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Download ประกอบการสอนนักศึกษาแพทย์ชั้นปีที่4 จัดทาโดย
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ประกอบการสอนนักศึกษาแพทย์ชนปี ั ้ ที่4 จัดทาโดย แพทย์หญิงรุ่งนภา ลออธนกุล, พบ. Anatomy and Physiology Laboratory Evaluation ◦ Thyroid function tests ◦ Radioiodine Uptake and Thyroid scanning ◦ Thyroid ultrasound ◦ Fine needle aspiration Thyroid disorders ◦ Thyrotoxicosis ◦ Hypothyroidism ◦ Thyroid nodule/ Multinodular goiter Size 12-20 g. in normal adults Anterior to the trachea between cricoid cartilage and suprasternal notch Williams Textbook of Endocrinology 11th edition 2 biologically active thyroid hormones: ◦ Thyroxine (T4) : product of the thyroid gland ◦ 3,5,3'-triiodothyronine (T3) : product of the thyroid and of many other tissues, in which it is produced by deiodination of T4 3,3',5'-triiodothyronine (reverse T3, rT3), which has no biological activity. Williams Textbook of Endocrinology 11th edition Iodide trapping Diffusion Transport into colloid Deiodination of DIT, MIT to yield tyrosine Oxydation of I- and incorporate into tyrosine residue within Tg Combination DIT+DIT=T4 MIT+DIT=T3 Release of T4, T3 into circulation Uptake of Tg by endocytosis, fusion with lysosome, proteolysis Thyroid function tests Radioiodine Uptake and Thyroid scanning Thyroid ultrasound Fine needle aspiration TSH : Thyroid stimulating hormone Total T3 and T4 (binding with TBG) Free T3 and T4 Thyroid hormone levels TSH Diagnosis Hyperthyroidism Central hypothyroidism or Non thyroidal illness or Primary hypothyroidism Subclinical hypothyroidism or Inappropriate TSH secretion Subclinical hyperthyrodism Thyroid binding globulin Thyroid binding globulin Pregnancy Nephrotic syndrome, malnutrition Chronic active hepatitis Cirrhosis Acute intermittent porphyria Active acromegaly Estrogen, methadone, heroin, perphenazine Androgen, salicylate, prednisolone Genetic defects Genetic defects Selectively transports radioisotopes of iodine 123I, 131I, 99mTc pertechnetate Thyroid imaging and quantitation of radioactive tracer fractional uptake Thyrotoxicosis Refers to the classic physiologic manifestations of excessive quantities of thyroid hormones. Hyperthyroidism Reserved for disorders that result from sustained overproduction of hormone by thyroid itself. Primary hyperthyroidism Graves’ disease Toxic multinodular goiter Toxic adenoma Secondary hyperthyroidism TSH-secreting pituitary adenoma Chorionic gonadotropin-induced Gestational hyperthyroidism Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Amiodarone Thyrotoxicosis factitia Autoimmune thyroid disease Autoantibodies specific to Graves’ disease are directed against the TSHR (TSHRAbs : TSab, TSI) ) and behave as thyroid stimulating antibodies Fatigue Heat intolerance Weight loss to an effective diet Dyspnea Palpitation Lid retraction..“Stare” Lid lag Increased adrenergic tone Graves’ Ophthalmopathy Soft tissue involvement Proptosis Extraocular muscle involment Corneal involment www.thyroidmanager.org www.thyroidmanager.org Warm and moist skin Palmar erythema Hair : fine and friable Plummer’s nails: Onycholysis typical involving the 4th and 5th fingers Vitiligo Graves’ disease Thyroid acropachy Pretibial myxedema Onycholysis Thyroid acropachy www.thyroidmanager.org Thyroid acropachy Pretibial myxedema www.thyroidmanager.org Size, shape, consistency, tenderness, mobility Bruits Graves’ disease Diffuse goiter Soft to firm and rubbery Bruits : upper and lower pole Tachycardia Widening of the pulse pressure Atrial fibrillation Heart failure Means-Lerman scratch : Heart sounds are enhanced, particularly S1, and a scratchy systolic sound along the LPSB, resembling a pleuropericardial friction rub. Anxiety / Psychosis Tremor Hyperactive reflexes Acute thyrotoxic encephalopathy (rare) Chorea / athetoid movement (rare) Myopathy Hypokalemic periodic paralysis TSH , T3 & T4 Positive TSHRAbs Increased radioactive iodine uptake (RAIU) Medication Antithyroid Drugs : PTU, MMI B-Adrenergic antagonist drugs Glucocorticoids Inorganic Iodide Iodine-Containing Compounds Potassium Perchlorate Lithium Carbonate Rituximab Thyroid ablation Radioactive iodine Surgery Iodide trapping Perchlorate Diffusion Transport into colloid Thionamide Deiodination of DIT, MIT to yield tyrosine Oxydation of I- and incorporate into tyrosine residue within Tg Combination DIT+DIT=T4 MIT+DIT=T3 High dose PTU Release of T4, T3 into circulation Uptake of Tg by endocytosis, fusion with lysosome, proteolysis Iodine Propylthiouracil (PTU), Methimazole (MMI) Inhibit thyroid hormone synthesis Immunosuppressive actions PTU : blocking of the conversion of thyroxine (T4) to triiodothyronine (T3) Dose adjustment is not necessary in persons who have impaired liver or kidney function. Characteristic MMI PTU 10-50 1 Administration oral oral Serum half-life (hours) 4-6 1-2 Duration of action (hours) >24 12-24 Decreased Normal Normal Normal Transplacental passage and level in breast milk Low Even lower Inhibition of T4/T3 conversion No Yes 1-2 times daily 2-3 times daily Relative potency Metabolism during liver disease Metabolism during kidney disease Dosing Endocrinol Metab Clin N Am 38 (2009) 355–371 Side effect Polyarthritis ANCA+ vasculitis Frequency 1-2% Rare Comments Mostly PTU Agranulocytosis 0.1-0.5% May be more common with PTU Hepatitis Cholestasis 0.1-0.2% Rare PTU MMI Skin reactions : rash, pruritus Arthralgias Gastrointestinal symptom Abnormal sense of taste Occasional sialadenitis Defined as an absolute granulocyte count < 500/mL Often occurs within the first 3 months of therapy Most experts do not recommend routine monitoring of granulocyte count during treatment. Patients should be instructed to stop medication and to seek medical attention if they develop a fever or a sore throat. If the granulocyte count <1000/mL, the drug should be stopped. Endocrinol Metab Clin N Am 38 (2009) 355–371 Recurrence rate is 50 - 60% Most cases of relapse occur within 3 - 6 months of stopping the drug. Most women in remission who become pregnant have a postpartum relapse of GD or develop postpartum thyroiditis Life-long follow-up is recommended. Medical treatment : 1.5 – 2 years Endocrinol Metab Clin N Am 38 (2009) 355–371 RAI is considered effective, safe, and relatively inexpensive. Isotope of choice is 131I. Increased risk of ophthalmopathy Following 131I therapy, 50-70% of patients become euthyroid within 6- 8 weeks Endocrinol Metab Clin N Am 38 (2009) 355–371 Indications Patient preference Children, adolescents, pregnant women Large goiters (whether causing pressure symptoms or for cosmetic reasons) Suspicion of thyroid malignancy +/-Pre-existing Graves’ ophthalmopathy Total or nearly total thyroidectomy Endocrinol Metab Clin N Am 38 (2009) 355–371 Complications Permanent damage to the recurrent laryngeal nerve Hypoparathyroidism Transient hypocalcemia Postoperative bleeding Wound infections The formation of keloids Endocrinol Metab Clin N Am 38 (2009) 355–371 Advantages Disadvantages Thionamides -No radiation hazard -No surgical and anesthesiologic risks -No permanent hypothyroidism -OPD -Recurrent rate high (>50%) -Frequent testing required -Common mild side effect -Rare but potentially lethal side effects Radioactive iodine -Definitive treatment -No surgical and anesthesiologic risks -OPD, rapidly performed -Rapid control of hyperthyroidism in most -Low cost -Side effects mild, rare, transient -Normalizes thyroid size within 1 yr -Potential radiation hazard -Worsening of thyroid eye disease -Decreasing efficacy with increasing goiter size -May need to be repeated -Hypothyroidism eventually develops in most cases Thyroidectomy -Definitive treatment -No radiation hazard -Rapid normalization -Definitive histological -Most effective in cases with pressure symptoms -Cost, IPD -Anesthesiologic risks -Hypoparathyroidism 1-2% -Damage recurrent laryngeal nerve, bleeding, infection -Hypothyroidism Hyperthyroidism arises in multinodular goiter (MNG) Autonomous function Usually occurs after the age of 50 in patients who have had nontoxic MNG Treatment: Radioactive iodine or surgery Radioiodine uptake และ thyroid scan พบว่ามี heterogeneous uptake โดยมีทงส่ ั ้ วนที่ high และ low uptake Hyperfunctioning nodule Nodule diameter > 3 cm Typically in patients in their 30-40 years old Treatment: Radioactive iodine or surgery Thyroiditis with Pain Subacute granulomatous thyroiditis Infectious thyroiditis Thyroiditis without Pain Painless thyroiditis Postpartum thyroiditis Drug-induced thyroiditis : Amiodarone, Lithium Subacute nonsuppurative thyroiditis, de Quervain's thyroiditis, viral thyroiditis, or subacute thyroiditis Predominates in female, 30-50 years old History of an upper respiratory infection, typically 2-8 weeks beforehand Mumps, coxsackie, influenza, adenoviruses and echoviruses Malaise, upper respiratory tract infection Gradual or sudden pain in thyroid gland, radiates to the ear, jaw by turning head or swallowing Neck pain, tender diffuse goiter Transient, usually subsiding in 2-8 weeks Subacute granulomatous thyroiditis Thyrotoxic phase Day 10-20 Hypothyroidism phase Day 30-63 Euthyroidism Laboratory Elevated T4 and/or T3, RAIU that is low, High ESR/CRP FNA Widespread infiltration with neutrophils, lymphocytes, histiocytes and giant cells High dose aspirin 600 mg oral q 4-6 hours NSAIDs COX2 Severe pain : glucocorticoids (prednisolone 40-60 mg/day) Thyrotoxic phase : β-adrenagic blockers Hypothyroidism : Levothyroxine 50-100 µg/day May occur postpartum or spontaneous In postpartum syndrome, symptoms present 3-6 month after delivery Similar to subacute thyroiditis but painless Radioiodine uptake and thyroid scan : low uptake Primary Autoimmune hypothyroidism Iatrogenic Drugs: iodine excess, lithium, ATDs Congenital hypothyroidism Iodine deficiency Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis Transient Silent thyroiditis, including postpartum thyroiditis Subacute thyroiditis Secondary Hypopituitarism: tumors, pituitary surgery or radiation, infiltrative disorder, Sheehan’s syndrome, trauma Isolated TSH deficiency Hypothalamic disease History Asymptomatic Fatigue, lethergy Cold intolerance Puffiness Dry skin Hair loss Sleepiness Depression Constipation Obstructive sleep apnea Carpal tunnel syndrome Woman : Galactorrhea and menstrual disturbance Most common cause of hypothyroidism Autoimmune thyroid disease thyrocyte destruction Woman, 30-50 years May be asymptomatic Signs & symptoms slowly progress Thyroid gland : Goiter, Firm in consistency Puffy appearance Enlargement of tongue Loss of temporal aspect of eyebrows Queen Ann’s sign Dryness and coarseness of the skin Cardiovascular system Bradycardia Narrowing of pulse pressure Pericardial effusion Respiratory system Pleural effusion (rare) Obstructive sleep apnea Alveolar hypoventilation Alimentary Weight gain, loss appetite Constipation Ascites : associated with pleural & pericardial effusion CNS and PNS Loss of intellectual function Depression/ dementia Delayed muscle contraction and relaxation Myoclonus Carpal tunnel syndrome Laboratory TFT : FT3, FT4 TSH Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) Chronic thyroiditis : intrathyroidal lymphocytic infiltration Thyroid lymphoma should be suspected if there is rapid, usually painful, enlargement of the thyroid gland Half-life : 7 days About 80% of the hormone is absorbed relative slowly. Typical dose : 1.6-1.8 µg/kg IBW per day Complete equilibration of free T4 ~ 6 weeks Adverse effects: Bone loss, AF Monitoring Primary hypothyroidism : TSH Secondary hypothyroidism : free T4 Benign Nodules (95%) Carcinomas (5%) Hyperplastic nodules (85%) Papillary (81%) Adenomas (15%) Follicular and Hurthle cell (14%) Cysts (<1%) Medullary (3%) Anaplastic (2%) Historical features Young (<20 years) or Old (>60 years) Male Neck irradiation during childhood or adolescent Rapid growth Recent changes in speaking, breathing or swallowing Family history of thyroid malignancy or MEN2 Physical examination Firm and irregular consistency Fixation to overlying tissues Vocal cord paralysis Regional lymph adenopathy -Nodules >1 cm should be evaluated -Nodules <1 cm that require evaluation because of… Suspicious US findings Associated lymphadenopathy History of head and neck irradiation History of thyroid cancer in one or more first-degree relatives Rapid growth and hoarseness Pertinent physical findings suggesting possible malignancy Thyroid Volume 19 Number 11, 2009 Low TSH 123I History, physical, TSH Normal or high TSH Not functioning Diagnostic US or 99Tc scan Hyperfunctioning Evaluate and Tx for hyperthyroidism Nodule on US Do FNA Result of FNA No nodule on US Elevated TSH Evaluate and tx for hypothyroidism Normal TSH FNA not indicated Thyroid Volume 19 Number 11, 2009 Result of FNA Nondiagnostic Repeat US guided FNA Malignant PTC Pre-op US Nondiagnostic Surgery Close F/U or surgery Not hyperfunctioning Suspicious for PTC Hürthle cell neoplasm Interminate Benign Follicular neoplasm Follow Consider 123I scan if TSH low normal Hyperfunctioning Thyroid Volume 19 Number 11, 2009 Prevalence 12%, Female predominate Mostly asymptomic Large goiters, which may compress the trachea, esophagus and neck vessels Inspiratory stridor, dysphagia, choking sensation FNA Small and asymptomatic goiter can be monitored by clinical examination and evaluated periodically with U/S No significant benefit of thyroxine therapy Surgery : obstructive symptoms, large goiters, substernal goiter
