THYROID DISORDER

Diana Holidah
Bagian Farmasi Klinik dan Komunitas
Fakultas Farmasi – Universitas Jember
 ANATOMY OF THYROID GLAND

• The thyroid gland is located anterior and caudal to the cartilages of the
larynx and is the largest endocrine gland in adults.
• The follicles are the functional, secretory units of the thyroid gland
HORMON SYNTHESIZED
THE THYROID PRODUCES AND
SECRETES 2 METABOLIC HORMONES

• Thyroxine (T4 ) and triiodothyronine (T3)

• Required for homeostasis of all cells
• Influence cell differentiation, growth, and
metabolism
• Considered the major metabolic hormones because
they target virtually every tissue
HYPOTHALAMIC-PITUITARY-THYROID AXIS
NEGATIVE FEEDBACK MECHANISM
 PRODUCTION OF T4 AND T3

• T4 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 T4 per day
• T3 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 T4 in
peripheral tissues
• About 20% comes from direct thyroid secretion
 METABOLIC EFFECTS OF T3

• 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
OVERVIEW OF THYROID DYSFUNCTION

• Hypothyroidism

• Hyperthyroidism
TYPICAL THYROID HORMONE LEVELS
IN THYROID DISEASE

TSH T4 T3

Hypothyroidism High Low Low

Hyperthyroidism Low High High

THYROID DISEASE SPECTRUM
Overt Hypothyroidism
TSH >4.7 IU/mL, Free T4 Low

Subclinical Hypothyroidism
TSH >4.7 IU/mL, Free T4 Normal

Euthyroid
TSH 0.5-4.7 IU/mL, Free T4 Normal

Hyperthyroidism
TSH <0.5 IU/mL, Free T3/T4 Normal or Elevated

0 5 10
TSH, IU/mL
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.
HYPOTHYROIDISM
 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
SYMPTOMS DAN SIGN
 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.
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)
 CHRONIC AUTOIMMUNE THYROIDITIS
(HASHIMOTO THYROIDITIS)
• Occurs when there is a severe defect in thyroid hormone
synthesis
• a chronic inflammatory autoimmune disease characterized by
destruction of the thyroid gland by autoantibodies against
thyroglobulin, thyroperoxidase, and other thyroid tissue components
• Patients present with hypothyroidism, painless goiter, and other
overt signs
• Persons with autoimmune thyroid disease may have other
concomitant autoimmune disorders
• Most commonly associated with type 1 diabetes mellitus
• Will often have significantly elevated anti-TPO ab
 SUBCLINICAL HYPOTHYROIDISM

Definition
• An isolated elevated TSH level in the setting of normal T 3 and T4 levels
• Symptoms may be present or absent

Prevalence
• Worldwide prevalence between 1% and 10%
• Highest rates are in women older than 60 years of age
• Over the age of 74, 16% of men and 21% of women have the disorder

Cooper DS. N Engl J Med. 2001;345:260-265.

PROGRESSION OF THYROID DISEASE

Subclinical Overt Hypothyroidism

Euthyroid Hypothyroidism

TSH

Normal
Range

T3
T4

Years

Ayala AR, et al. Endocrinologist. 1997;7:44-50.

TREATMENT OF HYPOTHYROIDISM
 THERAPY INITIATION AND TITRATION

• Therapy with levothyroxine sodium products requires

individualized patient dosing
• Careful titration: use a formulation with consistent doses
• Clinical evaluation: symptoms resolve more slowly than TSH response
• Laboratory monitoring: need consistent, sensitive TSH measurements

• Individualized patient dosing is influenced by

• Age and weight
• Cardiovascular health
• Severity and duration of hypothyroidism
• Concomitant disease states and treatment

Endocr Pract. 2002;8:457-469.

Singer PA, et al. JAMA. 1995;273:808-812.
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.
 AACE 2002 POSITION STATEMENT ON THE
MANAGEMENT OF HYPOTHYROIDISM

―Bioequivalence of levothyroxine preparations is based on

total T4 measurement and not TSH levels; therefore,
bioequivalence is not the same as therapeutic
equivalence.
Furthermore, various brands of levothyroxine are not
compared against a levothyroxine standard.
Preferably, the patient should receive the same brand of
levothyroxine throughout treatment.‖

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE

FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND HYPOTHYROIDISM. ENDOCRINE PRACTICE Vol 8 No. 6 November/December 2002
PRIMARY HYPOTHYROIDISM
TREATMENT ALGORITHM
Initial Levothyroxine Dose

6-8 Weeks

TSH >3.0 IU/mL Repeat TSH Test TSH <0.5 IU/mL

TSH 0.5- 2.0 IU/mL

Symptoms Resolved

Increase Continue Dose Decrease

Levothyroxine Levothyroxine
Dose by Dose by
12.5 to 25 g/d Measure TSH at 6 Months, 12.5 to 25 g/d
Then Annually or Singer PA, et al. JAMA. 1995;273:808-812.
When Symptomatic Demers LM, Spencer CA, eds. The National Academy of Clinical
Biochemistry Web site. Available at:
http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed July 1, 2003.
HYPERTHYROIDISM
SYMPTOMS & SIGN OF HYPERTHYROIDISM
THYROTOXICOSIS AND HYPERTHYROIDISM
DEFINITIONS

• Thyrotoxicosis
• The clinical syndrome of hypermetabolism that
results when the serum concentrations of free T 4,
T3, or both are increased
• Hyperthyroidism
• Sustained increases in thyroid hormone
biosynthesis and secretion by the thyroid gland

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and
Clinical Text. 8th ed. 2000.
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
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
 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 131I is recommended treatment

Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and
Clinical Text. 8th ed. 2000.
 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 hESR
• Does not respond to anti-thyroid medication or RAI
treatment
• TOC is steroids and other adjunctive therapy
 SUBCLINICAL HYPERTHYROIDISM:
DEFINITION

• Subnormal TSH level

• Normal total or free serum T 4 and T3 levels
• Few or no signs or symptoms of hyperthyroidism

Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott,
Williams & Wilkins; 2000;1001.
POTENTIAL CONSEQUENCES OF
SUBCLINICAL HYPERTHYROIDISM

• Decreased bone density with increase risk of

osteopenia or osteoporosis
• Increased risk of cardiac arrhythmias, especially in the
elderly
• Increased risk of miscarriage in pregnancy
• May or may not have obvious symptoms
SHOULD SUBCLINICAL
HYPERTHYROIDISM BE TREATED?
Depends on the individual circumstances and presentation of
the patient:
• Usually will treat if TSH < 0.1
• If TSH between 0.1 and 0.5:
• May initially observe only and follow for development of overt
hyperthyroidism (especially if young and otherwise healthy patient)
• Should consider treatment if evidence of potential complications of
hyperthyroidism (osteopenia or osteoporosis, a-fib), if frail/elderly
or (possibly) if symptoms
TREATMENT OF HYPERTHYROIDISM
 TREATMENT OF HYPERTHYROIDISM

• Antithyroid drugs
• Inhibit the synthesis of T4 and T3
• 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.
ADJUNCTIVE THERAPY OF
HYPERTHYROIDISM

• Beta blockers
• Corticosteroid therapy
• Bile acid sequestrants
• Iodide
WHICH TREATMENT TO CHOOSE?

Depends on:
• Patient preference
• Severity of hyperthyroidism
• Evidence of complications of hyperthyroidism
• Pregnancy
• The cause of hyperthyroidism
 SYMPTOM RELIEF

1. Rehydration is the first step

2. β – blockers to decrease the sympathetic excess
 Propranalol, Atenelol, Metoprolol
3. Rate limiting CCBs if β – blockers contraindicated
4. Treatment of CHF, Arrhythmias
5. Calcium supplementation
6. Lugol solution for ↓ vascularity of the gland
COMPLICATIONS

Thyroid storm – extreme hyperthyroidism

Symptoms include:
• high fever
• dehydration
• tachycardia
• high-output cardiac failure
• coma
ANTI THYROID DRUGS (ATD)

considerations Methimazole Propylthiouracil

Efficacy Very potent Potent
Duration of action Long acting BID/OD Short acting QID/TID
In pregnancy Contraindicated Safely can be given
Mechanism of action Iodination, Coupling Iodination, Coupling
Conversion of T4 to T3 No action Inhibits conversion
Adverse reactions Rashes, Neutropenia Rashes, ↑Neutropenia
Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO
 HOW LONG TO GIVE ATD ?

• Reduction of thyroid hormones takes 2-8 weeks

• Check TSH and FT4 every 4 to 6 weeks
• In Graves, many go into remission after 12-18 months
• In such pts ATD may be discontinued and followed up
• 40% experience recurrence in 1 yr. Re treat for 3 yrs
• Treatment is not life long. Graves seldom needs surgery
• MNG and Toxic Adenoma will not get cured by ATD
• For them ATD is not the best, Treat with RAI.
 RADIO ACTIVE IODINE (RAI RX.)

• In women who are not pregnant

• In cases of Toxic MNG and TSA
• Graves disease not remitting with ATD
• RAI Rx is the best treatment of hyperthyroidism in adults
• The effect is less rapid than ATD or Thyroidectomy
• It is effective, safe, and does not require hospitalization
• Given orally as a single dose in a capsule or liquid form.
• Very few adverse effects as no other tissue absorbs RAI
 RADIO ACTIVE IODINE (RAI RX.)

• I123 is used for Nuclear Scintigraphy (Dx.)

• I131 is given for RAI Rx. (6 to 8 milliCuries)
• Goal is to make the patient hypothyroid
• No effects such as Thyroid Ca or other malignancies
• Never given for children and pregnant/lactating women
• Not recommended with patients of severe Ophthalmopathy
• Not advisable in chronic smokers
 SURGICAL TREATMENT

• Subtotal Thyroidectomy, Total Thyroidectomy

• Hemi Thyroidectomy with contra-lateral subtotal
• ATD and RAI Rx are very efficacious and easy
• Surgical treatment is reserved for MNG with
1. Severe hyperthyroidism in children
2. Pregnant women who can’t tolerate ATD
3. Large goiters with severe Ophthalmopathy
4. Large MNGs with pressure symptoms
5. Who require quick normalization of thyroid function
DIETARY ADVICE

• Avoid Iodized salt, Sea foods

• Excess amounts of iodide in some:
• Expectorants, x-ray contrast dyes,
• Seaweed tablets, and health food supplements

These should be avoided because The iodide interferes

with or complicates the management of both ATD and RAI
Rx.
 SUMMARY OF HYPERTHYROIDISM

Hyperthyroidism Age % Enlarged Pain RAIU Treatment

Graves (TSI Ab
20 - 40 60% Diffuse None ↑↑ ATD – 18 m
eye, dermo, bruit)

Toxic MNG > 50 20% Lumpy Pressure ↑ RAI, Surgery

Single Adenoma 35 - 50 5% Single None ± RAI, ATD

S Acute Thyroiditis Any age 15% None Yes ↓↓ NSAID, Ster.

TSH is markedly low, FT4 is elevated

THANK YOU