Upload
ashley-fitzgerald
View
219
Download
1
Embed Size (px)
Citation preview
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