THYROID DISEASES

PRESENTING PROBLEMS IN THYROID DISEASE Hypothroidism Thyrotoxicosis Goitre Malignancy and other tumors Autoimmune disease Sick euthyroid syndrome

Clinical syndromes TSH T4 T3 Disease Undetectable Raised Raised Primary thyrotoxicosis Undetectable Normal Raised Primary T3-toxicosis Undetectable Normal Normal Subclinical thyrotoxicosis Undetectable Raised L, N, H Sick euthyroidism/non-thyroidal illness Undetectable Low Low Secondary hypoth,Transient thyroiditis Normal Low Low Secondary hypothyroidism elevated 5-20 Low Low Primary or Secondary hypothyroidism Elevated > 20 Low Low Primary hypothyroidism elevated 5-20 Normal Normal Subclinical hypothyroidism Elevated 20-500 Normal Normal Artefact Elevated High High Non-compliance R,Secondary thyrotoxicosis

Thyrotoxicosis Etiology Multinodular goitre Autonomously functioning solitary thyroid nodule Thyroiditis Subacute (de Quervain's) Post-partum Iodide-induced Drugs (e.g. amiodarone) Radiographic contrast media Iodine prophylaxis programme Extrathyroidal source of thyroid hormone Factitious hyperthyroidism Struma ovarii TSH-induced TSH-secreting pituitary adenoma Choriocarcinoma and hydatidiform mole Follicular carcinoma ± metastases

Graves Disease Autoimmune disorder Abs directed against TSH receptor with intrinsic activity. Thyroid and fibroblasts Responsible for 60-80% of Thyrotoxicosis More common in women

Clinical features weight loss with a normal or increased appetite heat intolerance palpitations, tremor and irritability Tachycardia, AF palmar erythema lid lag. lid retraction palpable goitre, but experienced clinicians can discriminate the diffuse soft goitre of Graves' disease from the irregular enlargement of a multinodular goitre. Graves' disease causes other features of ophthalmopathy, including periorbital oedema, conjunctival irritation, exophthalmos and diplopia. Pretibial myxoedema

Graves Disease Other Manifestations Pretibial mixoedema Thyroid acropachy Onycholysis Thyroid enlargement with a bruit frequently audible over the thyroid

Graves Disease Eye Signs N - no signs or symptoms O – only signs (lid retraction or lag) no symptoms S – soft tissue involvement (peri-orbital oedema) P – proptosis (>22 mm)(Hertl’s test) E – extra ocular muscle involvement (diplopia) C – corneal involvement (keratitis) S – sight loss (compression of the optic nerve)

Diagnosis of Graves Disease TSH , free T4  Thyroid auto antibodies Nuclear thyroid scintigraphy (I123, Te99)

Management Antithyroid drugs are introduced at high doses, e.g. carbimazole 40-60 mg daily or prophylthiouracil 400-600 mg daily. There is subjective improvement within 10-14 days and the patient is usually clinically and biochemically euthyroid at 3-4 weeks, when the dose can be reduced. The maintenance dose is determined by measurement of T4 and TSH(1-2y). Subtotal thyroidectomy Patients must be rendered euthyroid with antithyroid drugs before operation. Potassium iodide, 60 mg 8-hourly orally, is often added for 2 weeks before surgery to inhibit thyroid hormone release and reduce the size and vascularity Radioactive iodine 131I is administered orally as a single dose and is trapped and organified in the thyroid B-blockers to control symptoms, steroid for ophthalmopathy

Hypothyroidism Clinical features depend on the duration and severity of hypothyroidism. infiltration of many body tissues by the mucopolysaccharides, hyaluronic acid and chondroitin sulphate low-pitched voice and poor hearing slurred speech due to a large tongue carpal tunnel syndrome non-pitting oedema (i.e. myxoedema) periorbital puffiness is often striking and facial pallor due to vasoconstriction and anaemia lemon-yellow tint to the skin due to carotenaemia, purplish lips and malar flush bradycardia., cold intolerance.

Hypothyroidism etiology Primary HASHIMOTO'S thyroiditis posess positive thyroid peroxidase autoantibodies and a firm goitre who may or may not be hypothyroid 'spontaneous atrophic hypothyroidism' for hypothyroid patients without a goitre in whom TSH receptor-blocking antibodies may be more important than antiperoxidase antibodies. Post-thyroid abalation Iodin and other drugs Radiation Secondary hypothyroidism Hormone resistance

Transient Hypothyroidism during the first 6 months after subtotal thyroidectomy 131I treatment of Graves' disease post-thyrotoxic phase of subacute thyroiditis post-partum thyroiditis.

Lab Investigations of Hypothyroidism TSH , free T4  Ultrasound of thyroid – little value Thyroid scintigraphy – little value Anti thyroid antibodies – anti-TPO S-CK , s-Chol , s-Trigliseride  Normochromic or macrocytic anemia ECG: Bradycardia with small QRS complexes

Treatment of Hypothyroidism Levothyroxine If no residual thyroid function 1.5 μg/kg/day Patients under age 60, without cardiac disease can be started on 50 – 100 μg/day. Dose adjusted according to TSH levels In elderly especially those with CAD the starting dose should be much less (12.5 – 25 μg/day)

SUBACUTE (DE QUERVAIN'S) THYROIDITIS patients are usually females aged 20-40 years In its classical painful form, subacute thyroiditis is a virus-induced (e.g. Coxsackie, mumps or adenovirus) transient inflammation of the thyroid gland. pain may radiate to the angle of the jaw and the ears, and is made worse by swallowing, coughing and movement of the neck inflammation in the thyroid gland 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. a period of hypothyroidism of variable severity before the follicular cells recover and normal thyroid function is restored within 4-6 months Low-titre thyroid autoantibodies appear transiently in the serum, and the erythrocyte sedimentation rate (ESR) is usually raised NSAID ,prednisolone 40 mg daily for 3-4 weeks

Acute Thyroiditis Bacterial – Staph, Strep Fungal – Aspergillus, Candida, Histoplasma, Pneumocystis Radiation thyroiditis Amiodarone (acute/ sub acute) Painful thyroid, ESR usually elevated, thyroid function normal

Chronic Thyroiditis Hashimoto’s Autoimmune Initially goiter later very little thyroid tissue Rarely associated with pain Insidious onset and progression Most common cause of hypothyroidism TPO abs present (90 – 95%)

Thyroiditis The most common form of thyroiditis is Hashimoto thyroiditis, this is also the most common cause of long term hypothyroidism The outcome of all other types of thyroiditis is good with eventual return to normal thyroid function

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)

Solitary 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 Result Benign Observe and repeat FNAC 1 year Malignant Surgery Indeterminate serum TSH normal Surgery Serum TSH low Scintiscan Inadequate Repeat FNA

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; Follicular 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 Medullary cancer 5% of thyroid cancers Variant of follicular cancer Lymph node spread slightly higher than follicular cancer Lees avidity for 131I Medullary cancer 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

Thyroid cancer Anaplastic cancer Lymphoma Undifferentiated Rapidly growing, often inoperable Invade locally, metastasize both locally and distantly Mean survival 6 months 5 year survival rate 7% Lymphoma Rare, rapidly enlarging tumour Primary or secondary Seventh decade, 6:1 F/M ratio 5 year survival rate 75-80%, when confined to thyroid

Thyroid cancer Treatment of thyroid cancer Papillary cancer < 1.5 cms Lobectomy & isthmusectomy > 1.5 cms Total thyroidectomy Follicular cancer Total thyroidectomy Hurthle Total thyroidectomy Medullary Total thyroidectomy & central neck dissection

Thyroid cancer Adjuvant therapy Surveillance TSH suppression Post operative radioactive Iodine ablation External beam radiotherapy Surveillance Serum thyroglobulin levels CXR or CT scan Repeat 131I if positive