Graves' Disease Lecture 2 PDF

Lecture 2 : Thyrotoxicosis, Grave’s Disease Dr.Bayar A.Qasim: MRCP (London), FKBMS, Endo Diploma (UK), SCE Endo/Diabetes(UK) Endocrine Tutor at University of South Wales (UK)  Graves’ disease Graves’ disease can occur at any age but is unusual before puberty...

Lecture 2 : Thyrotoxicosis, Grave’s Disease Dr.Bayar A.Qasim: MRCP (London), FKBMS, Endo Diploma (UK), SCE Endo/Diabetes(UK) Endocrine Tutor at University of South Wales (UK)  Graves’ disease Graves’ disease can occur at any age but is unusual before puberty and most commonly affects women aged 30–50 years. The most common manifestation is thyrotoxicosis with or without a diffuse goitre. Graves’ disease also causes ophthalmopathy and, rarely, pretibial myxoedema Also called Graves orbitopathy or thyroid eye disease. Very rarely thyroid acropachy (a periosteal hypertrophy, indistinguishable from finger clubbing). These extrathyroidal features usually occur in thyrotoxic patients, but can occur in the absence of thyroid dysfunction.  Proptosis (Bulging Eyes) Why it occurs: The immune system attacks the muscles and fat around the eyes, B causing inflammation and swelling. The tissues behind the eyeballs (in the eye socket) thicken, pushing the eyeballs forward, leading to the characteristic “bulging” appearance known as exophthalmos. + A Graves’ disease. (A) Bilateral ophthalmopathy in a 42-year- old man. The main symptoms were diplopia in all directions of gaze and reduced visual acuity in the left eye. The periorbital swelling is due to retrobulbar fat prolapsing into the eyelids, and increased interstitial fluid as a result of raised intraorbital pressure. (B) Transverse CT of the orbits, showing the enlarged extraocular muscles. This is most obvious at the apex of the left orbit (arrow), where compression of the optic nerve caused reduced visual acuity. orbitoputhy AgoPw°Y pretibiwl myxedema  ( Autoimmune process ) When the eyes bulge forward, the eyelids might not → orbitopathy fully close, which can prevent proper lubrication of the eyes. This causes dryness, leading to a sensation of grittiness, as if there’s sand in the eyes. ' The immune attack causes ( autoimmune disease occurs together ) inflammation in the soft tissues around the eyes, leading to swelling *  thickening and swelling of the skin, usually over the shins (pretibial area). It occurs due to the buildup of certain substances, Thyroid Acropacuy like mucopolysaccharides, in the skin, caused by the autoimmune attack seen in thyroid disorders. Although it’s called “myxedema,” it has no direct connection with hypothyroidism-induced myxedema. pretibial myxedema = Grave's or thyroid dermutoputhy Specifically, the body’s immune response causes fibroblast activation in these areas, leading to increased production of connective tissue, swelling, and sometimes bone formation. Thyroid acropachy is a rare complication associated with autoimmune thyroid diseases, particularly Graves’ disease. It is characterized by swelling and thickening of the skin and soft tissues of the hands and feet, clubbing of the fingers and toes, and sometimes bone changes. Pathophysiology These antibodies are termed thyroid-stimulating immunoglobulins or TSH receptor antibodies (TRAb) and can be detected in the serum of 80– 7 95% of patients with Graves’ disease. TRAB usually agonist are termed so TSI but antagonist they maybe → blocking TRAB t hypothyroidism Graves’ disease has a strong genetic component. There is 50% concordance for thyrotoxicosis between monozygotic twins but only 5% concordance between dizygotic twins.  T SH t f f -14 1° TR Ab → thyroid sciwtigruphy  Management: For patients under 40 years of age, most clinicians adopt the empirical approach of prescribing a course of carbimazole and recommending surgery if relapse occurs, 131I is employed as first- or second-line treatment in c. those aged over 40. Radio-iodine ablation Radioiodine ablation (RIA), also called radioactive iodine therapy (RAI), is a common and highly effective treatment used to manage certain thyroid conditions, particularly Graves’ disease, toxic multinodular goiter, and thyroid cancer. It works by using radioactive iodine (I-131) to destroy overactive thyroid cells or thyroid tissue. In contrast, radioiodine ablation is highly selective because it is absorbed only by thyroid cells (or thyroid cancer cells), minimizing exposure to other organs and tissues. Management Common indications Contraindications Disadvantages/complications and stop all drugs send for Radio - iodine Hypersensitivity rash 2% ~ Agranulocytosis 0.2% Antithyroid Hepatotoxicity (with Breastfeeding (propylthiouracil drugs(carbimazole, First episode in patients < 40 yrs propylthiouracil) – very rare but suitable) I propylthiouracil) always 2nd line after potentially fatal carbimeiole , unless the > 50% relapse rate usually within 2 Patient is is in Ti of Pregnancy yrs of stopping drug breastfeeding , to be or Planning pregnant. Large goitre Poor drug compliance, especially in Hypothyroidism (~25%) Previous thyroid surgery young patients Transient hypocalcaemia (10%) Subtotal thyroidectomy Dependence on voice, e.g. opera Recurrent thyrotoxicosis after Permanent hypoparathyroidism (1%) near total thyroideotomy is singer, lecturer Recurrent laryngeal nerve palsy (1%) course of antithyroid drugs in young a now first line in some countries patients , effect dyspnea dysphonia mass ( , like Ugg dysphuyeu ) or suspicious cancer on FNAC Pregnancy or planned Hypothyroidism, ~40% in first year, Patients > 40 yrs Recurrence pregnancy within 6 mths of 80% after 15 yrs Radio-iodine a.k.a following surgery irrespective of age treatment ← Most likely treatment to result in Radioactive iodine ablation Other serious comorbidity Active Graves’ ophthalmopathy exacerbation of ophthalmopathy Antithyroid regimens: Antithyroid drugs should be introduced at high doses (carbimazole 40–60 mg daily or propylthiouracil 400–600 mg daily). Usually, this results in subjective improvement within 10–14 days and renders the patient clinically and biochemically euthyroid at 3–4 6- 8 weeks. You should start at the maximum tolerated dose and then taper once the patient is clinically improving. At this point, the dose can be reduced and titrated to maintain T4 and TSH within their reference range. In most patients, carbimazole is continued at 5–20 mg per day for 12–18 months. in the hope that remission will occur Patients with thyrotoxicosis relapse in at least 50% of cases, usually within 2 years of stopping treatment. 50 -70%  2ND regimen:blocking thyroid hormone synthesis with carbimazole 30–40 mg daily and adding levothyroxine 100–150 µg daily as replacement therapy (a ‘block and replace’ regime). why ? the that Patients has mixed anti bodied CTRAb & Anti Tpu ) when You give problem is some - so carbima.NU , they will develop hypothyroidism. You give Tu they will get hyperthyroidism thats why we will block the gland & replace Ta The most common side effect od carbimazole is rash. Agranulocytosis is a rare but potentially serious complication Patients should be warned to stop the drug and seek medical advice immediately, should a severe sore throat or fever develop whilst on treatment. Propylthiouracil is associated with a small but definite risk of hepatotoxicity It should, therefore, be considered second-line therapy to carbimazole and only be used during pregnancy or breastfeeding Why Use the Block and Replace Regimen? The goal of the Block and Replace regimen is to provide immediate relief from hyperthyroidism and achieve euthyroidism  Thyroid surgery Patients should be rendered euthyroid with antithyroid drugs before operation. Potassium iodide, 60 mg 3 times daily orally, is often added for 2 weeks before surgery to inhibit thyroid hormone release and reduce the size and vascularity of the gland, making surgery technically easier. While complications of surgery are rare and 80% of patients are euthyroid, 15% are permanently hypothyroid and 5% remain thyrotoxic. for this is subtotal removal. = that's why many surgeons do near total thyroidectomy Which means always result in hypothyroidism → give Leuotnyro ✗ me for life Radioactive iodine: 131I is administered orally as a single dose, and is trapped and organified in the thyroid in most centres, approximately 400 MBq (10 mCi) is given orally. This regimen is effective in 75% of patients within 4–12 weeks. During the lag period, symptoms can be controlled by a β-blocker or, in more severe cases, by carbimazole. However, carbimazole reduces the efficacy of 131I therapy because it prevents organification of 131I in the gland, and so should be avoided until 48 hours after radio-iodine administration. If thyrotoxicosis persists after 6 months, a further dose of 131I can be given. The disadvantage of 131I treatment: hypothyroidism. 131I is usually avoided in patients with Graves’ ophthalmopathy. In women of reproductive age, pregnancy must be excluded before administration of131I and avoided for 6 months thereafter; men are also advised against fathering children for 6 months after receiving 131I. Subclinical thyrotoxicosis Serum TSH is undetectable, and serum T3 and T4 are at the upper end of the reference range. These patients are at increased risk of atrial fibrillation and osteoporosis, and hence the consensus view is that they have mild thyrotoxicosis and require therapy, usually with 131I. Otherwise, annual review is essential, as the conversion rate to overt thyrotoxicosis with elevated T4 and/or T3 concentrations is 5% each year. - - Symptoms these need treatment " S" 08% + hN°↳×i ↳ subeditor - n Atrial - fibrileitren - old eye Non-thyroidal illness (‘sick euthyroidism’) https://youtu.be/II9vYa79XEk This typically presents with a low serum TSH, raised T4 and normal or low T3, in a patient with systemic illness who does not have clinical evidence of thyroid disease. These abnormalities are caused by decreased peripheral conversion of T4 to T3!! e As thyroid function tests are difficult to interpret in patients with non-thyroidal illness, it is wise to avoid performing thyroid function tests unless there is clinical evidence of concomitant thyroid disease.  → no function , just suppress TSH is " w°yi¥towt PW" gecoeerf is this * → initially µ in acute illnesses like DKA , the deiodinase so converted enzyme D, is inhibited Tu not to Tz but the Ds is still active so all the Ty converted to rTz. r -13 doesn't have any function of -13 except that it can suppress TSH So you. finally have : - normal/low t -13 Ty , normal / Low TSH Apr -13  Transient Thyroiditis Subacute (de Quervain’s) thyroiditis Post-partum thyroiditis Subacute (de Quervain’s) thyroiditis In its classical painful form, subacute thyroiditis is a transient inflammation of the thyroid gland occurring after infection with Coxsackie, mumps or adenoviruses. There is pain in the region of the thyroid that may radiate to the angle of the jaw and the ears, and is made worse by swallowing, coughing and movement of the neck. The thyroid is usually palpably enlarged and tender. Systemic upset is common. Affected patients are usually females aged 20–40 years. Painless transient thyroiditis can also occur after viral infection and in patients with underlying autoimmune disease. ESR is very high The pain and systemic upset usually respond to simple measures such as (NSAIDs). Occasionally, however, it may be necessary to prescribe prednisolone 40 mg daily for 3–4 weeks. The thyrotoxicosis is mild and treatment with a β-blocker is usually adequate.  Irrespective of the clinical presentation, inflammation in the thyroid gland occurs and is associated with release of colloid and stored thyroid hormones, but also with damage to follicular cells and impaired synthesis of new thyroid hormones. As a result, T4 and T3 levels are raised for 4–6 weeks until the pre-formed colloid is depleted. Thereafter, there is usually a period of hypothyroidism of variable severity before the follicular cells recover and normal thyroid function is restored within 4–6 months Post-partum thyroiditis https://youtu.be/Uqiu6rSg2rk The maternal immune response, which is modified during pregnancy to allow survival of the fetus, is enhanced after delivery and may unmask previously unrecognised autoimmune If the woman has autoimmune thyroid disease thyroid disease (Anti TPO +ve). Hidden Hashimoto disease (like Hashimoto’s), this hypothyroidism phase → 's can be persistent and long-lasting, leading to the need for thyroid hormone replacement. Surveys have shown that transient biochemical disturbances of thyroid function occur in 5– 10% of women within 6 months of delivery. However, symptomatic thyrotoxicosis presenting for the first time within 12 months of childbirth is likely to be due to post-partum thyroiditis and the diagnosis is confirmed by a negligible radio-isotope uptake. The clinical course and treatment are similar to those of painless subacute thyroiditis. Post-partum thyroiditis tends to recur after subsequent pregnancies, and eventually patients progress over a period of years to permanent hypothyroidism. It is likely that these are early patients of hashimoto’s disease that are just brought to attention by the post-partum period in which immunity is enhanced.  non-toxic, diffuse thyroid enlargement Goiter : simple and Multinodular https://youtu.be/wuzBUVFXIeM  Multinodular Goiter (MNG) Patients with thyroid enlargement in the absence of thyroid dysfunction or positive autoantibodies (i.e. with ‘simple goitre’) as young adults may progress to develop nodules. develop, potentially leading to toxic multinodular goiter (TMNG) or subclinical thyrotoxicosis. These nodules grow at varying rates and secrete thyroid hormone ‘autonomously’, thereby suppressing TSH-dependent growth and function in the rest of the gland. Ultimately, complete suppression of TSH occurs in about 25% of cases, with T4 and T3 levels often within the reference range (subclinical thyrotoxicosis) but sometimes elevated (toxic multinodular goitre)  Clinical presentation Multinodular Goiter (MNG) Multinodular goitre is usually diagnosed in patients presenting with thyrotoxicosis, a large goitre with or without tracheal compression, or sudden painful swelling caused by haemorrhage into a nodule or cyst. The goitre is nodular or lobulated on palpation and may extend retrosternally; however, not all multinodular goitres causing thyrotoxicosis are easily palpable. Very large goitres may cause mediastinal compression with stridor, dysphagia and obstruction of the superior vena cava. Hoarseness due to recurrent laryngeal nerve palsy can occur  Diagnosis of Multinodular Goiter (MNG) The diagnosis can be confirmed by ultrasonography and/or thyroid scintigraphy. In patients with large goitres, a flow-volume loop is a good screening test for significant tracheal compression. If intervention is contemplated, a CT or MRI of the thoracic inlet should be performed to quantify the degree of tracheal displacement or compression and the extent of retrosternal extension. In toxic multinodular goitre, treatment is usually with 131I or antithyroid drugs with higher relapse rate In thyrotoxic patients with a large goitre, thyroid surgery may be indicated. Simple diffuse goitre This form of goitre usually presents between the ages of 15 and 25 years, often during pregnancy, and tends to be noticed by friends and relatives rather than the patient. Occasionally, there is a tight sensation in the neck, particularly when swallowing. The goitre is soft and symmetrical, and the thyroid enlarged to two or three times normal. There is no tenderness, lymphadenopathy or overlying bruit. Concentrations of T3, T4 and TSH are normal and no thyroid autoantibodies are detected in the serum. No treatment is necessary and the goitre usually regresses. In some, however, the unknown stimulus to thyroid enlargement persists and, as a result of recurrent episodes of hyperplasia and involution during the following 10–20 years, the gland becomes multinodular with areas of autonomous function.