1. Thyroid Disorders
Eric J Milie, D.O.

2. 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

3. 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

4. Thyroid Anatomy continued

5. Function of Thyroid Gland
Secretes thyroid hormones, which regulate metabolism throughout the body
Two hormones secreted: Thyroxine (T4) and Triiodothyronine (T3)

6. 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

7. Chemical Structure

8. 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

9. Some Thyroid Hormone Responsibilities
Heart rate
Respiratory rate
Rate of caloric consumption
Skin maintenance
Growth
Fertility
Digestion
Heat regulation

10. 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

11. Sodium-Iodine Symporter

12. 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)

13. TRH-TSH-Thyroid Hormone Feedback Loop

14. 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)

15. Hypothalamic-Pituitary-Thyroid Axis

16. 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

17. Goiter

19. 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)

20. 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

21. 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

22. 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

23. RAIU continued

24. 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

25. 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

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

27. CRT

28. 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

29. Thyroid Ultrasound

30. 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)

31. 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

32. Euthyroid Sick Syndrome: Definition
Clinical condition in which patients suffering from severe non-thyroid illness are clinically euthyroid but biochemically dysthyroid

33. Euthyroid Sick Syndrome: Precipitating Factors
Fasting
Starvation
Anorexia nervosa
Protein malnutrition
Surgical trauma
Hyperthermia
Myocardial infarction
Chronic renal failure
Diabetic ketoacidosis
Cirrhosis
Sepsis

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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)

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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

46. Graves’ Ophthalmopathy
Most frequent extrathyroidal manifestationof Graves’ disease
Fortunately, most patients with only minor involvement, amenable to non-aggressive treatment

48. Graves’ Exophthalmos: Picture

49. Management of Nonsevere Exophthalmos
Management of nonsevere Graves’ ophthalmopathy13
Sign and/or symptom
Therapeutic measure
Photophobia
Foreign body sensation
Eyelid retraction; increased intraocular pressure
Lag ophthalmos
Mild diplopia
Sunglasses
Artificial tears and ointments
ß-Blocking eyedrops
Nocturnal taping of the eyes
Prisms
Correction of hyper- or hypothyroidism
Elimination of risk factors (smoking)
Reassurance on the natural history of the disease

50. Management of Severe Exophthalmos
Management of severe Graves’ ophthalmopathy13
Established methods
Glucocorticoids a. Oral b. Intravenous c. Local
Supervoltage orbital radiotherapy
a. Rehabilitative surgery b. Orbital decompression c. Extraocular muscle surgery d. Eyelid surgery
Novel treatments under investigation
1. Somatostatin Analogues
2. Octreotide
3. Lanreotide
4. Intravenous immunoglobulins
5. Nonestablished methods
6. Cyclosporinea
7. Plasmapheresis
8. Anecdotal treatments
9. Cyclophosphamide
10. Bromocriptine
11. Metradinazole

51. Infiltrative Dermopathy of Graves’ Disease

53. 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

54. 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.

55. 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

56. Toxic Adenoma: Treatment
Unless contraindicated, radioactive iodine (131I) - higher doses are usually necessary.
Production of hypothyroidism is rare.

57. Toxic Adenoma: Imaging

58. 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

59. Plummer’s Disease: Clinical Presentation
A middle-aged person with 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.

60. 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

61. 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

62. Plummer’s Disease: Imaging

63. 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

64. 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

65. Thyrotoxicosis Factitiae: Treatment
Reduce or suspend T4 therapy.
Normalization may take 6 weeks or longer

66. 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

67. 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

68. 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.

69. 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

71. 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

72. 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

73. 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.

74. 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.

76. Thyroiditis Inflammation of the thyroid gland
Classified as chronic, subacute, and acute
Can initially present as hyperthyroidism, ramification may result in hypothyroidism

77. 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

78. 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

79. 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

80. 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 µg/day

81. Hashimoto’s

82. 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

83. 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

84. 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

85. 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.

86. 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

87. 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

88. 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

89. 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

90. Acute Thyroiditis: Etiology

91. 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

92. 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

93. 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

94. 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

95. 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
Normal

96. 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

97. 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

98. 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

99. 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

100. 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

101. 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

102. 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

104. Thyroid Disease: Review
Condition
TSH
Free T4
Free T3
Other
Graves’ Disease
↓↓↓ ↑
Usually ↑
Thyroid scan with diffuse isotope uptake
Toxic Adenoma ↓
↑ or Normal
thyroid scan shows functioning nodule and suppression of other thyroid tissue
Toxic Multi-nodular Goiter
thyroid scan shows enlarged gland with multiple active nodules
Thyroiditis
Variably ↑
thyroid scan shows low radioiodine uptake, thyroglobulin level markedly raised.
Factitious Hyper-thyroidism
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 ↓
N/A

105. 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

106. 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

107. 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

108. References
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