Thyroid Gland Hypothyroidism & Hyperthyroidism Dr. Zahoor

Thyroid Gland The metabolism of Virtually all nucleated cells of many tissues in the body is controlled by thyroid hormone Over activity (Hyperthyroidism) and under activity (Hypothyroidism) of the gland are most common of all endocrine problems

Thyroid Gland Anatomy: It has two lateral lobes connected by Isthmus It moves on swallowing as it is attached to thyroid cartilage and trachea Embryologically it originates from the base of the tongue and then descends therefore sometimes remnants of thyroid can be found at the base of tongue (Lingual thyroid)

Thyroid Gland Anatomy: Thyroid gland has follicles lined by cuboidal epithelial cells. Inside the follicle is colloid (Iodinated glycoprotein Thyroglobulin) which is synthesized by follicular cells. Each follicle is surrounded by basement membrane, between follicular cells there are parafollicular cells containing calcitonin secreting C cells

Follicular & parafollicular cells

Thyroid Gland Physiology: Thyroid gland synthesizes two hormones T3 – Triiodothyronin: acts at Cellular level T4 - L – Thyroxin: which is prehormone More T4 is produced than T3 in thyroid but T4 is converted to T3 in periphery

Thyroid Gland Physiology: In Plasma more than 99% of T4 and T3 is bound to protein (Thyroxin Binding Globulin TBG, Thyroid Binding PreAlbumin TBPA) and Albumin

Thyroid Gland Physiology: Control of hypothalamic–pituitary–thyroid axis: Hypothalamus produces TRH – Thyrotropin releasing hormone, it stimulates pituitary to secrete TSH – Thyroid Stimulating Hormone. TSH stimulates activity of Thyroid Follicular cells T3 & T4 are secreted in circulation by follicular cells T3 & T4 has negative feedback effect on Hypothalamus and pituitary

Physiological Effect of Thyroid Hormone

Primary Hypothyroidism Thyroid Gland Thyroid Function Test: Free T4 Free T3 and TSH are available and test can be done at anytime of the day Free T3 ↑ Free T4 ↑ ↓ TSH Thyrotoxicosis 1 T3 N or Low Free T4 ↓ Or Low Normal TSH ↑ Primary Hypothyroidism 2 Free T4 ↓ or Low Normal TSH Deficiency (Pituitary) 3

HYPOTHYROIDSM

Hypothyroidism It is usually primary due to disease of thyroid, but may be secondary to hypothalamic – pituitary disease (decreased TSH drive) It is more common in females

Hypothyroidism Autoimmune Hypothyroidism It is most common cause and associated with antithyroid antibodies It is six time more common in females It has association with other autoimmune diseases e.g. pernicious anemia, Vitiligo etc.

Hypothyroidism Hashimotos Thyroiditis This is a form of autoimmune thyroiditis, more common in females and occurs in late middle age Causes atrophic changes and regeneration leading to goiter formation TPO ( Thyroid per oxidase) antibodies are present in high titer (> 1000 IU/L) Patient may be hypothyroid or Euthyroid, though they may go through initial toxic phase Levothyroxin is given when patient is hypothyroid

Hypothyroidism Post Partum Thyroiditis This is transient phenomena, observed after pregnancy It may cause Hyperthyroidism, Hypothyroidism It is due to result of modifications to the immune system in pregnancy It is usually self limiting or leads to hypothyroidism

Defects of Thyroid Hormone Synthesis Iodine Deficiency Iodine is required for synthesis of T3 & T4 We take iodine in diet, if deficient than people get goiter ( due to TSH stimulation) Patient may be euthyroid or hypothyroid Iodine deficiency is problem in many countries e.g. Netherlands, India, Asia, Africa, Russia Efforts are made to prevent iodine deficiency by adding iodine in common salt.

Defects of Thyroid Hormone Synthesis Dyshormonogenesis Rare condition, due to genetic defect in the synthesis of thyroid hormone Patient develops hypothyroidism with goiter Note—Some people have Genetic defect causing sensorineural deafness due to mutation at chromosome 7, they have goiter( hypothyroid) also and this condition is called Pendred Syndrome

Hypothyroidism Symptoms and Signs *Bold type indicate important symptoms and signs

Hypothyroidism

Hypothyroidism Myxoedema: It refers to Hypothyroidism plus accumulation of mucopolysaccharide in subcutaneous tissue Patient is slow, thick skin, dry hair, deep voice, weight gain, cold intolerance, bradycardia, constipation

Hypothyroidism Children with Hypothyroidism: Have slow growth velocity Have poor school performance Young Females with Hypothyroidism Hypothyroidism should be excluded in all women with Oligomenorrhoea, amenorrhoea, menorrhagia, infertility, Hyperprolactinimia

Hypothyroidism Investigations: Serum Free T3, Free T4 and TSH High TSH confirms primary Hypothyroidism, free T4 is low Other investigations: Anemia – usually normocytic normochromic But may be Macrocytic (due to associated Pernicious anemia ) Microcytic – in women due to menorrhagia

Increase serum creatinine Kinase – with associated Myopathy Hypothyroidism Other Investigations: Increase serum creatinine Kinase – with associated Myopathy Hypercholesterolemia and hypertriglyceridaemia Hyponatremia – due to increase ADH

Hypothyroidism Treatment: Thyroxin – T4 is given for life Dose 100 Micrgram daily for young patients 50 microgram for small, old patient to be increased to 100 microgram after 2 – 4 days If patient has IHD start with 25 Microgram daily and increase dose at 3 – 4 week interval ( monitor by serial ECG) Aim of treatment is to restore T4 & TSH within normal range Improvement on T4 takes 2 weeks or more and resolution of symptoms takes about 6 months

Hypothyroidism Treatment for Myxoedema: It is severe hypothyroidism and patient may present with confusion or even COMA Myxoedema Coma is very rare, hypothermia is often present and patient may have severe cardiac failure, pericardial effusion, hypoventilation, hypoglycemia, hyponatremia Mortality is high

Hypothyroidism Treatment for Myxoedema: T3 orally or IV 2.5-5 microgram 8 hourly O2 Hydrocortisone 100 mg IV 8 Hourly Glucose infusion Gradual rewarming

HYPERTHYROIDISM

Hyperthyroidism Hyperthyroidism (Thyrotoxicosis) is common, affecting 2-5% of all females Female-Male ratio 5:1 Age 20-40 years More than 99% cases are caused by intrinsic thyroid disease, pituitary cause is extremely rare

Graves Disease This is most common cause of hyperthyroidism and is due to autoimmune process IgG antibodies bind to TSH receptors in the thyroid and stimulate thyroid hormone production (IgG behaves like TSH) TSH receptor antibodies (TSHR – Ab antibodies) are specific for Graves Disease Graves Disease is associated with autoimmune disorders such as pernicious anemia, Vitiligo and myasthenia gravis

Other Causes of Hyperthyroidism/Thyrotoxicosis Solitary toxic adenoma/nodule It is cause of 5% cases of hyperthyroidism usually remit after antithyroid drugs Toxic multinodular goitre Commonly occurs in older woman Anti thyroid drugs control hyperthyroidism

Other Causes of Hyperthyroidism/Thyrotoxicosis De Quervain’s thyroditis This is transient hyperthyroidism due to inflammatory process, probably viral in origin There is fever, maliase, pain in the neck, tachycardia and local thyroid tenderness Thyroid function test show - Hyperthyroidism - Increased ESR

Other Causes of Hyperthyroidism/Thyrotoxicosis De Quervain’s thyroditis Thyroid function test show (cont) - Thyroid uptake show suppression of uptake in acute phase - Hypothyroidism, usually transient, may follow after few weeks Treatment of acute phase - Aspirin - Predinisolone

Other Causes of Hyperthyroidism/Thyrotoxicosis Amiodarone – induced thyrotoxicosis (AIT) Amiodarone is anti arrhythmic drug – class 111 and causes hyperthyroidism

Symptoms and Signs of Hyperthyroidism *Bold type indicate important symptoms and signs

Clinical Features of Hyperthyroidism The eye signs of lid lag and stare May occur with hyperthyroidism of any cause Graves dermopathy Pretibial myxoedema – is in filtration of the skin on the shin Thyroid Acropachy – very rare and consist of clubbing, swollen fingers and periosteal new bone formation

Clinical Features of Hyperthyroidism (cont) Atrial Fibrillation in the elderly Is frequent presentation Children with hyperthyroidism May present – excessive height, hyperactivity

Pretibial myxoedema

Differential Diagnosis Anxiety (Sympathetic Stimulation) There is tachycardia, tremor, but cold clammy hand In hyperthyroidism, there is tachycardia tremor, warm hands, eye signs, diffused goitre, weight loss despite increase appetide

Hyperthyroidism Investigations Serum TSH is suppressed, free T4 or T3 are raised Thyroid per oxidase (TPO) and thyroglobulin antibodies are present in most cases of Graves disease Thyroid stimulating immunoglobulin (TSI) are present in Graves disease

Hyperthyroidism Treatment Three options are available 1. Anti thyroid drugs 2. Radio active iodine 3. Surgery Carbimazole – 20-40mg/day 8 hourly or single dose Propylthioracial (PTU) – 100-200mg 8 hourly They inhibit the formation of thyroid hormones Propranolol (Beta Blocker) is used for symptomatic relief

Hyperthyroidism Treatment Side effects of drugs Carbimazole – rash, nausea, vomiting, arthralgia, agranulocytosis, jaundice PTU – rash, nausea, vomiting, agranulocytosis NOTE – As agranulocytosis is the side effect, therefore, patient is advised if he has sore throat, he should report to hospital for investigation

Hyperthyroidism Treatment (cont) 2. Radioactive Iodine – 131Iodine Can be given to all patients Is contraindicated in pregnancy and during breast feeding 3. Surgery Subtotal thyroidectomy/thyroidectamy Side effects – laryngeal nerve palsy occur in 1% Transient hypocalcemia up to 10% Permanent hypoparathyroidism < 1%

Hyperthyroidism in Pregnancy During pregnancy Propylthioracial (PTU) is preferred because there are reports of congenital abnormalities with Carbimazole TSI – thyroid stimulating immunoglobulin cross the placenta and stimulate fetal thyroid Carbimazole and PTU cross the placenta T4 (Thyroxin) very poorly crosses the placenta If necessary surgery can be performed in second semester of the pregnancy

Thank you