Clinical Tips in Management of Thyrotoxicosis

Dr. Sanoop Kumar Sherin Sabu M.D.,(Int Med)

Hyperthyroidism- Only raised Hormones. No clinical features

Thyrotoxicosis- There is clinical features of hyperthyroid state

Thyrotoxicosis crisis- life threatening manifestations of hyperthyroid state

Subclinical hyperthyroidism- THS is suppressed. But T4, and T3 is normal

Practical areas while managing hyperthyroidism.

1. Causes of hyperthyroidism
2. Normal individuals
3. Pregnancy and Infants
4. Hyperthyroidism in Children
5. People at high risk of relapse after treatment
6. Thyrotoxicosis treatment
7. Indications for Radio iodine Ablation and Surgery

Causes of hyperthyroidism

1. Grave disease – MC
2. Acute thyroiditis
3. Sub-acute thyroiditis
4. Post-partum thyroiditis
5. Drug induced thyroiditis
6. Factitious thyrotoxicosis
7. Ectopic thyroid hormone production- Struma ovary
8. Pituitary tumors
9. Toxic MNG
10. Toxic / hyper active solitary nodule of thyroid

Grave disease – MC

High risk group for recurrence

• Young age
• Males
• Smokers
• Large goiter
• TRAb Remains positive even after 12-18 months of treatment

Tips of treatment

• Prefer Carimazole/ methimazole since  over PTU (Propyl Thio Uracil)
  • Less hepatotoxic
  • Has effect to suppress the autoimmunity by immunomodulation effect
  • T1/2 is 8 hours, even then OD dose is sufficient is some cases since it concentrates in the follicles
  • May start with  10- 20 mg OD initially, may increase upto to TID based on response . Maximum daily dose is 100mg/day
• Free T4 , T3 and TSH should be Checked.  
• Initially check every 4 weeks and adjust the dose of Carbimazole 5-10 mg each to make both free T4 and T3 normal.
• If free T4 is normalized but T3 is still high the stable dose should be continued for another  1-3 months to bring down t3 levels
• Even after attaining euthyroid state the stable dose should be continued for atleast 12-18 months due to the immunomodulation effect of anti-thyroid drugs. This will reduce the recurrence rate of graves
• TSH takes 6-12 months to normalize
• After 12-18 months of euthyroid state with minimum dose of antithyroid drug- Carbimazole 5mg per day / PTU 100mg per day , then the drug can be discontinued. Then follow up after 6 weeks . if Remains Euthryoid — annual follow up is only needed.
• Major Side effects-
  • Skin Rash – anti histamine is usually enough
  • Hepatitis- PTU- May need to discontinue
  • Cholestasis- Carbimazole/ Methimazole
  • Aplasia Cutis- Carbimazole/ Methimazole

Block Replacement Therapy  ( controversial concept)

• Indication – In hyperthyroid individuals on antithyroid drugs with constant fluctuation between hypothyroidism and hyper thyrosidism
• Pathology- such individuals will have both TSH- Receptor inhibiting and TSH-Receptor Stimulating (TR-antibody )  antibodies.
• Rx- Give the stable dose of antithyroid drug with + Levothyroxine replacement to meet the  physiological need and maintain in euthyroid state
• Concept- The antithyroid drug is to be continued to attain the immunomodulatory benefit of the drug. And levothyroxine is to be supplemented to achieve euthyroid state

Treatment of Thyrotoxicosis Crisis

 It is a life threatening emergency with tachycardia/ hypertension/ hypotension/ cardiac failure/ hyperthermia/ anxiety , in a k/c/o hyperthyroidism.

• DOC- Propanolol 40mg 1-1-1 Or Iv Esmolol 5mg. ( inhibits the adregenic effects and also the peripheral conversion of T4 to T3)
• Ant thyroid drug of choice-PTU- it has antithyroid effect and also inhibit the periphera conversion of T4 to T3
  • Dose- PTU 500mg In NG tube stat—– then 200mg TID
• Also give 5 Drops of SSKI qid

Patient not responding to ant thyroid drugs

• Usually graves disease respond to antihtyroid drugs. But few might not
• But Toxic MNG/ Toxic single nodule of thyroid might be difficult to control using the ani-thyroid drugs
• So if treated for graves with 12-18 months if high doses of antithyroid drugs- 20mg TID C or 200mg TID PTU, if the patient do not become thyroid, consider
  • Radio-iodine ablation
  • Surgery

Radio-iodine therapy

• Iodine 131 580MBq Stat is given
• Preparation
  • Stop antithyroid drugs at least 3-5 days prior
  • Restart anti-thyroid drugs only after 7-10 days
• Pregnant women, infants , children should not come near the patient who received radio-iodine therapy for at least 10 days since there are chances that the iodine radiations affects the them
• Mild pain due to radiation thyroiditis may remain for 7-10 days
• Even after radio Iodine Ablation for 2-3 months anitthyroid drugs should be continued
• Usually after RIA patients end up in hypothyroid state and they might need lifelong levothyroxine supplementation, which is easier than treating hyperthyroidism
• RIA can be tried after 3 months again if the first one fails
• Absolute Contraindication s
  • Pregnancy
  • Infancy
  • Lactation
• Relative contraindication s
  • Smokers- increased chance of orbitopathy
  • Severe ophtalmopathy- use steroid before RIA

Surgery

• Give SSKI 1 drops TID for 10 days prior to the surgery since it decrease the vascularity and causes hypothyroid state

Other causes of Hyperthyroidism

Acute thyroiditis

• Usually caused by  suppurative  infection of thyroid
• Seen in patients with remnant  4^th pharyngeal pouch derivative pharyngeal cleft which harbors infection to the glands
• Causes pain full thyroid swelling, with fever, and pus
• FNAC – will confirm the organism causing the infection
• Treatment- Antibiotics, surgical drainage/ thyroidectomy

Subacute thyroidistis-

• Subacute infections caused by various virus, mumps, TB , etc
• It presents as sore throat / URTI followed by painfully enlarged gland
• The follicles get damaged and thyroglobulin is released into blood
• Initially there is hyperthyroid state, followed by hypothyroid state and then euthyoidism is achieved
• ESR elevated usually like more than 100
• T4>>>t3. Cos follicles contain T4. So T4/T3 ratio is very high when compared to graves
• Thyroglobulin ++
• Anti- Tg antibody- Negative / positive. Not reliable
• Anti-TOP negative
• TR-antibody negative
• Iodine uptake scan- Cold
• Treatment- NSAID.
  • Steroid may be needed if very severe pain/ systemic features
  • Prednisolone 20-40mg / day taper over 8 weeks
  • After tapering if there is relapse, restart the high dose as before and continue for few weeks.
  • Every 2 weeks check for TSH, FT4, T3 and if the patient goes to hypothyroid state supplement levothyroxine
  • There is no role for Anti- thyroid drugs

Silent Thyroiditis / Painless thyroiditis of pregnancy

• Usually seen
  •  post pregnancy
  • h/o underlying other auto immune disease
  • type 1 DM
• Silent , non pain full hyperthyroidism. For  6 weeks. After which patient goes to hypothyroid state for 12 weeks . then achieves Eu-thyroid state,
• Usually only 1 phase become clinically evident
• Anti- TPO ++ post partum
• Normal ESR
• Iodine scan- decreased uptake
• Rx
  • No need steroids
  • Propranolol 20-40mg
  • If hypothyroid- supplement thyroxine
  • Every year follow up for development of Hashimoto’s thyroiditis

Chronic thyroiditis-

• Hashimotos thyroiditis
• Rediel/ fibrosing thyroiditis – tamoxefine & sugery.  It can be associated with IG-G4 related diseases and other site fibrosis like retroperitoneal, mediastinum, biliary tree, orbit

Facticiuous thyroiditis – due to over dose of thyroxine supplements

Pituitary adenoma

• TSH increase / normal with high T4/ T3
• Diffusely enlarged thyroid gland

Stuma ovary – causes high Free t4/T3 and even high TSH

Iodine excess states

Amiodrione induced thyrotoxicosis

Toxic MNG

Toxic Solitary Nodule Thyroid

Drugs causing hyperthyroidism

• Interferon Alpha ( hepatitis B/C)
• IL-2 blockers
• TKI – ( sumitinib, ornetinib- Ca lung)
• These drugs can cause- painless thyroiditis, hypothyroidism, or graves
• Women who had anti-TPO positive prior to treatment are at high risk of development of thyroid illness

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