THYROID PROBLEMS FOR PHYSICIANS

Dr. Shyam Kalavalapalli

MRCP (London), CCT, FRCP (edin), MRCP(Diabetes & Endocrinology)
Consultant Endocrinologist (07396642302)
Worked for 16 years in the U.K. Trained at Cambridge, Oxford, Hammersmith (Imperial College London) and Manchester University Teaching Hospitals. Previously Consultant at Salford University Teaching Hospital Published and presented at National and International Journals and Conferences.

Anatomy of the Thyroid Gland

Epiglottis Red blood cells Colloid Follicular cells Thyroid gland Isthmus Parafollicular cells

Thyroid cartilage

Trachea

Location1

In the anterior neck, on the trachea and interior to the larynx Butterfly-shaped with two lateral lobes connected by isthmus1 Superior and inferior thyroid arteries2
2

Structure

Blood supply

1. Marieb E, Hoehn K. Human Anatomy and Physiology. 2007:620-625. 2. Jameson J, Weetman A. Harrison's Principles of Internal Medicine. 2008:2224-2247.

Feedback Effect of Thyroid Hormone to Decrease Anterior Pituitary Secretion of TSH

Hypothalamus (? Increased temperature)

(Thyrotropinreleasing hormone)

TSH-R Basal NIS I-

Anterior pituitary

cAMP

I-

Apical TPO Thyroid stimulating hormone DIT Tg-MIT Tg + I-

Tg Follicular cell

Iodination Hypertrophy Increased secretion Thyroid Iodine

Guyton, H. Textbook of Medical Physiology. 2007: 931-943. Jameson J, Weetman A. Harrison's Principles of Internal Medicine. 2008: 2224-2247.

TFT A practical review

Hypothalamus TRH

Pituitary T4 T3 Thyroid Gland Liver T4 T3 T4 T3 Liver Adapted from Merck Manual of Medical Information. ed. R Berkow. 704:1997.
TR

TSH

Target Tissues
Heart

Bone CNS

Thyroid Function Tests

Thyroid function tests are performed on serum specimens using either manual or automated methods employing specific antibodies Serum TSH level measurement remains the single best indicator of thyroid function

Test Serum thyrotrophic/thyroid-stimulating hormone (TSH) Serum triiodothyronine Free triiodothyronine Serum thyroxine Free thyroxine Thyroid anti-TPO antibodies Thyroglobulin antibody titer Thyroid function tests, thyroid antibody 24 hours uptake fine I131 needle aspiration biopsy are some
1. Joshi S. Journal of The Association of Physicians of India; 2011: 14-20. 2. SI Units for Clinical Data. University of North Carolina.

Normal Range1,3 0.5-4.7 mIU/L 0.92-2.78 nmol/L (59.74-180.52 ng/dL) 0.22-6.78 pmol/L (14.3-440.26 pg/dL) 58-140 nmol/L (4.5-10.88 g/dL) 10.3-35 pmol/L (0.8-2.72 ng/dL) Varies Varies tests, radioactive iodine uptake and 5%-35% thyroiditis tests to diagnose
5

Algorithm for Diagnosis of Thyroid Dysfunction

TSH

High

Normal

Low

Free T4

Free T4

Low

Normal

Normal

High

Hypothyroidism

Subclinical Hypothyroidism

Subclinical Hyperthyroidism

Hyperthyroidism

Joshi S. Journal of The Association of Physicians of India; 2011:14-20.

Recent Prevalence Data North India

April 2012
N= 4409

Thyroid Disorder
Overt Hypothyroidism Subclinical Hypothyroidism Anti TPO Positivity Hyperthyroidism Goiter

Prevalence (%)
4.2 19.3 13.3
( Ab 35 -102 g/L)

Males (%)
1.6 15.9 6.1
( Ab >102 g/L)

Females (%)
1.9 21.4 10.8
( Ab >102 g/L)

1.13 9.6

0.7 3.3

1.4 13.3

High prevalence of subclinical hypothyroidism was not correlated with either thyroid autoimmunity or iodine intake
Marwaha et al ,Status of Thyroid Function in Indian Adults: Two Decades After Universal Salt Iodization, JAPI april 2012 VOL. 60 32-36 7

Primary Hypothyroidism: Etiology

Thyroid dysfunction

Autoimmune thyroiditis (Hashimotos thyroiditis) Congenital absence or defect in the thyroid tissue Thyroid removal by surgery Radio ablation by radio active iodine or irradiation Destruction of thyroid tissue caused by infiltrative disorders

Impaired synthesis of thyroid hormone

Iodine deficiency Congenital enzymatic defects Drug-mediated: thionamides, amiodarone, lithium, aminoglutethimide

Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.

Secondary Hypothyroidism: Etiology

Reduced secretion of TRH or TSH

Hypothalamic disorders
Tumor (lymphoma, germinoma, glioma) Infiltrative disorders (sarcoidosis, hemochromatosis, and histiocytosis)

Hypopituitarism
Mass lesions Pituitary surgery Pituitary irradiation Hemorrhagic apoplexy (Sheehans syndrome) Lymphocytic hypophysitis

Ladenson P, Kim M. Cecil Medicine. 2008:1698-1713.

Clinical Manifestations: Symptoms

Symptoms1,2

Tiredness/ weakness Dry skin Cold sensation Hair loss Poor concentration/memory loss Constipation Weight gain with poor appetite Dyspnea Hoarseness of voice Menorrhagia Paresthesia Hearing impairment

1. 2.

Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713. Jameson JL, et al. Harrison's Principles of Internal Medicine. 2008: 2224-2247.

10

Clinical Manifestations: Signs

Signs1,2

Cold peripheral extremities Dry, coarse and yellow skin Puffiness of face, hands and feet Hair loss and brittle nails Bradycardia/ diastolic hypertension Delayed tendon reflex relaxation Peripheral edema Serous cavity effusions Normal/enlarged/atrophied thyroid gland Delayed linear growth in children Delayed or precocious puberty Pseudohypertrophy of muscles
11

Hypothyroidism in children

1. 2.

Ladenson P and Kim M. Cecil Medicine. 2008:1698-1713. Jameson JL et al. Harrison's Principles of Internal Medicine. 2008: 2224-2247.

Laboratory Diagnosis

TSH assay:
Primary test to establish the diagnosis
Overt hypothyroidism

Additional tests:
Estimation of free T3 and T4 Test for thyroid autoantibodies Thyroid scan/ultrasonography

T3/T4

TSH

Subclinical hypothyroidism
TSH

T3/T4

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

12

Ultrasonography of the Thyroid

Ultrasonography provides accurate information on the size, shape, and texture of the thyroid gland

It is the most valuable technique to evaluate the anatomy of the thyroid gland

Mostly used for detecting nodular thyroid disease1 The thyroid gland is slightly more echo-dense than the adjacent structures because of its iodine content2

1. Gharib H, et al. Endocr Pract. 2010;16 (suppl 1):1-43. 2. Ultrasonography of the thyroid. Thyroid manager org website.

13

Ultrasonography of the Thyroid (Contd)

Sonogram of the neck in the transverse plane showing normal right thyroid and isthmus

Sonogram of the left lobe of the thyroid gland in the transverse plane showing a rounded lobe of a goiter

L=small thyroid lobe, I=isthmus, T=tracheal ring (dense white arc is calcification, distal to it is the artifact), C=carotid artery (note the enhanced echoes deep to the fluid-filled blood vessel), J=jugular vein, S=sternocleidomastoid muscle, m=strap muscle.

L=enlarged lobe, I=widened isthmus, T=trachea, C=carotid artery (note the enhanced echoes deep to the fluid-filled blood vessel), J=jugular vein, S=sternocleidomastoid muscle, m=strap muscle, E=esophagus.

14
Ultrasonography of the thyroid. Thyroidmanager org website.

Treatment Overview

Goal: To mimic normal, physiological levels and alleviate signs, symptoms, and biochemical abnormalities

Treatment should be tailored to individual needs

Treatment of choice: Levothyroxine (LT4) replacement therapy

Desiccated thyroid hormone and T3+T4 mixture: Insufficient evidence and not recommended for replacement therapy by the AACE guidelines

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

15

Subclinical Hypothyroidism

16

Subclinical Hypothyroidism

Criteria defining subclinical hyperthyroidism:

Slightly elevated serum TSH levels FT4 and T3 levels within the reference range

Most common cause: autoimmune thyroiditis (Hashimotos disease) Predisposing factors

Advancing age Greater iodine consumption

Often asymptomatic May represent early thyroid failure

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

17

Subclinical Hypothyroidism

Progression to overt hypothyroidism

Occurs in 3-20% patients Patients with goiter and thyroid antibodies at higher risk for progression

Associated risks

Progression to overt hypothyroidism

Cardiovascular effects Hyperlipidemia Neuropsychiatric effects

1. 2.

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13. \http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

18

Comorbid Conditions
AUTOIMMUNE DISORDERS

HYPERLIPIDAEMIA

HYPOTHYROIDISM

INFERTILITY

DEPRESSION

1. 2.

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. Duntas LH, Biondi B. Semin Thromb Hemost. 2011;37(1):27-34.

22

Levothyroxine: Dosing

Recommended mean daily dose of LT4 therapy: 1.6 mcg/kg of body weight Initiate with 12.5 mcg daily to a full replacement dose of LT4 depending on age, weight, and cardiac status Reassess TSH and/or free T4 after 6 weeks Follow up after 6 months and thereafter annually, once TSH is in normal range

Adjust doses as appropriate in case of absorption variability and drug interactions Keep in mind that inappropriate dose adjustments can lead to increased costs due to additional patient visits and laboratory tests

AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

23

Levothyroxine: Drug Interactions

Increase LT4 dose with

Drugs that reduce thyroxine production: lithium, iodine-containing drugs, and amiodarone Drugs that reduce thyroxine absorption: sucralfate, ferrous sulfate, cholestyramine, colestipol, aluminum-containing antacids, and calcium supplements Drugs that increase thyroxine metabolism: rifampin, phenobarbital, carbamazepine, warfarin, and oral hypoglycemic agents

Decrease LT4 dose with

Drugs that displace thyroxine from binding proteins: furosemide, mefenamic acid, salicylates, vitamin C

1. 2.

Hueston WJ. Treatment of Hypothyroidism. American family physician. 64(10): 1717-1724. AACE medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006:1-13 http://www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf.

24

Summary

Hypothyroidism can be either subclinical or overt based on the level of severity. LT4 is recommended by the AACE for effective treatment of both subclinical and overt hypothyroidism. Because of narrow therapeutic index of LT4, even small changes in the dose of LT4 can shift a patient from a euthyroid to a hyperthyroid or hypothyroid state. The AACE advocates use of high-quality brand preparation of LT4 Appropriate dose adjustments of LT4 is required in case of absorption variability and drug interactions The major co-morbid conditions associated with overt and subclinical hypothyroidism include diabetes mellitus, infertility, depression and hyperlipidemia

What is Myxedemic Coma?

Myxedemic coma is decreased LOC associated with severe hypothyroidism. Myxedemic coma generally used to mean CRITICAL hypothyroidism 30% mortality.

Physical Findings

Comatose or semi comatose Dry coarse skin Hoarse voice Thin dry hair Delayed reflex relaxation time Hypothermia Pericardial, pleural effusions, ascites

Etiology of Myxedemic Coma

Undiagnosed Undertreated

(Hashimotos thyroiditis, post surgery/ablation Precipitants of most common)

Acute Precipitant

Myxedemic Coma

Myxedemic Coma Infection Trauma Vascular: CVA, MI, PE Noncompliance with Rx Any acute medical illness

Pathogenesis of Myxedema

When should Myxedema be considered

Altered LOC
Structural vs metabolic causes of decreased LOC

Hypoventilatory Resp Failure

Narcotics, Benzodiazepines, EtOH intoxication, OSA,

obesity hypoventilation, brain stem CVA, neuromuscular disorders (MG, GBS)

Hypothermia
Environmental Medical: pituitary or hypothalamic lesion, sepsis

Management of Myxedemic Coma

Levothyroxine is the cornerstone of Mx Levothyroxine 500 ug po/iv (preferred over T3) Ischemia and arrythmias possible: monitor Other Intubate/ventilate prn Fluids/pressors/thyroxine for hypotension Thyroxine for hypothermia Stress Steroids: hydrocortisone 100 mg iv

Hyperthyroidism

Algorithm for Diagnosing Hyperthyroidism

Signs and symptoms of hyperthyroidism Measure TSH level

Suppressed TSH level Measure free T4 level

Elevated TSH level (rare) Measure free T4 level High

Normal Measure free T 3 level

High Primary hyperthyroidism Thyroid uptake Secondary hyperthyroidism Image pituitary gland High

Normal Subclinical hyperthyroidism Resolving hyperthyroidism Medication Pregnancy Nonthyroid illness

Elevated T3 toxicosis Low

Measure thyroglobulin Diffuse Decreased Increased Graves disease Nodular

Exogenous hormone

Thyroiditis lodide exposure Extraglandular production

Multiple areas Toxic multinodular goiter

One hot area Toxic adenoma

Reid JR. AAFP. 2005;72(4):623-630.

34

Hyperthyroidism: Diagnosis

Radioactive iodine uptake and scanning useful tool to diagnose and evaluate thyrotoxicosis

Thyroid sonography diagnoses thyroid nodules and goiter that may not be readily apparent on examination

Sonographic doppler flow assessment helps distinguish between Graves disease and thyrotoxicosis caused by nonhypermetabolic destructive thyroiditis

Sahay RK. JAPI. 2011;59:26-31.

16

Treatment and Management

Thyrotoxicosis: Treatment and Management

Treatment
Antithyroid drugs (Methimazole)

Mechanism of Action
Inhibit the formation of thyroid hormone by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin Inhibit the coupling of these iodotyrosyl residues to form thyroglobulin

Dosage
Methimazole 30 to 40 mg once daily

Therapeutic Uses
Definitive treatment, to control the disorder in anticipation of a spontaneous remission in Graves disease In conjunction with radioactive iodine Controls the disorder in preparation for surgical treatment

Side Effects
Common: rash, urticaria, fever, and arthralgia Less frequent: pain and stiffness in the joints, paresthesias, headache, nausea, skin pigmentation, and hair loss Rare: agranulocytosis, drug fever, hepatitis, and nephritis

Propylthiouracil has lesser adherence rates and more toxicity, thus its use is restricted Methimazole and its pro-drug carbimazole are more effective in this regard

1. Farwell AP. The Pharmacological Basis of Therapeutics. 2006: 1511-1540. 2. Jameson JL.. Harrisons Principles of Internal Medicine. 2008;2224-2247. 3. Cooper D. J Clin Endocrinol Metab. 2009;96(6):1881-1882.

37

Thyrotoxicosis: Treatment and Management (Contd)

Treatment
Iodides

Mechanism of Action
High concentrations of iodide influence iodine metabolism by the thyroid gland Inhibits synthesis of iodotyrosines and iodothyronines (Wolff-Chaikoff effect)

Dosage
Minimum effective dose in most patients: 6 mg iodide per day Strong iodine solution (Lugols solution) 3 to 5 drops t.i.d. Saturated solution of potassium iodide (SSKI) 1 to 3 drops t.i.d.

Therapeutic Uses
Preoperative period in preparation for thyroidectomy Conjunction with antithyroid drugs and propranolol Protects the thyroid from radioactive iodine fallout following a nuclear accident in the treatment of thyrotoxic crisis

Side Effects
Angioedema, laryngeal edema, serum-sickness type of hypersensitivity, thrombotic thrombocytopenic purpura, fatal periarteritis nodosa Skin lesions, gastric irritation, diarrhea, fever, anorexia, depression

Farwell AP. The Pharmacological Basis of Therapeutics. 2006: 1511-1540.

38

Thyrotoxicosis: Treatment and Management (Contd)

Treatment
Radioactive iodide

Mechanism of Action
Gets trapped by thyroid, incorporated into iodoamino acids, is deposited in the colloid of the follicles, from which it is liberated Acts only on the parenchymal cells of the thyroid

Dosage
I131 7,000 to 10,000 rads per gram of thyroid tissue administered orally

Therapeutic Uses
Used widely in the treatment of hyperthyroidism and in the diagnosis of disorders of thyroid function

Side Effects
Delayed hypothyroidism, long response time, worsening of ophthalmopathy, salivary gland dysfunction Very rare: thyroid storm

Farwell AP. The Pharmacological Basis of Therapeutics. 2006: 1511-1540

19

Possible Risks of Treatment with I-131

I-131 is administered orally & is tasteless & odorless. Often one time treatment is adequate. Absolutely contraindicated in pregnancy. Be sure patient is not pregnant (treatment or test), Hypothyroidism is the only known side effect. It occurs: 50% in 10 years, 75% in 20 years and probably 100% in longer follow-ups.

Thyrotoxicosis: Adjuvant Therapy

Drugs used for symptomatic treatment of thyrotoxicosis

-adrenergic receptor antagonists propranolol 20 to 40 mg q.i.d. or atenolol 50 to 100 mg daily

Reduce sympathetic or adrenergic effects such as tachycardia, tremor, anxiety, and palpitation

Calcium channel blockers diltiazem 60 to 120 mg q.i.d.

Controls tachycardia and decreases the incidence of supraventricular tachyarrhythmias

Dexamethasone 0.5 to 1 mg b.i.d. or q.i.d.

Rapid treatment of the severely thyrotoxic patients

20

Farwell AP. The Pharmacological Basis of Therapeutics. 2006: 1511-1540.

Amiodarone induced thyrotoxicosis

About 3% of amiodarone-treated patients in the United States become hyperthyroid. (Hypothyroidism is more common than hyperthyroidism) Two basic mechanisms in AIT Type I Increase synthesis of T4 and T3 - Pre-existing multinodular goiter or latent Graves disease. More commonly seen in iodine-deficient areas of the world Type II Direct toxic effect of amiodarone causing thyroiditis and hence release of T4 and T3 without increased hormone synthesis. More commonly seen in iodine-sufficient countries

Amiodarone induced thyrotoxicosis treatment

Type I AIT . Drugs-Thionamide (PTU or methimazole) is the first line therapy (whether amiodarone is continued or discontinued). Higher than average doses are often needed . Radioiodine ablation if the RAIU is high enough. . Surgery only if refractory to antithyroid drug therapy. Type II AIT . Glucocorticoids Prednisone 40-60 mg/day. Continue therapy for one to two months before tapering Mixed type I and type II AIT . Combination of glucocorticoid and thionamine initially. A rapid response suggests type II, the thionamide can then be tapered or stopped. A poor or slow initial response argues for type I AIT

Nonthyroidal illness (Euthyroid Sick Syndrome)

Abnormal findings on TFT that occur in the setting of a NTI without preexisting hypothalamic-pituitary and thyroid gland dysfunction. The most prominent alterations are low serum T3 and elevated reverse T3 (rT3). Serum TSH, T4, and FT4 are also affected in variable degrees based on the severity and duration of the NTI.

Probable mechanism: - Decreased or inhibition of 5-monodeiodination (endogenous cortisol or exogenous glucocorticoid therapy, non-esterified fatty acids, cytokines TNF, IF, IL6.) - The peripheral production of T3 is decrease, but its clearance is unchanged; whereas, the production of rT3 is unchanged, while its clearance is diminished Treatment is not needed. After recovery from an NTI, these thyroid

Thyroid Storm

What is Thyroid Storm? Malignant or critical thyrotoxicosis

Etiology of Thyroid Storm

Undiagnosed Undertreated
(Graves disease or Multinodular toxic goiter)

Acute Precipitant

Thyroid Storm

10% of hospital admissions 20% mortality D/D: Sepsis, CNS infection, psychiatry illness

KEY FEATURES of Thyroid Storm

Fever Tachycardia Altered LOC Features of underlying Hyperthyroidism

Weight loss, heat intolerance, tremors, anxiety, diarrhea,

palpitations, sweating, CP, SOB Goiter, eye findings, pretibial myxedema Level of Thyroid function is not discriminatory, but organ dysfunction is the criteria

Treatment of Thyroid Storm

Sympathetic outflow

Triangle of Treatment Production and release of thyroid hormone Peripheral conversion (T4 T3)

Summary of Management

Supportive care Identification and treatment of the precipitating event Blocking the release and effects of Thyroid Hormone - Propylthiouracil (PTU) 1000mg loading and 1200mg/day tds or Carbimazole - Propranolol IV 1mg every 10 to 15 minutes until symptoms are controlled. - Hydrocortisone 100 mg IV 8 hourly. - Iodine acts by inhibiting hormone release but should not be given until 1 hour after PTU administration. - Plasmapheresis/ plasma exchange/ hemodialysis

Goiter

Goiter: Overview

Abnormal enlargement of the thyroid gland1 Occurs in conditions of hyperthyroidism, hypothyroidism, or euthyroidism1 The global goiter prevalence is >2 billion with more than 40 million in India2 Overall prevalence of 5.4% hypothyroidism, 1.9% hyperthyroidism, and 7.5% of autoimmune thyroiditis in goitrous subjects2 Increased frequency of single and multiple thyroid nodules in women over 45 years of age3 About 200 million people are at a risk of iodine deficiency disease in India2

1. American Thyroid Association. 2005. 2. Sahay RK. JAPI. 2011;59:26-31. 3. Henneman. Thyroid manager website. 2010.

25

Goiter: Etiology

Iodine deficiency

Lack of iodine leads to decreased levels of thyroid hormones Pituitary gland stimulates thyroid gland to produce hormone through TSH signals

Hashimotos thyroiditis

Autoimmune condition, where there is destruction of the thyroid gland by ones own immune system

Graves disease

Thyroid stimulating immunoglobulin (TSI) stimulates the thyroid gland to enlarge TSI also stimulates the thyroid gland to produce more thyroid hormones

Multinodular disease

Presence of one or more nodules within the gland leading to enlargement of thyroid gland

Others

Genetic factors, infections in the thyroid gland, or tumors (benign and cancerous)
26

Goiter. Thyroid org website. 2009.

Goiter: Clinical Features

Most goiters are asymptomatic

Presence of goiter

Sudden onset of localized pain and swelling

Reveals a symmetrically enlarged, nontender, generally soft gland without palpable nodules
Normal

Enlargement of the thyroid gland leads to tracheal or esophageal compression

Jameson JL. Harrisons Principles of Internal Medicine. 2008;2224-2247.

27

Diffuse Nontoxic Goiter

Diffuse nontoxic (simple goiter)1

Diffuse enlargement of the thyroid gland that occurs in the absence of nodules and hyperthyroidism Absence of nodules and presence of uniform follicles that are filled with colloid Caused mainly due to iodine deficiency, occurs in >5% of the population Surgery is carried out in patients experiencing obstructive manifestations I131 therapy is used in elderly patients or in patients with large goiters2

Natural history of simple goiter3

Age (in years)

Goiter Tracheal compression/deviation T3, T4 levels TSH levels

15-25
Diffuse No Normal Normal

35-55
Nodular Minimal Normal Normal or undetectable

>55
Nodular Raised Raised Undetectable 28

1. Jameson JL. Harrisons Principles of Internal Medicine. 2008;2224-2247. 2. Schlumberger MJ. Williams Textbook of Endocrinology. 2008;411-438. 3. Walker BR. Davidsons Principles and Practice of Medicine. 2002;683-746.

Multinodular Goiter

Prevalent in 12% of adult population More common in women Characterized by difficulty in swallowing, respiratory distress, or plethora Voice hoarseness indicative of malignancy

Multinodular goiter

Pulmonary function tests used to assess the effects of compression and to detect tracheomalacia

CT or MRI used evaluate the anatomy of goiter and the extent of substernal extension Radioiodine 370 to 1070 MBq is administered Treatment with glucocorticoids Surgery indicated in patients with acute compression
29

1. Jameson JL. Harrisons Principles of Internal Medicine. 2008;2224-2247. 2. Farwell AP. The Pharmacological Basis of Therapeutics.2006:1511-1540.

Goiter: Investigations

Laboratory investigation

Measurement of serum TSH and free T4 Thyroid autoantibodies

Imaging

Ultrasonography Scintigraphy, rarely used CT and MRI scans

Levy EG. Thyroid today website. 2010.

33

Goiter: Diagnosis

Methods available for measuring goiter:

Neck inspection and palpation Thyroid ultrasonography

A thyroid is considered goitrous when each lateral lobe has a volume greater than the terminal phalanx of the thumbs of the subject being examined1 WHO classification for grading goiter2
Grades
Grade 0

Description
No presence of goiter (impalpable and invisible thyroid) Neck thickening is present as a result of enlarged thyroid, which is palpable, however, not visible in normal position of the neck; the thickened mass moves upwards during swallowing. Includes nodular goiter if thyroid enlargement remains invisible Neck swelling, visible when the neck is in normal position, corresponding to enlarged thyroid found in palpation
32

Grade 1

Grade 2

1. Marwaha RK. JAPI. 2011;59:7-10. 2. Jayakumar RV. JAPI. 2011;59:11-13.

Thyroid Neoplasms: Overview

Classification of Thyroid Neoplasms
Benign Follicular epithelial cell adenomas Macrofollicular (colloid) Normofollicular (simple) Microfollicular (fetal) Trabecular (embryonal) Hurthle cell variant (oncocytic) Malignant Follicular epithelial cell Well-differentiated carcinomas - Papillary carcinomas - Follicular carcinomas Undifferentiated (anaplastic) carcinomas C-cell (calcitonin-producing) Medullary thyroid cancer Other malignancy Lymphomas Sarcomas Metastases Others

Jameson JL. Harrisons Principles of Internal Medicine. 2008;2224-2247.

31

Toxic Multinodular Goiter

Includes features of goiter, subclinical hyperthyroidism, or mild thyrotoxicosis

Patients exhibit atrial fibrillation or palpitation, tachycardia, tremor, nervousness, and weight loss

Antithyroid drugs in combination with beta blockers can be used to control the clinical features of thyrotoxicosis

Radioiodine used to treat areas of autonomy and decrease mass of goiter

Surgery indicated in patients with underlying thyrotoxicosis and goiter

30

Jameson JL. Harrisons Principles of Internal Medicine. 2008;2224-2247.

Radioiodine Uptake

Useful to differentiate the type of thyrotoxicosis A set dose of I123 is given and 24 hr later a radiation detector is placed over the thyroid to determine the percentage of the dose that was taken up by the thyroid RAIU is high in : Graves disease, TSH-secreting pituitary tumor, hot nodules, hCG secreting tumor, iodine deficiency RAIU is low in : thyroiditis, thyroiditis factitia, iodine excess (contrast dye, amiodarone-induced thyrotoxicosis type 2)

Thyroid Scans

Scintiscan, or radionuclide scan A radioidine or Tc99m is given, and a scintillation scanner produces a rough picture indicating how these isotopes localize in the thyroid. Useful in nodular disease to determine whether a nodule is hot or cold. A hot functioning nodule is nearly always benign. A cold nodule has 5% chance of being malignant and should be further evaluate

Thyroid Ultrasound

Determine the size and the content of nodules (cystic or solid, or mixed.) Select site for biopsy FNA Provide assistance in therapeutic procedure (cyst aspiration, ETOH injection, laser therapy) and facilitate the monitoring of the effects of treatment. Worrisome characteristics: hypoechogenicity, microcalcification, irregular margins, increased nodular blood flow and evidence of margin or regional lymphadenopathy

Fine Needle Aspiration

First test of choice in euthyroid patient with a (palpable) nodule. False negative rate is 1-11%, and false positive rate of 1-8% About 69-74% of specimens are benign, 22-27% are indeterminate or suspicious, and about 4% are positive for cancer Cannot differentitiate microfollicular from follicular carcinoma. Sampling errors can be minimize by using ultrasound-guided biopsy.

Causes of Thyroid Nodularity

Benign
Follicular Adenomas Multinodular goiter (colloid adenoma) Hashimotos thyroiditis Cysts (colloid, simple, hemorrhagic)

Causes of Thyroid Nodularity

Malignant
Papillary Carcinoma Follicular Carcinoma Medullary Carcinoma Anaplastic and poorly differentiated carcinoma Primary lymphoma of the thyroid Metastatic carcinoma (especially breast and

renal cell carcinoma)

Low Suspicion
Family history of autoimmune disease (eg, Hashimotos thyroiditis) Family history of benign thyroid nodule or goiter Presence of thyroid hormonal dysfunction Pain or tenderness associated with nodule Soft, smooth, and mobile nodule

Hegedus: N Engl J Med, Volume 351(17).October 21, 2004.1764-1771

Radionuclide Scanning

Used to identify whether a nodule is functioning. Functioning nodules are nearly always benign Approximately 90 percent of nodules are nonfunctioning 5 percent of nonfunctioning nodules are malignant Thus, in the patient with a suppressed level of serum thyrotropin, radionuclide confirmation of a functioning nodule may obviate the need for biopsy.

Scintigraphy
Usually either Technetium or Radioiodine Normal follicular cells will trap both but only radioiodine is added to tyrosine and stored in the colloid space Both benign and almost all malignant neoplastic tissue concentrate both radioisotopes less than normal thyroid tissue 5-8% of warm or cold nodules are malignant

Cold Nodules
Thyroiditis Fibrosis Cyst Non-functioning Adenoma Multinodular Goiter Malignancy

Scintigraphy

Scintigraphy

Limitations of Scintigraphy
Two dimensional scanning technique Inability to measure the size of a nodule accurately Missed malignant thyroid nodules

Case
TR is a 40 year old female who presents for her annual physical. On exam, you palpate a 1.5x 2 cm nodule in the thyroid gland. The nodule is non-tender and mobile. Both her TSH and free T4 are normal. What test would you order next?

Ultrasonography

Facilitate fine needle aspiration biopsy of a nodule Assess the comparative size of nodules, lymph nodes, or goiters in patients who are under observation or therapy Evaluate for recurrence of a thyroid mass after surgery

Normal Right Thyroid Lobe

Goiter

Incidentalomas

FNAC Limitations

Hypocellular aspirates may be observed in cystic nodules, or they may be related to biopsy technique. The absence of malignant cells in an acellular or hypocellular specimen does not exclude malignancy. Inability to reliably distinguish a benign follicular neoplasm from a malignant neoplasm. Aspirates may be required from multiple sites of the nodule to improve sampling.

FNAC

Ultrasound Guided FNAC

FNAC

1. Follicular

1. Lymphocytes hashimotos

1. Colloid

Subacute (granulomatous) thyroiditis multinucleate giant cell

FNAC

papillary tissue fragment

1. Psammoma bodies

1. Azurophilic granules containing calcitonin

Anaplastic

Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule

Hegedus: N Engl J Med, Volume 351(17). October 21, 2004. 1764-1771