thyroid diseases DISEASES OF THE THYROID GLAND

DISEASES OF THE THYROID GLAND Wei Cai Thyroid Anatomy • Case 1 • History • A 55-year-old man presents with swelling of left anterior neck. • He has noted increased appetite over past month • no weight gain, • Sweeting • More frequent bowel movements over the same period. Physical Exam • • • • • • • BMI 21 Heart rate is 82 Blood pressure is 110/76. Ocular stare Lid lag. The thyroid gland is asymmetric to palpation. There is a 3 x 2.5 cm firm nodule in left lobe of the thyroid. Questions 1. What is his primary problem? • Write down your DDx 2. What laboratory tests would you order to evaluate this patient • Please write down the tests and give to your mate Probable Hyperthyroidism • The history of – increased appetite (without weight gain) – increased bowel motility • classic for hyperthyroidism. – The heart rate is mildly elevated, – The hyperthyroidism findings : ocular stare, lid lag, and an enlarged thyroid grand . Grave's disease ? • Supporting evidences: • The orbital symptoms – This associated with Grave's disease • Inflammation and swelling of retro-orbital tissues not from the elevation in thyroid hormone. Evidences against Grave’s disease • The thyroid is asymmetrical • Nodule, – whereas the thyroid gland in Grave's disease is symmetrically enlarged and homogeneous Something to think a bit more • What else can a nodule associated with the thyroid gland be ? • Parathyroid adenoma , What will you do? • Check the patient's calcium status. What else? • Elevation of alkaline phosphatase (due to active bone resorption). Laboratory Tests 1 • Thyroid stimulating hormone (TSH) – Where is it made from ? • Free T4 – In Australia, free T4 assay is not routinely available; – Free Thyroxine Index (FTI) which is proportional to free T4. This gives an indication of free thyroxine levels, being high in hyperthyroidism and low in hypothyroidism. The test lacks specificity. FTI • The free thyroxine index has generally been replaced by Thyroxine (free) in the assessment of thyroid function, but is occasionally useful when a free T4 result is suspected of being anomalous, which is the preferred initial test for assessment of thyroid status. The test results : • • • • • • • • Patient's value Reference range Calcium, total (S)2.6mmol /l 2.1-2.6 Phosphorus 1.6mmol/l 0.8-1.6 Alkaline phosphatase (S) 160 U/L 49 – 120 T4, Total (S) 12.2 ug/dl 5 - 11.5 T3, Total (S) 311 ng/dl 100 – 215 TSH (S) <0.1 uU/ml 0.7 -7.0 Free thyroxine index (FTI) 14.6 6 - 11.5 More Questions 1. How would you interpret these results? 2. What additional tests would you order? Hyperthyroidism most likely • Strongly suppressed TSH • Elevated FTI and T3 • Don’t forget The tests for parathyroid problems Further testing • Additional testing to prove Grave's disease • Imaging to determine the nature of the nodule associated with the thyroid. • Grave's disease is strongly associated with the presence of anti-thyroid microsomal antibodies, while other antibodies against thyroid epitopes (e.g., thyroglobulin) occur in Hashimoto's thyroiditis. • Furthermore, the thyroid hyper-function that occurs in Grave's disease can be assessed by: – directly by measuring the rate radio-iodine uptake into the thyroid gland. – Serum was obtained for anti-thyroid antibody testing More blood tests This Patient Antithyroglobulin Ab. neg. Normal neg Antimicrosomal Ab TSI pos. (1:1280) neg. Pos 1:120 neg thyroid scan thyroid scan • to evaluate the uptake of radioactive iodine into the thyroid gland showed increased radio-activities uptake. • The radio-iodine uptake was homogeneously increased over the entire gland except in the area of the palpable nodule, where uptake was decreased. (Cold nodular) Questions 1. How would you interpret these additional tests? 2. What would you wish to do next to finalize the diagnosis? Consistent with Grave's disease • The anti-thyroid antibody tests and radioiodine uptake results make a diagnosis of Grave's disease solid at this point. However, the finding that radio-iodine uptake is decreased in the area of the nodule suggests that there is an additional problem in the thyroid gland that is separate from Grave's disease. Diagnosis and course • The finding of cold nodular suggests that a thyroid neoplasm might be present. • fine needle aspirate (FNA) requested • The FNA : papillary carcinoma of the thyroid. • Final diagnosis – Grave's disease with papillary carcinoma Course • • • • Surgical thyroidectomy thyroid hormone replacement therapy. ablation with iodine-131. Iodine-131 scans remained negative over a twoyear course. Solitary Thyroid Nodule • History – Duration, recent enlargement, voice change, H/O hypo/hyperthyroidism, irradiation, F/H goitre/cancer • Physical examination – Dominant nodule, movement on deglutition, cervical lymph nodes, fixation, hardness • Thyroid function studies – – – – Serum TSH T4 & T3 levels Antibody levels; ATA, AMA 1:100 Thyroid imaging; Scanning (99mTc, 123I, 131I) Physical Examination • search for signs of abnormal thyroid function and the extrathyroidal features of ophthalmopathy and dermopathy (see below). • inspecting patient from the front and side, and noting any surgical scars, obvious masses, or distended veins. Physical exam • Palpation with both hands from behind • slightly flexed to relax the neck muscles. • locating the cricoid cartilage, the isthmus can be identified and followed laterally to locate either lobe. • Swallow sips of water, thyroid mobile • A bruit over the gland indicates increased vascularity,. Physical examination • Large retrosternal goitres can cause venous distension over the neck ( Pemberton's sign). • Assessment for lymphadenopathy in the supraclavicular and cervical regions of the neck. Imaging for Thyroid Nodule • CXR • Ultrasound – – – – Solid/cystic Multicentric Lymph node involvement Ultrasound-assisted FNA • CT/MRI of neck – Mainly for large/recurrent cancers – Vascular/lymphatic invasion – Cervical/mediastinal metastasis Solitary Thyroid Nodule • FNAC (Fine Needle Aspiration Cytology) – – – – Easy, safe, cost effective Negative predictive value False Negative rate False Positive rate 89%- 98% 6% 4% • FNAC Cytodiagnosis – Benign • Colloid adenoma, thyroiditis, cyst – Malignant • Papillary (70%), follicular (15%), medullary (5%-10%), anaplastic(3%), lymphoma (3%), metastasis (rare) – Indeterminate • Microfollicular, Hurthle cell, embryonal neoplasm Radioiodine Uptake and Thyroid Scanning • 123I, 125I, 131I) and 99mTc pertechnetate, • Nuclear imaging of Graves' disease is characterized by an enlarged gland and increased tracer uptake that is distributed homogeneously. • Toxic adenomas appear as focal areas of increased uptake. • In toxic multinodular goiter, the gland is enlarged—often with distorted architecture—and there are multiple areas of relatively increased or decreased tracer uptake. Nuclear Scan • Subacute thyroiditis is associated with very low uptake because of follicular cell damage and TSH suppression. Thyrotoxicosis factitia is also associated with low uptake. • So-called cold nodules, can be malignant (5 to 10%) • hot nodules, are almost never malignant Thyroid Ultrasound • Using 10-MHz instruments, – Good spatial resolution – detection of nodules and cysts >3 mm. • ultrasound is useful for monitoring nodule size, for guiding FNA biopsies, and for the aspiration of cystic lesions. • Ultrasound is also used in the evaluation of recurrent thyroid cancer, including possible spread to cervical lymph nodes. Hypothyroidism • Iodine deficiency remains the most common cause of hypothyroidism worldwide. • In Australia, autoimmune disease (Hashimoto's thyroiditis) • Iatrogenic causes (treatment of hyperthyroidism) Symptoms of Hypothyroidism (Descending Order of Frequency) • • • • • • • • Symptoms Tiredness, weakness, Dry skin Feeling cold, Hair loss Difficulty concentrating and poor memory, Constipation Weight gain with poor appetite Dyspnea, Hoarse voice Menorrhagia (later oligomenorrhea or amenorrhea), Paresthesia Impaired hearing Signs • Dry coarse skin; cool peripheral extremities • Puffy face, hands, and feet (myxedema) • Diffuse alopecia • Bradycardia • Peripheral oedema • Delayed tendon reflex relaxation • Carpal tunnel syndrome • Serous cavity effusions Autoimmune Hypothyroidism • Autoimmune hypothyroidism may be associated with a goiter (Hashimoto's, or goitrous thyroiditis) • some patients may have minor symptoms, this state is called subclinical hypothyroidism with low TSH and normal T4 Laboratory Evaluation Autoimmune thyroid disease (AITD) • Three principal thyroid autoantigens are involved in AITD. – thyroperoxidase (TPO),…….TPOAb – thyroglobulin (Tg).. The pathologic role of TgAb remains unclear – TSH receptor……TSH receptor autoantibodies (TRAb), either mimic TSH…Hyperthyroid Graves, or action of TSH and cause hypothyroidism Evaluation of hypothyroidism. • TPOAb+, thyroid peroxidase antibodies present; TPOAb–, thyroid peroxidase antibodies not present. TSH, thyroidstimulating hormone. Differential Diagnosis • An asymmetric goiter in Hashimoto's thyroiditis may be confused with – a multinodular goiter – thyroid carcinoma, in which thyroid antibodies may also be present. • Ultrasound can be used to show the presence of a solitary lesion or a multinodular goiter, rather than the heterogeneous thyroid enlargement typical of Hashimoto's thyroiditis. • FNA biopsy Treatment • T4 dose of 1.6mcg/kg per day (100150mcg) • requirements are relatively great during the first year of life, • high circulating T4 level is usually needed to normalize TSH. • Early treatment with T4 results in normal IQ levels, but subtle neurodevelopmental abnormalities may occur in those with the most severe hypothyroidism . Treatment of Myxoedema coma • high mortality rate. – – – – unconsciousness, seizures. Hypothermia Hypothyroidism signs and symptoms. Treatment of Myxedema coma • MCQs – – – – – – Hydrocortisone T4 intravenously T3 small dose intravenously High dose T3 to reverse coma quickly Levothyroxine 500mcg iv T3 not recommended in pregnancy because of preferential use of T4 by the developing brain. – monitor TSH and T4 levels every 6–8 weeks and adjust thyroxine dosage to achieve required Treatment of myxoedema • Levothyroxine : bolus loading dose 500 g, iv or NGT – continued at a dose of 50 to 100 g/d. • Or liothyronine (T3) intravenously or via nasogastric tube, – 10 to 25 g every 8 to 12 h. because T4 /T3 conversion is impaired in myxedema coma. – excess liothyroxine has the potential to provoke arrhythmias. Hydrocortisone in Myxeoedema coma • hydrocortisone (50 mg every 6 h) should be administered, as there is impaired adrenal reserve in profound hypothyroidism. • Prevent hypothermias Thyrotoxicosis • Questions: – Thyrotoxicosis is the synonymous Hyperthyroidism ?????? No according to Harrison • Thyrotoxicosis is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, • Hyperthyroidism is the result of excessive thyroid function. Causes of Thyrotoxicosis Primary hyperthyroidism Graves' disease Toxic multinodular goitre Toxic adenoma Functioning thyroid carcinoma metastases • Activating mutation of the TSH receptor • Activating mutation of Gs (McCune-Albright syndrome) • • • • • Thyrotoxicosis without hyperthyroidism • Silent thyroiditis • Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma • Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue • Secondary hyperthyroidism • TSH-secreting pituitary adenoma • Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis • Gestational thyrotoxicosisa Graves' Disease • Graves' disease accounts for 60 to 80% of thyrotoxicosis • The hyperthyroidism of Graves' disease is caused by TSI that are synthesized in the thyroid gland as well as in bone marrow and lymph nodes. Grave’s Clinical Manifestations • Symptoms (Descending Order of Frequency) • Hyperactivity, irritability, dysphoria • Heat intolerance and sweating • Palpitations • Fatigue and weakness • Weight loss with increased appetite • Diarrhoea • Symptoms of Thyrotoxicosis • • • • • • • • • Polyuria Oligomenorrhea, loss of libido Signsa Tachycardia; atrial fibrillation in the elderly Tremor Goiter Warm, moist skin Muscle weakness, proximal myopathy Lid retraction or lag Symptoms of Thyrotoxicosis • • • • • • Gynecomastia The skin is usually warm and moist. Palmar erythema; onycholysis; pruritus, alopecia occurs in up to 40% of patients. Grave’s Lab Evaluation • TSH suppressed • unbound thyroid hormone increased. • In 2 to 5% of patients , only T3 is increased (T3 toxicosis). • T4 toxicosis, with elevated total and unbound T4 and normal T3 levels, is seen when hyperthyroidism is induced by excess iodine, • Measurement of TPO antibodies is useful in differential diagnosis. • Measurement of TBII or TSI will confirm the diagnosis but is not needed routinely. A BIT MORE • There are 3 types of autoantibodies to the TSH receptor currently recognized: – TSI, Thyroid stimulating immunoglobulins: – TGI, Thyroid growth immunoglobulins: these antibodies bind directly to the TSH receptor :growth of thyroid follicles. – TBII, Thyrotrophin Binding-Inhibiting Inmunoglobulins: these antibodies inhibit the normal union of TSH with its receptor. And actually act as if TSH itself Evaluation of thyrotoxicosis. • Evaluation of thyrotoxicosis. aDiffuse goiter, positive TPO antibodies, ophthalmopathy, dermopathy; can be confirmed by radionuclide scan. TSH, thyroid-stimulating hormone. Grave’s disease Treatment Reducing thyroid hormone synthesis, • antithyroid drugs, • Reducing the amount of thyroid tissue with radioiodine (131I) treatment • Subtotal thyroidectomy. Drugs • . Propylthiouracil(PTU) block T4…..>T3. Conversion. – shorter half-life of this drug (90 min) – Cost • carbimazole • Thyroid function tests and clinical manifestations are reviewed 3 to 4 weeks after starting treatment, Thyrotoxic crisis • Thyrotoxic crisis, also named as thyroid storm ? MCQs except: 1. 2. 3. 4. 5. fever, delirium, seizures, coma, vomiting, diarrhoea, and jaundice. The mortality rate due to cardiac failure The mortality rate due to arrhythmia, or hyperthermia Drugs Side effects • • • • • Rash, urticaria, fever, arthralgia (1 to 5% of patients). Rare but major side effects include hepatitis, an SLE-like syndrome, and, most importantly • most importantly, agranulocytosis (<1%). Beta blocker • Propranolol (20 to 40 mg every 6 h) or longer acting beta blockers, such as atenolol, may be helpful to control adrenergic symptoms, especially in the early stages before antithyroid drugs take effect. The need for anticoagulation with warfarin should be considered in all patients with atrial fibrillation. If digoxin is used, increased doses are often needed in the thyrotoxic state Radioiodine • 1. 2. 3. MCQs except: causes progressive destruction of thyroid cells can be used as initial treatment Can be used as relapses after a trial of antithyroid drugs 4. Radioactive treatment induced thyrotoxic criseis can be minimized by pretreatment with antithyroid drugs for at least a month before treatment 5. Patient can conceive safely 5 months after treatment END • End • End Thyroid Cancer • Incidence 1% • M/F ratio 3:1 • Risk factors – Radiation exposure – External • Medical treatment for benign conditions • Medical treatment for malignancies • Environmental exposure- Nuclear weapons or accidents – Internal • Medical treatment of benign condition with I131 • Diagnostic tests with I131 • Environmental- fallout from nuclear weapons – Other factors • • • • Diet- Iodine deficiency, goitrogens Hormonal factors- female gender predominance Benign thyroid disease Alcohol Thyroid Cancer • Pathology • Papillary carcinoma; – – – – – 60-70% of all cases Multifocal Nonencapsulated, but circumscribed Lymphatic spread 80% 10 year survival • Follicular carcinoma – 15-20% of thyroid cancers – Usually encapsulated – 60% 10 year survival Thyroid Cancer • Hurthle cell neoplasm – – – – – – – – – – 5% of thyroid cancers Variant of follicular cancer Lymph node spread slightly higher than follicular cancer Lees avidity for 131I Parafollicular C cells Autosomal dominance inheritance in 20% Unilateral involvement in sporadic, bilaterality in familial forms Calcitonin secretion Metastasis both by lymphatic and blood stream 10 year survival 90% in localised disease, 70% with cervical mets, 20% with distant mets • Medullary cancer Thyroid cancer • Anaplastic cancer – – – – – – – – – Undifferentiated Rapidly growing, often inoperable Invade locally, metastasize both locally and distantly Mean survival 6 months 5 year survival rate 7% Rare, rapidly enlarging tumour Primary or secondary Seventh decade, 6:1 F/M ratio 5 year survival rate 75-80%, when confined to thyroid • Lymphoma Thyroid cancer • Staging and Prognosis • AGES and AMES scoring systems – – – – – A G M E S Age of patient Tumour Grade Distant metastasis Extent of tumour Size of tumour • Both scoring systems have identified 2 distinct subgroups; – Low-risk group; Men 40years or younger, women 50 or younger, without distant metastasis (bone & lungs) – Older patients with intrathyroid follicullar/papillary carcinoma, with minor capsular involvement with tumours < 5cms in diameter – High –risk group; All patients with distant metastasis – All older patients with extrathyroid papillary/follicular carcinoma & tumours >5 cms regardless of extent of disease Thyroid cancer • Treatment of thyroid cancer • Papillary cancer – < 1.5 cms – > 1.5 cms Lobectomy & isthmusectomy Total thyroidectomy • Follicular cancer • • Hurthle Medullary Total thyroidectomy Total thyroidectomy Total thyroidectomy & central neck dissection Thyroid cancer • Adjuvant therapy – TSH suppression – Post operative radioactive Iodine ablation – External beam radiotherapy • Surveillance – Serum thyroglobulin levels – CXR or CT scan – Repeat 131I if positive Parathyroid Disorders • Hyperparathyroidism – Primary; most commonly PARATHYROID ADENOMA 80%-85% – Primary chief-cell hyperplasia – Parathyroid carcinoma 1% • Signs and Symptoms – – – – – Nonspecific and involve multiple organs Skeletal system; Osteitis fibrosa cystica, osteoclastomas, etc Kidneys; Kidney stones, nephrocalcinosis. Gastrointestinal tract; Vague abdominal pain, PUD, pancreatitis Neuromuscular & neuropsychiatric; muscle weakness, fatigue, lassitude, forgetfulness, depression, psychomotor retardation – Thyroid cancer esp nonmedullary thyroid cancer – Hypertension, hyperuricemia, gout, Idiopathic hypertrophic subaortic stenosis, band keratopathy Parathyroid Disorders • Diagnostic Methods – Blood chemistry; Hypercalcemia, hypophosphatemia, hyperchloremia, raised alkaline phosphatase. – Urinalysis; hypercalciuria,. • Ultrasonography – Wide discrepancy, sensitivity (36%- 76%) – Inferior, juxtathyroidal or intrathyroidal glands better visualised – Substernal, retrotracheal, retroesophageal glands difficult to visualise • Nuclear Medicine (Sestamibi scan) – Wash out scan – Taken up by mitochondria – Both false positive and false negative results • CT and MRI • Angiography & venous sampling • Intraoperative localisation