inflammation of the salivary gland), gastrointestinal disturbances, allergic reactions and rashes
  73. 73. Adverse reactions and alternatives Potassium Iodide ° Potassium iodide is also not recommended for those who have had an allergic reaction to iodine, and people with dermatitis herpetiformis and hypocomplementemic vasculitis, conditions that are linked to a risk of iodine sensitivity
  74. 74. Adverse reactions and alternatives Potassium Iodide ° Potassium iodide is also use in Cough syrups ° Potassium iodide (oral solution containing 1 g/ mL; also known as saturated solution of potassium iodide [SSKl]) has been used as an expectorant in the symptomatic management of chronic pulmonary diseases where tenacious mucus complicates the condition (e. g., bronchial asthma, bronchitis, pulmonary emphysema). However, efficacy not established and the drug generally has been replaced by more effective and safer expectorants
  75. 75. Potassium Iodide Dosage and Administration ° Oral Administration ° Oral solution (also known as saturated solution of potassium iodide [SSK| ]): Dilute dose in glassful of water, fruitjuice, or milk. To minimize GI irritation, take dose with food or milk
  76. 76. Potassium Iodide Dosage and Administration ° Manufacturer provides calibrated dropper marked to deliver specific amount of dose. ° If administered using standard medicinal dropper, each drop (0.05 mL) contains 50 mg of potassium iodide
  77. 77. Potassium Iodide Dosage and Administration ° Strong iodine oral solution containing 50 mg of iodine and 100 mg of potassium iodide per mL (also known as Lugo| ’s solution; commercially available but not FDA approved): - Then you can give this as 2ml / day ° Dilute dose in water or juice.
  78. 78. Potassium iodide Dosage and Administration ° Dosage Hyperthyroidismf ° Preoperative Use in Patients with Graves’ Disease then give ° Oral solution containing 1 g/ mL (also known as saturated solution of potassium iodide [SSKl]): 150-350 mg (3-7 drops or 0.15-0.35 mL) 3 times daily for 10 days in immediate preoperative period Or tablet 150mg-300mg / day
  79. 79. Potassium Iodide Dosage and Administration ° Thyroid Storm (Thyrotoxicosis Crisis) ° Oral solution containing 1 g/ mL (also known as saturated solution of potassium iodide [SSK| ]): 50-250 mg (1-5 drops or 0.05-0.25 mL) 3 times daily suggested by some clinicians
  80. 80. Potassium Iodide Dosage and Administration ° Potassium iodide is indicated only in preparation for thyroidectomy and treatment of thyroid crises
  81. 81. ° Thioamides also known as thiourylenes are class of drugs that are used to control thyrotoxicosis, Graves Disease and used as preparative therapy before radiotherapy or surgery
  82. 82. * Antithyroid drugs are most often used as the primary treatment for persons with Graves‘ disease, in whom "remission, " have occured which is usually is defined as remaining biochemically euthyroid for one year after cessation of drug treatment, in such cases and for maintaining remissions low doses of 9,—v-«cantithyroid drugs are used
  83. 83. ii Antithyroid drugs are not generally considered to be primary therapy for patients with toxic multinodulargoiters and solitary autonomous nodules, because spontaneous remissions rarely occur I9-9 i~ ‘vii ‘V’ V
  84. 84. ° Members of the thioamide group include ° Methimazole ° Carbimazole (Carbimazole is converted in body to methimazole) ° and Propylthiouracil
  85. 85. ° The decision to use antithyroid drugs during pregnancy must be weighed against the risks and benefits of radioiodine and surgery , since radio iodine can cause fetal abnormalities and cancer i'l’lOl'€
  86. 86. ii Antithyroid drugs might be preferable in patients with severe Graves‘ eye disease, in whom radioiodine therapy has been associated with worsening ophthalmopathy I9-9 i~ ‘vii ‘V’ V
  87. 87. s The Thioamides act by multiple mechanisms. The major action is to prevent hormone synthesis by * Inhibiting the thyroid peroxidase thereby * Blocking iodine organification -Conversion of iodide to iodine and uniting of iodine with tyrosines. It also blocks coupling of the iodotyrosines(MIT, D|T ETC). They also block uptake of iodotyrosines from the colloid by . ..~"‘*‘: .i follicular cells by endocytosis It V as;
  88. 88. ° They also block iodine release from peripheral hormone. They however do not block uptake of iodide by the gland
  89. 89. * Propylthiouracil and (to a much lesser extent) methimazole inhibit the peripheral deiodination of T4 to T3 . I mean to say inhibits conversion of T4 to T3 in peripheral target organs s The onset of these agents is slow, often requiring around one month before stores of ~T4 are depleted .9
  90. 90. iijfi . G -I! 9 99/‘ ‘ Adverse reactions Skin eruptions (such as macules and papules), urticaria, dermatitis, fever, and arthralgia; 0.03% of all patients develop agranulocytosis. Hepatotoxicity Vasculitis Lupus erythematosus Lymphadenopathy (Diseased lymph nodes) Polyserositis ‘i r
  91. 91. ‘I The most serious complication is agranulocytosis, this is the acute shortage of white cells neutrophils & eosinophils. It occurs those over 40, and those on high doses of Methimazole or Carbimazole I9-9 i~ ‘vii ‘sr V in 0.3-0.6% of patients. The risk is increased in A
  92. 92. ‘I The result is normally reversed soon after ceasing to take the drug. Antibiotic treatment may be necessary to treat resultant infections. There is a 50 % cross sensitivity between Methimazole and Propylthiouracil; thus switching drugs is not recommended I9-9 i~ ‘vii ‘V’ V
  93. 93. ‘I There is little evidence that the bulging eyes by Grave's disease are cured by Thioamides I9-9 i~ ‘vii ‘V’ V
  94. 94. Carbimazole and Methimazole ° All thioamides are taken orally ° Carbimazole is rapidly converted to Methimazole, which is pharmacologically active
  95. 95. Carbimazole and Methimazole ° A single 30-40 mg dose can exert an antithyroid effect for 24 hours. ° Thus in mild to moderate cases a single daily dose may be taken. Around a month is required for the drug to take effect as the thyroid may have large stores of hormone which must be depleted
  96. 96. Carbimazole ° After administration of Carbimazole, only methimazole can be detected in serum and thyroid tissue. Conversion of Carbimazole to methimazole appears to be an enzymatic process
  97. 97. Carbimazole ° Methimazole plasma levels are lower after Carbimazole administration than after equal amounts (on a weight basis) of methimazole; 10 mg Carbimazole are equivalent to 6-7 mg methimazole
  98. 98. * Carbimazole is indicated in * Hyperthyroidism. * Preparation for thyroidectomy in hyperthyroidism. ° Graves’ disease ii toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate _ treatment option. .1- . !i" . .. ‘: lit, iv‘: * Therapy prior to and post radio-iodine treatment ‘
  99. 99. Carbimazole Dose ° Adult dosage ---Range 15-60mg/ day ° Mild cases give 5mg TID to 10mg BD ° Moderate cases give 10mg TID ° severe cases give 20mg BD to 20mg TID
  100. 100. ii Once the euthyroid state is reached then give Maintenance dose usually in the range 5 mg to 15 mg per day, which may be taken as a single daily dose I9-9 i~ ‘vii ‘V’ V
  101. 101. ‘I The dose should be titrated against thyroid function until the patient is euthyroid in order to reduce the risk of over-treatment and resultant hypothyroidism I9-9 i~ ‘vii ‘V’ V
  102. 102. ‘I Serial thyroid function monitoring is recommended, together with appropriate dosage modification in order to maintain a euthyroid state I9-9 i~ ‘vii ‘V’ V
  103. 103. 4* Patients should be seen monthly for the first year; and thereafter at 3 or 6 monthly intervals ° Once a remission has been secured, maintenance dosage should be continued for at least 12 months even up to 2 years I9-9 i~ ‘vii ‘V’ V
  104. 104. Carbimazole ° Carbimazole is also given for preparation of Thyrotoxic Patients for Surgery prior to thryoidectomy. |t should be continued up to the time of operation but should be prescribed together with iodide during the last 2 weeks
  105. 105. ii One of the main drawbacks of antithyroid drugs is that some patients experience a relapse of their symptoms upon decreasing the dose of the antithyroid medicine I9-9 “ iii ‘.9 V
  106. 106. ii Antithyroid medications usually alleviate your hyperthyroid symptoms in six to 12 weeks. I9-9 i~ ‘vii ‘V’ V
  107. 107. Carbimazole ° While there is no standard for how long you will take the medication, you will most likely continue with it for 12 to 18 months or 2 years. That time period, combined with a gradual, controlled decrease in your dosage, lessens your chance of developing hyperthyroidism again
  108. 108. Methimazole Dose ° Methimazole Dosage Range 15-60mg/ day
  109. 109. Methimazole Dose ° Mild hyperthyroidism: 5 mg orally every 8 hours. ° Moderately hyperthyroidism: 10 mg orally every 8 hours (up to 40 mg per day). ° Severe hyperthyroidism: 20 mg orally every 8 hours. ° Maintenance: 5 to 15 mg orally daily
  110. 110. Methimazole ° Precautions ° Because methimazole may cause hypoprothrombinemia and bleeding, prothrombin time should be evaluated during therapy, especially before surgical procedures ° Methimazole has been given as a once daily dose in the morning
  111. 111. * Propylthiouracil is rapidly absorbed, reaching peak levels after about 1 hour and also broken down by the liver *9 Most of the ingested dose is excreted by the kidneys in 24 hours as inactive glucuronide I9-9 i~ ‘vii ‘V’ V
  112. 112. ii Propylthiouracil acts more rapidly as it inhibits conversion of T4 to T3. * As a single 100 mg dose can inhibit 60% of iodine complexation for 7 hours the drug can be taken at 6 to 8 hourly intervals I9-9 i~ ‘vii ‘V’ V
  113. 113. Propylthiouracil Dose ° The initial dose is 150- 300 mg daily given as 50 to 100mg TID ° In patients with severe hyperthyroidism the initial dose may be increased to 400 mg daily given as 100mg QID ° An occasional patient will require 600 to 900 mg daily initially. The usual maintenance dose is 100 to 150 mg daily given as 50mg BD or TID
  114. 114. Propylthiouracil ° Dose is selected also according to co- morbidities. Like elderly patient with decreased hepatic, renal, or cardiac function, and of concomitant disease ° Treatment should be also individualized, according to the severity of symptoms and signs of hyperthyroidism and response to therapy
  115. 115. ‘I Usually after one or 2 weeks, but certainly after 4 weeks of therapy, objective signs of clinical improvement should be seen. V is 3.” t_ .9 i~ ii ‘i%'/ V
  116. 116. Propylthiouracil ° The patient should be examined regularly by the physician and the dose adjusted until the patient is euthyroid (usually after 1-2 months). At this stage, the dose should be reduced by 33% every 4 to 6 weeks to a maintenance dose of 50 mg 2 or 3 times daily and continued for 1- 2 years.
  117. 117. ii Usually within 1 to 2 years, a prolonged remission in 50% of the cases can be expected. The course of therapy may some times last for 3 years. * When remission is observed, Propylthiouracil should be withdrawn over a period of 1 to 2 9,1. _ months under close supervision. Ii‘ E’ "ti
  118. 118. ii Because of severe hepatic failure in some patients, especially children, Propylthiouracil is now recommended only in special situations (eg, in the 1st trimester of pregnancy, in thyroid storm). Upper side of doses to be needed in severe cases like thyroid crises or thyroid storm t_.9 i~ 9vii ‘iv V
  119. 119. Propylthiouracil ° Dose in children ° Children under 6 years: Not recommended ° Children 6-10 years: Initially 50 to 150mg once daily or in divided doses
  120. 120. Propylthiouracil ° Methimazole is actually preferred first-line agent because of once daily dosing. ° Much safer than PTU ° Lower risk of Agranulocytosis at moderate doses ° Does not carry the same liver toxicity risk as PTU
  121. 121. it . I‘ i‘,9 «L V ‘iii 1 is 99/‘ ‘ Reasons to use PTU instead of Methimazole are Rapid onset of action Lactation Pregnancy (both PTU and Methimazole are Category D) Use PTU in first trimester & Methimazole in second and third trimester ii. i i
  122. 122. * Renal Impairment-Dose adjustment not necessary for PTU * Methimazole does not affect peripheral conversion of T4 * Methimazole absorbed more slowly than PTU but is longer acting. V is 3.” t_ .9 i~ 9vii ‘V V
  123. 123. Propylthiouracil - Special warnings and precautions for use ° Because of the risk of agranulocytosis it is advised that patients should be warned to report to their doctor in the event of a sore throat, fever, mouth ulcers, bruising, malaise, non-specific illness or other symptoms of infection immediately. - A full blood count should be performed and treatment should be discontinued immediately if there is clinical or laboratory evidence of neutropenia or aplastic anaemia arise
  124. 124. ‘I The treatment with PTU is effective only after a latent period of up to one month because all the preformed hormone has to be used up before circulatory concentrations will fall. V is 3.” t_ .9 i~ ii ‘i%'/ V
  125. 125. 9*. ’ . I‘ I . is iv“ -. , ‘l ; sv Concomitant use of a beta-blocker is usually recommended to help control the symptoms of thyroid storm. * Usual Adult Dose for Alcoholic Liver Damage * 100 mg orally 3 times a day. While data are limited, long-term administration (up to 2 years) may reduce mortality associated with alcoholic liver disease. : ‘ ‘ . - iii '4'
  126. 126. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism During such conditions you only have to realise that larger or upper range doses of antithyroid drugs are used
  127. 127. Typical treatment pattern as in thyroid crises or thyroid storm or severe h erth roidism ° Initially a large dose of Propylthiouracil is administered in thyroid crises or thyroid storm or severe hyperthyroidism. I mean to say use doses on higher side as already ranges given. ° This is used in preference to Methimazole as it has a faster antithyroidal effect
  128. 128. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° On responding to this treatment the dose will bereduced. ° Often the patient is placed on 30-40 mg of Methimazole daily if by some reason PTU not given. ° Methimazole is preferred as is exerts its effect for a longer time than Propylthiouracil
  129. 129. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Once the condition is under control the dose will be reduced to a maintenance dose of 5-15 mg of Methimazole or carbimazole. It is at this point that the side effects become rare and the immune system can recover
  130. 130. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism If at anytime the immune system becomes compromised treatment is stopped and antibiotics administered
  131. 131. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Maintenance dose is decided by serum levels ofT4 and TSH which are to be maintained in normal range ° Pts with T4 and TSH levels fluctuating between hyperthyroid and hypothyroid levels are treated by addition of T4 150 mcg per day as replacement therapy
  132. 132. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism Total duration of therapy is usually 18-24 months
  133. 133. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Give also beta blockers 40-80 mg 6 hourly ° Treatment to reduce peripheral action of thyroid hormones ° Beta blockade: IV Propranolol - titrate against heart rate using increments of 0.5 mg to a total of 10 mg. Give further doses 4-6 hrly. Drug of choice: inhibits peripheral conversion ofT4 to T3.
  134. 134. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° — Although B blockers are of benefit in thyroid storm precipitated by high catecholamine concentrations associated with surgery it is not clear if thyroid storm due to other causes is as responsive to B blockade ° Diltiazem, Reserpine and Guanethidine should be considered in patients in whom beta lockade is contraindicated
  135. 135. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Contrast media may block peripheral thyroid hormone receptor ° Glucocorticoids, PTU, oral contrast media, Amiodarone block peripheral conversion of T4 to T3
  136. 136. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Supportive therapy - Glucose for nutrition. - Steroids: hydrocortisone 300 mg loading followed by 100 mg TDS. - Relative hypoadrenalism occurs as a result of increased metabolism of corticosteroids ° —Sedation ° NG suction Vitamins (especially thiamine).
  137. 137. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism - Active cooling. Chlorpromazine 25-50 mg 4-6 hrly to prevent shivering ° — Fluid replacement. Patients tend to be fluid depleted because of increased insensible loss, diarrhoea and vomiting and decreased ADH secretion ° - Cooling should be attempted before specific therapy is given for congestive cardiac failure. Howeverjudicious use of inotropes and diuretics may be necessary
  138. 138. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Clearance of many drugs is increased and a shortening of dose intervals may be necessary. (Dose intervals will have to be increased again once thyroid storm is controlled). Anti- coagulants and adrenergic drugs are exceptions. ° - Avoid salicylates and Frusemide both of which cause abrupt increases in free thyroid hormones
  139. 139. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° - Anecdotal reports of successful treatment of cases unresponsive to ° conventional treatment with plasma exchange and charcoal haemoperfusion. ° Surgery ° Uncontrolled DM ° Labour clampsia
  140. 140. Typical treatment pattern as in thyroid crises or thyroid storm or severe hyperthyroidism ° Other precipitants include excessive palpation of thyroid, incomplete pre-op preparation, inadequate peri-operative dose of beta blockers, use of radio-iodine in unprepared patients, drugs such as iodides in patients with impaired autoregulation, haloperidol, massive overdose of thyroid hormone
  141. 141. Surgical treatment ° Subtotal thyroidectomy is treatment of choice ° Indications are ° Pt too young for radioactive iodine therapy or in reproductive years ° When antithyroid drugs fail ° Sensitivity reactions to antithyroid drugs t under 40 years with large goiter
  142. 142. Surgical treatment ° Preparation for thyroidectomy should include pretreatment with Propranolol , Carbimazo| e and potassium iodide 60 mg twice daily for 14days before surgery
  143. 143. Radioactive | odine(Iodine-131) ° Iodine-131(131|), also called radioiodine, is an important radioisotope of iodine ° It is associated with nuclear energy, medical diagnostic and treatment procedures, and natural gas production.
  144. 144. Radioactive | odine(| odine-131) ° Radio-iodine is significant contributor to the health hazards from open-air atomic bomb testing in the 1950s. This is because I-131 is a major uranium, plutonium fission product
  145. 145. Radioactive | odine(Iodine-131) ° High doses of the isotope are sometimes less dangerousthan low doses, since they tend to kill thyroid tissues that would otherwise become cancerous as a result of the radiation. For example, children treated with moderate dose of I-131 for thyroid adenomas had a detectable increase in thyroid cancer, but children treated with a much higher dose did not.
  146. 146. Radioactive | odine(Iodine-131) ° Likewise, most studies of very-high-dose I-131 for treatment of Graves disease have failed to find any increase in thyroid cancer, even though there is linear increase in thyroid cancer risk with I-131 absorption at moderate doses.
  147. 147. Radioactive | odine(| odine-131) ° When 131i is present in high levels in the environment from radioactive fallout, it can be absorbed through contaminated food, and will also accumulate in the thyroid.
  148. 148. Radioactive | odine(Iodine-131) ° As it decays, it may cause damage to the thyroid. The primary risk from exposure to high levels of 131i is the chance occurrence of radiogenic thyroid cancer in later life. Other risks include the possibility of non—cancerous growths and thyroiditis
  149. 149. Radioactive | odine(Iodine-131) ° The risk can be mitigated by taking iodine supplements, raising the total amount of iodine in the body and, therefore, reducing uptake and retention in the face and chest and lowering the relative proportion of radioactive iodine.
  150. 150. Radioactive | odine(Iodine-131) ° However, such supplements were not distributed to the population living nearest to the Chernobyl nuclear power plant after the disaster, though they were widely distributed to children in Poland.
  151. 151. Radioactive | odine(| odine-131) ° A common treatment method for preventing iodine-131 exposure is by saturating the thyroid with regular, non-radioactive iodine- 127, as an iodide or iodate salt.
  152. 152. Radioactive | odine(| odine-131) ° The thyroid will absorb very little of the radioactive iodine—131 after it is saturated with non-radioactive iodide, thereby avoiding the damage caused by radiation from radioiodine.
  153. 153. Radioactive | odine(Iodine-131) ° The most common method of treatment is to give potassium iodide to those at risk. The dosage for adults is 130 mg potassium iodide per day, given in one dose, or divided into portions of 65 mg twice a day
  154. 154. Radioactive | odine(Iodine-131) ° There is reason for caution about taking potassium iodide or iodine supplements, as their unnecessary use can cause conditions such as the Jod-Basedow phenomena, and the Wo| ff—Chaikoff effect, trigger and/ or worsen hyperthyroidism and hypothyroidism respectively, and ultimately cause temporary or even permanent thyroid conditions
  155. 155. Radioactive | odine(Iodine-131) ° It can also cause sialadenitis (an inflammation of the salivary gland), gastrointestinal disturbances, allergic reactions and rashes.
  156. 156. Radioactive | odine(Iodine-131) ° Potassium iodide is also not recommended for those who have had an allergic reaction to iodine, and people with dermatitis herpetiformis and hypocomplementemic vasculitis, conditions that are linked to a risk of iodine sensitivity
  157. 157. Radioactive | odine(| odine-131) ° The use of a particular ‘Iodine tablet‘ used in portable water purification has also been determined as somewhat effective at reducing radioiodine uptake
  158. 158. Radioactive | odine(Iodine-131) ° The administration of known goitrogen substances can also be used as a prophylaxis in reducing the bio-uptake of iodine, (whether it be the nutritional non-radioactive iodine- 127 or radioactive iodine, radioiodine - most commonly iodine-131, as the body cannot discern between different iodine isotopes)
  159. 159. Medical and pharmaceutical uses of RAI ° It is used in nuclear medicine therapeutically and can also be seen with diagnostic scanners if it has been used therapeutically. Use of the 131i as iodide salt exploits the mechanism of absorption of iodine by the normal cells of the thyroid gland. Examples of its use in radiation therapy are those where tissue destruction is desired after iodine uptake by the tissue.
  160. 160. Medical and pharmaceutical uses of RAI ° Major uses of 131i include the treatment of thyrotoxicosis (hyperthyroidism) and some types of thyroid cancer that absorb iodine. The 131i is thus used as direct radioisotope therapy to treat hyperthyroidism due to Graves‘ disease, and sometimes hyperactive thyroid nodules (abnormally active thyroid tissue that is not malignant).
  161. 161. Medical and pharmaceutical uses of RAI ° The therapeutic use of radioiodine to treat hyperthyroidism from Graves‘ disease was first reported by Saul Hertz in 1941.A| so used in treating pheochromocytoma and neuroblastoma
  162. 162. Medical and pharmaceutical uses of RAI ° It can be seen in diagnostic scans after its use as therapy, because 131i is also a gamma- emitter. Emits an image ° While as beta radiation of it causes damage and destruction of thyroid cells
  163. 163. Medical and pharmaceutical uses of RAI ° Because of the carcinogenicity of its beta radiation in the thyroid in small doses, I-131 is rarely used primarily or solely for diagnosis (although in the past this was more common due to this isotope's relative ease of production and low expense).
  164. 164. Medical and pharmaceutical uses of RAI ° Instead the more purely gamma-emitting radioiodine iodine-123 is used in diagnostic testing (nuclear medicine scan of the thyroid)
  165. 165. Post-treatment isolation ° Patients receiving I-131 radioiodine treatment are warned not to have sexual intercourse for one month (or shorter, depending on dose given), and women are told not to become pregnant for six months afterwards.
  166. 166. Post-treatment isolation ° "This is because a theoretical risk to a developing fetus exists, even though the amount of radioactivity retained may be small and there is no medical proof of an actual risk from radioiodine treatment.
  167. 167. Post-treatment isolation ° Such a precaution would essentially eliminate direct fetal exposure to radioactivity and markedly reduce the possibility of conception with sperm that might theoretically have been damaged by exposure to radioiodine
  168. 168. Post-treatment isolation ° Is there any special preparation needed for the procedure? ° You should not eat or drink after midnight on the day of the procedure. If you have been taking anti-thyroid medications, you must stop at least three days before the therapy is given. Frequently, the anti-thyroid medication is stopped for five to seven days before therapy
  169. 169. How is the procedure performed? ° Treatment for hyperthyroidism is almost always done on an outpatient basis because the dose required is relatively small. The radioiodine I-131 is swallowed in a single dose, in capsule or liquid form, and is quickly absorbed into the bloodstream in the gastrointestinal (GI) tract and concentrated from the blood by the thyroid gland, where it egins destroying the g| :and's cells.
  170. 170. How is the procedure performed? ° Although the radioactivity from this treatment remains in the thyroid for some time, it is greatly diminished within a few days. The effect of this treatment on the thyroid gland usually takes between one and three months to develop, with maximum benefit occurring three to six months after treatment.
  171. 171. How is the procedure performed? ° Usually, a single dose is successful in treating hyperthyroidism. However, rarely, a second treatment is needed, and very rarely a third treatment may be needed.
  172. 172. Preparing for radioactive iodine treatment ° Before you have radioactive iodine treatment, you may have a man made type of thyroid stimulating hormone called recombinant human TSH (rhTSH) for a few weeks. It helps any thyroid cancer cells in the body to take up radioactive iodine. Or, your doctor may ask you to stop taking your thyroid hormone tablets. They call this thyroid withdrawal
  173. 173. Preparing for radioactive iodine treatment You stop taking the tablets for 4 weeks if you are taking T4 (thyroxine) or 2 weeks if you are taking T3 (liothyronine). This is because the I- 131 works best when the levels of another hormone called TSH (thyroid stimulating hormone) are high. The levels of TSH in your blood start to rise as soon as you stop taking thyroid hormone tablets.
  174. 174. Preparing for radioactive iodine treatment ° In some situations, your doctors may not ask you to take thyroid hormone tablets until after your surgery and radioactive iodine treatment have finished.
  175. 175. Preparing for radioactive iodine treatment ° Lowiodine diet ° You will be asked to start eating a low iodine diet 2 weeks before you have radioactive iodine treatment. You need to have a low iodine diet because too much iodine in your body can stop the treatment working so well.
  176. 176. Preparing for radioactive iodine treatment ° You should not have ° lodised table salt or sea salt ° Cough medicine ° Fish and seafood ° Vitamin supplements that say they contain iodine
  177. 177. Preparing for radioactive iodine treatment ° You should also cut out any food coloured pink with the additive E127. So, do not eat ° Spam or salami ° Tinned strawberries ° Glace cherries ° Pink pastries or sweets
  178. 178. Protecting other people from the radioactivity ° Being in a room on your own (isolation) protects other people from radiation. Pregnant women and children will not be allowed into your room. Other visitors will only be able to stay for a short time each day. And the amount of time the staff will be allowed into your room is limited.
  179. 179. Protecting other people from the radioactivity ° It is important that you know that you are not at any risk from the radiation. The staff in the hospital give this treatment to many people. So, the amount of radiation they are exposed to has to be limited.
  180. 180. Protecting other people from the radioactivity ° After radioactive iodine treatment ° A few days after the treatment your doctors will check to see if the radioactivity has dropped to a safe level. Once it has, you will be able to go home. You may be told that you shouldn't be in contact with children, pregnant women or breastfeeding mothers for a short time
  181. 181. Protecting other people from the radioactivity ° Possible short term side effects include ° Inflammation of the salivary glands (where your spit is made) - you can have painkillers if needed
  182. 182. Protecting other people from the radioactivity ° You may also have a dry mouth and your nurse can give you artificial saliva ° Inflammation of the mouth — you can have anti inflammatory mouthwash ° Short term changes to taste and smell — this usually resolves within 4 to 8 weeks ° Nausea which usually lasts a couple of days - you can have anti sickness medicine for this
  183. 183. Protecting other people from the radioactivity ° Neck pain and swelling— this is not very common and you can have anti inflammatory medicine to reduce the swelling and pain
  184. 184. Protecting other people from the radioactivity Possible long term side effects include Blockage of the tear ducts and you may have a lot more tears than normal — this can be treated by unblocking the tear ducts Temporary reduction in testosterone in men Temporary stopping of periods or heavier periods in women
  185. 185. Protecting other people from the radioactivity ° Temporary disturbance in how your bone marrow works — your doctor will monitor this ° Lung problems — your doctor will monitor this and you will have treatment, if necessary ° Second tumours— these are rare, but if you are concerned you can ask your doctor or clinical nurse specialist to discuss this with you
  186. 186. Protecting other people from the radioactivity ° Travelling after radioactive iodine treatment ° lfyou are planning to travel abroad you should be aware that recent treatment with radioactive iodine may set off radiation alarms at airports. This could happen up to 12 weeks after your treatment. So, to avoid problems make sure you take a certificate from the hospital or a letter from your doctor telling about the treatment you have had.
  187. 187. Protecting other people from the radioactivity ° Radioactive iodine (also called iodine-131, or I-131) is commonly used to treat thyroid cancer. It is given by mouth. The thyroid gland and the cancer cells absorb the radioactive iodine, which is toxic. It destroys the cancer cells and normal thyroid cells.
  188. 188. Protecting other people from the radioactivity ° Radioactive iodine may be used: ° After surgery to destroy cancer cells left behind and to reduce the risk of the cancer recurring (adjuvant radiation therapy) ° As the primary treatment to destroy cancer cells, if the cancer has spread
  189. 189. Protecting other people from the radioactivity ° The amount of radiation given during treatment, and when and how it is given, may be different for each person.
  190. 190. Protecting other people from the radioactivity ° Usually after thyroid surgery, the person is placed on thyroid hormone pills to replace the thyroid hormone from the missing thyroid gland.
  191. 191. Protecting other people from the radioactivity ° Shortly before receiving the I-131, the person will either have thyroid hormone replacement stopped, or will receive recombinant TSH (Thyrogen), an artificial form of TSH that will increase the level of TSH while the person continues to take thyroid hormone pills.
  192. 192. After treatment - After treatment ° A whole body iodine scan is usually done 7-10 days after treatment to see if there are any remaining cancer cells. If there are, then the person may receive another treatment with I- 131. The doctors will also check the person's thyroglobulin blood levels. Thyroglobulin is a protein shed by thyroid cancer cells and is considered a tumour marker. Rising levels of thyroglobulin usually indicate that the cancer has returned.
  193. 193. After treatment ° RAI ablation is recommended if the tumor is over 4 cm in size, extends beyond the borders of the thyroid gland, has spread to the lymph nodes, or if the tumor has spread outside of the neck. RAI is usually not recommended if the cancer is less than 1 cm in size and if there is no evidence of cancer outside the thyroid.
  194. 194. After treatment ° There is some controversy as to whether or not cancers between 1 and 4 cm that have not spread outside the thyroid should or those with multiple spots of cancer in the thyroid should be treated with RAI. In these situations, the use of RAI will be determined by your physician.
  195. 195. When and how is RAI performed? ° When and how is RAI performed? ° RAI is usually done 3 to 6 weeks after surgery, depending on how the patient is prepared for the iodine treatment. The dose of RAI is given by mouth, usually in a pill. One week after receiving the dose, a whole body scan will be performed to show where the iodine collects ' the body.
  196. 196. When and how is RAI performed? ° Uptake is normally seen in the salivary glands, gastrointestinal tract, and urinary bladder. Normal uptake may also be seen in the liver. Seeing these areas light up on scan does NOT mean that thyroid cancer has spread to these organs.
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