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Thyroid Benign Disease JAMAL ALDARAWSHEH MD CONSULTANT ENDOCRINOLOGIST PRINCESS BASMA TEACHING HOSPITAL HYPERTHYROIDISM HYPERTHYROIDISM SIGNS AND SYMPTOMS Skin: Increased Sweating and heat intolerance, onycholysis, hyperpigmentation, pruritus and thinning of the hair. Eyes: Stare and lid lag, exophtalmos if graves disease Cardiac: Palpitations, exertional dyspnea, anginal-like chest pain, tachycardia, atrial fibrillation, CHF GI: Weight loss, diarrhea Neuro-psych: Anxiety, restlessness, irritability, emotional lability, psychosis, agitation, and depression Metabolic/Endocrine: Hyperglycemia, low serum total and high-density lipoprotein (HDL) cholesterol GRAVES’ DISEASE Signs and symptoms of hyperthyroidism Exopthalmos, proptosis, lid lag, orbital edema Diffuse goiter TSH receptor antibodies Increased RAI uptake MUST KNOW T4 and T3 are produced in thyroid gland but T3 is the active component. T3 can also come form T4. T4-to-T3 conversion is stopped by starvation, liver disease and certain drugs (propylthiouracil, propranolol, prednisone) T4 and T3 are circulating as bound proteins-TBG (thyroid binding globulin) If TBG goes up-T4 and T3 would go up. If TBG goes down-T4 and T3 would go down. GENERAL RULE Hyperthyroidism with a high radioiodine uptake indicates de novo synthesis of hormone. Hyperthyroidism with a low radioiodine uptake indicates either inflammation and destruction of thyroid tissue with release of preformed hormone into the circulation, or an extrathyroidal source of thyroid hormone. FACTITIOUS VS. SUBACUTE THYROIDITIS FACTITIOUS HYPERTHYROIDISM SUBACUTE THYROIDITIS THYROID GLAND Painless gland Painful gland SERUM THYROGLOBULIN Low/Normal High SEDIMENTATION RATE Normal High Thyroid benign disease 1)Hyperthyroidism Diffuse Toxic Goiter Toxic Multinodular Goiter Toxic Adenoma Thyroid Storm 2)Hypothyroidism 3)Thyroiditis 4)Riedels Thyroiditis 5)Goiter 6)Solitary Thyroid Nodule Age and Sex Age Graves disease 20 to 40 Toxic MNG > 50 yrs Toxic Single Adenoma 35 to 50 Sub Acute Thyroiditis age Any Sex M : F ratio Graves Disease 1: 5 to 1:10 Toxic MNG 1: 2 to 1: 4 Hyperthyroidism This disease result from an excess of circulating thyroid hormone.that may arise from a number of condition(graves disease,drug induced,thyroiditis,thyroid cancer…) its very important to distinguish disorders: 1.Cause excess production of hormone such as graves disease from 2.An other condition which release stored hormone such as thyroiditis. First disorder characterized by increasing in radioactive iodine uptake. Diffuse toxic Goiter(Graves disease) Its an autoimmune disease with a strong familial predisposition.there is a high incidence in female especially between 40_60 years. the exact etiology of this disease is not known but some condition such as iodine excess,lithium therapy,bacterial & viral infection…suggested as triggers.genetic factor especially present of HLADQA1.0501,HLADR3,HLAB8 also play important role. The clinical manifestation of graves disease divided into 2category: 1.those related to hyperthyroidism & 2.those specific to Graves disease. Hyperthyroid symptom include:heat intolerance,incresed sweating & thirst,weight loss,palpitation,fatigue,diarrhea,increased incidence of miscarriages,… Nearly 50% of patiant have ophthalmopathy & 1 to 2% have dermopathy.eye symptoms include lid lag(von graefes sign),spasm of upper eyelid revealing the sclera(dalrymple sign),conjunctival swelling & congestion(chemosis)… Diagnostic tests: the diagnosis of hyper thyroidism is made by a suppressed TSH with or without an elevated free T4 or T3 level.but if eye sign are present other tests are not needed.in patient with out eye sign (I 123)uptake with diffusely enlarged gland can confirm diagnosis. Other tests including:determining T3 level(in T3 toxicosis), anti TG antibodise,TPO antibodies,TSAB Treatment: graves disease may be treated by any of 3 treatment modalities: 1.Antithyroid drugs 2.radioactive iodine therapy(RAI) 3.thyroidectomy 1.Antithyroid medications: generally are administered before RAI ablation or surgery. Drugs: Propylthiouracil(PTU) have less side effect Methimazole the proper dose of drugs depend on TSH & T4 levels. 2.Radioactive iodine therapy: This method most often used in: Older patient with small or moderate sized goiter. * Patient with relapse after medical or surgical therapy. * Those in whom 2other method are contraindicated. * Absolute contraindication: pregnancy 3.Surgical treatment Patients with coexistent thyroid cancer,those who refuse RAI therapy or have severe ophtalmopathy or have life threatening reaction to antithyroid medication should undergo surgery. Toxic Multinodular Goiter Occur in older individuals with nontoxic multinodular goiter,over several years become autonomous and cause hyperthyroidism. Sign & diagnostic studies are similar to Graves disease. Treatment surgical + thyroid hormone suppression therapy(to prevent recurrence) RAI is recommended in patient with high risk for surgery. Toxic Adenoma In this disease hyperfunction of single nodule cause hyperthyroidism,especially in young patients. RAI scanning shows a hot nodule with suppression the rest of thyroid gland. These nodules are rarely malignant. Treatment Small nodule need medication therapy & RAI Large nodule surgery Thyroid storm Is condition of hyperthyroidism accompained by fever,agitation,cardiovascular dysfunction that may result from infection , surgery,or trauma. Treatment:administration of B_blocker,corticosteroid & Lugols iodine,oxygen supplemention & control of hemodynamic. 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 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 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 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 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 5. Who require quick normalization of thyroid function 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 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 Toxic Single Adenoma 35 - 50 5% None ± RAI, ATD Yes ↓↓ NSAID, Ster. eye, dermo, bruit) Single S Acute Thyroiditis Any age 15% None 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 Hypothyroidism Standard Guideline Diagnosis Raised TSH and Low FT4 = overt hypothyroidism Treatment Start 50-100 mcg levothyroxine Only 12.5 -25 mcg in the elderly or cardiac patients Re assess after 8 weeks (exceptions) Aim of treatment is TSH within reference range; once normal then annual follow up Optimising Therapy Remember to take it - time place Before meal 1 hour, Morning? Not with iron, calcium, aluminium (4 hrs) Decide dosing and testing strategy , age , heart dis , AF, post menopause TSH >0.1 Reassess after other diagnoses, » drug changes, Sertraline, phenytoin, carbamazepine Coeliac disease Higher doses needed if athyrotic , less T3 conversion. Subclinical hypothyroidism Raised TSH and normal FT4 and FT3 Adverse Metabolic and lipids Consider trial of treatment if symptoms Pregnancy now or later? Treat as Hypothyroid Treatment of Subclinical and Clinical Hypothyroid in the Pregnant and Pre-pregnant woman 1999 NEJM TSH above normal, the mother and pregnancy are at increased risk. The foetus is at risk of a lower IQ measured as -7 points between ages 7-9. So treat all Subclinical pre-pregnant women Hypothyroidism Deficiency in circulating levels of thyroid hormone lead to hypothyroidism and cause neurologic impairment and retardation in neonates(cretinism). hypothyroidism also may occur in Pendreds syndrome.(associated with deafness) and turners syndrome. In adult symptoms are non specific:weight gain,cold intolerance,constipation,dry skin,dry hair,sever hair loss…. Laboratory findings: low level of T3 &T4 In primary hypothyroidism raised TSH level In second hypothyroidism suppressed TSH level Treatment :administering T4 Dosage depend on condition of patient. Hypothyroidism Anti-Thyroid Antibodies Markers of Chronic Thyroiditis Anti- Thyroglobulin Antibodies Does not Correlate with hypothyroidism Anti-Thyroid Peroxidase Antibodies (formerly known as Anti-microsomal Antibodies) Correlate with the development of hypothyroidism Anti- TSH Receptor Antibodies TSHRAb Used in the diagnosis and monitoring of Graves’ TSI (Thyroid Stimulating Immunoglobulin) TBII (TSH Binding Inhibitory Immunoglobulin) Severity of Primary Hypothyroidism by Thyroid Levels TSH rises first and abruptly Decline of T4 and T3 slower and later Serum T3 Level Should not be Used to Diagnose Hypothyroidism R10. Serum total T3 or assessment of serum free T3 should not be done to diagnose hypothyroidism Grade A, BEL 2; Upgraded because of many independent lines of evidence and expert opinion. When Should Antithyroid Antibodies Be Measured? R1.Thyroid peroxidase antibody (TPOAb) measurement should be considered when evaluating patients with subclinical hypothyroidism. Grade B, BEL 1; Downgraded. If positive, hypothyroidism rate of 4.3% versus 2.6% per year. Therefore, may or may not influence the decision to treat . TSH is Lower Particularly in 1st trimester Free T4 in pregnancy unreliable 10 weeks gestation +100 20 30 40 E2 TBG hCG +50 TT4 % Change 0 vs. Non-pregnant TSH FT4 -50 1st. Trimester 2nd. Trimester 3rd. Trimester Pregnancy Thyroid Testing Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in 1st trimester provides strong physiological evidence to support redefining TSH upper limit of normal in 1st trimester to 2.5 mIU/liter. Negro, J Clin Endocrinol Metab. 2010 Sep;95(9) Pregnancy normal-range TSH values R. 14.2 In pregnancy, the upper limit of the normal range should be based on trimesterspecific ranges for that laboratory. If trimesterspecific reference ranges for TSH are not available in the laboratory, the following upper normal reference ranges are recommended: first trimester, 2.5 mIU /L; second trimester,3.0 mIU/L; third trimester, 3.5 mIU/L. Grade B, BEL 2. Role for TPOAb? R3. TPOAb measurement should be considered when evaluating patients with infertility, particularly recurrent miscarriage. Grade A, BEL 2; upgraded because of favorable risk-benefit potential . Treatment of TPOAb+ Women? R20. Treatment with L-thyroxine should be considered in women of child-bearing age with normal thyroid hormone levels when they are pregnant or planning a pregnancy including assisted reproduction if they have or have had positive levels of serum TPOAb, particularly when there is a history of miscarriage or past history of hypothyroidism Grade B, BEL 2 Thyroid hormone should not be used to treat obesity R30. Thyroid hormone should not be used to treat obesity in euthyroid patients. Grade A, BEL 2 Upgraded to A because of potential harm— inconclusive benefit and induces subclinical hyperthyroidism Hypothyroidism and the Heart Hypertension (Diastolic) Diastolic Dysfunction Elevated Cholesterol* Long Q-T Syndrome Serum CK Elevation (*Statin Hazard?) Coagulopathy Treatment of TSH between 5 and 10? Depends… R16. Treatment should be considered particularly if they have symptoms suggestive of hypothyroidism, positive TPO antibodies or evidence of atherosclerotic cardiovascular disease, heart failure or have associated risk factors for these diseases. Grade B, BEL 1; evidence not fully generalizable to stated recommendation and there are no prospective, interventional studies. Vanderpump MP et al. 1995 Clin Endo 43:55-68 (EL2). Vanderpump MP & Tunbridge WM 2002 Thyroid 12:839-47 (EL4). Hollowell JG et al. 2002 JCEM 87:489-99 (EL1). Huber G et al. 2002 JCEM 87:3221-26 (EL2). McQuade C et al. 2011 Thyroid 21:837-43 (EL3). Ochs N et al. 2008 Ann Treatment of TSH levels > 10 is recommended R15. Patients whose serum TSH levels exceed 10 mIU/L are at increased risk for heart failure and cardiovascular mortality, and should be considered for treatment with L-thyroxine. Grade B, BEL 1; not generalizable and meta-analysis does not include prospective interventional studies. Hypothyroid patients treated with normalized TSH are still more likely to feel poorly (Saravan Clinical Endo 2002; Boeving Thyroid 2011) Surks et al. 2004 JAMA 291:228-38 (EL4). Rodondi N et al. 2010 JAMA 304:1365-74 (EL2). Razvi S et al. 2010 JCEM 95:1734-40 (EL3). Gencer B et a.2012 Circulation Epub before print (EL1). Initiating therapy in overt hypothyroidism Recommendation 22.7.1: When initiating therapy in young healthy adults with overt hypothyroidism, beginning treatment with full replacement doses should be considered. Grade B, BEL 2 Recommendation 22.7.2: When initiating therapy in patients older than 50-60 years old with overt hypothyroidism, without evidence of coronary heart disease, an L-thyroxine dose of 50 mcg daily should be considered. Grade D, BEL 4 Initiating treatment in subclinical hypothyroidism Recommendation 22.8: In patients with subclinical hypothyroidism initial Lthyroxine dosing is generally lower than what is required in the treatment of overt hypothyroidism. A daily dose of 25 to 75 mcg should be considered, depending on degree of TSH elevation. Further adjustments should be guided by clinical response and follow up laboratory determinations including TSH values. Grade B, BEL 2 Question 3.12 How should hypothyroidism be treated and monitored? R23. L-thyroxine should be taken with water consistently 30 to 60 minutes before breakfast or at bedtime 4 hours after the last meal. It should be stored properly per product insert and not taken with substances or medications that interfere with its absorption. Grade B, BEL 2. Bolk N et al. 2010 Arch IM 170:1996-2003 (EL2). Bach-Huynh TG 2009 JCEM 94:3905-12 (EL2.) Thyroiditis Classified into acute,subacute,and chronic forms. Acute(suppurative)thyroiditis: Thyroid gland is resistant to infection but some times infectious agents can seed it *Via the hematogenous *After penetrating trauma *Due to immunosuppression…… This disease is more common in children and characterized by severe neck pain(radiating to jaws or ear),fever,chill,odynophagia,&dysphonia. The diagnosis confirm by leukocytosis on blood tests and FNAB for Grams stain,culture,and cytology. Treatment: Antibiotic + drainage of abscesses. Subacute Thyroiditis Can occur in the painful or painless forms.exact etiology is not known but: Painful: viral infection,genetic(HLAB35) In this disease cytotoxic T lymphocytes stimulate and damage thyroid follicular cell. Its common in women,characterized by sudden or gradual onset of neck pain.the gland is large,tender & firm.(T4,T3.ESR high / TSH low The disorder progresses through 4stage: Hyperthyroidism , euthyroidism, hypothyroidism, euthyroidism. Treatment Aspirin,NSAID,thyroid hormone therapy,& some times thyroidectomy Painless: may be an autoimmune disease and especially occur in women after delivery. symptoms and clinical course are similar to painful form. Treatment B-blocker, thyroid hormone, and some times thyroidectomy or RAI ablation Choronic thyroiditis lymphocytic Is an autoimmune process initiated by the activation of CD4 T helper lymphocytes which destruct thyrocytes. antibodies directed against 3main Ag: Tg,TPO,TSH-R Disease is common in women between 3040years.minimally or moderately enlarged firm granular gland discover in examination.FNAB can be useful that in pathology we see follicles lined by Ashanazy cell. Diagnostic studies: Elevated TSH and present of thyroid autoantibody confirm the diagnosis. Treatment: thyroid hormone,surgery(for suspicion of malignancy,or cosmetic deformity) Riedels Thyroiditis Is rare variant of thyroiditis which characterized by replacement of all or part of the thyroid parenchyma by fibrous tissue.it presents as painless,hard(woody) neck mass. Symptom include: Dysphagia ,dyspnea, hoarsness, choking, hypothyroidism, hypoparathyroidism… Biopsy is necessary. Treatment : surgery Goiter Familial goiter resulting from dificiencies in enzymes necessary for thyroid hormone synthesis hypothyroidism Endemic goiter resulting from iodine deficiency and can be treated by iodine. Clinical feature:most patients are asymptomatic,although patients often complain of pressure sensation in the neck. We can find soft enlarged gland(simple goiter)or nodules of various size(in multinodular goiter) Thyroid tests are usually normal. Treatment: Patient with small,diffuse goiter do not need treatment In large goiter thyroid hormone therapy can be useful. 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 Rx. Grave’s No RAIU Low RAIU Single Adenoma, MNG www.drsarma.in High T3 Toxicosis Normal Sub-clinical Hyper F/u in 6-12 wks Sub Acute Thyroiditis, I2, ↑ Thyroxine Solitary thyroid nodule History such as time of onset,change in size of nodule and associated symptom(pain,dysphagia,dyspnea…) is very important. We should ask from ionizing radiation and familial history of malignancy. Nodules that are hard,or fixed to surrounding structure are most likely to be malignant. Diagnostic investigations FNAB has become the most important test. After FNAB nodules can be categorized into:beningsuspicious-malignant Ultrasound is inexpensive and noninvasive method that can be helpful for detecting nonpalpable thyroid nodule,differentiating solid from cystic nodule.calcification…. Solitary Thyroid Nodule Algorithm for Thyroid Nodule Thyroid Nodule Low TSH Normal TSH TC 99 Nuclear Scan Hot Nodule RAI Ablation, Surgery or ATD FNAC or US guided biopsy Cold Nodule 4% Malignant Surgery 10% 69% Suspicious or follicular Ca Benign T4 suppression www.drsarma.in Cyst 17% Non diagnostic – repeat FNAC Surgery or Cytology management But in patient with history of previous irradiation of thyroid gland or familial thyroid cancer, surgery should be done.