THYROTOXICOSIS TREATMENT IN ADULTS,CHILDREN AND PREGNANCY

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1.      How do we treat Thyrotoxicosis in children?
·        Antithyroid drugs
·        Surgery
·        Radioiodine Ablation(RAI).

      Although thyroid surgery and radioiodine ablation are gaining popularity among children many endocrinologist still prefer ATDs as initial line of management.
 
RAI is preferred for children above 10 years nowadays
 

Source:uptodate


2.      What are the ATDs?
·        Methimazole
·        Propylthiouracil(PTU).

Methimazole is preferred in children as PTU can cause severe liver failure in children.


3.      What is the dose of Methimazole?
0.5 to 1 mg/kg/day in 1 or 2 divided doses
Drug formulation – 5mg or 10 mg tablet.


4.      Side effects
·        Minor S/E occurs in 10-20% cases
·        Severe reactions occur in 2-5%
·        S/E usually occur within 3 months of therapy
·        Transient urticarial rash can occur and is treated with antihistamine.
 
Agranulocytosis with severe reactions (TLC <500/cumm) are fatal side effects that occur in 0.1 to 0.5% cases.


ATDs should be discontinued.
 
Thus any patient on ATDs with fevere, pharyngitis and other symptoms of immunodeficiency should have a WBC counts done.
 
5.      What is transient agranucytopenia?
WBC count below 2000 without signs and symptoms is a benign condition which doesn’t lead to fatal agranuloctosis.
ATDs can be continued.
 
6.      What are other S/E?
Lupus like polyarthritis
Hepatitis
Glomerulonephritis
ANCA positive vasculitis
 
7.      What is the side effect of PTU?
Hepatoxicity which might lead to liver failure

 


8.      What is the m/c hepatic S/E of Methimazole?
Cholestatic Jaundice
 
9.      What baseline Ix are done before starting PTU?
CBC
ALT
AST
S.bilirubin
 
10.      What are the congenital malformations associated with Methimazole?
Methimazole exposure may be associated with aplasia cutis, omphalocele,choanal atresia, and urinary system malformations,
 
11.      What are the congenital malformations associated PTU?
Propylthiouracil may be associated with malformations of the head, neck, and urinary system.
 
12.      How should we monitor treatment?
 
By TSH, fT4  and Total T3 levels
 
Clinical improvement becomes apparent in 3-4 weeks and adequate response is seen in 3-4 months.
 
Remission is seen in 25% after 2 years of treatment and in 30-50% cases after 4-10 years of treatment.
 
Relapse can occur after 6-12 months of stopping treatment
 
In those cases restart treatment with ATDs or go for definitive treatment with RAI or Sx.
 
13.      How can we treat the catecholamine induced effects like lid lag, tachycardia, and palpitations?
 
Thyroid hormones potentiate the action of catecholamine.
Propranolol and Atenolol are beta blockers used.
However these drugs are nit definitive treatment for Graves or Ophthalmopathy.
 
Atenolol is cardioselective so can be better for palpitation.
 
Propranolol can prevent T4 to T3 conversion.
 
Anyone can be used as per physicians choice.
 
14.      How to stop ATDs?
        2 methods
·        Dose titration method
Gradually taper the drug until it reaches lowest level i.e 2.5 mg to 5 mg per day to maintain euthyroid and then stop the drug but with frequent monitoing
 
·        TRBabs – assay of TRBabs can be done. If present less likely to go into remission.
 
15.      What are the indications of RAI?
·        Children not responding to ATDs.
·        Children above 10 years of age.
 
16.      What are contraindications of RAI?
·        Children below 5 years as radiation exposure is associated with higher risk of cancer.
·        Large glands as surgery is a better approach.
·        Thyrotoxicosis due to destruction like thyroiditis, Hashimotos as they have low iodine uptake which is prime mechanism for RAI.

·        PREGNANCY AND BREAST FEEDING ARE ABSOLUTE CONTRAINDICATIONS
·        Use it with caution in graves Ophthalmopathy and smokers – better to avoid.
 
·        No contact with pregnant and breast feeding lady after RAI therapy as chances of transfer is present for 5-7 days.
 
17. How do we prepare patients for RAI?
·        Treat patients with ATDs to make them euthyroid to prevent radiation thyroiditis
·        Stop ATDs 3-5 days prior to ATDs so that radiolabelled iodine will be taken up by the gland.
 
Propylthiouracil appears to have a prolonged radioprotective effect and should be stopped for a longer period before radioiodine is given, or a larger dose of radioiodine will be necessary.
 
18. Which radiolabelled iodine is used?
·        I131
 
19. What are the doses?
For children above 10 years and adults – 10-15 mCi
For children between 5-10 years - <10 mCi
 
 
20. What are the complications?
·        Risk of radiation cancer
·        Permanent Hypothyroidism
·        Risk of thyrotoxicosis initially
 
21. In case of failure can we repeat the dose?
Yes if no effect is seen can be given again after 6 months.
 
22. What are the indications of surgery?
·        Large goiter
·        Failed ATDs and Sx is preferred over RAI
·        Children <5 years with failed Sx
 
23. Near total thyroidectomy is preferred.
Total thyroidectomy is also done. Subtotal is usually deferred.
 
24. How do we prefer patients before surgery?
·        ATDs so that patients will be euthyroid
·        Iodine for reducing gland vacularity thus minimizing bleeding during surgery.
Potassium iodide and iodine (Lugol's solution: 8 mg/drop, 20 drops per mL), 1 drop by mouth three times daily, or
 
Potassium iodide (SSKI; Thyroshield: 35 to 50 mg/drop), 1 drop by mouth daily
·        A beta blocker such as atenolol (1 to 2 mg/kg once daily) over this same 7- to 10-day period will help to reduce adrenergic symptoms.

25. What are the complications of surgery?
·        Permanent hypothyroidism
·        Hypoparathyroidism
·        Recurrent laryngeal nerve palsy

Source:uptodate


                            ADULTS

1.      ATDs
·        Methimazole is preferred to PTU
·        Methimazole is given at 10-20mg 8-12 hrly
·        PTU 100-200 mg 8-12 hourly
·        Dose are titrated as per clinical and lab monitoring
·        Propranolol/Atenolol are often started before ATDs for symptomatic relief

2.      What is block-replace regimen?
Rarely high doses of ATDs are started with Levothyroxine to prevent hypothyroididm by high doses.

3.      Side effect profile are similar.

4.      Radioiodine as discussed earlier.

5.      Surgery similar to pediatrics

6.      How do we treat thyroid opthalmopathy?
For mild to moderate cases symptomatic treatment:
·        Artificial tear
·        Avoid smoking
·        For exposure keratitis use eye patches during sleep.
·        For edema upright positioning during sleep or a diuretic
·        Selenium can be used
·        Oral steroids can be used.
For severe cases:
·        IV methyprednisolone
·        Decompression surgery
·        External beam radiotherapy.
 
The US FDA has approved teprotumumab, to be sold as Tepezza, the first drug for the treatment of adults with thyroid eye disease.
Teprotumumab, a human monoclonal antibody against the insulin-like growth factor 1 receptor IGF-1R has been effective in adults with ophthalmopathy.

7.     How do we treat thyroid dermatopathy?
·        Thyroid dermopathy does not usually require treatment, but it can cause cosmetic problems or interfere with the fit of shoes.
·        Surgical removal is not indicated. If necessary, treatment consists of topical,high-potency glucocorticoid ointment under an occlusive dressing.
·        Octreotide may be beneficial in some cases.
 
                            PREGNANCY

8.      WHAT IS THE TREATMENT OF CHOICE FOR HYPERTHYROIDIDM IN PREGNANCY?
ATDs aka thionamides are treatment modality of choice
Surgery not necessary unless patient develop agranulocytosis or allergy to ATDs.
 
9.      How to choose drug?
Beta blockers are used for symptomatic relief – Propranolol and Metoprolol are used.
Atenolol is not used due to risk of fetal growth retardation and hypoglycemia.
Prolonged use of other beta blockers is also not advocated.
 
                            SCENARIOS
A.     What can be the options for women diagnosed with Graves' disease prior to pregnancy who are taking methimazole?
                                     I.        Definite therapy before Pregnancy either RAI or Sx.
 
                        Women should then postpone pregnancy until they have become                            euthyroid following definitive treatment and on replacement therapy.
 
                        This option is recommended for women who are requiring high                                doses of methimazole to maintain a euthyroid state.
 
                                   I.          Switch to PTU before trying to conceive. This option is most                                       reasonable in younger women with normal periods who are                                       expected to conceive within one to three months.
 
 
                                   II.        Switch to PTU as soon as the pregnancy test is confirmed. This                               option is more reasonable for older women and women having                               difficulty conceiving. It is recommended that a pregnancy test be                               obtained weekly.
 
                                    III.      Discontinue methimazole with careful monitoring of thyroid function                            tests (weekly throughout the first trimester, then monthly). This                                option is best chosen for women who have already been treated                                with methimazole for 12 to 18 months, have a normal TSH level on                            low-dose therapy, and are thyrotropin receptor antibody (TRAb)                                negative.
 
If hyperthyroidism recurs after discontinuation, the patient should be treated with PTU (if relapse occurs in the first trimester) or methimazole (if relapse occurs after the first trimester).
 
B.     What shall be done if hyperthyroidism is confirmed in 1st trimester of pregnancy?
Start on PTU and then switch to Methimazole in 2nd trimester
 
 
C.     If pregnancy is confirmed in 2nd trimester start on Methimazole.
 
It is because Methimazole and carbimazole are more teratogenic than PTU they are avoided in the first trimester i.e in the period of organogenesis.
 

THANK YOU 
DR NISCHAL

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