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HYPERTHYROIDISM A Practical Approach to Dx. and Rx. Dr. R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist www.drsarma.in Clinical Exam. of Thyroid www.drsarma.in Have patient seated on a stool / chair Inspect neck before & after swallowing Examine with neck in relaxed position Palpate from behind the patient Remember the rule of finger tips Use the tips of fingers for palpation Palpate firmly down to trachea Pemberton’s sign for RSG Where to look for Thyroid ? www.drsarma.in Clinical Anatomy of Thyroid www.drsarma.in Clinical Exam of Thyroid www.drsarma.in Clinical Exam of Thyroid www.drsarma.in Clinical Exam of Thyroid www.drsarma.in Thyromegaly www.drsarma.in Hyperthyroidism A hyper metabolic biochemical state It is a multi system disease with Elevated levels of FT4 or FT3 or both What is thyrotoxicosis ? What is hyperthyroidism ? What are the various causes ? How to differentiate the causes ? What is the appropriate treatment ? www.drsarma.in Causes of Hyperthyroidism 1. Graves Disease – Diffuse Toxic Goiter 2. Plummer’s Disease – Toxic MNG 3. Toxic phase of Sub Acute Thyroiditis - SAT 4. Toxic Single Adenoma – STA 5. Pituitary Tumours – excess TSH 6. Molar pregnancy & Choriocarcinoma (↑↑ βHCG) 7. Metastatic thyroid cancers (functioning) 8. Struma Ovarii (Dermoid and Ovarian tumours) 9. Thyrotoxicosis Factitia ; INF, Amiodarone, SSRIs www.drsarma.in Graves Disease The most common cause of thyrotoxicosis (50-60%). Organ specific auto-immune disease The most important autoantibody is Thyroid Stimulating Immunoglobulin (TSI) or TSA TSI acts as proxy to TSH and stimulates T4 and T3 • • • • www.drsarma.in Anti thyro peroxidase (anti-TPO) antibodies Anti thyro globulin (anti-TG) Anti Microsomal and other Autoimmune diseases - Pernicious Anemia, T1DM RA, Myasthenia Gravis, Vitiligo, Adrenal insufficiency. Graves Disease I 123 or TC 99m Normal v/s Graves www.drsarma.in Graves Disease www.drsarma.in Toxic Multinodular Goiter (TMG) TMG is the next most common hyperthyroidism - 20% More common in elderly individuals – long standing goiter Lumpy bumpy thyroid gland Milder manifestations (apathetic hyperthyroidism) Mild elevation of FT4 and FT3 Progresses slowly over time Clinically multiple firm nodules (called Plummer’s disease) Scintigraphy shows - hot and normal areas www.drsarma.in Toxic Multinodular Goiter (TMG) www.drsarma.in Toxic Multinodular Goiter (TMG) www.drsarma.in Sub Acute Thyroiditis (SAT) SAT is the next most common hyperthyroidism – 15% T4 and T3 are extremely elevated in this condition Immune destruction of thyroid due to viral infection Destructive release of preformed thyroid hormone Thyroid gland is painful and tender on palpation Nuclear Scintigraphy scan - no RIU in the gland Treatment is NSAIDs and Corticosteroids www.drsarma.in Toxic Single Adenoma (TSA) TSA is a single hyper functioning follicular thyroid adenoma. Benign monoclonal tumor that usually is larger than 2.5 cm It is the cause in 5% of patients who are thyrotoxic Nuclear Scintigraphy scan shows only a single hot nodule TSH is suppressed by excess of thyroxines So the rest of the thyroid gland is suppressed www.drsarma.in Toxic Single Adenoma (TSA) Nucleotide Scintigraphy www.drsarma.in Age and Sex Age Graves disease 20 to 40 Toxic MNG > 50 yrs Toxic Single Adenoma 35 to 50 Sub Acute Thyroiditis Any age Sex M : F ratio www.drsarma.in Graves Disease 1: 5 to 1:10 Toxic MNG 1: 2 to 1: 4 Nucleotide Scintigraphy www.drsarma.in Clinical Features 1. Those that occur with any type of thyrotoxicosis 2. Those that are specific to Graves disease 3. Non specific changes of hyper metabolism www.drsarma.in Common Symptoms 1. 2. 3. 4. 5. 6. 7. 8. 9. Nervousness Anxiety Increased perspiration Heat intolerance Tremor Hyperactivity Palpitations Weight loss despite increased appetite Reduction in menstrual flow or oligo-menorrhea www.drsarma.in Common Signs 1. Hyperactivity, Hyper kinesis 2. Sinus tachycardia or atrial arrhythmia, AF, CHF 3. Systolic hypertension, wide pulse pressure 4. Warm, moist, soft and smooth skin- warm handshake 5. Excessive perspiration, palmar erythema, Onycholysis 6. Lid lag and stare (sympathetic over activity) 7. Fine tremor of out stretched hands – format's sign 8. Large muscle weakness, Diarrhea, Gynecomastia www.drsarma.in Specific to Graves Disease Diffuse painless and firm enlargement of thyroid gland Thyroid bruit is audible with the bell of stethoscope Ophthalmopathy – Eye manifestations – 50% of cases 1. 2. 3. Sand in eyes, periorbital edema, conjunctival edema (chemosis), poor lid closure, extraocular muscle dysfunction, diplopia, pain on eye movements and proptosis. Dermoacropathy – Skin/limb manifestations – 20% of cases 4. Deposition of glycosamino glycans in the dermis of the lower leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called (pre tibial myxedema) www.drsarma.in Clinical Presentations www.drsarma.in MNG and Graves Huge Toxic MNG www.drsarma.in Diffuse Graves Thyroid Higher grades of Goiter Toxic MNG www.drsarma.in (Diffuse) Graves Grade IV Toxic MNG Huge Toxic MNG www.drsarma.in Huge Toxic MNG Thyroid Ophthalmopathy Proptosis Lid lag www.drsarma.in Ophthalmopathy in Graves Periorbital edema and chemosis www.drsarma.in Ophthalmopathy in Graves Occular muscle palsy www.drsarma.in Laka Laka Laka Severe Exophthalmia www.drsarma.in Thyroid Dermopathy www.drsarma.in Pink and skin coloured papules, plaques on the shin Graves with Acropathy Graves Goiter www.drsarma.in Acropathy Thyroid Acropathy Clubbing and Osteoarthropathy www.drsarma.in Onycholysis www.drsarma.in Non specific changes 1. 2. 3. 4. 5. 6. 7. www.drsarma.in Hyperglycemia, Glycosuria Osteoporosis and hypercalcemia ↓ LDL and Total Cholesterols Atrial fibrillation, LVH, ↑ LV EF Hyper dynamic circulatory state High output heart failure H/o excess Iodine, amiodarone, contrast dyes FREE THYROXINE or FT4 Nine Square Approach PRIMARY HYPERTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH www.drsarma.in FREE THYROXINE or FT4 Nine Square Approach SUB CLINICAL HYPERTHYROID LOW NORMAL HIGH THYROID STIMULATING HORMONE - TSH www.drsarma.in Diagnosis 1. Typical clinical presentation 2. Markedly suppressed TSH (<0.05 µIU/mL) 3. Elevated FT4 and FT3 (Markedly in Graves) 4. Thyroid antibodies – by Elisa – anti-TPO, TSI 5. ECG to demonstrate cardiac manifestations 6. Nuclear Scintigraphy to differentiate the causes www.drsarma.in Algorithm for Hyperthyroidism Measure TSH and FT4 TSH, FT4 N TSH, FT4 Primary (T4) Thyrotoxicosis Measure FT3 TSH, FT4 N TSH, FT4 N Pituitary Adenoma FNAC, N Scan Features of Grave’s Yes No Rx. Grave’s www.drsarma.in RAIU Low RAIU Single Adenoma, MNG High T3 Toxicosis Normal Sub-clinical Hyper F/u in 6-12 wks Sub Acute Thyroiditis, I2, ↑ Thyroxine Treatment Options 1. Symptom relief medications 2. Anti Thyroid Drugs – ATD Methimazole, Carbimazole Propylthiouracil (PTU) 3. Radio Active Iodine treatment – RAI Rx. 4. Thyroidectomy – Subtotal or Total 5. NSAIDs and Corticosteroids – for SAT www.drsarma.in Symptom Relief Rehydration is the first step 2. β – blockers to decrease the sympathetic excess Propranalol, Atenelol, Metoprolol 3. Rate limiting CCBs if β – blockers contraindicated 4. Treatment of CHF, Arrhythmias 5. Calcium supplementation 6. SSKI or Lugol solution for ↓ vascularity of the gland 1. www.drsarma.in Anti Thyroid Drugs (ATD) Imp. considerations Methimazole Propylthiouracil Efficacy Very potent Potent Duration of action Long acting BID/OD Short acting QID/TID In pregnancy Contraindicated Safely can be given Mechanism of action Iodination, Coupling Iodination, Coupling Conversion of T4 to T3 No action Inhibits conversion Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia Dosage 20 to 40 mg/ OD PO www.drsarma.in 100 to 150mg qid PO How long to give ATD ? Reduction of thyroid hormones takes 2-8 weeks Check TSH and FT4 every 4 to 6 weeks In Graves, many go into remission after 12-18 months In such pts ATD may be discontinued and followed up 40% experience recurrence in 1 yr. Re treat for 3 yrs. Treatment is not life long. Graves seldom needs surgery MNG and Toxic Adenoma will not get cured by ATD. For them ATD is not the best. Treat with RAI. www.drsarma.in Radio Active Iodine (RAI Rx.) In women who are not pregnant In cases of Toxic MNG and TSA Graves disease not remitting with ATD RAI Rx is the best treatment of hyperthyroidism in adults The effect is less rapid than ATD or Thyroidectomy It is effective, safe, and does not require hospitalization. Given orally as a single dose in a capsule or liquid form. Very few adverse effects as no other tissue absorbs RAI www.drsarma.in Radio Active Iodine (RAI Rx.) I123 is used for Nuclear Scintigraphy (Dx.) I131 is given for RAI Rx. (6 to 8 milliCuries) Goal is to make the patient hypothyroid No effects such as Thyroid Ca or other malignancies Never given for children and pregnant/ lactating women Not recommended with patients of severe Ophthalmopathy Not advisable in chronic smokers www.drsarma.in Surgical Treatment Subtotal Thyroidectomy, Total Thyroidectomy Hemi Thyroidectomy with contra-lateral subtotal ATD and RAI Rx are very efficacious and easy – so Surgical treatment is reserved for MNG with 1. Severe hyperthyroidism in children 2. Pregnant women who can’t tolerate ATD 3. Large goiters with severe Ophthalmopathy 4. Large MNGs with pressure symptoms Who require quick normalization of thyroid function 5. www.drsarma.in Preoperative Preparation ATD to reduce hyper function before surgery βeta blockers to titrate pulse rate to 80/min SSKI 1 to 2 drops bid for 14 days This will reduce thyroid blood flow And there by reduce per operative bleeding Recurrent laryngeal nerve damage Hypo parathyroidism are complications www.drsarma.in Dietary Advice Avoid Iodized salt, Sea foods Excess amounts of iodide in some www.drsarma.in Expectorants, x-ray contrast dyes, Seaweed tablets, and health food supplements These should be avoided because The iodide interferes with or complicates the management of both ATD and RAI Rx. Summary of Hyperthyroidism Hyperthyroidism Graves (TSI Ab Age % Enlarged Pain RAIU Treatment 20 - 40 60% Diffuse None ↑↑ ATD – 18 m Toxic MNG > 50 20% Lumpy Pressure ↑ RAI, Surgery Single Adenoma 35 - 50 5% None ± RAI, ATD Yes ↓↓ NSAID, Ster. eye, dermo, bruit) Single S Acute Thyroiditis Any age 15% None www.drsarma.in TSH is markedly low, FT4 is elevated Thyrotoxicosis Factitia Excessive intake of Thyroxine causing thyrotoxicosis Patients usually deny – it is willful ingestion This primarily psychiatric disorder May lead to wrong diagnosis and wrong treatment They are clinically thyrotoxic without eye signs of Graves High doses of Thyroxine lead to TSH suppression This causes shrinkage of the thyroid Stop Thyroxine and give symptom relief drugs www.drsarma.in Algorithm for Thyroid Nodule Thyroid Nodule Low TSH Normal TSH TC 99 Nuclear Scan Hot Nodule RAI Ablation, Surgery or ATD Cold Nodule 4% Malignant Surgery www.drsarma.in FNAC or US guided biopsy 10% 69% Suspicious or follicular Ca Benign T4 suppression Cyst 17% Non diagnostic – repeat FNAC Surgery or Cytology Case # 1 A patient complains of “sandy” sensation in his eyes,weight loss, and a tremor. His extraocular muscles are inflammed. His thyroid is diffusely enlarged and non tender. The most likely diagnosis is a. Iodine deficiency b. Sub-acute thyroiditis c. Multinodular goiter d. Graves’ disease e. Silent thyroiditis www.drsarma.in Case # 2 A 55 year old woman is anxious, irritable, frequent semi solid stools and she reports weight loss of 5 kgs in the past six months. She was having a lumpy bumpy painless swelling in her neck for past 20 years. The most likely diagnosis is a. Iodine deficiency goiter b. Sub-acute thyroiditis c. Multinodular goiter d. Graves’ disease e. Solitary toxic adenoma www.drsarma.in Case # 3 A 60 year patient from a mountain region complains of constipation. He has a heart rate of 60, dry thick skin, and a tongue that has scalloped edges from teeth indentation. He has a goiter. The most likely diagnosis is a. Iodine deficiency b. Subacute thyroiditis c. Graves’ disease d. Silent thyroiditis www.drsarma.in Case # 4 A 25 year old woman is three months pregnant. She has a large goiter. Her exam is otherwise normal. Her thyroid tests are normal. You recommend a. Cassava five times weekly b. Fish three times weekly c. Formula milk for the baby when it is born d. A very low salt diet www.drsarma.in Case # 5 A 72 year old man complains of tremor and inability to concentrate. On exam, he has a heart rate of 100 beats per minute. He has a large goiter with many nodules. He has a fine tremor. His serum T4 is very high and TSH is very low. Treatments that are likely to improve his symptoms are a. Iodine therapy b. Ethanol injection of his thyroid (PEI) c. 6 weeks of Methimazole d. Radio Active Iodine therapy www.drsarma.in Case # 6 In Nuclear Scintigraphy Scan I123 uptake is very high in the thyroid of patients with a. Silent thyroiditis b. Single functional adenoma c. Sub-acute thyroiditis d. Acute ingestion of animal thyroid extract e. Graves’ disease www.drsarma.in Let us start applying www.drsarma.in