Thyroid Disorders

Eric J Milie, D.O.

Objectives

Understand basic interactions of the hypothalamic-pituitary-thyroid axis

Recognize the various causes of hypo- and hyperthyroid

Differentiate between acute, subacute, and chronic thyroiditis in terms of clinical picture and treatment

Explain the work-up required for a patient with a solitary thyroid nodule

Thyroid Anatomy

Small gland located in anterior portion of neck

Attached to larynx Two halves (lobes) connected by isthmus Resembles a butterfly or bow-tie From Greek word meaning shield Each lobe roughly 4cm long, 1-2cm wide Cannot normally be seen, barely palpable in

healthy adult

Thyroid Anatomy continued

Function of Thyroid Gland

Secretes thyroid hormones, which regulate metabolism throughout the body

Two hormones secreted: Thyroxine (T4) and Triiodothyronine (T3)

Thyroid Hormones

T4, the major hormone produced by the thyroid, has only slight effect on controlling body’s metabolism

T4 converted to T3 (active thyroid hormone) mainly in the liver and kidney

Many factors effect conversion rate, including body’s need from moment to moment and presence or absence of illness

Chemical Structure

Thyroid Hormones continued

T4 de-iodinated in liver and kidney, resulting in T3 and reverse T3 (inactive)

Thyroid hormones poorly soluble in water, so 99% protein bound

Principle carrier is thyroxine binding globulin, a glycoprotein synthesized by the liver

Some Thyroid Hormone Responsibilities

Heart rate Respiratory rate Rate of caloric consumption Skin maintenance Growth Fertility Digestion Heat regulation

Role of Iodine

Chief component of thyroid hormones, essential for their production

Iodine concentrated from blood via the Sodium-iodide symporter, so-called “iodine trap”

In areas where there is not sufficient levels of iodine (Great Lakes, Swiss Alps, Tasmania), iodine must be supplimented

In U.S., salt iodized, so iodine deficiency is rare

Sodium-Iodine Symporter

Thyroid Stimulating Hormone

Chief stimulator of thryoid hormone synthesis is TSH (Thyroid Stimulating Hormone), released from anterior pituitary

Most important controller of TSH secretion is Thyrotropin Releasing Hormone (TRH) from hypothalamic neurons

Secretion of TRH, and hence TSH, inhibited by high blood levels of thyroid hormones (negative feedback loop)

TRH-TSH-Thyroid Hormone Feedback Loop

Hypothalamic-Pituitary Axis Feedback loop pat of so-called “hypothalamic

pituitary axis” As thyroid hormone levels in blood increase,

negative feedback to hypothalamus and pituitary Leads to shut-down of thyroid producing follicles When circulating levels of thyroid hormone stabilize,

process begins anew Axis influenced by other factors, including

environmental factors (cold exposure leads to increase in thyroid hormone production in rodent models)

Hypothalamic-Pituitary-Thyroid Axis

Goiter Formation as Dysfunction of Hypothalmic-Pituitary-Thyroid Axis Insufficient dietary intake of iodine leads to

insufficient production of T3 and T4 Hypothalamus responds with increasing

levels of circulating TRH Causes pituitary to release more TSH Secondary function of TSH is thyroid cell

growth Prolonged exposure to high levels of TSH

results in goiter

Goiter

Thyroid Gland- Diagnostic Studies

No single test is 100% accurate in diagnosing thyroid disease, so usually combination of two or more tests ordered

TSH level is most common test ordered for monitoring of thyroid function

High levels of TSH usually indicative of under active thyroid gland (hypothyroid)

Low levels usually indicative of over active thyroid gland (hyperthyroid)

Diagnostic Tests continued

Measurement of T4 by radioimmunoassay (RIA) reflects the amount of T4 circulating in the blood.

Usually combined with T3 uptake to give a “free T4 level,” which corrects for other medications which influence the routine T4 test

Diagnostic Tests continued

Thyroid Binding Globulin may be ordered for patients with unexplained elevations or deficiency of T4 and T3

Excess or deficiency of TBG will alter the measurement of T3 and T4, but not the action of the hormones

Hereditary trait can cause excessive or deficient levels of TBG

Iodine Uptake Scan Radioactive iodine administered to patient Iodine concentrated in the thyroid or excreted in the

urine Uptake measured at various time intervals Does not measure hormone levels, merely avidity of

thyroid for iodine and clearance rate relative to kidney function

Diseases resulting in excessive production of thyroid hormone generally associated with increased RAIU, diseases resulting in decreased production generally show decreased RAIU

RAIU continued

Thyroid Scan

Usually done at same time as RAIU Useful in identifying nodules and defining if

they are “hot” or “cold” Measuring size of goiter prior to treatment Follow-up in thyroid cancer patients after

surgery Locating thyroid tissue outside of neck, such

as at base of tongue or in the chest

Thyroid Scan

Two types, camera scan and Computerized Rectilinear Thyroid scan

Camera scan most common, takes 5-10 minutes

CRT developed in the 1990’s, improves clarity, more precisely identifies nodules, and provides information on both function and size

Camera Scan

Camera scan images showing “hot nodule” (left) and “cold nodule” (right)

CRT

Thyroid Ultrasound

Screening tool for suspected thyroid nodule Can identify if nodule is cystic or solid, but

provides little help determining if it is benign or malignant

Can detect changes in nodule’s size Useful in assisting with needle biopsy of

thyroid

Thyroid Ultrasound

Ultrasound Characteristics Suggesting Benign Nodule

Sharp edges around entire nodule (well circumscribed)

Nodule filled with fluid and not live tissue (cystic)

Multiple nodules throughout the thyroid No blood flowing through nodule on Doppler

(suggest cystic lesion)

Fine Needle Biopsy

Most reliable test to determine whether “cold” nodule cancerous or benign

Provides definitive diagnosis in up to 75% of biopsies

Further discussion later in presentation

Euthyroid Sick Syndrome: Definition

Clinical condition in which patients suffering from severe non-thyroid illness are clinically euthyroid but biochemically dysthyroid

Euthyroid Sick Syndrome: Precipitating Factors

Fasting Starvation Anorexia nervosa Protein malnutrition Surgical trauma Hyperthermia

Myocardial infarction Chronic renal failure Diabetic ketoacidosis Cirrhosis Sepsis

Euthyroid Sick Syndrome: Lab Findings

T4 concentration is normal or decreased T4-binding to TBG is decreased T3 concentration is decreased rT3 concentration is increased TSH concentration is normal Thyroid scans usually normal

Euthyroid Sick Syndrome: Pathogenesis

When people are sick or malnourished or have had surgery, the thyroid hormone T4 is not converted normally to the active T3 hormone

Large amounts of reverse T3 accumulate Despite this abnormal conversion, the thyroid

functions normally No treatment is necessary, as thyroid function is

preserved Laboratory tests normalize once the underlying

illness resolves

Hyperthyroid: Definition

Condition of excess functional activity of the thyroid gland

Characterized by increased basal metabolism, goiter, and disturbances of the autonomic nervous system

Affects women 3:1 more than men

Hyperthyroid: Types

Graves’ disease Toxic nodular goiter (Plummer’s disease) Toxic adenoma Therapeutic induced hyperthyroid (Lugol’s,

amiodarone, etc.) Thyroiditis Primary and/or metastatic follicular carcinoma TSH producing tumor of the hypophysis

Hyperthyroid: Common Symptoms and Signs

Heat intolerance, excessive sweating, and moist skin

Hyperactivity and tenseness Weight loss (unintentional) Fine tremors, palpitations, and tachycardia Infiltrative dermopathy Ocular signs, including lid lag, exophthalmus,

and conjunctival injection Generalized pruritis

Hyperthyroid: Diagnostic Work-up

History and physical Blood chemistries, including hormone levels

and specific antibodies Ultrasound Thyroid scan Fine needle biopsy (particularly with

hyperthyroidism associated with nodularity)

Grave’s Disease

Autoimmune disease associated with the production of antibodies that bind to TSH receptors in the follicular cells of the thyroid and activate these cells to produce T4 and T3.

These antibodies therefore simulate TSH - TSH has no part in this hyperfunctioning

Graves’ Disease: Pathophysiology

Most common form of adult hyperthyroidism Peaks in 3rd and 4th generations Clinical presentation includes all

aforementioned signs and symptoms; ocular and dermatological signs pathognomonic

Bilateral exophthalmos occurs in 40-50% of Graves’ patients- unilateral involvement is rare

Graves’ Disease continued

T3 and T4 concentrations increased TSH level decreased Autoimmune antibodies to TSH receptors RAI and Tc-99m studies are increased Scans usually show mildly enlarged thyroid

which concentrates isotope evenly and intensely

Graves’ Disease- Therapy (Conservative)

Treatment with antithyroid drugs (Propranolol, propylthiouricil, methimazole)

Long term remission rate with conservative treatment is low (30-50%)

Propranolol β-blocker; makes patient eumetabolic but not euthyroid

Other drugs block iodothyronine hormone synthesis

Graves’ Disease- Therapy: Surgery

Treatment of choice if patient younger than 21 years of age, is sensitive to iodine, or who have very large goiters

In good hands, recurrence rate is low (2-9%)with a 3% incidence of hypothyroidism

Side effects: vocal cord paralysis and hypoparathyroidism

Graves’ Disease- Therapy: Radioactive Iodine-131

Therapy of choice for women past childbearing years and adult males

No proven increase in incidence of carcinoma, leukemia, etc.

25% of patients will be hypothyroid one year after treatment; incidence increases 2%/year for the next 20 years

Graves’ Ophthalmopathy

Most frequent extrathyroidal manifestationof Graves’ disease

Fortunately, most patients with only minor involvement, amenable to non-aggressive treatment

Graves’ Exophthalmos: Picture

Management of Nonsevere Exophthalmos

Management of nonsevere Graves’ ophthalmopathy13

Sign and/or symptom Therapeutic measure

Photophobia Foreign body sensationEyelid retraction; increased

intraocular pressureLag ophthalmosMild diplopia

Sunglasses Artificial tears and ointmentsß-Blocking eyedrops

Nocturnal taping of the eyesPrismsCorrection of hyper- or

hypothyroidismElimination of risk factors

(smoking)Reassurance on the natural history

of the disease

Management of Severe ExophthalmosManagement of severe Graves’ ophthalmopathy13

Established methods 1. Glucocorticoids

a. Oralb. Intravenousc. Local

2. Supervoltage orbital radiotherapy3. a. Rehabilitative surgery

b. Orbital decompressionc. Extraocular muscle surgeryd. Eyelid surgery

4. Novel treatments under investigation1. Somatostatin Analogues2. Octreotide3. Lanreotide4. Intravenous immunoglobulins5. Nonestablished methods6. Cyclosporinea7. Plasmapheresis8. Anecdotal treatments9. Cyclophosphamide10. Bromocriptine11. Metradinazole

Infiltrative Dermopathy of Graves’ Disease

Toxic Adenoma: Definition

Autonomous hyperfunctioning nodule surrounded by normal functioning tissue

Rarely two or more adenomas exist in normally functioning thyroid

No clear cause; neither antibodies nor TSH involved

Nodule must be 2.5-3cm in size to produce hyperthyroidism

Toxic Adenoma: Presentation

Symptoms and signs of hyperthyroidism. No exophthalmos. No infiltrating dermopathy. The thyroid gland may be enlarged, but is

generally of normal size. On palpation, a non-tender, mildly firm nodule

is palpable.

Toxic Adenoma: Diagnosis

T3 and T4 levels are elevated. The TSH concentration is decreased. Specific antibodies are absent. On Radioisotope scan, the thyroid gland is

usually of normal size. One hot nodule - rest of the gland is cool

Toxic Adenoma: Treatment

Unless contraindicated, radioactive iodine (131I) - higher doses are usually necessary.

Production of hypothyroidism is rare.

Toxic Adenoma: Imaging

Toxic Multinodular Goiter (Plummer’s Disease) enlarged multinodular goiter commonly found in

areas of iodine deficiency in which patients with long-standing non-toxic goiter develop thyrotoxicosis

One or more of the nodules begin to hyperfunction autonomously

Encompasses a spectrum of different clinical entities ranging from a single hyperfunctioning nodule within an enlarged thyroid gland having additional non-functioning nodules to multiple hyperfunctioning areas (nodules) scattered throughout the gland barely distinguishable from non-functioning nodules and ordinary thyroid tissue

Plummer’s Disease: Clinical Presentation

A middle-aged person with 10 - 15 years history of an enlarged gland.

The general symptoms and signs of hyperthyroidism.

Exophthalmos is absent. Infiltrative dermopathy is absent. The gland is enlarged and multinodular.

Plummer’s Disease: Diagnosis

The serum T3 and T4 levels are raised. The TSH concentration is decreased. No auto-immune antibodies are present Scan shows an enlarged, multinodular gland. One, two or more nodules are hot

(overactive) and in between cool and cold nodules

Plummer’s Disease: Treatment

Similar to treatment for Grave’s disease Plummer’s disease is more resistant to 131I

therapy than Graves’ - apparently because the areas (nodules) of low activity at the time of therapy become active as the hyperactive nodules are destroyed and more TSH is released.

Induction of hypothyroidism is rare

Plummer’s Disease: Imaging

Thyrotoxicosis Factitiae

syndrome of hyperthyroidism that results from an overdosage of thyroid hormone - T3 or T4.

Clinical signs and symptoms similar to other causes of hyperthyroidism

No exophthalmos or dermopathy

Thyrotoxicosis Factitiae: Diagnosis

T3 therapy: serum concentration of T3 is increased, serum T4 is decreased, and TSH concentration is decreased.

T4 therapy: serum T3 concentration is increased, T4 concentration is increased, TSH level is decreased.

RAI uptake by thyroid is decreased The thyroid gland is not enlarged. Scan image shows a cool thyroid

Thyrotoxicosis Factitiae: Treatment

Reduce or suspend T4 therapy. Normalization may take 6 weeks or longer

Hamburger Thyrotoxicosis Several outbreaks of thyrotoxicosis have been attributed to a

practice, now banned in the US, called "gullet trimming” Meat in the neck region of slaughtered animals is ground into

hamburger Thyroid glands are reddish in color and located in the neck, it's

not unusual for gullet trimmers to get thyroid glands into hamburger or sausage

Outbreak of thyrotoxicosis in Minnesota and South Dakota that was traced to thyroid-contaminated hamburger. A total of 121 cases were identified in nine counties, with the highest incidence in the county having the offending slaughter plant. The patients complained of sleeplessness, nervousness, headache, fatique, excessive sweating and weight loss

Iodine-precipitated Hyperthyroidism With iodine deficiency production of T4 and T3 decreases, so

more TSH is released and thyroid stimulation increases, resulting in enlargement of the thyroid (goiter)

If iodine intake is increased in such a patient the enlarged gland may produce excess amounts of T3 and T4, and hyperthyroidism develops.

Excess iodine intake by euthyroids and hyperthyroids may suppress TSH secretion and thus produce hypothyroidism or it may produce hyperthyroidism by activating hormogenesis in patients with deranged special thyroidal systems, so-called Jod-Basedow phenomenon

Lastly, it may elicit hyperactivity in normal thyroid glands by deranging the function of the cells

Secondary Hyperthyroidism

This term refers to hyperthyroidism precipitated by excess TSH secretion by a pituitary tumour or by other tumours (e.g. choriocarcinoma, struma ovarii, etc.)

Clinical signs and symptoms same as other causes of hyperthyroidism, without exophthalmos

The T3, T4 and TSH concentrations are raised The thyroid is enlarged and the isotope uptake is

diffusely increased.

Hypothyroidism

condition where insufficient thyroid hormones are produced

Two main types are distinguished,. primary and secondary hypothyroidism

Primary hypothyroidism by far more common Primary Hypothyroidism can be subdivided

into hypothalamic-pituitary causes vs. thyroidal causes

Hypothyroidism: Causes Primary

1. Primary (thyroidal) hypothyroidism           1. Loss of functional thyroid tissue                     1. chronic autoimmune thyroiditis                     2. reversible autoimmune hypothyroidism (silent and postpartum thyroiditis, cytokine-induced thyroiditis).                     3. surgery and irradiation (131I or external irradiation)                     4. infiltrative and infectious diseases, subacute thyroiditis                     5. thyroid dysgenesis           2. Functional defects in thyroid hormone biosynthesis and release                     1. congenital defects in thyroid hormone biosynthesis                     2. iodine deficiency and iodine excess                     3. drugs: antithyroid agents, lithium, natural and synthetic goitrogenic chemicals

Hypothyroidism: Causes Secondary

2. Central (hypothalamic/pituitary) hypothyroidism           1. Loss of functional tissue                     1. tumors (pituitary adenoma, craniopharyngioma, meningioma, dysgerminoma, glioma, metastases)                    2. trauma (surgery, irradiation, head injury)                     3. vascular (ischemic necrosis, hemorrhage, stalk interrruption, aneurysm of internal carotid artery)                     4. infections (abcess, tuberculosis, syphilis, toxoplasmosis)                     5. infiltrative (sarcoidosis, histiocytosis, hemochromatosis)                     6. chronic lymphocytic hypophysitis                     7. congenital (pituitary hypoplasia, septooptic dysplasia, basal encephalocele)           2. Functional defects in TSH biosynthesis and release                     1. mutations in genes encoding for TRH receptor, TSHß, or Pit-                     2. drugs: dopamine; glucocorticoids; L-thyroxine withdrawal

3. "Peripheral" (extrathyroidal) hypothyroidism                     1. Thyroid hormone resistance                    2. Massive infantile hemangioma

Hypothyroidism: Signs and Symptoms A dull facial expression, a hoarse voice, slow speech, a puffed

face with swollen periorbital tissues. These changes are the result of mucopolysaccharide (hyaluronic acid and chondroitin sulphate) infiltration of the tissues.

The patient is cold-intolerant due to low metabolic rate. Drooped eyelids and the hair is sparse; the skin is coarse, dry,

scaly and thick. Modest weight gain. Signs of intellectual impairment - frank psychosis (myxoedema

madness) may develop. A yellowish colour of the skin due to carotenaemia, and

pruritis.11 Bradycardia, cardiac arrhythmia, etc.

Hypothyroid: Lab Studies

Anemia: normo-/micro-/macrocytic. T4 and T3 concentrations are low, and TSH

concentration is high in the primary type. T4, T3 and TSH are low in the secondary

type. TRH and/or TSH tests differentiate between

primary and secondary hypothyroidism.

Thyroiditis

Inflammation of the thyroid gland Classified as chronic, subacute, and acute Can initially present as hyperthyroidism,

ramification may result in hypothyroidism

Hashimoto’s Thyroiditis

A chronic inflammation of the thyroid with lymphocytic infiltration of the gland caused by autoimmune factors

Most common cause of primary hypothyroidism in North America

Women to men 8:1, rate increases in both sexes with age

A family history of thyroid disorders is common, and incidence is increased in patients with chromosomal disorders, including Turner's, Down, and Klinefelter's syndromes

Hashimoto’s: Signs and Symptoms

Painless enlargement of the thyroid gland Examination reveals a nontender goiter, smooth or

nodular, firm, and more rubbery than the normal thyroid; many patients have hypothyroidism when first seen

Other forms of autoimmune disease are common There may be an increased incidence of thyroid

neoplasia, particularly papillary carcinoma and thyroid lymphoma

Hashimoto’s: Diagnosis Laboratory findings early in the disease consist of

normal T4 and TSH levels and high titers of thyroid peroxidase antibodies and less commonly anti-thyroglobulin antibodies

The thyroid radioactive iodine uptake may be increased, perhaps because of a defect in organification of iodide in conjunction with a gland that continues to trap iodine

Later in the disease, the patient develops hypothyroidism with decreased T4, decreased thyroid radioactive iodine uptake, and increased TSH

Hashimoto’s: Treatment

usually requires lifelong replacement therapy with thyroid hormone to decrease goiter size and treat the hypothyroidism

Occasionally, the hypothyroidism is transient The average oral replacement dose with L-

thyroxine is 100-120 µg/day

Hashimoto’s

Subacute Thyroiditis (de Quervain’s Thyroiditis)

Acute inflammatory disease of the thyroid, probably caused by a virus

Frequently a history of mumps The gland shows giant cell infiltration but

lymphocyte infiltration is absent Female patients outnumbered male patients

in a ratio of 3-6:1 Although the disease has been described at

all ages, it is rare in children

Subacute Thyroiditis: Presentation

Condition is characterized by sudden onset of sore throat, tenderness of the neck and low grade fever

Disease may reach its peak within 3 to 4 days and subside and disappear within a week, but more typically, a gradual onset extends over 1 to 2 weeks and continues with a fluctuating intensity for 3 to 6 weeks

Thyroid gland is typically enlarged two or three times the normal size or larger and is tender to palpation

The condition is often confused with pharyngitis or otitis media

Subacute Thyroiditis: Presentation continued

Approximately one-half of the patients present during the first weeks of the illness, with symptoms of thyrotoxicosis, including nervousness, heat intolerance, palpitations, tremulousness, and increased sweating

As the disease process subsides, transient hypothyroidism occurs in about one-quarter of the patients

Ultimately thyroid function returns to normal and permanent hypothyroidism occurs in less than 10 percent of the cases

Subacute Thyroiditis: Diagnosis

History and clinical examination. An elevated erythrocyte sedimentation rate. The T4 level is elevated, the TSH is down. The 131I-uptake is down in the presence of

elevated T4, and a radioisotope scan (99mTcO4-) shows a cool thyroid or the thyroid is not visualized.

Subacute Thyroiditis: Treatment In some instances, no treatment is required Mainstay of treatment is analgesia Initial therapy with Aspirin or NSAIDs May need to treat with corticosteroids (Typically, Prednisone 40mg

daily to begin with, followed by a long taper of up to six weeks) Relief of symptoms with treatment almost diagnostic Alternatively oral cholecystographic agents (such as sodium ipodate

or sodium iopanoate) may be used safely and effectively for the management of hyperthyroidism in these patients even when they have relapsed after corticosteroid therapy

The recurrent rate of subacute thyroiditis after cessation of prednisone therapy is about 20% but no difference has been found in routine laboratory data between recurrent and non-recurrent groups of patients

Levothyroxine administration may be useful in situations where the patient is not already hyperthyroid due to the release of thyroidal contents into the circulation

Subacute Thyroiditis: Prognosis

In 90% or more of patients, there is a complete and spontaneous recovery and a return to normal thyroid function

However, the thyroid glands of patients with subacute thyroiditis may exhibit irregular scarring between islands of residual functioning parenchyma, although the patient has no symptom

Up to 10% of the patients may become hypothyroid and require permanent replacement with levothyroxine

Acute (Infectious) Thyroiditis

Thyroid extremely resistant to infection, therefore infectious thyroiditis rare

However, in certain situations, particularly in children a persistent fistula from the pyriform sinus may make the left lobe of the thyroid particularly susceptible to abscess formation

Occasionally, acute bacterial supporative thyroiditis occurs in children receiving cancer chemotherapy

Acute Thyroiditis: Etiology

Virtually any bacteria can infect the thyroid Strep, Staph, pneumococcus, salmonella,

bacteroides, t. pallidum, pasturella, and mycobacterium all documented

In addition, fungal infections, including cryptococcus, have been reported

Most commonly, however, especially in children, infection of the thyroid gland is a result of direct extension from an internal fistula from the pyriform sinus

Acute Thyroiditis: Etiology

Acute Thyroiditis: Presentation The dominant clinical symptom is pain in the region of the thyroid

gland which may subsequently enlarge and become hot and tender

The patient is unable to extend the neck and often sits with the neck flexed in order to avoid pressure on the thyroid gland

Swallowing is painful There are usually signs of infection in structures adjacent to the

thyroid, local lymphadenopathy as well as temperature elevation and, if bacteremia occurs, chills

Gas formation has been noted with suppurative thyroiditis Pediatric presentation more typical than adult In general, no sign of hypo- or hyperthyroidism

Acute Thyroiditis: Diagnosis

History, physical, and clinical suspicion most important

Patient more ill appearing than in subacute The T3, T4 and TSH levels are usually

normal, and the rT3 is increased A radioisotope scan shows an enlarged gland

with diffusely increased isotope uptake If lesion localized on ultrasound or scan,

needle biopsy diagnostic

Acute Thyroiditis: Treatment

Surgical removal of fistulous tract in pediatric patients with communication with pyriform sinus

Systemic antibiotics with broad spectrum coverage needed for some patients

Must add fungal coverage in immunocompromised patients

Acute Thyroiditis: Prognosis

some patients with thyroiditis, the destruction may be sufficiently severe that hypothyroidism results

Patients with a particularly diffuse thyroiditis should have follow-up thyroid function studies performed to determine that this has not occurred

Surgical removal of a fistula or branchial pouch sinus is required to prevent recurrence when this is present

Clinical Differences Between Thyroiditis Types

Subtype Etiology Neck Pain

RAIU TSH T4 Autoantibodies

Chronic lymphocytic (Hashimoto's disease)

Autoimmune

No ± ± ± Present

Subacute granulomatous Viral Yes ↓ ↓ ↑ Absent

Microbial inflammatory Bacterial, fungal, parasitic

Yes ± Normal Normal Absent

Amiodarone and Thyroid

Amiodarone used to treat cardiac arrythmias Structurally similar to thyroid hormone,

comprised of 39% iodine Patients on amiodarone may become hypo-

or hyperthyroid If hypothyroid, stop amiodarone and give T4

Amiodarone Induced Hyperthyroid Two Types: Type I and Type II Type 1: In this type underlying thyroid pathology is present, for

example multinodular or diffuse goiter (thyroid enlarged) and in these patients amiodarone precipitates typical Jod-Basedow with increased blood T4 and T3 levels and a decreased blood TSH level

Radioisotope studies show a diffusely or multinodular enlarged gland (goiter) with normal or increased 131I or 99mTc uptake

Ultrasound shows a nodular or enlarged thyroid gland Improves with use of perchlorate, which promotes iodine

expulsion from thyroid

Amiodarone Induced Hyperthyroid continued

Type II: In this type there is no evidence of underlying thyroid pathology

The gland is small and it may be tender Radioisotope studies (131I or 99mTc) show a small

gland with low or absent radioisotope uptake Ultrasound images are normal The onset of the condition is often explosive The condition is treated by steroids, in addition to

perchlorate

Thyroid Nodule One in 12 to 15 young women has a thyroid nodule One in 40 young men has a thyroid nodule More than 95 percent of all thyroid nodules are benign (non-

cancerous growths) Some are actually cysts which are filled with fluid rather than

thyroid tissue Most people will develop a thyroid nodule by the time they are 50

years old The incidence of thyroid nodules increases with age 50% of 50 year olds will have at least one thyroid nodule 60% of 60 year olds will have at least one thyroid nodule 70% of 70 year olds will have at least one thyroid nodule

Thyroid Nodule continued

Ninety-five percent of solitary thyroid nodules are benign

Thyroid cancers typically present as a dominant solitary thyroid nodule, cold nodule on scan

Papillary carcinoma accounts for 60 percent, follicular carcinoma accounts for 12 percent, and the follicular variant of papillary carcinoma accounting for six percent

Fine needle biopsy is a safe, effective, and easy way to determine if a nodule is cancerous

Features Favoring Benign Nodule Family history of Hashimoto's thyroiditis

Family history of benign thyroid nodule or goiter

Symptoms of hyperthyroidism or hypothyroidism

Pain or tenderness associated with a nodule

Soft, smooth, mobile nodule

Multinodular goiter without a predominant nodule (lots of nodules, not one main nodule)

“Warm" nodule on thyroid scan (produces normal amount of hormone)

Simple cyst on ultrasound

Factors Favoring Malignant Nodule Age less than 20 Age greater than 70 Male gender New onset of swallowing difficulties New onset of hoarseness History of external neck irradiation during childhood Firm, irregular and fixed nodule Presence of cervical lymphadenopathy (swollen hard lymph nodes

in the neck) Previous history of thyroid cancer Nodule that is "cold" on scan (shown in picture above, meaning the

nodule does not make hormone) Solid or complex on ultrasound

Thyroid Disease: ReviewCondition TSH Free T4 Free T3 Other

Graves’ Disease ↓↓↓ ↑ Usually ↑ Thyroid scan with diffuse isotope uptake

Toxic Adenoma ↓ ↑ or Normal ↑ or Normal thyroid scan shows functioning nodule and suppression of other thyroid tissue

Toxic Multi-nodular Goiter

↓ ↑ or Normal ↑ or Normal thyroid scan shows enlarged gland with multiple active nodules

Thyroiditis ↓ Variably ↑ Variably ↑ thyroid scan shows low radioiodine uptake, thyroglobulin level markedly raised.

Factitious Hyper-thyroidism

↓ ↑ ↑ or Normal low radioiodine uptake on thyroid scan and absent thyroglobulin levels

Pregnancy Normal ↑ total T4

Normal free T4

↑ total T3

Norma free T3

positive pregnancy test

Steroid therapy, Severe Illness, etc.

Normal or ↓ Normal Normal N/A

Question 1 A 60 year old woman comes to your clinic for examination of a

“lump” in her neck. On physical examination, a soft, smooth, mobile nodule is palpated in the left lobe of the thyroid. Thyroid scan ordered through your clinic shows a 1cm “hot” nodule at the superior pole of the left thyroid lobe. Which of the following should you tell your patient when she asks about the results of her tests?

A. This lesion most likely represents cancer and an urgent surgical referral must be sought

B. Lesions such as these are exceedingly rare in patients her age

C. 95% of these lesions are benign D. She most likely has an infection of the thyroid and will require

inpatient antibiotic therapy

Question 2 A 35 year old African American female presents to your clinic

with a two week history of palpitations, excessive sweating, and a recent 15 pound weight loss, though she is “always eating.” Also, she notices that the front of her neck is “fuller” than usual and her eyes “bug-out.” She has a history of Lupus, but has otherwise been healthy. Routine laboratory tests are ordered. Which of the following would you expect to find?

A. Elevated level of TSH B. Decreased level of T4 C. Decreased level of T3 D. Auto-antibodies to TSH receptors E. Anti-thyroglobulin antibodies

Question 3 While working in the Emergency Department of a local

community hospital, a five year old boy is brought in by his parent’s because of a “sore throat.” The child has leukemia, and has received chemotherapy for the same two weeks prior to his presentation. On exam, the child appears lethargic. There is a noticeably enlarged lump in the area of the left lobe of the thyroid gland, which elicits a painful response when palpated. Upon further questioning, the parents state that he hasn’t eaten well over the past 2-3 days because of “difficulty swallowing.” Which of the following is the most likely diagnosis?

A. Acute infectious thyroiditis B. Sick Euthyroid Syndrome C. Hamburger Thyrotoxicosis D. Hashimoto’s Thyroiditis E. Plummer’s Disease

References American Association of Clinical Endocrinologists medical guidelines for

clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002 Nov-Dec;8(6):457-69

Bartalena L. Pinchera A, Macocci C. Management of Graves’ ophthalmopathy: Reality and prespectives. Endocrine Reviews 2000; 21:168-199.

Beers, Mark MD et al. The Merck Manual of Diagnosis and Therapy Seventh Edition. Merck, New York, 1995

Braunwald, et al. Harrison’s Principals of Internal Medicine, 15th Edition. McGraw, New York. 2001.

Klopper JF. Diagnosis and management of amiodarone-induced hyperthyroidism. SA Med J 1999; 89:453-454.

Murray IPC and Ell PJ. (1998) Nuclear Medicine in Clinical Diagnosis and Treatment. 2nd Ed. Churchill Livingstone, Edinburgh: 136-142.

O'Reilly DS; Thyroid function tests-time for a reassessment.;BMJ 2000 May 13;320(7245):1332-4.

Student BMJ . Interpreting Thyroid Function Tests.  www.emedicine.com