Disorders of Thyroid Function - Copy.ppt

Thyroid funtion test

1. Anatomy of the Thyroid Gland

2. Follicles: the Functional Units of
the Thyroid Gland
Follicles Are the Sites
Where Key Thyroid
Elements Function:
• Thyroglobulin (Tg)
• Tyrosine
• Iodine
• Thyroxine (T
4
)
• Triiodotyrosine (T
3
)

3. The Thyroid Produces and
Secretes 2 Metabolic Hormones
•Two principal hormones
–Thyroxine (T
4
) and triiodothyronine (T
3
)
•Required for homeostasis of all cells
•Influence cell differentiation, growth, and
metabolism
•Considered the major metabolic hormones
because they target virtually every tissue

4. Thyroid-Stimulating Hormone
(TSH)
•Regulates thyroid hormone
production, secretion, and growth
•Is regulated by the negative feedback
action of T
4 and T
3

5. Hypothalamic-Pituitary-Thyroid Axis
Negative Feedback Mechanism

6. Production of T
4 and T
3
•T
4
is the primary secretory product of the thyroid
gland, which is the only source of T
4

•The thyroid secretes approximately 70-90 g of T
4
per day
•T
3 is derived from 2 processes
–The total daily production rate of T
3
is about 15-30 g
–About 80% of circulating T
3
comes

from deiodination of T
4
in peripheral tissues
–About 20% comes from direct thyroid secretion

7. T
4
: A Prohormone for T
3
•T
4 is biologically inactive in target
tissues until converted to T
3
–Activation occurs with 5' iodination of the
outer ring of T
4
•T
3 then becomes the biologically
active hormone responsible for the
majority of thyroid hormone effects

8. Thyroid Hormones Stimulate
Metabolic Activities in Most Tissues
•Thyroid hormones (specifically T
3
) regulate
rate of overall body metabolism
–T
3
increases basal metabolic rate
•Calorigenic effects
–T
3 increases oxygen consumption by most
peripheral tissues
–Increases body heat production

9. Metabolic Effects of T
3
•Stimulates lipolysis and release of free fatty
acids and glycerol
•Induces expression of lipogenic enzymes
•Effects cholesterol metabolism
•Stimulates metabolism of cholesterol to bile
acids
•Facilitates rapid removal of LDL from plasma
•Generally stimulates all aspects of
carbohydrate metabolism and the pathway for
protein degradation

10. Additional Effects of T
3
•Initiates or sustains differentiation and growth
•Stimulates formation of proteins, which exert
trophic effects on tissues
•Essential for neural development and
maturation and function of the CNS
•Important for normal reproductive function
•T
3 is considered the major regulator of
mitochondrial activity

11. Disorders of Thyroid Function

12. Overview of Thyroid Dysfunction
•Hypothyroidism
•Hyperthyroidism

13. Typical Thyroid Hormone Levels
in Thyroid Disease
TSH T
4
T
3
Hypothyroidism High Low
Low
Hyperthyroidism Low High
High

14. Hypothalamic-Pituitary-Thyroid Axis
Negative Feedback Mechanism

15. Thyroid Disease Spectrum
0 105
TSH, IU/mL
Subclinical Hypothyroidism
TSH >4.7 IU/mL, Free T
4
Normal
Overt Hypothyroidism
TSH >4.7 IU/mL, Free T
4
Low
Euthyroid
TSH 0.5-4.7 IU/mL, Free T
4
Normal
Hyperthyroidism
TSH <0.5 IU/mL, Free T
3/T
4 Normal or Elevated
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000.
Canaris GJ, et al. Arch Intern Med. 2000;160:526-534.
Vanderpump MP, et al. Clin Endocrinol (Oxf). 1995;43:55-68.

16. Hypothyroidism

17. Hypothyroidism
•Hypothyroidism is a disorder with multiple
causes in which the thyroid fails to
secrete an adequate amount of thyroid
hormone
–The most common thyroid disorder
–Usually caused by primary thyroid gland failure
–Also may result from diminished stimulation of the
thyroid gland by TSH

18. Tiredness
Forgetfulness/Slower Thinking
Moodiness/ Irritability
Depression
Inability to Concentrate
Thinning Hair/Hair Loss
Loss of Body Hair
Dry, Patchy Skin
Weight Gain
Cold Intolerance
Elevated Cholesterol
Family History of Thyroid Disease or
Diabetes
Muscle Weakness/
Cramps
Constipation
Infertility
Menstrual Irregularities/
Heavy Period
Slower Heartbeat
Difficulty Swallowing
Persistent Dry or Sore Throat
Hoarseness/
Deepening of Voice
Enlarged Thyroid (Goiter)
Puffy Eyes
Clinical Features of
Hypothyroidism

19. Hypothyroidism: Types
•Primary hypothyroidism
–From thyroid destruction
•Central or secondary hypothyroidism
–From deficient TSH secretion, generally due to sellar
lesions such as pituitary tumor or craniopharyngioma
–Infrequently is congenital
•Central or tertiary hypothyroidism
–From deficient TSH stimulation above level of pituitary—ie,
lesions of pituitary stalk or hypothalamus
–Is much less common than secondary hypothyroidism
Bravernan LE, Utiger RE, eds. Werner & Ingbar's The Thyroid.
8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000.
Persani L, et al. J Clin Endocrinol Metab. 2000; 85:3631-3635.

20. Primary Hypothyroidism:
Underlying Causes
•Congenital hypothyroidism
–Agenesis of thyroid
–Defective thyroid hormone biosynthesis due to enzymatic defect
•Thyroid tissue destruction as a result of
–Chronic autoimmune (Hashimoto) thyroiditis
–Radiation (usually radioactive iodine treatment for thyrotoxicosis)
–Thyroidectomy
–Other infiltrative diseases of thyroid (eg, hemochromatosis)
•Drugs with antithyroid actions (eg, lithium, iodine, iodine-
containing drugs, radiographic contrast agents, interferon alpha)
•In the US, hypothyroidism is usually due to chronic
autoimmune (Hashimoto) thyroiditis

21. Treatment of Hypothyroidism

22. Hypothyroidism Treatment Goal
Euthyroidism
•The goal of hypothyroidism therapy is to
replace thyroxine to mimic normal,
physiologic levels and alleviate signs,
symptoms, and biochemical
abnormalities
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

23. Hypothyroidism Treatment
•Levothyroxine sodium is the treatment of choice for
the routine management of hypothyroidism
–Adults: about 1.7 g/kg of body weight/d
–Children up to 4.0 g/kg of body weight/d
–Elderly <1.0 g/kg of body weight/d
•Clinical and biochemical evaluations at 6- to 8-week
intervals until the serum TSH concentration is
normalized
•Given the narrow and precise treatment range for
levothyroxine therapy, it is preferable to maintain the
patient on the same brand throughout treatment
Singer PA, et al. JAMA. 1995;273:808-812.
Endocr Pract. 2002;8:457-469.

24. Disorders Characterized by
Hyperthyroidism

25. Thyrotoxicosis and Hyperthyroidism
Definitions
•Thyrotoxicosis
–The clinical syndrome of hypermetabolism that
results when the serum concentrations of free
T
4, T
3, or both are increased
•Hyperthyroidism
–Sustained increases in thyroid hormone
biosynthesis and secretion by the thyroid gland
The 2 terms are not synonymous
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

26. Hyperthyroidism
Underlying Causes
•Signs and symptoms can be caused by any
disorder that results in an increase in circulation
of thyroid hormone
–Toxic diffuse goiter (Graves disease)
–Toxic uninodular or multinodular goiter
–Painful subacute thyroiditis
–Silent thyroiditis
–Toxic adenoma
–Iodine and iodine-containing drugs and radiographic
contrast agents
–Trophoblastic disease, including hydatidiform mole
–Exogenous thyroid hormone ingestion

27. Nervousness/Tremor
Mental Disturbances/ Irritability
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Vision
Changes
Enlarged Thyroid (Goiter)
Menstrual Irregularities/
Light Period
Frequent Bowel Movements
Warm, Moist Palms
First-Trimester Miscarriage/
Excessive Vomiting in Pregnancy
Hoarseness/
Deepening of Voice
Persistent Dry or Sore Throat
Difficulty Swallowing
Palpitations/
Tachycardia
Impaired Fertility
Weight Loss or Gain
Heat Intolerance
Increased Sweating
Family History of
Thyroid Disease
or Diabetes
Signs and Symptoms of
Hyperthyroidism
Sudden Paralysis

29. Initial Evaluation of a Patient with
Hyperthyroidism
•TSH, FT4, FT3
•Thyroid uptake and scan
•Thyroid stimulating immunoglobulins (if
suspect Grave’s disease)

30. Graves Disease
(Toxic Diffuse Goiter)
•The most common cause of
hyperthyroidism
–Accounts for 60% to 90% of cases
–Incidence in the United States
estimated at 0.02% to 0.4% of the
population
–Affects more females than males,
especially in the reproductive age
range
•Thyroid stimulating
immunoglobulins may be
positive in some patients and
helpful for diagnosis

32. Toxic Multinodular Goiter
•More common in places with lower iodine intake
–Accounts for less than 5% of thyrotoxicosis cases in
iodine-sufficient areas
•Evolution from sporadic diffuse goiter to toxic
multinodular goiter is gradual
•Thyrotropin receptor mutations and TSH
mutations have been found in some patients
with toxic multinodular goiters
•Surgery or
131
I is recommended treatment
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

33. Thyroiditis
•Different types: subacute, chronic, other
•RAI imaging will show decreased uptake
•In subacute thyroiditis: thyroid may be
exquisitely tender on exam
•Some may have + anti TPO ab, + anti-TG ab
and ESR
•Does not respond to anti-thyroid medication
or RAI treatment
•TOC is steroids and other adjunctive therapy

34. Treatment of Hyperthyroidism

35. Treatment of Hyperthyroidism
•Antithyroid drugs
–Inhibit the synthesis of T
4 and T
3
•Radioactive iodine therapy
–Iodine 131 taken up by functioning thyroid tissue
can decrease thyroid hormone production
•Surgical resection
–Remove hyperplastic and adenomatous tissues
–Restore normal thyroid function and,
consequently, pituitary function
Braverman LE, et al. Werner & Ingbar’s The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

36. Adjunctive Therapy of
Hyperthyroidism
•Beta blockers
•Corticosteroid therapy
•Bile acid sequestrants
•Iodide