Guided By:

Dr. Sahila

Dr. R.K.Garyali

&

Submitted By: Nandita Sharma , Needhika Chibber, Nitasha Choudhary, Palak Gupta, Payal Gupta

THYROID GLAND

THYROID GLAND
INTRODUCTION:
found in the neck, inferior to (below) the thyroid cartilage (also known as the 'Adam's Apple') at approximately the same level as the cricoid cartilage. The thyroid gland produces thyroid hormones, principally triiodothyronine (T3) and thyroxine (T4). These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. T3 and T4 are synthesized utilizing both iodine as well as tyrosine. The thyroid gland also produces a hormone called 'calcitonin', which plays a role in calcium homeostasis. The thyroid gland is controlled by the hypothalamus and pituitary The most common problems of the thyroid gland consist of an over-active thyroid gland, referred to as 'hyperthyroidism', and an under-active thyroid gland, referred to as 'hypothyroidism'. The thyroid is one of the larger endocrine glands, weighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy.

ANATOMY:
The thyroid gland is a butterfly-shape organ and is composed of two conelike lobes or wings, lobus dexter (right lobe) and lobus sinister (left lobe), connected via the isthmus. The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath. It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence, or 'Adam's Apple'), and extends inferiorly to approximately the fifth or sixth tracheal ring. The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea, composed of an internal and external layer. The external layer is anteriorly continuous with the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the carotid sheath. The gland is covered anteriorly with infrahyoid muscles and laterally with the sternocleidomastoid muscle. On the posterior side, the gland is fixed to the cricoid and tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia to form the posterior suspensory ligament of Berry. Between the two layers of the capsule and on the posterior side of the lobes there are on each side two parathyroid glands.

ARTERIAL SUPPLY:
superior thyroid artery, a branch of the external carotid artery, inferior thyroid artery, a branch of the thyrocervical trunk, And sometimes by the thyroid ima artery, branching directly from the brachiocephalic trunk.

VENOUS SUPPLY:

superior thyroid veins, draining in the internal jugular vein, inferior thyroid veins, draining via the plexus thyroideus impar in the left brachiocephalic vein.

LYMPHATICS:

lateral deep cervical lymph nodes pre- and parathacheal lymph nodes.

NERVE SUPPLY:

The gland is supplied by parasympathetic nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve.

BLOOD SUPPLY OF THYROID GLAND

Embryological development:
In the fetus, at 34 weeks of gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar and the copula linguae at a point latter indicated by the foramen cecum. The thyroid then descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct.

DEVELOPMENT OF THYROID GLAND

At the microscopic level, there are three primary features of the thyroid: Follicles: The thyroid is composed of spherical follicles that selectively absorb iodine (as iodide ions, I-) from the blood for production of thyroid hormones. Twenty-five percent of all the body's iodide ions are in the thyroid gland. Inside the follicles, colloid serve as a reservoir of materials for thyroid hormone production and, to a lesser extent, act as a reservoir for the hormones themselves. Colloid is rich in a protein called thyroglobulin. Thyroid epithelial cells: (or "follicular cells") The follicles are surrounded by a single layer of thyroid epithelial cells, which secrete T3 and T4. When the gland is not secreting T3/T4 (inactive), the epithelial cells range from low columnar to cuboidal cells. When active, the epithelial cells become tall columnar cells. Parafollicular cells: (or "C cells") Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells, which secrete calcitonin.

Histology:

HISTOLOGY OF THYROID GLAND

Physiology :

The primary function of the thyroid is production of the hormones triiodothyronine (T3), thyroxine (T4), and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is several times more powerful than T4, which is largely a prohormone, The system of the thyroid hormones T3 and T4. Thyroxine (T4) is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (Tg). Iodine is captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO) and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on Tg, and on free tyrosine. RAPPING OF IODIDE Upon stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb Tg and cleave the iodinated tyrosines from Tg in lysosomes, forming T4 and T3 (in T3, one iodine atom is absent compared to T4), and releasing them into the blood. OXIDATION OF IODIDE Deiodinase enzymes convert T4 to T3.[14] Thyroid hormones that are secreted from the gland is about 80-90% T4 and about 10-20% T3.[11][10] Cells of the brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development.[15] A transport protein that seems to be important for T4 transport across the blood-brain barrier (OATP1C1) has been identified.[16] A second transport protein (MCT8) is important for T3 transport across brain cell membranes

PLASMA IODIDE

TRAPPING OF IODINE

OXIDATION OF IODIDE

IODINATION OF TYROSINE IN THYROID GLAND TO FORM MIT AND DIT

COUPLING TO FORM T4,T3

STORAGE IN THYROID GLAND

RELEASE OF T4,T3 IN BLOOD

PERIPHERAL CONVERSION OF T4 TO T3

DEIODINATION

CLINICAL EXAMINATION OF THYROID SWELLING:

COMPLAINTS:
1. 2. 3. 4. 5. 6. 7. Swelling Rate of growth Dyspnoea Dysphagia Hoarseness of voice indicates malignancy Toxic features suggestive of hyperthyroidism Symptoms of hypothyroidism : poor appetite, abnormal deposition of fats in the supraclavicular region, intolerance to cold, failing memory, deep hoarse voice. lethargy etc, 8. Sudden pain, thyroid swelling and fever

PAST HISTORY FAMILY HISTORY

ON EXAMINATION:
INSPECTION:
1. 2. 3. 4. 5. Location or the swelling Size and shape Surface : can be of: Smooth Irregular Nodular Borders : usually round Swelling moves up with deglutition

PALPATION:
It should be done from behind. 1. Size, shape and border should be confirmed. 2. Consistency Soft Firm Hard 3. Confirm the movement with deglutition by holding the thyroid gland.

PERCUSSION:
Percussion over the sternum gives a resonant note in normal cases, in retrosternal goitres, it gives a dull note.

AUSCULTATION:
Should be done in the upper pole because : superior thyroid artery is a direct branch of external carotid artery and it is more superficial than thyroid artery Presence of thrill and bruit are the features of toxic goitre.

SYSTEMIC EXAMINATION: Includes:

CNS and eye signs Skeletal system examination to rule out metastasis CVS examination

DIAGNOSIS:

Following anatomical features should be noted: thyroid gland is in front of the neck deep to pretracheal fascia moves up with deglutition Butterfly-shaped when whole gland is enlarged

Hyperthyroidism

refers to over activity of the thyroid gland leading to excessive synthesis of thyroid hormones and accelerated metabolism in the peripheral tissues. The center. secretion of thyroid hormone is no longer under the regulatory control of the hypothalamicpituitary

HYPERTHYROIDSM

Prevalence Women 2% Men 0.2% 15% of cases occur in patients older than 60 years of age

Increased pulse even in sleep Hot or moist palm Fine tremors Exopthalmos cardiac arrythmia

Tiredness emotional liability weight loss heat intolerance increase appetite diarrhoea

Clinical Symptoms Depends on Age of patient Magnitude of hormonal excess Presence of co-morbid condition

1. Catabolism 2. Enhancement of sensitivity to catecholamines

Clinical Symptoms

Clinical manifestations of hyperthyroidism are largely independent of its cause. However, causing disorder may have other effects.

Older patient presents with lack of clinical signs and symptoms, which makes diagnosis more difficult Thyroid storm is a rare presentation, occurs after stressful illness in under treated or untreated patient. Characteristics -Delirium -Dehydration -Severe tachycardia -Vomiting -Fever -Diarrhea

Skin

-Warm -May be erythematous (due to increased blood flow) -Smooth- due to decrease in keratin -Sweaty and heat intolerance -Onycholysis softening of nails and loosening of nail beds

Clinical symptoms
Hyperpigmentation -Due the patient increase ACTH secretion Pruritis -mainly in graves disease Thinning of hair Vitilago and alopecia areata -mainly due to autoimmune disease Infilterative dermopathy -Graves disease, most common on shins

Clinical symptoms

Eyes Stare Lid lag *Due to sympathetic over activity *Only Graves disease has ophthalmopathy -Inflammation of extraocular muscles, orbital fat and connective tissue. -This results in exopthalmos -More common in smokers

Clinical symptoms

Eyes

Impaired eye muscle function (Diplopia) Periorbital and conjunctival edema Gritty feeling or pain in the eyes Corneal ulceration due to lid lag and proptosis Optic neuritis and even blindness

Cardiovascular System

Increased cardiac output (due to increased oxygen demand and increased cardiac contractibility. Tachycardia Widened pulse pressure High output heart failure

Cardiovascular System Atrial fibrillation, 10-20% of patients. More common in elderly Atrial ectopy 60% of A-fib will convert to normal sinus rhythm with treatment (4-months of becoming euthyroid) Mitral valve problems LVH and cardiomyopathy

Low total cholesterol Low HDL Low total cholesterol/HDL ratio

Dyspnea on rest and with exertion Oxygen consumpation and CO2 production increases. Hypoxemia and hypercapnea, which stimulates ventilation Respiratory muscle weakness Decreased exercise capacity Tracheal obstruction May exacerbate asthma Increased pulmonary arterial pressure

GI System

-Weight loss due to increased calorigenesis -Hyperdefecation -Malabsorption -Steatorrhea -Celiac Disease (in Graves Disease) -Hyperphagia (weight gain in younger patient) -Anorexia- weight loss in elderly -Dysphagia -Abnormal LFT especially phosphate

Hematological System Normochromic normocytic anemia Serum ferritin may be high Graves disese ITP Pernicious anemia Anti-neutrophiliac antibody

GU System Urinary frequency and nocturia Enuresis is common in children

GU System
Women Increased SHBG High serum estradiol Low free estradiol High LH Reduce mid-cycle LH surge Oligomenorrhea and amenorrhea Anovulatory infertility

GU System Men High SHBG High total testosterone Low free testosterone High serum LH High serum estradiol Gynecomastia Decreased libido Erectile dysfunction Decreased or abnormal sperm

Skeletal System

Bone resorption Increased porosity of cortical bone Reduced volume of trabecular bone Serum alkaline phosphate is increased Increased osteoblasts Inhibit PTH secretions Decreased calcium absorption and increased excretion Osteoporosis, Fractures

Skeletal System Graves disease is associated with thyroid acropathy -Clubbing of nails -Periosteal bone formation in metacarpal bone or phalanges

Neuromuscular System

Tremors-outstretched hand and tongue Hyperactive tendon reflexes

Psychiatric Hyperactivity Emotional lability Anxiety Decreased concentration Insomnia

Muscle Weakness

Proximal muscle weakness in 50% pts. Decreased muscle mass and strength May take up to six months after euthyroid state to gain strength Hypokelemic periodic paralysis especially in Asian men (cause is not known) Myesthenia Gravis, especially in Graves disease.

Endocrine Increased sensitivity of pancreatic beta cells to glucose Increased insulin secretion Antagonism to peripheral action of insulin Latter effects usually predominate leading to intolerance.

anti thyroid drugs: carbimazole:10mgTDS propylthiouracil beta adrenergic blocker iodine

Serum t3 (1.2 3 nmol/ltr) Serum t4 (55- 150 nmol/ltr) Serum TSH ( 0 5 IU) Serum creatinine Serum cholesterol Serum calcitonin Thyroid autoantibody level Thyroid scintigraphy

 Goitre

is defined as diffused enlargement of the thyroid gland.. CLASSIFICATION: 1. Simple non - toxic a)Diffuse hyperplastic - Physiological # Puberty # Pregnency

- Primary iodine deficiency - Secondary iodine deficiency # goiterogens, drugs, dietary flouride b) colloid goitre c) nodular goitre d) solitary non toxic nodule e) recurrent non toxic nodule

2.

Toxic a) Diffuse primary Graves disease b) Multinodular secondary plummers disease c) Toxic nodule d) Recurrent toxicosis 3. Neoplastic a) Benign # papillary adenoma # follicular adenoma

b) Malignant # papillary follicular carcinoma # medullary carcinoma # anaplastic carcinoma 4. Thyroditis # Hashimotos # Riedels 5. Rare causes (amyloid)

initially in TSH levels; diffuse active lobules Later - TSH levels; inactive follicles which are colloid fillled C/F: - More in females (9:1) - Middle age - Inhereted defect in case of early childhood goitre

End stage result of diffuse hyperplastic Pathogenesis persistant TSH stimulation

diffuse hyperplasia of gland

fluctuation of TSH levels

mixed areas of active and inactive lobules active lobules vascular & hyperplastic
haemorrhages occur with necrosis in the centre nodule formation

coalecse together Multinodular goitre C/F: - Slowly progressive - firm, non tender - Inc. in size signifies malignant transformation Investigation: - C.B.C

X- Ray neck - Indirect laryngoscopy - Isotope scan - Ultrasonography - FNAC COMPLICATIONS: - Secondary thyrotoxicosis - Follicular carcinoma - Haemorrhage in a nodule - Tracheal obstruction
-

TREATMENT: - Partial or subtotal thyroidectomy - l- thyroxine (post op)

- Multiple

nodules

CAUSES: - Thyroid adenoma - papillary carcinoma - One nodule palpable in MNG TYPES - Toxic - Non toxic C/F:

-Single palpable nodule - smooth n firm INVESTIGATION: -Ultrasound neck - FNAC - T3 , T4 & TSH levels -Radioisotope TREATMENT: -Hemithyroidectomy -Total thyroidectomy with L- thyroxine ( 0.3mg)

- Radio iodine therapy

arises from lower pole of nodular goitre common in short neck individuals nodule gets drawn in superior mediastinum due to negative intra throacic pressure TYPES: - Substernal ( palpable in lower neck)

-Plunging goitre ( intra throacic goitre due to inc. pressure) -Intra throacic goitre C/F: -Dysponea at night -Cough and stridor -Dysphagia -Engorgment of neck veins -Dull node on percussion over sternum -Can be nodular toxic or malignanat

INVESTIGATION: -Chest X Ray -Isotope study ( I 123) TREATMENT: -Surgical removal -Radio iodine therapy

HYPOTHYROIDSM

An underactive thyroid gland; a glandular disorder resulting from insufficient production of thyroid gland

CONGENITAL:cretinism ACQUIRED:MYXEDEMA

Auto immune Iatrogenic

THYRODITIS CHRONIC LYMPHOCYTIC THYROID NON-GERTERIES GOITERUS HASHIMOTOS

Surgery Radiation Iodine therapy Drugs

bradycardia Cold extremites Dry skin and hair Periorbital puffiness Hoarse voice Slow movements Delayed ankel jerk Peripheral edema

Tiredness Parathesia Mental lethargy Cold intolerance Weight gain Menstrual disturbance Constipation dyspnea

Thyroxin oral tab.0.10mg to 0.20mg OD Precaution in old or cardiac patient,decrease the dose tri-idothyroxin 20microgm TDS I.V hydrocortisone 1gm divided doses and day

Thyroiditis is an inflammation of the thyroid gland. It may be painful and tender when caused by an infection or trauma, or painless when caused by an autoimmune condition or medications. There are several types of thyroiditis. The most common forms are : Hashimoto's disease subacute granulomatous thyroiditis postpartum thyroiditis subacute lymphocytic thyroiditis drug-induced thyroiditis

Most forms of thyroiditis result in three phases:

overactive thyroid (hyperthyroidism) underactive thyroid (hypothyroidism) return to normal. When the thyroid is inflamed, it often releases an excess of thyroid hormone, resulting in hyperthyroidism. Alternatively, when the supply of thyroid hormone is depleted, the body has too little, and hypothyroidism results. Young to middle-aged women are at greatest risk, however, some forms of thyroiditis occur in both men and women of all ages. With some forms, hypothyroidism may develop years later even if the thyroiditis has resolved.

 Depending on the type of thyroiditis, the thyroid gland can have one of the following characteristics: Firm and enlarged, but not tender Enlarged and painful, with pain extending to the jaw or ears Enlarged, but not painful Enlarged on only one side, hard like a stone, and sticking to other neck structures SIGNS AND SYMPTOMS: You may also have one or more of the following symptoms: Cool, dry skin, slow pulse rate (fewer than 60 beats per minute), swelling around the eyes, hoarseness, or slow reflexes No desire to eat, feeling tired and unenergetic, and a slight fever A rapid heartbeat, slight nervousness, anxiety, weight loss of 5 10 pounds, and increased sweating

Immune disorders, viruses, and fever disorders can cause thyroiditis. Sometimes thyroiditis develops if you have Graves' disease (an autoimmune disorder that causes hyperthyroidism). Certain drugs, such as amiodarone, interferon-alpha, inter leukin-2, or lithium can also cause thyroiditis. Pregnant women who test positive for the thyroid antibody during their first trimester have a 30 - 50% chance of developing thyroiditis during the postpartum period. In some cases or thyroiditis, there is no identifiable cause.

Drug Therapies Depending on the particular type of thyroiditis, a physician may prescribe one or more of the following treatments: Levothyroxine, if hypothyroidism or large goiter present Aspirin, to relieve pain and inflammation Corticosteroid medications (such as prednisone or dexamethasone), to reduce inflammation in severe cases Propanolol, for hyperthyroidism Thyroxine, to replace thyroid hormone (in cases of hypothyroidism) Short-term beta-blockers, for hyperthyroid symptoms Antibiotics

A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland (such as hyperthyroidism) . Other indications for surgery include cosmetic (very enlarged thyroid), or symptomatic obstruction (causing difficulties in swallowing or breathing). One of the complications of "thyroidectomy" is voice change and patients are strongly advised to only be operated on by surgeons who protect the voice by using electronic nerve monitoring. Most thyroidectomies are now performed by minimally invasive surgery using a cut in the neck of no more than 2.5 cms(1 inch). . After the removal of a thyroid patients usually take prescribed oral synthetic thyroid hormones to prevent the most serious manifestations of the resultant hypothyroidism. Less extreme variants of thyroidectomy include: "hemithyroidectomy" (or "unilateral lobectomy") -- removing only half of the thyroid "isthmectomy" -- removing the band of tissue (or isthmus) connecting the two lobes of the thyroid

A "thyroidectomy" should not be confused with a "thyroidotomy"

Malignancy Cosmetic reasons Goiter which is untreatable by medical methods Severe hyperthyroidism refractory to conservative treatment Orbitopathy in Graves' disease Removal and evaluation of a thyroid nodule whose FNAC results are unclear

Main steps of Thyroidectomy: Exposure - horizontal neck incision, +/raising of flaps, +/- division of strap muscles Identification of essential structures Recurrent and ext. branch of superior laryngeal nerve, parathyroid glands Devascularization Superior thyroid artery Inferior thyroid artery while protecting the supply to the parathyroids

Resection Exploration of other pathology - e.g. contralateral lobe, lymph nodes Closure

Hypothyroidism/Thyroid insufficiency in up to 50% of patients after ten years Thyrotoxic crisis/Thyroid storm Laryngeal nerve injury in about 1% of patients, in particular the recurrent laryngeal nerve: Unilateral damage results in a hoarse voice. Bilateral damage presents as laryngeal obstruction on removal of the tracheal tube and is a surgical emergency: an emergency tracheostomy must be performed. Recurrent Laryngeal nerve injury may occur during the ligature of the inferior thyroid artery. Hypoparathyroidism temporary (transient) in many patients, but permanent in about 1-4% of patients Anesthetic complications Infection Stitch granuloma

Haemorrhage/Hematoma
This may compress the airway, becoming lifethreatening. A suture removal kit should be kept at the bedside throughout the postoperative hospital stay. Surgical scar/keloid

 I. II. III. IV. I.

BENIGN ADENOMAS Follicular adenoma Papillary adenoma Hurthle cell adenoma Colloid adenoma MALIGNANT TUMOURS (Dunhill classification ) PRIMARY WELL DIFFERENTIATED CARCINOMA

98

Papillary carcinoma (60 % ) Follicular carcinoma ( 17 % ) Papillofollicular carcinoma behaves like papillary carcinoma of thyroid Hurthle cell carcinoma behaves like follicular carcinoma

POORLY DIFFERENTIATED CARCINOMA

Anaplastic carcinoma ( 13 % )

ARISING FROM PARAFOLLICULAR CELLS

Medullary carcinoma (6 % )

99

ARISING FROM LYMPHATIC TISSUE Malignant lymphoma (4 % ) II. SECONDARY ( METASTASIS ) Malignant melanoma ( rare ) Renal cell carcinoma Breast carcinoma produce secondaries in the thyroid due to blood spread

10 0

Radiation either external or radioiodine can cause papillary carcinoma thyroid. Pre existing multinodular goiter. It turns into follicular carcinoma of thyroid. Medullary carcinoma thyroid is often familial.

10 1

It is 60 % common. Common in females and young age group. TSH levels in the blood of these patients are high, so it is called HORMONE DEPENDENT TUMOUR. Slowly progressive and less aggressive tumour. Commonly multicentric. Spreads within the gland through intra thyroidal lymphatics. No blood spread.
10 2

The benign tumours of thyroid gland are not uncommon. They are present as a solitary nodule. Diagnosis is established by histological examination. Treatment by hemithyroidectomy/lobectomy. FNAC cannot distinguish follicular adenoma from follicular carcinoma. Hence a frozen section is arranged.

10 3

i.
ii. iii.

ETIOLOGY Irradiation to the neck during childhood. Complication of Hashimotos thyrioditis. TYPES Occult ( < 1.5 cm ) Intrathyroidal Extrathyroidal GROSS FEATURES It can be soft, firm, hard, cystic. It can be multinodular or solitary. It contains brownish black fluid.

10 4

MICROSCOPY Made up of colloid filled follicles with papillary projections. In some cases calcified lesions are found which are called as PSAMMOMA bodies. These are diagnostic of papillary carcinoma of thyroid. Characteristic pale, empty nuclei are present which are called as ORPHAN ANNIE EYED NUCLEI. (intranuclear cytoplasmic inclusions ) CLINICAL PRESENTATION o Young females are commonly affected. ( age of 20 40 years ).

10 5

It can be present as soft or hard or firm, solid or cystic, solitary or multinodular swelling. Compression features are uncommon. Often discrete lymph nodes in the neck are palpable. Thyroid may or may not be palpable. When not palpable it is called as occult ( hidden ) Few patients present late to the hospital with fixed nodes in the neck, and fixed thyroid to the trachea with or without recurrent laryngeal nerve paralysis.

10 6

DIAGNOSIS Routine investigations such as blood examination, chest x ray, laryngoscopy, are to be done. Radioisotopes scan shows cold nodule. TSH level in the blood is higher. FNAC ( fine needle aspiration cytology ) can demonstrate colloid filled follicles with papillary projections, hence preoperative diagnosis is possible with FNAC.

10 7

TREATMENT o Near total thyroidectomy o Suppressive dose of L THYROXINE 0.3 mg OD life long. o Block dissection ( functional block ) is required if lymphnodes are involved. o If small lymph nodes are present Berry picking may be done ( not accepted now ). PROGNOSIS Prognosis is good One of the curable malignancies.

10 8

AMES scoring. A: age, < 40 years has better prognosis. M: distant metastasis E: extent of the primary tumor. S: size of the tumor. AGES scoring A: age, < 40 years has better prognosis. G: pathologic grade of the tumor. E: extent of the primary tumor. S: size of the primary tumor. Size < 4 cm has better prognosis.

10 9

Incidence: constitutes 17 % of cases. Common in females. Can occur either de novo or in a pre existing multinodular goitre. More aggressive tumor. Spreads mainly through blood into the lungs, bones and liver. Spreads to lymph nodes of neck occassionaly. Bone secondaries are vascular, warm, pulsatile and localised.
11 0

ETIOLOGY Usually arises in a multinodular goitre, especially endemic goitre. Occurs in de novo. CLASSIFICATION NON INVASIVE, which means minimal invasion. INVASIVE refers to angio invasion and capsular invasion. The tumor cells lines the blood vessels and get dislodged into the systemic circulation producing secondaries in the bone.

11 1

CLINICAL PRESENTATION Swelling in the neck, firm or hard and nodular. Peak age group is around 40 years. Tracheal compression and stridor. Dyspnea, hemoptysis, chest pain during lung secondaries. Recurrent laryngeal nerve involvement causes hoarsness of voice, +ve Berrys sign. Pulsatile secondaries in the skul and long bones. ( metastasis in the flat bones ).

11 2

INVESTIGATIONS Routine investigations Thyroid scan can demonstrate cold nodule. FNAC of the cold nodule is inconclusive because capsular and angio invasion is not detected by FNAC. Frozen section biopsy is useful. Ultrasound abdomen, chest x ray, bone x ray are done to reveal osteolytic lesions. Alkaline phosphatase if increased, bone scan should be done.

11 3

TREATMENT Near - total thyroidectomy is done, along with block dissection if lymph nodes are enlarged. Maintenance dose of L thyroxine 0.1 mg OD is given lifelong. After near total thyroidectomy, a whole body, bone scan is done to see for metastasis in the bone. A single secondary can be treated by radiotherapy followed by oral radioiodine therapy. Multiple secondaries are treated by oral radioiodine therapy.

11 4

It is a variant of follicular carcinoma. It is more aggressive than follicular carcinoma. These tumors have more than 75 % of follicular cells having oncocytic features. Do not take up 131I. Secretes thyroglobulin. Hurthle cell adenoma even if well capsulated is highly malignant. It contains abundant oxyphill cells. It spreads to regional lymph nodes more than follicular carcinoma of thyroid.

11 5

TREATMENT Total thyroidectomy. In many cases lymph nodes are enlarged, hence modified radical neck dissection ( MRND ) is done. TSH suppression, follow up regularly done.

11 6

Incidence: 10 % 12 % of cases. The most rapidly growing thyroid malignancy. Advanced age group at presentation. Advanced nature of presentation. CLINICAL FEATURES Common in elderly woman around 60 70 years of age. Rapidly growing thyroid swelling of short duration. The surface is irregular and consistency is hard.
11 7

i.
ii. iii.

Very aggressive tumor causing Stridor and hoarseness of voice. Dysphagia Fixity to the skin. Involvement of isthmus and bilateral lateral nodes. Early infiltration of trachea ( stridor ) Infiltration of carotid sheath ( carotid artery pulsation not palpable ). +ve Berrys sign. Differential diagnosis intrinsic carcinoma of larynx.

11 8

DIAGNOSIS FNAC is diagnostic. TREATMENT Tracheostomy and isthmectomy are done to relieve respiratory obstruction temporarily. External radiotherapy. Prognosis is poor. Death occurs within 6 8 months.

11 9

Uncommon ( 5 % ) type of thyroid malignancy. Arises from parafollicular C cells, which is derived from ultimobronchial body. Contains characteristic amyloid stroma wherein malignant cells are dispersed. There maybe mucosal neuromas in lips, oral cavity. ( Sipple syndrome, MEN IIb ) TYPES Sporadic ( 80 - 90 % ).

12 0

Familial MCT MCT with MEN II syndrome. CLINICL FEATURES Thyroid swelling often with enlargment of neck lymph nodes. Diarrhea, flushing. Hypertension, pheochromocytomas and mucosal neuromas. Sporadic and familial types occur in adulthood whereas MEN syndrome II occurs in younger age groups.

12 1

HORMONES PRODUCED BY MCT Calcitonin Prostaglandins Serotonin ( 5 HT ) ACTH SPREAD Both by lymphatics and blood INVESTIGATIONS FNAC shows amyloid deposition with dispersed malignant cells and C cells hyperplasia.

12 2

Tumor marker calcitonin levels will be high. Ultrasound neck thyroid region. TREATMENT Total thyroidectomy + central node dissection + maintenance dose of L thyroxine. Neck lymph node block dissection if lymph nodes are involved. Adriamycin is drug used for chemotherapy. PROGNOSIS Sporadic MCT and MCT with MEN II are aggressive. Familial MCT with no MEN II has better prognosis.
12 3

It is rare. Hashimoto thyroiditis can pre dispose to malignant lymphoma. Older patients are commonly affected. Tumor is rapidly growing, large thyroid swelling. ( Primary lymphoma ). FNAC used to diagnose the condition. Chemotherapy is the main treatment. Often total thyroidectomy is done to enhance the results.

12 4

PARATHYROID GLAND

Parathyroid Gland Anatomy

Four Parathyroid glands are usually found posterior to the thyroid gland Total weight of parathyroid tissue is about 150mg Parathyroid hormone (PTH) is made by these glands

PTH is synthesized as the preprohormone (Preproparathyroid Hormone) by parathyroid gland chief cells The active form of PTH is cleaved from the preprohormone before release from the gland PTH is synthesized continously (it is either released from the gland or degraded) PTH is released by exocytosis in response to reduced plasma calcium Vitamin D feeds back to reduce PTH secretion as a secondary mechanism

BONE PTH stimulates bone osteoblasts to increase growth & metabolic activity PTH stimulated bone resorption releases calcium & phosphate into blood KIDNEY PTH increases reabsorption of calcium & reduces reabsorption of phosphate Net effect of its action is increased calcium & reduced phosphate in plasma INTESTINE Increases calcium reabsorption via vitamin D

Decreased Plasma Calcium Causes: Increased PTH Resulting in mobilization of bone Ca & phosphate, increased renal phosphate excretion & Ca retention and increased Vitamin D3 synthesis The outcome is a rise in plasma Ca levels & maintenance of normal phosphate levels

Estimated incidence is 1 case per 1000 men and 2-3 cases per 1000 women Incidence increases above age 40 Most patients with sporadic primary hyperparathyroidism are postmenopausal women with an average age of 55 years >80% of cases are caused by a solitary parathyroid adenoma Approximately 10% are caused by double adenoma

Symptomatic: Osteitis fibrosa cystica Nephrolithiasis Pathologic fractures Neuromuscular disease Life-threatening hypercalcemia ?Peptic Ulcer Disease ?Asymptomatic: Fatigue Subjective muscle weakness Depression Increased thirst Polyuria Constipation Musculoskeletal aches and pains

Symptomatic primary HPT NIH Consensus Development Panel 2002 Revised Guidelines [if any of the following are met]

Serum calcium greater than 1mg/dL above the upper limit of the reference range 24 hour urine calcium greater than 400 mg Creatinine clearance reduced by more than 30% compared with age-matched subjects Bone density at the lumbar spine, hip, or distal radius more than 2.5 SD below peak bone mass Age under 50 Patients for whom medical surveillance is not desirable or possible
creatinine clearance (mL/min) = ((urine creatinine in mg/dL) * (urine volume in mL)) / ((plasma creatinine in mg/dL) * (time period in minutes))

Neuropsychological abnormalities Several studies document improvement in HRQL after parathroidectomy Studies on neurobehavioral abnormalities have reported less consistent results with parathyroidectomy Cardiovascular abnormalities Symptomatic patients suffer from increased cardiovascular mortality before and after treatment Asymptomatic primary HPT is associated with LVH; some studies suggest this is reversible with parathyroidectomy Primary HPT patients have increased calcifications of mitral and aortic valve Perimenopausal women Asymptomatic primary HPT associated with increased bone turnover, reduced bone mineral density and higher risk for fractures

High-resolution ultrasound Sensitivity 65-85% for adenoma; 30-90% for enlarged gland Results suboptimal in pts with multinodular thyroid disease, pts with short thick neck, ectopic glands (15-20%) May be useful in detecting sestamibi scan negative adenomas CT with contrast/thin section Sensitivity of 46-87% Good for ectopic glands in the chest MRI Sensitivity of 65-80% Good for ectopic glands Sestamibi 85-95% accurate in localizing adenoma in primary HPT Sestamibi-SPECT Sensitivity 60% for enlarged gland and 98% for solitary adenomas

Scintigraphy Images

Traditional Sestamibi

Sestamibi-SPECT

Asymptomatic patients may elect to be closely followed and managed medically

Patients opting not to have surgery should have a serum calcium level drawn every 6 months and should have annual bone densiometry at all three sites

A recent study of pts with asymptomatic primary HPT showed that the majority of pts followed for ten years did not demonstrate an increase in serum calcium or PTH levels25% of patients had progressive disease including worsening hypercalcemia, hypercalciuria and reduction in bone massyounger patients more likely to have progression of disease

Estrogen SERMs

Dose required is high

Reduction in serum calcium and markers of bone turnover after 4 weeks Studies have shown increase in lumbar spine and femoral neck mineral density

Bisphosphonates

Calcium/Vitamin D Calcimimetic agents (Cinacalcet)

Under investigation for primary HPT

STIGMATA OF MEN I

Lipomas

Collagenomas Angiofibromas

Decreased GFR leads to reduced inorganic phosphate excretion and consequent phosphate retention Retained phosphate has a direct stimulatory effect on PTH synthesis and on cellular mass of the parathyroid glands Retained phosphate also causes excessive production and secretion of PTH through lowering of ionized Ca2+ and by suppression of calcitriol production Reduced calcitriol production results both from decreased synthesis due to reduced kidney mass and from hyperphosphatemia.

Low calcitriol levels, in turn, lead to hyperparathyroidism via both direct and indirect mechanisms. Calcitriol is known to have a direct suppressive effect on PTH transcription and therefore reduced calcitriol in CRD causes elevated levels of PTH Reduced calcitriol leads to impaired Ca2+ absorption from the GI tract, thereby leading to hypocalcemia, which then increases PTH secretion and production.

Secondary HPT

Clinical presentation Usually asymptomatic Diagnosis Elevated PTH in the setting of low or normal serum calcium is diagnostic If phosphorous is elevated, cause is renal If phosphorous is low, other causes of vit D deficiency should be sought Prevention Vit D replacement Phosphorus binders [Sevelamer] Treatment Medical Calcimimetic agents Surgical Considered in cases of refractory severe hypercalcemia, severe bone disease, severe pruritis, calciphylaxis, severe myopathy

Tertiary hyperparathyroidism develops in patients with longstanding secondary hyperparathyroidism, which stimulates the growth of an autonomous adenoma. A clue to the diagnosis of tertiary hyperparathyroidism is intractable hypercalcemia and/or an inability to control osteomalacia despite vitamin D therapy. Surgical Referral - calcium- phosphate product > 70 - severe bone disease and pain -intractable pruritus - extensive soft tissue calcification with tumoral calcinosis -calciphylaxis

Primary HPT

Secondary HPT (renal etiology) Tertiary HPT (renal etiology)

High calcium and phosphorus

Increased serum calcium Phosphorus in low normal range Urinary calcium elevated Low or normal serum calcium High phosphorus

Much less common than hyperparathyroidism Causes: 1. Parathyroid gland aplasia (DiGeorge syndrome) 2. Surgical treatment of hyperparathyroidism with removal of all parathyroid tissue 3. Idiopathic hypoparathyroidism usually caused by isolated autoimmune destruction of the parathyroid glands. Clinical findings 1. Ca++ levels are decreased while phosphate levels are increased 2. Neuromuscular excitability carpopedal spasm, laryngospasm, Chvostek sign, Trousseau phenomena (muscle spasm induced by pressure to the nerve) 3. Ca++ in the basal ganglia 4. Bony changes osteosclerosis to osteomalacia 5. Mental status changes irritability, psychosis, seizures 6. Cardiac arrthymias & arrest

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