Pharmacotherapy of Thyroid Disorders

Wollega University
Institute of Health Science
School of Pharmacy
Clinical Pharmacy Program

By:-Refisa Shifera (B.Pharm, MSc)

12/26/2024 1
 Introduction

ꭥ Thyroid disorders (TDs) encompass a variety of disease states

affecting TH production or secretion that result in alterations in
metabolic stability.

ꭥ Two general modes of presentation for TDs:

changes in size/shape of the gland

changes in secretion of hormone from the gland

ꭥ THs affect the function of virtually every organ system.

In children, critical for brain dev’t and normal growth & dev’t in later stages.

In adults, major role is to maintain metabolic stability.

12/26/2024 2
 Cont’d

ꭥ Generally, there are 5 types of thyroid dysfunction:

Hyperthyroidism (thyrotoxicosis): caused by an excess of THs

Hypothyroidism (myxedema): caused by deficiency of THs

Goiter: diffuse enlargement of the thyroid gland, caused by a

prolonged elevation of TSH

Thyroid nodule: focal enlargement of a portion of the gland,

caused by a benign or malignant neoplasm

Abnormal thyroid fn tests in a clinically euthyroid pt.

12/26/2024 3
 Epidemiology

ꭥ TD is a global health problem…….substantially impact well-being.

ꭥ The most common endocrine disorder next to DM (30-40% of

endocrine disorders)

ꭥ Africa represents the highest prev (>25%) of global burden TD.

ꭥ TDs affect ~ 5% to 15% of the general populn worldwide.

ꭥ Females are 3-4x > males to develop any type of TD.

12/26/2024 4
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

220-290 μg/d for pregnant and lactating women.

12/26/2024 5
 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
12/26/2024 6
 TH physiology

ꭥ Thyroid Gland is the largest endocrine gland in the body.

ꭥ Normal thyroid gland is 12–20 g in size, highly vascular & soft in consistency.
ꭥ It produces 2 biologically active hormones: Triiodothyronine (T3) & Thyroxine (T4).
ꭥ Thyroid follicles produce a protein called thyroglobulin (TG).
ꭥ T4 & T3 are produced by organification of iodine in the thyroid gland.
ꭥ Inorganic iodide enters thyroid follicular cells (iodide uptake)……oxidized by TPO
and covalently bound to tyrosine residues of TG (iodination of TG).
TPO has 3 fns: oxidation, organification, and coupling reaction.
ꭥ This generates monoiodotyrosine (MIT) & diiodotyrosine(DIT).
ꭥ MIT and DIT combine to form iodothyronines.
MIT & DIT join to form T3 and 2 DIT molecules form T4.
12/26/2024 7
 Cont’d
ꭥ T4 & T3 are transported in blood by 3 proteins:

Thyroid-binding globulin (TBG)…. Low conc. but high affinity for

THs (T4 > T3), carries 80% of bound hormones.
Transthyretin/TTR (aka TBPA)….. carries about 10% of T4 but little T3

Albumin…. high conc. but less affinity, carries about 10% of T4

& 30% of T3.

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.

ꭥ About 80% of total daily T3 prodn results from peripheral

deiodination of T4 to T3.

ꭥ T4 is the major circulating hormone secreted by thyroid.

20-fold more production than T3.

ꭥ T4 is highly protein-bound (99.97%), whereas T3 is less strongly
bound to plasma proteins (99.7%).

ꭥ T4 has relatively long t1/2 (~ 7 to 10 days) than T3 (24 hrs)

12/26/2024 9
 Cont’d

ꭥ THs prodn is regulated by TSH secreted by the anterior

pituitary.
TSH in turn is controlled by the -ve feedback from the
circulating level of free TH, and
+ve feedback influence of hypothalamic TRH.
ꭥ TH prodn is also regulated by extrathyroidal deiodination of
T4 to T3, which can be affected by:
nutrition, non-thyroidal hormones, drugs, and illness.
12/26/2024 10
 Cont’d

12/26/2024 11
 Physiologic Effects of Ths

12/26/2024 12
 I. HYPERTHYROIDISM (THYROTOXICOSIS)
ꭥ Hyperthyroidism: production of excessive amounts of THs by the
thyroid gland.

It is one cause of thyrotoxicosis

ꭥ Thyrotoxicosis: a clinical syndrome associated w/t prolonged

exposure to elevated levels of THs.

ꭥ Overt hyperthyroidism……..low TSH and high T4.

ꭥ Subclinical hyperthyroidism……..low TSH and normal T4.

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 Epidemiology
ꭥ Prevalence of overt hyperthyroidism……. 0.2-1.3% in iodine-
sufficient parts of the world.
ꭥ It affects about 2% of females & 0.1% of males.
ꭥ 15% of cases occur in pts >60 yrs of age.
ꭥ NHANE Survey III
Overt hyperthyroidism was 0.5%, subclinical hyperthyroidism
0.7% & overall prevalence 1.3%.
Prevalence of suppressed TSH peaks in age b/n 20-39 yrs,
declines b/n 40-79 yrs and increases again in age ≥80 yrs.
Abnormal TSH levels….. women affected >> men.

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 Epidemiology …
ꭥ Incidence of hyperthyroidism corresponds to iodine
nutrition.

higher rates in iodine-deficient countries.

mostly due to excess cases of toxic nodular goiters.

ꭥ Prevalence in Africa….lack of comprehensive popn-based

studies
12/26/2024 15
 Etiology
ꭥ Can be either primary or secondary.

ꭥ Primary
Increased stimulation,
2ndary to TRAbs (Graves disease/GD) and excess hCG secretion
(hyperemesis gravidarum & trophoblastic tumors).

Autonomous thyroid fn:

Toxic multinodular goiter, solitary toxic nodule & familial non-autoimmune
hyperthyroidism

Excess release of stored THs: Thyroiditis (auto-immune, infection,

amiodarone or radiation).

Exposure to excess iodine

12/26/2024 16
 Cont’d
ꭥ Secondary

Central:
inappropriate TSH secretion (TSH secreting pituitary
adenoma or pituitary resistance to THs)

Extra-thyroidal:
Excess intake of TH (iatrogenic or factitious),

Ectopic TH secretion (functional thyroid Ca metastases)

GD is the most common cause of hyperthyroidism.

12/26/2024 17
 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……….

70–80% of all cases in iodine-sufficient countries.

~50% of all cases in areas w/t iodine def

12/26/2024 18
 Cont’d
ꭥ Predominantly affects women (F:M ratio is 8:1)
ꭥ It is characterized by one or more of the ff
features:
Hyperthyroidism & Diffuse goiter

Ophthalmopathy (exophthalmos)

Dermopathy (pretibial myxedema) and

Acropachy (thickening of fingers or toes).
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 Cont’d

12/26/2024 20
 Cont’d
ꭥ Toxic Adenoma

About 5% of thyrotoxic patients.

A single nodular adenoma

Autonomous thyroid nodule w/t fn independent of pituitary & TSH

control.

Toxic adenomas are benign tumors that produce TH.

Amount of TH produced by the nodule is mass related

Hyperthyroidism usually occurs w/t larger nodules (>3 cm in diameter).

More common in older pts (>60 yrs) than in young pts.

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 Cont’d
ꭥ Toxic multi-nodular goiter (TMNG)
15% to 20% of all cases

ꭥ Follicles w/t autonomous fn coexist w/t normal or even nonfunctioning follicles.

ꭥ Pathogenesis is similar to that of toxic adenoma

ꭥ Thyrotoxicosis occurs when the autonomous follicles generate more TH than is

required.

ꭥ 10 times more common in iodine deficient area

Incidence 18.0 cases/100,000/yr in low-iodine intake areas

ꭥ Develops insidiously over several yrs.

ꭥ Predominantly affects older individuals w/t long-standing goiters.

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 Cont’d
ꭥ Thyroiditis
ꭥ Sub-acute
Abrupt onset due to leakage of hormones

Painful & often follows viral infection

Genetic predisposition exists

Recovery is generally complete w/in 2 to 6 months

Recurrences are extremely rare

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 Cont’d
ꭥ Painless
Silent & lymphocytic
Autoimmunity underlies most cases
Transient inflammation
Postpartum thyroiditis can occur in 5-10% cases in the
first 3-6 months
Transient hypothyroidism occurs before resolution
Permanent hypothyroidism occurs in 10–20% of cases

12/26/2024 24
 Cont’d
ꭥ Thyrotoxicosis Factitia

ꭥ Hyperthyroidism produced by the ingestion of exogenous

thyroid hormone.

ꭥ It may occur when TH is used…..

for inappropriate indications

excessive doses are used for accepted medical

indications, or

when intentional ingestion to lose weight

12/26/2024 25
 Cont’d

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
12/26/2024 26
 Clinical Presentation
ꭥ May occur due to catabolism or enhancement of sensitivity to
catecholamines.

ꭥ Sys & Sxs of thyrotoxicosis

ꭥ Neuropsychiatric:

Anxiety, irritability, restlessness

Fatigue, restless sleep

Increased appetite

Decreased attention span

ꭥ Neuromuscular:

Tremors, Proximal muscle weakness, Hyperreflexia

ꭥ Physical appearance: Weight loss, Hair loss

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 Cont’d
ꭥ Cardiovascular:
Palpitations, Tachycardia, Atrial fibrillation, ISH
ꭥ Thyroid gland: Enlarged gland (goiter); symmetrical in GD & unilateral in nodular
disease.
ꭥ Thermoregulation:
Increased sweating
Heat intolerance
ꭥ Ophthalmologic:
Blurred or double vision
Dry eyes, conjunctivitis, proptosis
ꭥ GIT: Increased frequency of stools
ꭥ Reproductive:
Amenorrhea/oligomenorrhea, Reduced libido,
Gynecomastia in males
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 Cont’d
ꭥ Thyroid Storm is a life-threatening medical emergency
characterized by:
Severe thyrotoxicosis
High fever (often >39.4°c)
Tachycardia, tachypnea, dehydration, delirium, coma, N/V and
diarrhea.

ꭥ Precipitating factors include:

Infection, trauma, surgery
Radioactive iodine (RAI) rx, and
Withdrawal from anti-thyroid drugs.
12/26/2024 29
 Diagnosis
ꭥ Measurement of TSH is the principal test for evaluation of
thyroid function
ꭥ Testing is indicated for pts w/t Sys & Sxs consistent w/t TD
(routine test is not recommended).
ꭥ First determine whether TSH is suppressed, normal, or elevated.

normal TSH level excludes majority of primary thyroid

dysfn cases.

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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.
12/26/2024 31
 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
12/26/2024 32
 Cont’d
ꭥ fT4 level is sufficient to confirm thyrotoxicosis, but 2–5%
of pts have only elevated T3 level (T3 toxicosis).

ꭥ If suppressed TSH but normal fT4 level….

fT3 level should be measured.

ꭥ Graves’ disease is Xized by undetectable TSH w/t a

more increase in T3 relative to T4.
+ve TRAb or TSI support a Dx of GD.

elevated TRAb levels are specific for GD.

12/26/2024 33
ꭥ A 24-hr RAIU (normal 10 – 30%)…usually necessary to

differentiate the etiologies.

elevated RAIU indicates true hyperthyroidism (the gland is

overproducing T4, T3 or both).

low RAIU…….excess TH is not a consequence of TG

hyperfunction (likely thyroiditis, exogenous TH ingestion, etc)

12/26/2024 34
 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.

ꭥ TSH-secreting pituitary adenomas are characterized by..

normal or elevated TSH and
elevated free/total T4 & T3.
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 NICE Thyroid Dx Pathways

12/26/2024 36
 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
12/26/2024 37
 Cont’d
ꭥ Treatment Modalities

ꭥ 3 treatment options are available

Surgery

Anti-thyroid drugs (ATDs)

Radioactive iodine (RAI)

Adjuncts: Beta-blockers and Iodides

12/26/2024 38
 Non-pharmacological Therapy
ꭥ Surgery (thyroidectomy) should be considered for pts with:
Symptomatic compression or large goiters (≥80 g),

Severe ophthalmopathy

Lack of remission on ATD treatment

Large thyroid nodules esp. If >4 cm, or

Documented or suspected thyroid malignancy

12/26/2024 39
 Cont’d
ꭥ Appropriate preparation of pt for thyroidectomy include:
Methimazole (MMI) is usually given until the pt is
biochemically euthyroid (usually 6 to 8 wks),

Followed by iodides (500 mg/day) for 10-14 days before

surgery
to decrease the vascularity of the gland.

Propranolol for several wks preoperatively and 7-10 days

after surgery
to maintain a pulse rate <90 beats/min.

12/26/2024 40
 Pharmacological Therapy
I. Anti-thyroid Drugs (Thionamides)
ꭥ PTU and MMI block TH synthesis by inhibiting…

TPO enzyme system, and

coupling of MIT and DIT to form T4 & T3.

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 ATD induces permanent remission rates of 40 – 50%.

ꭥ Monitor pts q6-12 mths after remission.

ꭥ If a relapse occurs, alternate therapy w/t RAI is preferred over a second course of
ATD.
12/26/2024 41
 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.
12/26/2024 42
 Cont’d
ꭥ Carbimazole, Methimazole (Tapazole)

ꭥ MMI is the active metabolite of Carbimazole.

ꭥ DOC for non-pregnant pts b/c of:

Low cost

Long half life

Lower incidence of SEs

Better compliance as can be given QD.

ꭥ Dose

Initial: 30-60 mg/day in 2-3 divided doses for 6–8 wks or until euthyroid.

Maintenance: 5-30 mg/day × 12–24 months.

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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
12/26/2024 44
 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:

1st trimester of pregnancy

risk of MMI-induced embryopathy may >> PTU-induced hepatotoxicity

Intolerance to MMI

Thyroid storm.

12/26/2024 45
 Cont’d
II. Iodides

ꭥ MOA

Acutely block release of TH,

Inhibit TH biosynthesis by interfering w/t intrathyroidal iodide use and

↓ size & vascularity of gland, ↑ firmness.

ꭥ Adjunctive therapy to:

Prepare pt w/t GD for surgery

Acutely inhibit TH release & quickly attain euthyroid state in severely

thyrotoxic pts w/t cardiac decompensation, or

Inhibit TH release after RAI therapy.

12/26/2024 46
 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………

autonomous tissue utilizes it for subsequent TH synthesis

ꭥ KI is available as…….
SSKI (38 mg iodide/drop) or
Lugol’s soln (6.3 mg iodide/drop).

ꭥ Typical starting dose of SSKI: 3–10 drops daily (120–400

mg) in water or juice.

12/26/2024 47
 Cont’d
III. Adrenergic Blockers
ꭥ Used widely to block adrenergic effects of thyrotoxicosis.

ꭥ Used to ameliorate sys (palpitations, anxiety, tremor & heat

intolerance).

have no effect on peripheral thyrotoxicosis, and

do not reduce TSAb or prevent thyroid storm.

12/26/2024 48
 Cont’d
ꭥ Propranolol & nadolol partially block conversion of T4 to
T3……………overall effect is small.

ꭥ Often used as adjunctive therapy………

With ATDs, RAI, or iodides when treating GD or toxic

nodules

In preparation for surgery or

In thyroid storm
ꭥ Primary therapy for thyrotoxicosis associated w/t thyroiditis

12/26/2024 49
 Cont’d
ATA Recommendation (ATA 2016)

Beta-adrenergic blockade is recommended in all pts

w/t symptomatic thyrotoxicosis.

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

May block T4 to T3 conversion at high doses

Doses required to relieve adrenergic sys vary

Initial dose of 20-40 mg PO QID is effective for most pts

Increase progressively until sys are controlled

Younger or more severely toxic pts may require 240–480 mg/day

Preferred agent for nursing & pregnant mothers

12/26/2024 51
 Cont’d
ꭥ Atenolol & Metoprolol: relative β-1 selectivity
ꭥ Esmolol

In ICU setting of severe thyrotoxicosis or storm.

ꭥ CCBs (Diltiazem, Verapamil)

if beta-blockade not tolerated or contraindicated.

12/26/2024 52
 Cont’d
IV. Radioactive Iodine (RAI)
ꭥ Sodium iodide-131
Initially disrupts hormone synthesis by incorporating into
THs & thyroglobulin.
Eventually, follicles develop cellular necrosis & fibrosis of
interstitial tissue.
ꭥ Agent of choice for GD, toxic autonomous nodules, and
TMNGs.

12/26/2024 53
 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:

Suppression of TH formation & secretion

Antiadrenergic therapy

Administration of corticosteroids and

Rx of ass/ted complications or precipitant factors.

ꭥ PTU

In large doses is the preferred ATD.

It blocks peripheral conversion of T4 to T3 in addition to

interfering with TH production.

ꭥ MMI has a longer DOA, which offers a theoretical advantage.

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 Cont’d
ꭥ Iodides
Rapidly block the release of preformed TH

Should be administered after a thionamide is initiated

ꭥ Antiadrenergic Therapy: esmolol is the preferred, short-acting

agent.

ꭥ Corticosteroids are generally recommended.

ꭥ General supportive measures, as indicated:

Acetaminophen as an antipyretic (avoid aspirin or other nsaids),

Fluid & electrolyte replacement,

Sedatives, digoxin, antiarrhythmics, insulin, and

Antibiotics
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 II. Hypothyroidism
ꭥ Defined as the clinical & biochemical syndrome resulting from
decreased TH production.

ꭥ Overt hypothyroidism:

elevated serum TSH level & reduced fT4.

ꭥ Subclinical or mild hypothyroidism:

elevated serum TSH with a normal fT4.

12/26/2024 57
 Epidemiology
ꭥ Hypothyroidism is common throughout the world.

ꭥ 1/3rd of the world’s populn lives in iodine-deficient areas.

ꭥ Prevalence of hypothyroidism
In iodine-sufficient countries…….ranges from 1-2%.

ꭥ In iodine-sufficient areas, prevalence of hypothyroidism in pregnancy

is ~2%.
ꭥ Incidence is higher among women & in the elderly.

~ 10x more prevalent in women than men.

Overt hypothyroidism occurs in 1.5-2% of women & 0.2% of men.

Incidence increases w/t age & high in >60 yrs of age.

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 Etiology
ꭥ Causes fall into 2 broad categories:

Primary hypothyroidism (thyroid gland failure).

Secondary hypothyroidism (hypothalamic-pituitary

malfunction)

12/26/2024 59
 Etiology…
ꭥ Primary hypothyroidism
Cause ~ 99% of cases of hypothyroidism.

Iodine def & autoimmune disease (Hashimoto thyroiditis)

account for the vast majority of cases.

Iodine deficiency…………..the most common cause of

hypothyroidism worldwide.

Autoimmunity is responsible for >90% of non-iatrogenic

hypothyroidism in iodine-sufficient areas.
12/26/2024 60
 Cont’d
ꭥ Primary hypothyroidism includes:

Chronic autoimmune thyroiditis (Hashimoto’s disease)

Iatrogenic hypothyroidism

Iodine deficiency

Congenital hypothyroidism
Drug-induced hypothyroidism (e.g., iodides, amiodarone, lithium,
interferon-α)
12/26/2024 61
 Cont’d
ꭥ Secondary hypothyroidism

ꭥ Is an uncommon cause resulting from:

Def. of TSH due to pituitary dysfunction.

Def. of TRH due to hypothalamic dysfunction

Isolated TSH deficiency or inactivity

ꭥ Central hypothyroidism is rare & affects both sexes equally.

Low or normal TSH level & disproportionately low fT4

It is more often associated w/t pituitary than hypothalamic disorders.

ꭥ Generalized (peripheral & central) resistance to TH is extremely

rare.

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 Clinical Presentation
ꭥ Typical Sys of hypothyroidism include:
weight gain, appetite is usually reduced

weakness, lethargy, depression

cold intolerance, constipation,

muscle cramps, myalgia & stiffness

fatigue, exercise intolerance,

loss of ambition or energy.
12/26/2024 63
 Clinical Presentation…
ꭥ Menorrhagia and infertility are common in women.
ꭥ May manifest as growth or intellectual retardation in
children.
ꭥ Goiter might or might not be present.

ꭥ Pts with end-stage hypothyroidism or myxedema coma,

can also present w/t:

hypothermia, confusion, stupor or coma, CO2 retention,

hypoglycemia, hyponatremia, and ileus.
12/26/2024 64
 Cont’d
ꭥ Physical signs include:

coarse skin & hair

cold or dry skin

periorbital edema, bradycardia, IDH and

slowed or hoarse speech.

ꭥ NB: the more severe the degree of hypothyroidism, the greater the number of
clinical findings.

Exceptions:

 older pts with hypothyroidism………often minimal or atypical sys (e.g.,

weight loss, deafness).

 Pts w/t mild or subclinical hypothyroidism……few or no sys.

12/26/2024 65
 Diagnosis
ꭥ Evaluating the patient suspected of hypothyroidism involves
TSH determination………..

Elevated TSH level is the first evidence of primary

hypothyroidism.

In secondary hypothyroidism, serum TSH concs are

generally low or normal.
12/26/2024 66
 Diagnosis
ꭥ fT4 assay should be included if:

suspicion of hypothyroidism is strong,

goiter is present, or

central hypothyroidism is part of the diff/tial Dx.

ꭥ Other tests: TPOAbs & anti-TG Abs are likely to be elevated in

autoimmune thyroiditis

ꭥ The principal differential Dx is b/n primary & central

hypothyroidism.
12/26/2024 67
 Cont’d
Parameters Primary Hypothyroidism Secondary Hypothyroidism

Serum TSH High Inappropriately low or normal

levels

Serum thyroid hormone Low or low-normal Low or low-normal

levels

Antithyroid antibodies Usually positive (if auto- Usually negative

(TPOAb) immune disease)

TRH stimulation tests Exaggerated TSH response Flat or delayed TSH response

Clinical features Symptoms are variable; Symptoms are variable and

goiter usually present; other can range from none to those
pituitary hormones of hypopituitarism; goiter
normal absent; other
pituitary hormones may be
12/26/2024 68
abnormal
 Treatment
ꭥ Goals of Therapy
Restore thyroid hormone concentrations in tissue

Provide symptomatic relief

Prevent neurologic deficits in newborns & children, and

Reverse the biochemical abnormalities of hypothyroidism.

12/26/2024 69
 Cont’d
ꭥ Levothyroxine (L-thyroxine, T4): the drug of choice for TH
replacement & suppressive therapy b/c………..

Chemically stable

Relatively inexpensive, active when given PO, free of

antigenicity, and

Has uniform potency.

ꭥ Levothyroxine administration results in a pool of TH that

is readily & consistently converted to T3.

12/26/2024 70
 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

ꭥ Average maintenance dose for most adults is ~125 µg/day.

ꭥ L-T4 dosage required to achieve euthyroidism varies widely, ranging
from 50-200 µg daily.
ꭥ Average full replacement dose of L-T4 is 1.6 µg/kg/day
ꭥ Levothyroxine is the DOC for pregnant women.

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 Cont’d
ꭥ Liothyronine (synthetic T3) has uniform potency
but has a…..
higher incidence of cardiac adverse effects,

higher cost, and

difficulty in monitoring with conventional laboratory tests.

ꭥ Liotrix (synthetic T4:T3 in a 4:1 ratio) is chemically

stable, pure, and has a predictable potency but is
expensive.
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 Evaluation of Therapeutic Outcomes
ꭥ Serum TSH concentration
the most sensitive & specific monitoring parameter for adjustment of L-T4 dose.
Concs begin to fall w/in hrs and are usually normalized w/in 2–6 wks.
ꭥ Check both TSH & T4 concs q6-8 wks until euthyroid state is achieved.

Elevated TSH level indicates insufficient replacement (needs

modest increase in L-T4 dose).
Suppressed TSH indicates reduction in L-T4 dose is warranted.
ꭥ After optimum TSH levels achieved, dose of L-T4 needs to be
continued & monitored on a regular basis.
ꭥ In pts w/t secondary hypothyroidism, monitor:
alleviation of the clinical syndrome & restoration of serum T4 to normal range.

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 The End!
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