THYROID = DISORDERS

THYROID=20 DISORDERS

HISTORY=20 :=20

Goitre=20 (Latin gutter =96 throat) is defined as enlargement of thyroid which has = been=20 recognised since 2700 B.C. even though not documented till 1619 by = FABRICUS =96 He=20 recognised that Goitre arose from Thyroid gland. The term =93 Thyroid = Gland=94=20 (Greek) thyreoeides =96 shield shaped) is attributed to Thomas Wharton = in his=20 Adenographia (1656). In 1776 Thyroid was classified as Ductless gland by = ALBRECHT VON HALLER. The = first=20 account of Thyroid surgery for treatment of Goitre was given by Roger = Frugard in=20 1170. In response to failure of medical treatment two setons were inserted at right = angles=20 into the goitre and tightened = twice=20 daily until the goitre separated. The open wound was treated with = caustic powder=20 and left to heal. However, the Thyroid surgery continued to be hazardous = with=20 prohibitive mortality rates more than 40% until the latter half of the=20 19^th century with advances in Anaesthesia and = antisepsis. The most notable surgeons were = Emile=20 Theodore Kocher (1841 =96 1917) and C.A Theodore Billroth (1829 =96 = 1894). In 1909=20 Kocher was awarded Noble prize for Medicine in recognition =93for his = work on the=20 physiology, pathology and surgery of thyroid = gland=94.

EMBRYOLOGY :=20

The=20 thyroid gland arises as an outpouching of the primitive foregut around=20 3^rd week of gestation. It originates at the base of the = tongue at=20 foramen cecum. The endodermal cells in floor of the pharynx grow = downwards and=20 form a bilobar solid organ. The original attachment between the foramen cecum and thyroid gland becomes = thyoglossal=20 duct which gets reabsorbed after 6 = weeks. Persistence of the duct leads = to=20 thyroglossal cyst and fistula. The very distal end of the remnant = occassionally=20 retained and mature as pyramidal = lobe in the adult thyroid. The well developed pyramidal lobe can = be=20 mistaken for a nodule. Calcitonin producing C cells arise from the = fourth=20 pharyngeal pouch and migrate into the lateral lobes of the thyroid. = These are=20 derived from Neuro ectodermal origin (Ultimo branchial bodies). The C = cells are=20 the only component of the Adult gland not of endodermal organ. = Thyroid=20 follicles appear by = 8^th=20 week and colloid formation begins by 11^th week of gestation.=20

THYROID=20 PHYSIOLOGY :

The=20 average requirement of Iodine is 0.1 mg which are derived from foods = such as=20 milk, fish, eggs. In the stomach and jejunum Iodine is rapidly converted = into=20 Iodide and absorbed in the blood which is uniformly distributed in the = extra=20 cellular space. Iodide is actively transported into thyroid = follicle cells by a ATP dependant = process.=20 Thyroid is the storage site of more than 90% of the body Iodine.=20

Thyroid=20 Hormone Synthesis Secretion & = Transport

The=20 synthesis of Thyroid hormone consists of =20 several steps. The first step is Iodide trapping, involves active = (ATP=20 dependant) transport of the Iodide across the thyrocyte (follicular = cell) via=20 intrinsic membrane protein, = the Na+=20 / I- symporter (NIS). = Thyro=20 globulin (Tg) is a large glyco protein (660 =96 kDa) which is present = in thyroid follicles and has 4 = tyrosyl=20 residues. The second step involves oxidation of Iodide to Iodine and = Iodination=20 of tyrosine residues on Tg, to monoiodotyrosines (MITs) and Diiodo = tyrosines=20 (DITs). Both the process are catalysed by thyroid peroxidase. The = recently=20 iodised protein Pendrin is to mediate Iodine efflux at the apical = membrane. The=20 3^rd step leads to coupling of two DITs to form T4 and one DIT = and MIT=20 to form T3 or reverse T3 (rT3). When stimulated by TSH the follicular = cells form=20 pseudopodia which encircle portion of cell membrane containing = thyroglobulin and=20 fuse with lysosomes. The=20 4^th step, the thyroglobulin is hydrolysed to = release=20 free T3 and T4 and mono and MITs and DITs. The latter are deiodinated to = yield=20 Iodide which is reused. In the euthyroid state T4 is produced and = released by=20 thyroid gland whereas only 20% of total T3 is produced by Thyroid. Most = of the=20 T3 is produced by peripheral deiodination of T4 in the liver muscles, = kidney and=20 anterior pitituary a = reaction that=20 is catalysed by 5=94 =96 mono deiodinase. Thyroid hormones are = transported in serum=20 bound to carrier proteins such as thyroid binding globulin (TBG). = Thyroxin=20 binding prealbumin (TBPA) and albumin. Only a fraction of (0.02%) of = thyroid=20 hormone is free (unbound) and is the physiologically active component. = T3 is the=20 most potent of the two thyroid hormones although its circulating plasma = level is=20 lower than that of T4. T3 is less tightly bound to protein in the plasma = than T4=20 and so it enters tissues more readily. T3 is 3 to 4 times more active = than T4=20 per unit weight, with half life of about 1 day compared to 7 days of=20 T4.

=20 The secretion of thyroid hormone is controlled by hypothalaminc = pitituary=20 thyroid axis. The hypothalamus produces a peptide thyrotropin releasing = hormone=20 (TRH) which stimulates the pituitary to release TSH or thyrotropin. = TSH 28 kDa glycopeptide which = mediates=20 Iodide trapping secretion and release of thyroid hormone TSH = secretion by the anterior pituitary and = is=20 regulated via by a negative feedback loop by T4 and T3 because the = pituitary has=20 the ability to convert T4 to T3 the latter is thought to be more = important in=20 this feedback control. T3 also inhibits release of TRH. The thyroid = gland is=20 also capable of a autoregulation = which allows it to modify its functions independent of TSH as an = adaption=20 to low iodide intake, the gland preferentially synthesizes T3 rather = than T4 and=20 thereby increasing the efficiency of the secreted hormone. In situations = of=20 Iodine excess Iodide transport peroxidase generation, synthesis and = secretions=20 of thyroid hormones are inhibited. Excessive large dose of Iodide may = lead to=20 increased organification followed by suppression, a phenomenon = called as WOLFF=20 =96 CHAIKOFF effect. = Elevated thyroid=20 hormone levels are found in pregnancy and in gynecological malignancies = such as=20 Hydatidform mole. In contrast steroids inhibit thyroid hormone = production. In=20 severely ill patients peripheral thyroid hormones are reduced without a=20 compensatory increase in TSH levels, the sick =96 Euthyroid low T3 = syndrome.=20

EVALUATION=20 OF PATIENT WITH THYROID DISEASE

Many=20 different tests are available to evaluate thyroid function. No single = test is=20 sufficient to assess thyroid function in all situations and the results = must be=20 interpreted in the = context of=20 clinical condition. =20

Serum TSH (Normal 0.5 to 5 = m units=20 / ml) TSH is most = sensitive and=20 specific for the diagnosis for hyper and hypothyroidism and for = optimising for=20 replacement or suppressive therapy.

Total=20 T4 and T3

T4 =96 55=20 =96 150 nonomoles / litre

T3 =96=20 1.5 to 3.5 nonomoles / = litre=20

They=20 are measured by radio immunoassay. Total T3 and T4 measures both free = and bound=20 thyroid hormones. Total T4 reflects the output of thyroid gland. Total T4 is increased in=20 hyperthyroid patients and = also in=20 those patients with increased Tg levels secondary to pregnancy, estrogen = and=20 progesterone etc., similarly Total T4 is decreased in = hypothyroidism and in patient with decreased = Tg levels=20 caused by anabolic steroid use, by protein losing disorders, Nephrotic syndrome.=20 Measurement of T3 levels is important clinically in hyperthyroid patients with normal T4 levels = who may=20 have T3 thyrotoxicosis. Total T3 levels are often increased in early=20 hypothyroidism.

FREE T4=20 AND T3

Not=20 routinely performed. Use of this test is confined to cases of early=20 hyperthyroidism in which total T4 levels may be normal but free T4 = levels are=20 raised. In patients with end organ resistance to T4 (Refetoff syndrome) = T4=20 levels are increased but TSH levels are normal. Free T3 is most useful = in=20 confirming the diagnosis of early hyperthyroidism in which levels of = free T4 and=20 T3 rise before total T4 and T3. =20 Free T4 levels may be measured indirectly using T3 Resin uptake=20 test. =

THYROID=20 ANTIBODIES =20

The=20 Thyroid antibodies include anti thyroglobulin (Anti- Tg), Antimicrosomal = or=20 Antithyroid peroxides (Anti-TPO) and Thyroid stimulating immunoglobulin=20 (TSI). Anti Tg and Anti = TPO=20 antibody levels do not determine the thyroid function. Instead they indicate the = underlying=20 disorder usually an autoimmune thyroiditis. Approximately, 80% of the = patients with=20 Hashimoto=92s thyroiditis have elevated thyroid antibody levels but = levels may=20 also be increased in patients with Grave=92s Disease, MNG and = occasionally thyroid=20 neoplasm. =

SERUM=20 THYROGLOBULIN =20

Thyroglobulin=20 is not normally released into the circulation in large amounts but = increases=20 dramatically in destructive processes of thyroid gland such as = thyroiditis or=20 over active states such as GRAVE=92s Disease and toxic MNG. The most important use for = Serum=20 thyroglobulin levels is in monitoring patients with differentiated = thyroid=20 cancer for recurrence, paticularly after total thyroidectomy and radio = active=20 Iodine oblation. =20

THYROID=20 IMAGING =

Both=20 Iodine =96 ¹²³I and ¹³¹I are used to image the Thyroid=20 gland. 123 Iodine emits = low dose=20 radiation and has a half life of 12-14 hrs in contrast 131 Iodine use = leads to=20 higher dose radiation exposure and has a half life of 8-10 days. Therefore, the former is used = for=20 imaging and the latter is used to screen and treat patients with = differentiated=20 thyroid cancers for metastatic disease. =20 The images provide information not only about the size and shape = of the=20 gland but also a distribution of functional activity. The areas that trap less = radioactivity=20 than the surrounding glands are termed =91Cold=92 whereas areas that = demonstrate=20 increased activity are termed =91Hot=92 and Warm if it is equal to the = surrounding=20 tissue. Technecium =96 = 99M=20 pertechnetate is taken up by thyroid gland and is used for thyroid=20 evaluation. This Isotope = is taken=20 up by Mitochondria but not organified. =20 It has the advantage of having a shorter half life and minimises=20 radiation exposure. It is = particularly sensitive for nodal metastasis. More recently, 18F-Floro = DeOxyGlucose=20 positron emition tomography (FDG PET) has been used for metastasis in = patients=20 with thyroid cancer in whom other imaging studies are negative. However, this technique is = expensive and=20 not widely available. =20

THYROID=20 ANATOMY

Normal=20 thyroid weighs 20-25 gms. The lobes are located adjacent to the thyroid=20 cartilage and connected in the midline by an isthmus which is located = just=20 inferior to cricoid cartilage. A pyramidal lobe which represents the = most caudal=20 end of the thyroglossal duct is found in approximately 50% of the = individuals=20 undergoing thyroid surgery. The thyroid lobes extend to the mid thyroid=20 cartilage superiorly and lie adjacent to the carotid sheath and = sternocleido=20 mastoid muscle laterally. The strap muscles are located anteriorly and = are=20 innervated by Ansa Hypoglossi / cervicalis. The thyroid is covered by a = true=20 capsule which is adherent to the thyroid and a false capsule by the = pretracheal=20 fascia of deep fascia of the neck =20 and condenses to form posteriorly Berrys ligament near the cricoid cartilage and = upper=20 tracheal rings.

=20

The=20 blood supply of the thyroid gland is by 2 sets of arteries. The superior = thyroid=20 artery from the external carotid which divides into anterior and = posterior=20 branches at the apices of the thyroid lobes. The inferior from the = thyrocervical=20 trunk shortly after their origin from the subclavian arteries. The = inferior=20 thyroid artery travel upward in the neck posterior to the carotid sheath = to=20 enter the thyroid lobes at the mid portion. A thyroidea ima artery from = the=20 aorta are innominate in 1-4% of the individuals to enter the isthmus or = replaced=20 the inferior thyroid artery. The=20 RLN is intimately associated with inferior thyroid branches and so=20 identification of the nerve before the branches could be ligated is = important.=20 Venous drainage from 3 sets of drains namely superior, middle and = inferior=20 thyroid veins. Superior drains into internal jugular vein, inferior to = the=20 brachiocephalic vein and the middle least consistent to the = brachiocephalic=20 vein.

=20

The=20 left RLN (Recurrent Laryngeal Nerve) crosses the Aortic arch, loops = around the=20 ligamentum arteriosum and ascends medialy =20 in the neck in tracheo- esophageal =20 groove. The right RLN arise from the right vagus. The nerve = crosses the I=20 port of subclavian to the Aorta before ascending in the neck, its course = being=20 more oblique than the left. Along their course in the neck, the RLN may = branch=20 and pass anteriorly or = posteriorly=20 or inter digitate with the branches of the inferior thyroid artery. The = right=20 RLN may be non-recurrent in 0.5-1% of the individuals and often = associated with=20 vascular anomaly. Non recurrent left RLN are rare and reported only in = right=20 sided Aortic arch. Identification of the nerve or the branches often = necessitate=20 mobilisation of the most lateral and posterior extent of thyroid gland, = the=20 tubercle of Zucker Kandl = at the=20 level of cricoid = cartilage. The=20 last segment of the nerve often =20 course below the tubercle and are closely approximated to the = ligament=20 of Berry. Branches of the = nerve=20 traverse the ligament in 25% of the individuals and are particularly = vulnerable to the=20 injury at this junction. = The nerve=20 terminates by entering the larynx posterior to crico thyroid = muscle. The RLN supply all the = intrinsic muscles=20 of the Larynx except cricoid thyroid which is innervated by external = laryngeal=20 nerve. Injury to the RLN (one), leads to paralysis of the ipsilateral = cord which=20 lies in paramedian or abducted position. The paramedian position results = in=20 normal but weak voice whereas abducted position leads to hoarse voice = and=20 in-effective cough. Bilateral RLN palsy leads to airway obstruction=20 necessitating tracheostomy or result in loss of voice and has = ineffective cough=20 and repeated respiratory infection from aspiration. Superior laryngeal = nerve is=20 closely associated with superior thyroid artery and superior pole = vessels should=20 not be ligated en masse but should be individually divided close to the = gland.=20 The nerve has been called Amelita Galla Curci or =93 High note nerve=94 = after the Opera=20 singer injury of which leads to inability to tense the ipsilateral vocal = cord=20 and hence difficulty for the high note, projecting the voice and voice fatigue during = prolonged=20 speech.

=20

The=20 lymph vessels drain into pretracheal, paratracheal, perithyroidal, = superior=20 mediastanal, reteropharyngeal, esopharyngeal and jugular chain lymph = nodes. The=20 central nodes are located in between carotid sheaths and nodes lateral = to the=20 carotid sheath are the lateral compartments. A thorough knowledge is = needed for=20 lymph node dissection especially in papillary and medullary carcinoma. =

A=20 scheme for evaluation of thyroid=20 enlargments.

=20

HYPOTHYROIDSM:=20

CLASSIFICATION

1. = ; =20 Autoimmune=20 Thyroiditis. (Chronic = Lymphocytic=20 Thyroiditis)

- = ; =20 Non=20 Goitrogenous =96 Primary Myxedema

- = ; =20 Goitrogenous=20 =96 Hashimoto=92s Thyroiditis

2. = ; =20 Iatrogenic

- = ; =20 After=20 Radio Iodine therapy

- = ; =20 After=20 Thyroidectomy

- = ; =20 After=20 Anti Thyroid drugs, Iodites etc

3. = ; =20 Dysharmono=20 Genesis

4. = ; =20 Goitrogens

5. = ; =20 Endemic Cretinism =96 Iodine=20 Deficiency

6. = ; =20 Secondary=20 to Pituitrary and Hypothalamic Disorders

7. = ; =20 Thyroid=20 agenesis

Deficiency in the=20 circulating levels of thryroid hormone levels leads to hypothyroidism.=20

CLINICAL=20 FEATURES

The = term Myxedema=20 should be reserved for severe thyroid failure and not applied to much = more=20 commoner mild thyroid deficiency. =20 The signs are dry skin, cold extremites, peri orbital puffiness,=20 bradikinesis =96 slow and poor movements, bradycardia, delayed = relaxation of ankle=20 jerks. The symptoms are = tiredness,=20 mental lethargy, apathy, cold intolerance, weight gain, constipation, = menstural=20 disturbances, and carpal tunnel syndrome. =20 Delayed relaxation of active jerks is the most useful clinical = sign in=20 diagnosing Hypothyroidism. =20

Hypothyroidism=20 in neonates leads to delayed milestones, neurological impairment, mental = retardation and cretinism. Cretinism when associated with nerve deafness = is called as Pendred syndrome = and so=20 immediate testing and treatment can prevent the neurological = impairment. In childhood hypothyroidism = leads to=20 abdominal distension, umbilical hernia, rectal prolapse. =

DIAGNOSIS

Low T4=20 and T3 and elevated TSH.

High=20 titre of antibodies in auto immune thyroiditis.

TREATMENT

Oral=20 Thyroxine 0.1 =96 0.2 mg given as a single dose because of its prolonged = action. Caution is = required in=20 elderly and Cardiac patients. =20 Better to start at a lower dose and increase accordingly. If rapid response is required = T3 may be=20 given.

In=20 Myxedema the signs and symptoms are accentuated in addition to the above = clinical features like Supra clavicular fullness, malar flush and yellow = tinge=20 to the skin. Myxedema = Coma occurs=20 in neglected cases which carries a high mortality. Body temperature is low and = patient is=20 warmed slowly in addition to Hydrocortisone IV and T3 in slow increasing = doses. =

HYPERTHYROIDISM

The=20 term Thyrotoxicosis is retained because the symptoms are not = attributable to=20 only to the rise levels of circulating hormones and also to all the=20 manifestations of the disease. =20 Clinically, Hyperthyroidism can present as diffuse (Graves) = Goitre, toxic=20 nodule, toxic nodular Goitre and Hyperthyroidism due to rare = causes.

Hyperthyrodism

Grave=92s=20 disease

Multinodular=20 goiter

Automomously=20 nodule

Thyroiditis

Subacute (de=20 Quervan=92s)

=20 Post-partum

0.5

Iodide=20 =96 induced

Drugs =96=20 Amiodarone

Radiographic = contrast media=20

Iodine prophylaxic = programe

Extrathyroidal=20

Factitious=20 hyperthyroidism

Struma=20 ovarii

0.2

TSH=20 =96 induced

Inappropriate TSH = secretion=20 by pituitary

Choriocarcinoma and = hydatidiform=20 mole

0.2

Follicular=20 carcinoma =B1=20 metastases

0.1

CLINICAL=20 FEATURES

The=20 symptoms are tiredness, emotional lability, heat intolerance, weight = loss,=20 excessive appetite, palpitations, etc. =20 The signs are hot moist palms, exophthalmos, lidlag, lid = retraction,=20 agitation, goitre, tachicardia.

=20

GRAVE=92s=20 DISEASE

Characterized=20 by diffuse vascular goitre, in=20 young patients, with frequent eye signs. =20 The Hypertrophy and Hyperplasia of thyroid gland are due to = abnormal=20 thyroid stimulating antibodies. Approximately 50 % of the patients have=20 clinically ophthalmopathy. = The eye=20 signs are lid lag(Von Grafe), spasm of the upper eyelid exposing the=20 sclera(Dalrymple=92s sign), a prominent stare. Infiltrative eye diseases = result in=20 periorbital edema, conjunctival swelling, congestion, proptosis, = limitation of=20 upward and lateral gaze(involvement of inf and lat rectus). Keratitis = and=20 ophthalmic nerve involvement leading to blindness. The etiology of eye = involvement is not=20 known. However orbital = fibroblast=20 and muscles are thought to share a common antigen with the thyrocytes = and TSH=20 receptors. Ophthalmopathy = results=20 from inflammation caused by cytokines released from killer T lymphocytes = and=20 cytotoxic antibodies. = Dermopathy=20 occurs in 1-2% of patients and is due to deposition of = glycosaminoglycans=20 leading to thick skin. =20

TOXIC=20 NODULAR GOITRE =20

Goitre=20 presenting for a long time and so found in middle ages or elderly = patients with=20 infrequent eye signs and more of Cardiac signs and symptoms. The nodules are inactive and = only the=20 internodal tissues are active. = In=20 some cases, a single nodule or one or two may become autonomous and = present as=20 toxic adenoma. =20

TOXIC=20 ADENOMA =

Here=20 the solitary nodule is overactive causing the symptoms of = Hyperthyroidism.

DIAGNOSIS =

Most=20 cases are diagnosed clinically. =20 Difficulty arises only in mild hyperthyroidism and = differentiation from=20 anxiety state when a Goitre is present. =20 Hyperthyroidism should be thought of during growth spurts = behaviour=20 problems, myopathy, tachycardia in the elderly, unexplained diarrhoea, = loss of=20 weight. =

- =20 Increaed=20 T3 and T4 levels and decreased or non detectable = TSH.

TREATMENT

Non-specific=20 measures are rest and sedation. =20

Three=20 diferent options

- = Antithyroid=20 drugs

- Radio Iodine=20 Treatment

-=20 Surgery

ANTI-THYROID=20 DRUGS are used as first line of = treatment=20 alone and in preparing the patients for surgery or radio Iodine = treatment. The drugs used are = Carbimazole,=20 Propylthiouracil, Beta-blockers. = Iodides as pre-operative preparation before surgery. Anti-thyroid drugs are used to = restore=20 the patients to euthyroid state and so maintain the patients for a = prolonged=20 period in the hope that permanent remission will occur. Anti-thyroid drugs will not be = helpful=20 in toxic nodule or toxic nodular Goitre except in preparation for = surgery. The disadvantage of = anti-thyroid drugs=20 is due to prolonged treatment period of more than 18 months to 24 months = More=20 than 50% of the patients will have recurrence of the disease after a = stoppage of=20 drugs. The side effects = of the drug=20 like fever, rashes, reversible granulocytopenia, peripheral neuritis,=20 polyarteritis, vasculitis and rarely agranulocytosis and aplastic = anemia. Patients are monitored for the = above=20 side effects. Surgery is = postponed=20 till the count is >1000/cumm. = Block and replacement treatment is also done to prevent = hypothyroidism=20 which reduces the recurrent rates. Relapse rate is highly variable = (40-60%)=20 especially patients who have poor compliance. The drug of choice is = carbimazole or=20 propylthiouracil. The = dose of=20 cabimazole is 5-10 mg 3 times daily and the dose is decreased after the = patient=20 is brought to Euthyroid state and the dose is maintained. Propylthiouracil is a drug of = choice,=20 especially in pregnant ladies as it minimally crosses the placenta. These drugs inhibit the = organic=20 binding of iodine and coupling (mediated by TPO) and in addition PTU = inhibits=20 the peripheral conversion of T4 to T3 making it useful for thyroid = storm. Both drugs cross placenta but = PTU has=20 lower risk and is preferable.

RADIOIODINE=20 TREATMENT: by RAI 131I

The=20 advantages are no drugs and so no side effect of the drugs except in = preparing the=20 patient i.e to bring to euthyroid state and also reduces overall = treatment=20 cost.

The=20 disadvantages are that (1) availability (2) not useful in preganant = patients or=20 patients who are eager to conceive (3) follow up essential for = malignancy (4)=20 all patints go into hypothyroidism who require lifelong thyroxine (5) = worsenig=20 of ophthalmopathy.

Dose is=20 calculated after a preliminary scan and consists of 8-12mci = administration=20 orally. Most patients are = euthyroid=20 within 2months and 50% within another 6 months and still another 50%=20 hyperthyroid require further dose. =20 After one year 2.5% of the people go into hypothyroidism and so = every=20 year.

RAI is=20 documented to lead to worsening of ophthalmopathy and comparatively less = with=20 surgery. No evidence of = longterm=20 problems like infertility and cancer rates are unchanged and a small = risk of=20 developing nodularity, thyroid ca, hyperparathyroidism and unexplained = increase=20 in cardiovascular mortality. = RAI is=20 more useful in older patients, moderately sized goiter, patients relapse = after=20 drugs or surgery and in patients where both drugs and surgery are=20 contraindicated.

SURGICAL=20 TREATMENT=20

Is=20 useful in individuals where RAI is contraindicated. It is useful in = young pts,=20 pregnant or desire to conceive, allergic to antithyroid medications, = large=20 goiter causing compression and relatively indicated in smokers, moderate = to=20 severe Grave=92s.

THYROID=20 STORM

Is a=20 condition of hyperthyroid state accompanied by fever, CNS agitation,=20 Cardiovascular dysfunction precipitated by by infection, surgery or = trauma;=20 occasionally resulting from amiodarone administration. This condition was once = associated with=20 high mortality is well managed in ICU setup with hemodyanamic support, = IV=20 hydrocortisone, B-blockers and iodides. =20

SOLITARY=20 NODULE THYROID

Refers=20 to the Single palpable nodule of the thyroid. It is a common disease of = the=20 thyroid gland. 5% to = 10% of =20 them turn out to = be=20 malignant and hence excision of the nodule =20 was advocated. = However in=20 the last decade with better understanding of the pathology and = refinements in=20 investigations many of = them are=20 managed conservatively = since most=20 of them are benign. = Nodules which=20 are high risk are identified and excised. =20 The ultimate decision for surgical intervention depends on the=20 cost-effective workup of the patient. =20 A proper history, clinical exam and investigations like US, = FNAC will lead to the ultimate = diagnosis and=20 surgical management. &n= bsp; =20

History:

The=20 high risk patient for malignancy are

- =20 age=20 under20 and over 50 years.

- =20 Male

- =20 Nodule=20 of short duration

- =20 Increase=20 in size with or without pain

- =20 Sudden=20 increase in size may suggest hemorrhage within a = nodule

- =20 Adherent=20 to the surrounding structures

- =20 Hoarseness=20 of voice suggest rec laryngeal N. palsy

- =20 h/o of=20 unexplained diarrhea suggest medullary ca of = thyroid

- =20 h/o of=20 exposure to radiation during childhood

- =20 h/o of=20 thyroid malignance in the family for medullay ca

Physical=20 Exam:

- =20 Solitary=20 thyroid swelling =20

- =20 Nodules=20 that are hard, gritty or fixed to the surrounding structures=20

- =20 Cervical=20 chain of lymph nodes and Delphi nodes &n= bsp; =20

Thyroid=20 Function Test

Are not=20 helpful since most patients are euthyroidand only when clinical = suspicion of=20 hyperthyroidism is present it is done. =20 In less than 1% of thyroid malignancy present as=20 hyperthyroidism

ULTRASOUND

The=20 investigation is helpful

- =20 since=20 it is noninvasive

- =20 can=20 detect if there nodule is single or multiple

- =20 cystic=20 or solid or mixed

- =20 us=20 guided FNAC could be done if the nodule is not palpable and=20 deep

- =20 and=20 directed for the solid component in a mixed echogenic=20 nodule.

- =20 The=20 chance of malignancy in multinodular goiter is less than=20 4%

- =20 and in pure cystic nodule it is = always=20 benign =

RadioNuclide=20 Imaging

The use=20 of Radionuclide imaging has declined for the management of solitary = nodule=20 thyroid.

- =20 Depending=20 on the uptake of radio-iodine they are classified as hot, warm and = cold

- =20 Hot-=20 more uptake than the surrounding thyroid

- =20 Warm- similar to the surrounding=20 thyroid

- =20 Cold-no=20 uptake

- =20 Chance=20 of malignancy in hot, warm, cold nodule is 4%,8% and 12%=20 respectively

FINE=20 NEEDLE ASPIRATION:

- =20 Single=20 most important test in the evaluation of thyroid = nodule

- =20 may be=20 performed with or without US guidance

- =20 with=20 fine guage needle 23G: 2 slides are prepared: one air dried and another = fixed=20 with 70% alcohol and=20 stained

- =20 If=20 bloody, FNAC repeated

- =20 after=20 FNAC the lesions are cateogorised as benign 65%, suspicious 20%, = Malignant 5%,=20 non diagnostic 10% &n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; =20

- =20 incidence=20 of false +ve is 1%, false =96ve is 3%

- =20 if=20 nondiagnostic repeated; = often=20 indicated follicular neoplasm

- =20 benign=20 lesions are cysts and colloid nodules; =20 risk of malignancy is <3%

- =20 risk of=20 malignancy in suspicious cytologyis 10 to 20%.

- =20 Diagnosis=20 of papillary ca of thyroid by FNAC is 100%

- =20 The=20 diagnosis of follicular ca cannot be made out and a diagnosis of = follicular=20 neoplasm is given. Pt = undergoes=20 surgery and frozen = section is=20 equally not diagnostic and final diagnosis is made out only after final = biopsy=20 report.

- =20 the=20 diagnosis of medullary ca and anaplastic can be made out by experienced=20 cytpathologist.

- =20 the=20 diagnosis of benign lesion is made out by the presence of colloid and=20 macrophages in the aspiration

MANAGEMANT

- =20 simple=20 cysts are aspirated; = repeated 2 or=20 3 times; If cyst persist = after=20 3^rd aspiration surgery is indicated

- =20 if cyst=20 >4cm and cyst is complex again surgery is = indicated

- =20 for=20 colloid nodule pt is observed serially by US ,FNAC and TG=20 levels.

- =20 L-thyroxine=20 suppression for benign nodules with the hope that most of them respond = to
TSH suppression; more = effective with=20 nodules <3cm.

- =20 one=20 should not markedly suppress TSH since the risk of osteoporosis and = cardiac=20 arrythmias exist; = throidectomy for=20 nodules which enlarge on TSH suppression, for compressive symptoms and = cosmetic=20 reasons. =

Back

&n= bsp; &nb= sp; &nbs= p; = ; =20

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; &nb= sp; &nbs= p; = ; =20

THYROID=20 CANCERS

= &n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp;

Thyroid=20 cancer represent <1% of all the malignancies 90 to95% of thyroid = cancers are=20 cateogorised as well differentiated arising from follicular cells. They are Papillary, follicular = ,mixed=20 papillary follicular, Hurtle cell neoplasm, anaplastic, medullary ca of=20 thyroid,lymphomas and other rare tumors Medullary ca of thyroid arises = from=20 parafollicular cells and constitute 6% of thyroid = cancers.

Papillary=20 cancer

Most=20 common of thyroid neoplasm with excellent prognosis. =

More=20 common in young females <40 years; 70 to 80% of thyroid cancers are = papillary=20 cancers.

H/o of=20 irradiation in childhood predisposes to papillary ca (for = acne,tonsillitis,=20 hodgkin=92s)

Diagnosis=20 depends on the finding of well differentiated papillary cytology which = sometimes=20 come with follicular architecture with minimal papillary architexture, a = follicular variant. Both = classical=20 and follicular variant have the same prognosis.

Individual=20 cell morphology consists of =20 intranuclear inclusion bodies,cellular grooving on FNAC; additional finding of = calcified clumps=20 of cells(sloughed papillary cells) known as psammoma bodies is = diagnostic=20 of papillary ca. Other = subtypes=20 have unpredictable aggressive behaviour. It tends to occur in older = patients=20 with worse prognosis.

Clinical=20 features =

Present=20 as thyroid nodule, more in females, as painless firm mass, or as lateral = neck=20 mass with normal thyroid; = most=20 patients have excellent prognosis with 95 % survival rate at=20 10yrs

The=20 prognosis generally depends of the clinical manifestation and its=20 pathology.

They=20 are grouped into high risk and low risk groups AMES by Cady and AGES by=20 Hay

Age at=20 diagnosis turn out to be the most important clinical prognosis; age = <40 yrs=20 is important prognostic factor for long term survival =

Similarly=20 size; size less than 4cm = and with=20 no metastasis has good prognosis

Low=20 risk

Age

<40

Sex

female

extension

No=20 local

extension

metastasis

Size

<2cm

grading

Well=20 diff

Poorly=20 diff

High=20 risk

>40

Male

Capsular=20 and extrathyroidal

extension

Regional,

distant

>4cm

The=20 study of DNA ploidy is to used to evaluate the clinical prognosis but = still=20 universal agreement does not exist about its value

For=20 lesions <1-2cm thyroid lobectomy and isthumectomy is=20 appropriate

For=20 lesions >4cm there is a high rate of metastasis and so total = thyroidectomy is=20 indicated with lymphnode dissection if palpable

The=20 advantages of total thyroidectomy =20 is 1)it enables RAI to effectively detect and treat residual and=20 metastatic diseases 2) makes Tg level a more sensitive marker for = recurrent or=20 persistent disease 3) eliminates the contralateral occult ca a site of=20 recurrence 4)reduces the risk of recurrence since 85% of the tumors are=20 multifocal and improves survival 5) decreases the 1% of risk of = progression to=20 undifferentiated or anaplastic ca 6) reduces the need for reoperative = surgery=20 with its attendant complication rate

The=20 advantages of less invasive surgery (lobectomy and isthumectomy) are 1) = total=20 thyroidectomy has higher=20 complication rate like recurrent laryngeal N palsy and = hypoparathyroidism 2)=20 recurrence in the remaining thyroid is unusual and <5% 3) tumor=20 multicentricity seems to have little prognostic value 4) people undergo = less=20 invasive surgery has almost good prognosis.

FOLLICULAR=20 CARCINOMA:

Is the=20 second cateogory of well diff ca

FTC=20 constitute 10% of all thyroid malignancy

It=20 occurs in older age groups; affecting females 3:1 ratio with=20 males

It has=20 increased incidence in areas of endemic goiter-iodine=20 deficiency

A=20 subtype of FTC which consists of oxyphilic cells is known as Hurtle cell = ca

Histopathology=20 shows variable picture of normal follicular epithelium to severe altered = cellular architecture- The diagnosis of FTC depends on the of follicular = cells=20 invading the capsule, lymphatic and vascular = system.

With=20 the above criteria it could be minimally invasive to widely=20 invasisve

Lymph=20 node involvement is unusual and is less than 10%

Widely=20 invasive tumour usually has distant metastasis involving lungs,bone and = other=20 organs

Clinically=20 presents as a painless thyroid mass; the existence of FTC in a = multinodular=20 goiter is about 10%; the=20 coexistence of lymphnode involvement is extremely = rare

Finding=20 of hoarseness, fixation of a mass suggest advanced disease and poor = prognosis;=20 extension into trachea and surrounding tissue carried out by CT or=20 MRI

Patients=20 are usually euthyroid; hyperfunctioning of = thyroid=20 malignancy is reported to be <2%.; US and FNAC is of limited value; = since=20 capsular invasion cannot be made out; even frozen section is notoriously = not=20 informative.

Treatment=20 is primarily surgical; the final biopsy report tells about the capsular=20 invasion

If the=20 lesion is confined to one lobe and <2cm hemithyroidectomy will=20 suffice

If=20 >2cm total thyroidectomy is indicated; lymph node dissection is not = indicated=20 and does not increase the survival rate

Prognosis=20 depends on the age and = patient=20 <40yrs has survivalof 95% at 10yrs

Comparing=20 papillary ca poorer prognosis; we diff FTC has 80% survival at 10yrs = compared to=20 poorly differentiated 60% at 10yrs

The=20 advantages and disadvantages of total thyroidectomy are same as = papillary ca=20

Postop=20 suppression with thyroxine with the assumption that TSH induced growth = of the=20 tumor is retarded

The=20 current trend do not recommend the high dose of thyroxine suppression = since=20

High=20 dose leading to osteoporosis

RAI is=20 most effective after total thyroidectomy and pats who have undergone = hemi or=20 subtotal throidectomy need a higher dose of = radioiodine

The=20 hurtle cell variant behaves like FTC and some say it has poorer = prognosis

ANAPLASTIC=20 CANCER=20

It=20 consists of <1% of thyroid malignancy

Most=20 aggressive

More=20 common in the elderly

By the=20 time of presentation itself is more advanced with local=20 infiltration

Cells=20 are poorly differentiated and some has well differentiated cells = improving the=20 prognosis and also telling the degration of well diff tumor to = anaplastic=20 variety

MEDULLARY=20 CARCINOMA =20

Consists=20 of 5 to 10% of thyroid malignancy

Involves=20 the parafollicular cells which are derived from the neural crest=20 cells

The=20 biological marker for the disease is calcitonin

It=20 occurs in sporadic and familial forms as MEN type2a and = 2b

The 2a=20 has a better prognosis

In=20 sporadic form it presents as a palpable mass single, unilateral and no = familial=20 disposition with elevated calcitonin levels; absence of a mass with = elevated=20 calcitonin levels should include a detailed workup of the family to rule = out MEN=20 syndromes

The=20 treatment in sporadic form is total thyroidectomy with or without = central=20 lymphnode dissection subject to the histopathological report. In sporadic form it is = confined to one=20 lobe; in MEN types the upper poles of both lobes are=20 involved

Central=20 lymphnode dissection involves appropriate staging; any palpable = lymphnode in the=20 lateral group requires modified radical neck dissection; calcitonin = levels are=20 undetectable after surgery; RAI is given for ablating the residual = thyroid and=20 distant metastasis

A scheme = for=20 evaluation of patients who present with metastatic cancer thought = possibly=20 to be from the thyroid.

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