Thyroid Disorders (1)
Thyroid Disorders (1)
Wollega University
Institute of Health Science
School of Pharmacy
Clinical Pharmacy Program
endocrine disorders)
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ꭥ > 2 b people (38% of world’s popn) have iodine def…….. resulting in 74 m
people with goiter.
ꭥ In areas of relative iodine def……..increased prev of goiter
ꭥ Severe deficiency …….hypothyroidism & cretinism.
ꭥ Effects of iodine def……most severe in pregnant women & babies.
ꭥ The recommended average daily intake of iodine:
150–250 μg/d for adults, 90–120 μg/d for children, and
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Risk Factors
ꭥ Risk factors for thyroid disease include:
Female sex
Age: men ≥ 60 yrs, women ≥ 50 yrs
Personal Hx or strong family Hx of thyroid disease
Diagnosis of other autoimmune diseases
Past Hx of neck irradiation
Previous thyroidectomy or RAI ablation
Drug therapies such as lithium and amiodarone
Dietary factors (iodine excess & iodine deficiency)
Certain chromosomal or genetic disorders
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TH physiology
ꭥ Only the unbound (free) THs enters into cells, elicit biologic effects,
and regulate TSH secretion.
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Cont’d
ꭥ T3 is 3-4x more potent than T4, but lower serum conc.
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Physiologic Effects of Ths
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I. HYPERTHYROIDISM (THYROTOXICOSIS)
ꭥ Hyperthyroidism: production of excessive amounts of THs by the
thyroid gland.
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Epidemiology …
ꭥ Incidence of hyperthyroidism corresponds to iodine
nutrition.
ꭥ Primary
Increased stimulation,
2ndary to TRAbs (Graves disease/GD) and excess hCG secretion
(hyperemesis gravidarum & trophoblastic tumors).
Central:
inappropriate TSH secretion (TSH secreting pituitary
adenoma or pituitary resistance to THs)
Extra-thyroidal:
Excess intake of TH (iatrogenic or factitious),
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Cont’d
ꭥ Graves Disease
ꭥ Autoimmune disease caused by autoreactive TRAbs.
ꭥ Unregulated stimulation of the TSH receptor……
increase TH production & release.
ꭥ Accounts for……….
Ophthalmopathy (exophthalmos)
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Cont’d
ꭥ Toxic Adenoma
control.
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Cont’d
ꭥ Toxic multi-nodular goiter (TMNG)
15% to 20% of all cases
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Cont’d
ꭥ Thyroiditis
ꭥ Sub-acute
Abrupt onset due to leakage of hormones
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Cont’d
ꭥ Thyrotoxicosis Factitia
ꭥ Drug-induced Hyperthyroidism
ꭥ Amiodarone may induce…….
thyrotoxicosis (2–3% of pts),
overt hypothyroidism (5% of pts),
subclinical hypothyroidism (25% of pts)
ꭥ Amiodarone-Induced Thyrotoxicosis
more common in iodine-deficient areas and
appears to be more common in men
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Clinical Presentation
ꭥ May occur due to catabolism or enhancement of sensitivity to
catecholamines.
ꭥ Neuropsychiatric:
Increased appetite
ꭥ Neuromuscular:
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Diagnosis…
ꭥ If initial TSH testing is normal, repeat testing is
unnecessary unless change in clinical condition.
ꭥ Abnormal TSH level finding must be followed by msr’t of
serum TH levels.
ꭥ Assays for serum total T4 & total T3 are widely available,
but…
T4 & T3 are highly protein-bound, and
numerous factors (illness, medications, genetic factors)
can influence protein binding.
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Cont’d
ꭥ Dx of hyperthyroidism is confirmed by suppressed TSH &
elevated free T4 level.
ꭥ Measurement of fT3 is rarely indicated in suspected TD.
ꭥ If TSH is low, check fT4 & fT3 ……………
fT4 & fT3 above the reference range diagnoses primary
hyperthyroidism
mildly low TSH (0.1–0.5 mIU/L) w/t normal fT4 & fT3 suggests…..
Mild or subclinical hyperthyroidism,
Non-thyroidal illness or
Interference from other medications
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Cont’d
ꭥ fT4 level is sufficient to confirm thyrotoxicosis, but 2–5%
of pts have only elevated T3 level (T3 toxicosis).
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Cont’d
ꭥ Thyrotoxicosis factitia should be suspected in a thyrotoxic
pt w/o evidence of……..
increased hormone production,
thyroidal inflammation, or
ectopic thyroid tissue
ꭥ A normal or elevated TSH level in any thyrotoxic pt indicates….
inappropriate production of TSH.
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Treatment
ꭥ Goals of Therapy
ꭥ Eliminate excess thyroid hormone;
ꭥ Minimize sys & long-term consequences of hyperthyroidism;
and
ꭥ Provide individualized therapy based on:
Type & severity of disease
Patient age & gender
Existence of non-thyroidal conditions, and
Response to previous therapy
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Cont’d
ꭥ Treatment Modalities
Severe ophthalmopathy
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Pharmacological Therapy
I. Anti-thyroid Drugs (Thionamides)
ꭥ PTU and MMI block TH synthesis by inhibiting…
ꭥ PTU (but not MMI) also inhibits the peripheral conversion of T4 to T3.
ꭥ Improv’t in Sys & lab. abnormalities should occur w/in 4-8 wks.
ꭥ ATD therapy should continue for 12-24 mths to induce a long-term remission.
ꭥ If a relapse occurs, alternate therapy w/t RAI is preferred over a second course of
ATD.
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Cont’d
ꭥ PTU
ꭥ DOC in………………..
Thyroid storm
Pregnancy (during 1st trimester) and
Breast-feeding
ꭥ Dose
Initial: 300-600 mg/day (usually in 3-4 divided doses) for
6-8 wks or until euthyroid state is achieved.
Maintenance: 50-300 mg/day, continue Rx for 12–24
months.
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Cont’d
ꭥ Carbimazole, Methimazole (Tapazole)
Low cost
Initial: 30-60 mg/day in 2-3 divided doses for 6–8 wks or until euthyroid.
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Cont’d
ꭥ Major adverse effects include:
Agranulocytosis (w/t fever, malaise, gingivitis,
oropharyngeal infection & granulocyte count <250/mm3)
Aplastic anemia
Lupus-like syndrome
Polymyositis
GI intolerance
Hepatotoxicity, and
Hypoprothrombinemia
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Cont’d
ꭥ ATA & FDA recommendation
PTU should not be considered 1st-line therapy in either adults or
children…..
b/c of serious hepatotoxicity risk.
Exceptions:
Intolerance to MMI
Thyroid storm.
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Cont’d
II. Iodides
ꭥ MOA
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Cont’d
ꭥ Are not used for routine Rx b/c of…..
paradoxical increase of TH release w/t prolonged use.
ꭥ Contraindicated in TMN goiter b/c………
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Cont’d
III. Adrenergic Blockers
ꭥ Used widely to block adrenergic effects of thyrotoxicosis.
In thyroid storm
ꭥ Primary therapy for thyrotoxicosis associated w/t thyroiditis
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Cont’d
ATA Recommendation (ATA 2016)
Esp. elderly pts & thyrotoxic pts w/t resting heart rates
>90 bpm or coexistent CVD.
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Cont’d
ꭥ Propranolol
Widely used
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Cont’d
ꭥ Atenolol & Metoprolol: relative β-1 selectivity
ꭥ Esmolol
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Cont’d
ꭥ IV. Radioactive Iodine (RAI)…
ꭥ β-blockers are the primary adjunctive therapy to RAI.
ꭥ If iodides are administered, should be given 3–7 days
after RAI.
ꭥ Medical therapy of any comorbid conditions should be
optimized prior to RAI therapy.
ꭥ Absolute contraindications:
Pregnancy & lactation
Thyroid malignancy confirmed or suspected
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Treatment of Thyroid Storm
ꭥ Initiate the following therapeutic measures promptly:
Antiadrenergic therapy
Antibiotics
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II. Hypothyroidism
ꭥ Defined as the clinical & biochemical syndrome resulting from
decreased TH production.
ꭥ Overt hypothyroidism:
ꭥ Prevalence of hypothyroidism
In iodine-sufficient countries…….ranges from 1-2%.
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Etiology…
ꭥ Primary hypothyroidism
Cause ~ 99% of cases of hypothyroidism.
Iatrogenic hypothyroidism
Iodine deficiency
Congenital hypothyroidism
Drug-induced hypothyroidism (e.g., iodides, amiodarone, lithium,
interferon-α)
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Cont’d
ꭥ Secondary hypothyroidism
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Clinical Presentation
ꭥ Typical Sys of hypothyroidism include:
weight gain, appetite is usually reduced
ꭥ NB: the more severe the degree of hypothyroidism, the greater the number of
clinical findings.
Exceptions:
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Diagnosis
ꭥ Evaluating the patient suspected of hypothyroidism involves
TSH determination………..
goiter is present, or
TRH stimulation tests Exaggerated TSH response Flat or delayed TSH response
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Cont’d
ꭥ Levothyroxine (L-thyroxine, T4): the drug of choice for TH
replacement & suppressive therapy b/c………..
Chemically stable
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Cont’d
ꭥ Initial Dose
for pts w/t longstanding disease & older pts w/o known cardiac disease…….
50 µg daily & increase after 1 mth
for older pts w/t known cardiac disease……
25 µg/day titrated upward in increments of 25 µg at mthly intervals
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Cont’d
ꭥ Liothyronine (synthetic T3) has uniform potency
but has a…..
higher incidence of cardiac adverse effects,
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The End!
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