Outline

Anatomy Physiology Physical Examination Laboratory evaluation Hypothyroidism Thyrotoxicosis Thyroiditis Goiter and nodular thyroid disease Thyroid cancer

ANATOMY

Regulation of thyroid axis

Thyroid hormone synthesis

Thyroid hormone synthesis

Thyroid hormone transport & metabolism

Serum binding proteins
Thyroxin binding globulin (TBG)
Low concentration (1 2 mg/dL) High affinity (80%) T4 > T3

Transthyretin (TTR)
Low affinity (10% T4, little T3)

Albumin
High concentration (3.5 g/dL) Low affinity (10% T4, 30% T3)

Thyroid hormone transport & metabolism

T3 is less tightly bound than T4 FT4 Free thyroid hormone is biologically available to tissues FT3 >>

Thyroid hormone transport & metabolism

Thyroid hormone action

Thyroid hormone action

Thyroid hormone resistance
Autosomal dominant T4 , TSH or inappropriately normal Mutations in TR receptor gene Goiter, attention deficit disorder, mild IQ reduction, delayed skeletal maturation, tachycardia, impaired metabolic responses to T4 Genetic counseling

Physical examination
Thyroid
Size Consistency Nodularity Tenderness Fixation Bruit

Other signs (eyes, skin, lymph nodes)

Laboratory evaluation
Thyroid hormone Test for etiology of thyroid dysfunction Radioiodine uptake / thyroid scanning Thyroid USG

Thyroid hormone
Thyroid Stimulating Hormone (TSH)
Influenced by alteration of T4 & T3 Screening test Immunochemiluminometric assay (ICMA) method sensitive to < 0.1 mU/L Variable result which is inappropriate with the thyroid hormone level pituitary disease

Thyroid hormone
Unbound thyroid hormone (FT4 & FT3)
Correspond to the biologically available hormone pool Direct method (competition with radiolabeled T4 or separation by ultracentrifugation) Indirect method (THBR)

Thyroid hormone
Total thyroid hormone (TT4 & TT3)
Influenced by thyroid hormone binding proteins level
Estrogen Genetic disorders Acute illness Drugs (phenytoin, carbamazepine, salicylates, NSAID)

Test for Etiology of thyroid dysfunction

TPO antibody
Normally found in 5 15% women and 2% men (+) in autoimmune hypothyroidism and Graves disease

TSI (Thyroid Stimulating Immunoglobulin)

Antibody that stimulate the TSH-R in Graves Predict neonatal thyrotoxicosis

Test for Etiology of thyroid dysfunction

Serum Thyroglobulin (Tg)
in thyrotoxicosis, except thyrotoxicosis factitia Follow up of thyroid cancer , post RAI, post total thyroidectomy

Rai uptake & thyroid scanning

Thyroid imaging using radioisotopes of iodine (123I, 125I, 131I) and pertechnetate (99mTc) Hot nodule vs cold nodule Follow up thyroid cancer

Rai uptake & thyroid scanning

Graves disease
Enlarged gland and tracer uptake homogenously

Toxic adenoma
Focal areas of increased uptake

Toxic MNG
Enlarged gland with multiple areas of relatively or tracer uptake

Subacute thyroiditis; thyrotoxicosis factitia

Very low tracer uptake

Thyroid ultrasound
Diagnosis of nodular thyroid disease Monitoring nodule size Aspiration of cystic lesions Evaluation of recurrent thyroid cancer and possibility of metastasis

hypothyroidism
Congenital hypothyroidism Iodine deficiency Autoimmune hypothyroidism Other causes of hypothyroidism

Congenital hypothyroidism
Prevalence
1 in 4.000 newborns Girls : boys = 2 : 1

Etiology
Idiopathic Thyroid gland dysgenesis (80 85%) Inborn errors of thyroid hormone synthesis (10 15%) TSH-R antibody mediated (5%)

Congenital hypothyroidism
Clinical manifestations
90% asymptomatic Prolonged jaundice, feeding problems, hypotonia, enlarged tongue, delayed bone maturation, umbilical hernia, permanent neurologic damage Other congenital malformations Adult hypothyroidism features

Congenital hypothyroidism
Diagnosis
Neonatal screening of TSH or T4

Treatment
Thyroid hormone (T4) 10 15 g/kg/day

Iodine deficiency

Iodine deficiency

Iodine deficiency
Clinical manifestations
Goiter Hypothyroidism Cretinism
Mental and growth retardation Selenium deficiency

Iodine deficiency
Diagnosis
Urinary iodine < 10 g/dL

Treatment
Iodine supplement
150 g/d for adults 90 120 g/d for children 200 g/d for pregnant women

Oversupply of iodine autoimmune thyroid disease

Autoimmune hypothyroidism
Classification
Goitrous thyroiditis (Hashimotos thyroiditis) Atrophic thyroiditis

Subclinical hypothyroidism Clinical / overt hypothyroidism

Autoimmune hypothyroidism
Prevalence
4 per 1000 women annually Women : men = 4 : 1 Racial Japanese >>> Age 60 years old

Autoimmune hypothyroidism
HLA-DR CTLA-4

Prevalence : 20 %
Racial : Asian Antibody against TSH-R blockade of TSH receptor hypothyroidism atrophy Transient hypothyroidism neonatal

Autoimmune hypothyroidism
Laboratory findings
TSH FT4 TPO antibody (+) Creatine phosphokinase Cholesterol, triglycerides Anemia (normocytic or macrocytic)

Other causes of hypothyroidism

Iatrogenic hypothyroidism
Post RAI treatment
3 4 months after treatment Follow up FT4 than TSH

Post subtotal thyroidectomy Chronic iodine excess, drugs (amiodarone)

Other causes of hypothyroidism

Secondary hypothyroidism
Concomitant other pituitary hormone deficiency TSH , normal, or slightly FT4 Goal of treatment
T4 level in the upper half of the reference ranges

TSH levels cannot be used to monitor therapy

Treatment of hypothyroidism
Clinical hypothyroidism
Levothyroxine daily
No residual thyroid function dose 1.6 g/kg or 100 150 g/day (+) residual thyroid function lower dose : 75 125 g/day Adjustment dose : 12.5 25 g increment / decrement

Goal of treatment : normal TSH (lower half of reference ranges)

Treatment of hypothyroidism
Clinical hypothyroidism
Monitor TSH 2 months after treatment / changes in dosage Effect of treatment : 3 6 months after TSH normalized Monitor TSH annually then 2 3 years if stable

Treatment of hypothyroidism
Subclinical hypothyroidism
Start treatment when TSH levels > 10 mU/L and sustains for > 3 months Levothyroxine 25 50 g/d Monitor TSH anually

Treatment of hypothyroidism
Pregnancy
Goal : maternal euthyroidism levothyroxine dose by > 50% during pregnancy

Elderly
levothyroxine dose by 20%

Pre operative
Euthyroid status

Treatment of hypothyroidism
Myxedema coma
Neurologic impairment (reduced level of consciousness, seizure) + hypothyroidism features Pathogenesis
Hypoventilation hypoxia, hypercapnia Hypoglycemia Dilutional hyponatremia

Treatment of hypothyroidism
Myxedema coma
Predisposition :
Elderly Respiration impairment by drugs Infection Heart disease CVA GI bleeding Exposure to cold

Treatment of hypothyroidism
Treatment of myxedema coma
Levothyroxine 500 g loading dose then 50 100 g/day per IV or NGT Liothyronine (T3) 10 25 g q8 hours per IV or NGT Levothyroxine 200 g + Lyothyronine 25 g IV bolus then levothyroxine 50 100 g/d + liothyronine 10 g q8hrs

Treatment of hypothyroidism
Treatment of myxedema coma
Supportive
External warming if temp < 300C Hydrocortisone 50 mg IV q6 hrs Broad spectrum antibiotic if infection suspected Ventilaory support Hypertonic saline or glucose IV solution Avoid sedative Monitor metabolism of other medications

thyrotoxicosis
Thyrotoxicosis
The state of thyroid hormone excess

Hyperthyroidism
The result of excessive thyroid function

graves disease
Epidemiology
60 80% of thyrotoxicosis Women > men Age ranges between 20 50 years old High iodine intake areas

Genetic factors (HLA-DR, CTLA-4, PTPN22) Environmental factors (stress, smoking, high iodine intake, post partum period)

Thyroid Stimulating Imunoglobulin (TSI) Thyroid Peroxidase Antibodies (TPO-Ab) (80%)

Infiltration of extraocular muscles by activated T cells released of cytokines fibroblast activation, synthesis of glycosamnoglycans disruption of muscle fibrils chronic inflammation fibrosed. OPHTHALMOPATHY and DERMOPATHY

pathophysiology
Carbohydrate, protein, lipid metabolism
metabolism appetite, BMR, heat intolerance, rarely basal body temperature synthesis < degradation of protein metabolism muscle wasting, weight loss lipogenesis < lipolysis FFA, chol & TG Accelerated turn-over of insulin aggravate DM

pathophysiology
Cardiovascular system
Hypermetabolism increased circulatory demands sympathetic tone, vagal tone tachycardia, positive inotropic palpitation symptom, systolic hypertension The need to dissipate excess heat vasodilatation warm, heat intolerance Production of NO vasodilation Decreased SVR diastolic + systolic hypertension widened pulse pressure Cardiac arrythmia heart failure

pathophysiology
Sympathetic nervous system
Thyroid hormone similar & additive to cathecolamine sensitivity of cathecolamine receptor in the cardiomyocytes & adipocytes

Central nervous system

Muscle weakness, insomnia fatigue Emotional labilities Hyperkinesia purposeless, jerky Fine tremor

Muscle
Antibody to TSH receptor in muscles Proximal muscle weakness, exacerbate MG, HPP

pathophysiology
Eyes
adrenergic tone stare phenomenon, lid lag / retraction

Skin & hair

Excess sweating & vasodilation moist, warm skin Fine , soft, friable hair & nail degradation of protein >>

pathophysiology
Alimentary system
caloric requirement appetite Hypermetabolism weight loss, frequency of defecation Hypermetabolism splanchnic oxygen consumption VS splanchnic blood flow hypoxia hepatic dysfunction jaundice, liver failure

Skeletal system
collagen breakdown osteoporosis, osteopenia, risk of fracture

pathophysiology
Renal function
renal blood flow, GFR, tubular reabsorption & secretion function mild proteinuria

Hematopoietic system
Direct effect of thyroid hormone to BM & production of erythropoeitin erythropoeisis Coexist with pernicious anemia (autoimmune disease) neutrophil, lymphocyte Coincidental with ITP sensitivity to warfarin reduce the warfarin dose in AF treatment

pathophysiology
Reproductive system
Thyroid autoantibody miscarriage conversion rate of androgens to estrogenic products gynecomastia, erectile dysfunction, menstrual irregularity Thyroid hormone influences the signaling of GnRH disruption of frequency and amplitude of FSH/LH pulse menstrual abnormality

graves disease
Graves ophthalmopathy
0 =No signs or symptoms 1 = Only signs (lid retraction or lag), no symptoms 2 = Soft tissue involvement (periorbital edema) 3 = Proptosis (> 22mm) 4 = Extraocular muscle involvement (diplopia) 5 = Corneal involvement 6 = Sight loss

graves disease
Thyroid dermopathy (5%)
Plus moderate / severe ophthalmopathy Typical pretibial myxedema Noninflamed, indurated plaque with a deep pink / purple color and orange-skin appearance

Thyroid acropachy (1%)

A form of clubbing fingers

features of graves disease

graves disease
Laboratory evaluation
TSH Unbound thyroid hormone TPO-Ab (+) TSI (+), not routinely needed Thyroid RAI uptake scan : diffuse, high uptake of radioiodine

graves disease
Clinical course
If untreated mortality (10 30%) Mild spontaneous relapses and remissions Post treatment iatrogenic hypothyroidism Ophthalmopathy worsen over the initial 3 6 mos then plateau phase (12 18 mos) with spontaneous improvement Dermopathy appears after 1 2 years, may improve spontaneously

graves disease
Treatment
Reduce thyroid hormone synthesis (antithyroid drugs) Reduce the amount of thyroid tissue (RAI or thyroidectomy) No single approach is optimal Multiple treatments may be required to achieve remission

graves disease
Treatment : Anti thyroid drugs
Thionamides
PTU, Carbimazole, Methimazole Inhibit the function of TPO Reducing oxidation and organification of iodide PTU
Inhibits deiodination of T4 T3 Short half life (90 mins) Dose : 100 200 mg q6-8 hrs

Carbimazole, Methimazole
Long half life (6 hours) Dose : 10 20 mg q8 12 hrs

graves disease
Treatment : Anti thyroid drugs
Monitor FT4 and clinical manifestations 1 months after treatment then annually Dose titration
PTU : 50 100 mg Carbimazole , methimazole : 2.5 10 mg

Block - replace regimen

Combination of high dose anti thyroid with levothyroxine

graves disease
Treatment : Anti thyroid drugs
Maximum remission rates (30 50%)
Titration regimen : 18 24 months Block - replace regimen : 6 months

Side effects
Rash, urticaria, fever, arthralgia (1 5 %) Hepatitis SLE-like syndrome Agranulocytosis (< 1%)

graves disease
Treatment : Radioiodine (131I)
Initial treatment or for relapses after trial with anti thyroid drugs Pre-RAI : give antithyroid drugs for a month then stopped 3 days (carbimazole) or several weeks (PTU) prior RAI Dose : 5 15 mCi, interval 6 months if needed Radiation safety precaution Risk of relapse, persistent hyperthyroidism, hypothyroidism, severe ophthalmopathy, thyroiditis

graves disease
Treatment : subtotal or near-total thyroidectomy
Relapse after antithyroid drugs, contraindicated to RAI, young px, large goiter Pre-op : antithyroid drugs + SSKI 3 drops po tid Complications : bleeding, laryngeal edema, hypoparathyroidism, damage to recurrent laryngeal nerves, recurrence (<2%), hypothyroidism

graves disease
Symptomatic treatment
Beta blocker (propanolol, atenolol)
Control adrenergic symptoms Dose : propanolol 20 40 mg q6hrs po

Pregnancy
PTU : low transplacental transfer, block T4 to T3 conversion Carbimazole : low risk of fetal aplasia cutis Lowest dose of antithyroid drugs Stop treatment in the last trimester

graves disease
Treatment of ophthalmopathy
Control of thyroid hormone level Cessation of smoking Explanation of natural history of ophthalmopathy Artificial tears, eye ointment, use of dark glasses to relieved eyes discomfort Upright sleeping position or diuretic for the periorbital edema Avoid corneal exposure during sleep

graves disease
Treatment of ophthalmopathy
Severe ophthalmopathy
Prednisone 40 80 mg/day, tapered by 5 mg every 2 wks Pulse methylprednisolone therapy (1 g in 250 ml of saline infused over 2 hours daily for 1 wk) followed by oral regimen Surgery (orbital decompression)

graves disease
Treatment of thyroid dermopathy
Surgical removal is not indicated Topical high potency glucocorticoid under an occlusive dressing Octreotide ??

THYROTOXIC CRISIS / THYROID STORM

Life - threatening exacerbation of hyperthyroidism, accompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice Mortality rate high (30%) Precipitating factors
Acute illness (stroke, infection, trauma, DKA) Surgery (esp. Thyroid surgery) RAI treatment of px with partially or untreated hyperthyroidism

Burch & Wartofskys Score for Thyroid Storm

Temp (C) Score 37.2-37.7 5 Tachycardi 99-109 Score 5 GI dysfunction Absent Score 0

37.8-38.2 10 38.3-38.8 15
38.9-39.3 20 39.4-39.9 25 40 30

110-119 120-129
130-140 140

10 15
20 25

Diarrhea, nausea/vomit, 10 abdominal pain

Severe (jaundice) Atrial fibrillation Absent Present 20 Score 0 10 Precipitant history Negative Positive Score 0 10

CHF Absent Pedal edema Bibasal rales Pulmonary edema

Score 0 5 10 15

CNS Absent Agitation Seizure, coma

Score 0 10 30

Delirium, lethargy 20

Burch & Wartofskys Score for Thyroid Storm

Score < 25: unlikely thyroid storm Score 25 44 : impending thyroid storm Score > 44: highly suggestive of thyroid storm

THYROTOXIC CRISIS / THYROID STORM

Treatment
Intensive monitoring and supportive care Identify precipitating factors PTU : 600 mg loading dose and 200 300 mg q6hrs po or NGT or rectum Stable iodide 1 hour post 1st dose of PTU
Block thyroid hormone synthesis via the WolffChaikoff effect SSKI 5 drops q6hrs po

Propanolol 40 60 mg po q4h or 2 mg iv q4h Dexamethasone 2 mg IV q6h Antibiotics, cooling, oxygen, IV fluids

Other causes of thyrotoxicosis

Destructive thyroiditis
Subacute or silent thyroiditis Short thyrotoxic phase (release of preformed thyroid hormones and catabolism of Tg) Low radionuclide uptake Circulating Tg

Other causes of thyrotoxicosis

TSH secreting pituitary adenoma
Inappropriately normal or TSH FT3 and FT4 Hyperthyroidism, diffuse goiter Pituitary tumor on MRI or CT scan

Thyroiditis

ACUTE THYROIDITIS
Suppurative infection of the thyroid Rare Risk factors
Presence of a piriform sinus Long standing goiter Degeneration in a thyroid malignancy

ACUTE THYROIDITIS
Clinical manifestations
Thyroid pain, often referred to the throat or ear Small, tender goiter, asymmetric, erythema over the thyroid site Fever Dysphagia Lymphadenopathy

ACUTE THYROIDITIS
Laboratory findings
ESR , WBC Normal thyroid function tests FNAB : infiltration by PMN leukocytes Gram stain and culture

Treatment
Antibiotic Surgery (abscess)

ACUTE THYROIDITIS
Complications
Tracheal obstruction Septicemia Retropharyngeal abscess Mediastinitis Jugular venous thrombosis

SUBACUTE THYROIDITIS
= de Quervains thyroiditis = granulomatous thyroiditis = viral thyroiditis (mumps, coxsackie, influenza, adenovirus, echovirus) Peak incidence at 30 50 years Women 3x > men

Subacute thyroiditis
Pathophysiology

SUBACUTE THYROIDITIS
Hallmark
1. Patchy inflammatory infiltrate with disruption of the thyroid follicles and multinucleated giant cells within some follicles 2. Follicular changes progress to granulomas accompanied by fibrosis 3. Normalization after several months

SUBACUTE THYROIDITIS
Clinical manifestations
Painful enlarged thyroid Fever Features of thyrotoxicosis or hypothyroidism Malaise Symptoms of URTI precede the disease Sore throat, jaw pain, ear pain

subAcute thyroiditis
Laboratory evaluation
Thyrotoxic phase
T4 and T3 , TSH ESR Low RAI uptake

Hypothyroid phase
T4 and T3 , TSH Normal or increase RAI uptake

Recovery phase Leukocytosis Thyroid antibodies (-)

subAcute thyroiditis
Treatment
Aspirin (600 mg q4-6hrs) or NSAID Glucocorticoid (Prednisone 40 60 mg/day, tapered down over 6 8 weeks) Monitor ESR, TSH, FT4 monthly Antithyroid drugs has NO role Beta adrenergic blockers may be given Levothyroxine (50 100 g/day) if hypothyroid phase is prolonged

Silent thyroiditis
= Painless thyroiditis = Post partum thyroiditis (3 6 mos after pregnancy) Underlying autoimmune thyroid disease Clinical course similar with subacute thyroiditis, except the pain

Silent thyroiditis
Laboratory evaluation
Thyroid function tests depend on the phase Low RAI uptake Normal ESR TPO antibodies (+)

Treatment
Glucocorticoid has NO role Brief beta blocker for severe thyrotoxic phase Levothyroxin for persistent hypothyroidism

Drug induced thyroiditis

Cytokines therapy (IFN - , IL-2) painless thyroiditis Amiodarone
Contains 39% iodine by weight Inhibits deiodinase activity, weak antagonists of thyroid hormone action

Drug induced thyroiditis

Amiodarone
Effects on thyroid function
Acute, transient suppression of thyroid function Hypothyroidism by inhibitory of high iodine load Thyrotoxicosis by a Jod-Basedow effect

Transient FT4 then FT3, rT3 Transient TSH

Drug induced thyroiditis

Amiodarone
Type 1 AIT
Underlying thyroid abnormality Increased iodine exposure excessive hormone synthesis (Jod-Basedow phenomenon) Doppler scanning : increased vascularity of thyroid

Type 2 AIT
No intrinsic thyroid abnormalities Due to drug-induced lysosomal activation destructive thyroiditis Doppler scanning : decreased vascularity of thyroid

Drug induced thyroiditis

Amiodarone
Treatment
Discontinue amiodarone if possible High doses of antithyroid drugs in type 1 AIT (?) Type 2 AIT
Oral contrast agents of iodine Glucocorticoid Lithium, blocks thyroid hormone release Near total thyroidectomy

chronic thyroiditis
Riedels thyroiditis
Rare, occurs in middle - aged women Insidious, painless goiter with local symptoms Hard goiter, asymmetric, fixed due to dense fibrosis Diagnosis : open biopsy Treatment
Surgical relief of compressive symptoms Tamoxifen

Sick euthyroid syndrome

Abnormalities of TSH or thyroid hormone in the absence of underlying thyroid disease Release of cytokines (IL-6, IL-12, IL-18) Laboratory findings
Low T3 syndrome Low T4 syndrome Increased rT3 Fluctuation TSH

Sick euthyroid syndrome

Acute severe illness
Acute liver disease TBG release initial rise of total thyroid hormones Acutely ill psychiatric px transient T4 Acute HIV infection initial rise of thyroid hormones Acute renal failure low T3, normal rT3

Sick euthyroid syndrome

Diagnosis is challenging ! Treatment is controversial ! Monitor patients thyroid function tests during recovery

Thyroid function in pregnancy

Transient hCG, stimulates TSH-R Estrogen induced rise in TBG Alteration in the immune system thyroid hormone metabolism by placenta urinary iodide excretion

Thyroid function in pregnancy

Clinical manifestations
Transient gestational hyperthyroidism Hyperemesis gravidarum

Treatment
Antithyroid drugs are rarely needed Parenteral fluid replacement TSH screening early in pregnancy

Goiter & nodular thyroid disease

GOITER & NODULAR THYROID DISEASE Etiology of goiter

Biosynthetic defects Iodine deficiency Autoimmune disease Nodular disease On physical exam : 3 7 % of adults On USG : > 25% of adults Solitary vs multiple Functional (toxic) vs nonfunctional (nontoxic)

Nodular thyroid disease

Diffuse nontoxic goiter

= Simple goiter, colloid goiter, endemic goiter, juvenile goiter Women > men Iodine deficiency Exposure to environmental goitrogens (cassava root, vegetables of the Cruciferae family)

Diffuse nontoxic goiter

Pathogenesis Iodine deficiency Compensatory effort to trap iodide & produce sufficient hormone TSH stimulation Thyroid enlargement

Diffuse nontoxic goiter

Clinical manifestations
Asymptomatic Sudden onset of localized pain & swelling Symmetrically enlarged, nontender, soft gland without palpable nodules Pembertons sign

Diffuse nontoxic goiter

Laboratory findings
Normal T3, TSH, T4 Low total T4 Slightly increased TSH Low urinary iodine ( < 10 g/dL) Thyroid scan : RAI uptake USG : not indicated unless a nodule is palpable

Diffuse nontoxic goiter

Treatment
Iodine or thyroid hormone replacement
Levothyroxine 100 g/d (young px) or 50 g/d (elderly) Adjust dosage to suppress TSH into low normal but detectable range Significant regression is seen in 3 6 months

Surgery if indicated (substernal goiter, cosmetic reason) followed by mild levothyroxine RAI

Multinodular nontoxic goiter

Prevalence
12% of adults Women > men Iodine deficient region

Pathogenesis
Genetic, autoimmune, environmental Hyperplastic response to locally produced growth factors and cytokines

Multinodular nontoxic goiter

Clinical manifestations
Asymptomatic Large goiter compression symptoms Sudden pain of goiter

Diagnosis
Physical examination Thyroid function test (usually normal) CT or MRI scan Barium swallow USG + biopsy

Multinodular nontoxic goiter

Treatment
Conservative (thyroid hormone replacement) Avoid contrast agents and iodine-containing substances RAI Surgery if needed

TOXIC MULTINODULAR GOITER

Pathogenesis similar with non toxic MNG Presence of functional autonomy (genetic abnormality ??) Subclinical hyperthyroidism or mild thyrotoxicosis Elderly TSH , T4 normal or slightly , T3 Thyroid scan : heterogenous with multiple regions of and uptake Tx : antithyroid drugs & beta blocker RAI Surgery

TOXIC SOLITARY NODULE = toxic adenoma

TOXIC SOLITARY NODULE

Mild thyrotoxicosis Thyroid scan :
focal uptake in the hyperfunctioning nodule Diminished uptake in the remainder of the gland

Treatment
RAI ablation Surgical resection Antithyroid drugs & beta blockers temporary effects Ethanol injection ablation

Thyroid cancer
Incidence : 9 / 100,000 per year Age : increasing with age, plateau after age 50s Women 2x > men

Thyroid cancer
Pathogenesis Radiation TSH and growth factors Oncogenes and tumor suppressor genes Increased rates of proliferation Impaired apoptosis Enhanced invasion, angiogenesis, and metastasis

Well differentiated thyroid cancer

Papillary thyroid Ca
The most common thyroid Ca (70 90%) Hallmark : psammoma bodies, cleaved nuclei with an orphan-Annie appearance caused by large nucleoli, formation of papillary structures Tends to invade locally and into adjacent structures in the neck Bone and lung metastases >>> Slow growth Excellent prognosis

Well differentiated thyroid cancer

Follicular thyroid Ca Iodine deficient regions >>> Difficult to diagnose by FNA Tends to spread hematogenous to the bone, lung, CNS Poor prognostic features
Distant metastases Age > 50 years Primary tumor size > 4 cm Hurthle cell histology Presence of marked vascular invasion

Well differentiated thyroid cancer

Treatment
Surgery
Near total thyroidectomy preferred

TSH suppression therapy

Levothyroxine Target : TSH at low detectable range (0.1 0.5 IU/L) Monitor FT4 to avoid excessive treatment

Radioactive iodine
131I ablation and treatment post surgery in high risk patients

Well differentiated thyroid cancer

Follow up Whole body thyroid scanning 6 months after thyroid surgery + ablation Thyroglobulin assay Monitor every 6 12 months If recurrent additional RAI ablation therapy

POORLY - DIFFERENTIATED THYROID CANCER

Anaplastic thyroid cancer Aggressive cancer Prognosis is poor (survival : 6 mos after diagnosis) RAI only for residual tumor Chemotherapy is ineffective External beam radiation therapy if responsive

Other forms of thyroid cancer

Thyroid lymphoma
Background : Hashimotos thyroiditis Rapid expanding thyroid mass Diffuse large cell lymphoma >>> Highly sensitive to external radiation

Other forms of thyroid cancer

Medullary thyroid carcinoma
Familial or sporadic, 5 10% of thyroid cancer MEN 2A, MEN 2B, Familial MTC Marker : elevated serum calcitonin No uptake of RAI Tx : surgical