Introduction

Pharmacotherapy of Thyroid Disorders  Thyroid disease is common, affecting approximately 5% to 15% of the
general population.
Overview of thyroid disorders  Women are three to four times more likely than men to experience any
Disorder TSH T4 and T3 type of thyroid disease.
 The typical thyroid disorders include hypothyroidism,
Thyrotoxicosis or Low or undetectable Increased hyperthyroidism, and nodular disease
hyperthyroidism
 Hypothyroidism is a clinical syndrome that results from a deficiency of

E Hashimoto’s thyroiditis, an autoimmune disorder, is the most common

Subclinical Low or undetectable Normal thyroid hormone.
hyperthyroidism

Hypothyroidism Elevated Decreased cause of primary hypothyroidism and appears to have a strong genetic
predisposition.

Subclinical Elevated Normal

 The typical symptoms of hypothyroidism include weight gain, fatigue,

nay
hypothyroidism sluggishness, cold intolerance, constipation, heavy menstrual periods,

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and muscle aches. A goiter might or might not be present

Introduction
Hypothyroidism
• Hyperthyroidism or thyrotoxicosis is the hypermetabolic

E
syndrome that occurs when the production of thyroid hormone
Guidelines for the Treatment of Hypothyroidism Prepared by the
is excessive. American Thyroid Association (ATA) Task Force on Thyroid
• Graves disease is the most common cause of hyperthyroidism. Hormone Replacement
• Other hyperthyroidism causes include: Toxic autonomous
nodular goiters, both unimodular & multinodular. Goals of therapy for hypothyroidism
• Graves disease is an autoimmune disorder characterized by one • To provide resolution of the patients’ symptoms and hypothyroid
or more of the following features: hyperthyroidism, diffuse signs.
goiter, ophthalmopathy, pretibial myxedema), and acropachy • To achieve normalization of serum thyrotropin (TSH) with normal H
(thickening of fingers or toes).
• The classic symptoms of hyperthyroidism include nervousness,
improvement of FT4 concentrations. improve
a
• To attain and maintain an euthyroid state
heat intolerance, palpitations, weight loss, insomnia, proximal
muscle weakness, frequent bowel movements, amenorrhea. • To avoid overtreatment (an euthyroid state), particularly in the
elderly.
mm
 Hasa.az
Patient type\complication Dose (L-Thyroxine) Comment
Hypothyroidism Uncomplicated adult 1.6–1.7 mcg/kg/d; 100–125 mcg/d average
replacement dose (sufficient in most patients to
An FT4 and TSH should be checked 6–8 weeks
after initiation of therapy
normalize the TSH ) usual increment 25 mcg
Goal of therapy for congenital hypothyroidism every 6–8 weeks

• The goal of therapy is a T4 in the upper normal range (10–18 mcg/dL or an FT4
of 2–5 ng/dL) during the first 2 weeks of therapy
Elderly
E
≤1.6 mcg/kg/d (50–100 mcg/d)
so Initiate T4 cautiously. Elderly may require less
than younger patients. Few patients older than 60
oocksomasia years require ≤50 mcg/day

Low FT4 and TT3 levels and elevated TSH levels seen Cardiovascular disease (angina, CAD) Start with 12.5–25 mcg/d. ↑ by 12.5–25 mcg/d These patients are very sensitive to cardiovascular

Monitoring congenital hypothyroidism :om seesaw s m

grow o rm every 2–6 weeks as tolerated effects of T4 . Even subtherapeutic doses can
precipitate severe angina, MI, or death

m s um
• Thyroid function tests should be routinely monitored 2 to 4 weeks after starting Long-standing hypothyroidism (>1 year) Dose slowly. Start with 25 mcg/d. ↑ by 25 mcg/d Sensitive to cardiovascular effects of T4 . Steady
therapy, then every 1 to 2 months during the first 6 months of life, every 3 to 4 every 4–6 weeks as tolerated state may be delayed because of ↓ clearance of T4

months until age 3, and finally, every 6 to 12 months until growth is complete. Pregnancy Most will require 45% ↑ in dose to ensure Evaluate TSH, TT4 , and FT4 I. Goal: normal
euthyroidism TSH and TT4 /FT4 I in upper-normal range to
Treatment of hypothyroidism prevent fetal hypothyroidism.

Levothyroxine is the thyroid replacement of choice for hypothyroidism
Its advantages includes stability, uniform potency, relatively low cost and lack
of allergenic foreign protein content
Pediatric (0–3 months)
0–15 mcg/kg/d The serum T4 should be increased rapidly to
minimize impaired cognitive function. In the
healthy term infant, 37.5– 50 mcg/d of T4 is
appropriate. Dose decreases with age (Page 2527,
Table 52-9)

Treatment of myxedema comanoo

some aroma
N Treatment of hypothyroidism
can
• In myxedema coma, intravenous (IV) therapy with a large (400 to 500 mcg) in • Triiodothyronine or (T3 ) is not recommended for routine thyroid hormone
patients younger than 55 years of age without cardiac disease is necessary to replacement.

reduce the high mortality rate.
• This initial T4 dosage for myxedema coma patient with cardiac disease should
be reduced to 300 mcg/day to avoid worsening his or her angina.
• Oral administration is permitted once GI function returns to normal. orangs
• The smallest oral maintenance dosage (without untoward effects) administered
should be 50 to 100 mcg/day of T4 or 10 to 15 mcg of T3 every 12 hours.
am
I
• Supportive measures include assisted ventilation, glucose for hypoglycemia,
a
restriction of fluids for hyponatremia, and the use of blood or plasma expanders
to prevent circulatory collapse and to maintain blood pressure.
of
1. Its primary use is for patients who require short-term hormone replacement therapy
and rarely in those in whom T4 conversion to T3 might be impaired.
2. Expensive and cardiotoxicity seen.
3. Proponents favoring thyroid treatment of the euthyroid sick syndrome identify T3 as
the hormone replacement of choice
• Liotrix is a combination of synthetic T4 and T3 in a physiological ratio of 4:1
• This preparation is subject to the same disadvantages common to all T3 -containing
preparations.
• Although it is stable and potent, but it is more expensive than other thyroid
preparations.

T soroom
or
Ta lo isms12h
 Treatment of hypothyroidism
• Cholestyramine, colestipol, iron sulfate, antacids, sucralfate, calcium
preparations—particularly the carbonate salt—and raloxifene can impair
levothyroxine absorption if these medications are administered at the same time.
• Cholesterol-lowering agents (e.g., lovastatin and phosphate binders are also
reported to interfere with levothyroxine absorption.
Hypothyroidism with cardiac problems
• If pt.s cardiac abnormalities are caused by hypothyroidism, adequate doses of
T4 will restore the heart size, normalize the diastolic blood pressure, reverse the
ECG findings, and normalize the serum enzyme elevations within 2 to 4 weeks
• However, improvement in myocardial function begins only at dosages of 50 to
75 mcg/day of T4, which may be tolerated poorly by cardiac patients.
• If patient is having MI or angina The angina and cardiac status should be
controlled before initiating T4 therapy
Monitoring
• Low FT4 and TT3 levels & elevated TSH levels seen. en s om
o owet
years
• FT4 or FT4 I and TSH should be checked about 6 to 8 weeks after the initiation
ta
of levothyroxine therapy because.
Tutsu sua stars
• • T4 has a half-life of 7 days, and three to four half-lives are needed to reach
steady-state levels
• Once an euthyroid state is attained, laboratory tests can be monitored every 3 to
6 months for the first year and then yearly thereafter.
• Pregnant women with hypothyroidism should be followed closely during the
first trimester with monthly monitoring of FT4 and TSH levels.
• T3 therapy should be monitored using the TSH and TT3 or FT3 levels.
Subclinical hypothyroidism
• Free thyroid hormone levels are normal, but the TSH level is elevated greater
than 10 microunits/mL (Normal TSH is 0.4 to 4 microunits/mL).
• Potential benefits of T4 treatment include
A. preventing progression to hypothyroidism,
B. improving the lipid profile and reducing cardiac risks
C. reversing symptoms of hypothyroidism.
o
• Patients with TSH levels >10 microunits/mL, a history of previously diagnosed
thyroid disease, elevated lipid levels, or evidence of positive thyroid antibodies
gained the most benefit from l-thyroxine therapy
Education for hypothyroidism patient
• Patients should be instructed to take levothyroxine on an empty stomach or at night and at
least 12 hours apart from the raloxifene and 4 hours apart from the iron, calcium, and
cholestyramine.
Foon
• Simultaneous co-administration of levothyroxine (T4) with soy proteins, coffee, or high-fiber
diets (e.g., oat bran, soybean) should also be avoided because T4 ’s absorption can be
impaired.
Education of pregnant patient with hypothyroidism
• Ingestion of the prenatal vitamins with iron and calcium should be separated by at least 4
hours from administration of T4 .
• The pregnant could also be instructed to take the T4 on empty stomach for better absorption.
• Patients should be reminded that it may take months for symptoms of hypothyroidism to
resolve and that treatment continues indefinitely.
• The TSH should be repeated in 6 weeks, and the dosage should be adjusted as needed.
 Goals of therapy for hyperthyroidism
The overall therapeutic goals are:
• To eliminate the excess thyroid hormone .
• To minimize the symptoms and long-term consequences of hyperthyroidism. o

Goal of therapy for digoxin in a hyperthyroidism patient with AF

• The goal of digoxin therapy should be a higher target heart rate (i.e., 100
beats/minute) than that achieved with digoxin in the euthyroid patient with atrial
fibrillation (AF) to minimize cardiac toxicity.

Dose not Tx indication

 Treatment of hyperthyroidism
Graves disease:
Iodides:
• They inhibit thyroid hormone release, they block organification, and they decrease the size
and vascularity of the thyroid gland.
• However, large doses may accentuate hyperthyroidism since they provide a significant
increase in available substrate for hormone synthesis.
• Therefore, iodides should not be used as primary therapy for Graves disease.
• Patients with recurrent hyperthyroidism after surgery or radioactive iodine (RAI) can
often be managed with iodides alone for 6 to 8 weeks & during this time lugol’s solution
should be avoided before RAI therapy. Bcoz Lugol’s solution prevents uptake of the RAI by
the thyroid gland
• Iodides also used in the treatment of thyroid storm.
• Stable iodine can be administered orally either as an unpleasant-tasting Lugol iodine solution
containing 8 mg/drop of iodide, or as the more palatable saturated solution of potassium
iodide, containing 50 mg/drop of iodide.
Thyroid storm
• Thyroid storm is a life-threatening medical emergency characterized by
decompensated thyrotoxicosis, high fever, tachycardia, tachypnea,
dehydration, delirium, coma, nausea, vomiting, and diarrhea.
• Even with aggressive treatment, the mortality rate is approximately 20%.
• Prompt initiation of therapy aimed at suppression of thyroid hormone formation
and secretion. Antiadrenergic therapy, administration of corticosteroids, and
treatment of associated complications or coexisting factors that may have
precipitated the storm is indicated.
notum
• Iodide (SSKI and Lugol’s solution) should be administered after thioamide is
o
to inhibit iodide utilization by the overactive gland. If iodide is administered
first, it could theoretically provide substrate to produce even higher levels of
thyroid hormone. So initially thioamides should be administered.
Treatment of hyperthyroidism
 Thioamides:
• They are the preferred treatment for children, pregnant women, and young adults with
uncomplicated Graves disease.
• Thioamides should also be given before treatment with RAI or surgery to deplete the gland of stored
Doused
thyroid hormone, which prevents subsequent thyroid storm.
• Untreated hyperthyroidism in the elderly can result in atrial fibrillation.
on
• In most hyperthyroid adults and children, methimazole (MMI) should be considered the thioamide of
choice due to increasing reports of hepatitis, some fatal, from Propylthiouracil (PTU).
• PTU should be reserved for use in thyroid storm; during the first trimester of pregnancy (may be
less teratogenic than MMI and in those allergic to methimazole who are not candidates for RAI or
surgery.
• Methimazole is effective when administered initially as a single dose compared with the multiple-
dose regimen required with PTU to achieve a euthyroid state. Methimazole is preferred over PTU
bcoz of less hepatoxicity.
unitidrto
Lessheraloxicity
Monitoring of thioamides therapy for hyperthyroidism
Before thioamides are administered
• a baseline FT4 and TSH should be obtained.
• A baseline white blood cell (WBC) count with differential. agranulocytosis
• Baseline liver function tests can assist in the evaluation of thioamide- induced hepatotoxicity.
• A repeat FT4 and TSH should be obtained after 4 to 6 weeks on therapy.
• Once the patient is euthyroid on maintenance dosages, thyroid function tests can be obtained every 3 to
6 months.
Education
• All patients receiving thioamides should be questioned closely during the first 2 months of therapy for
symptoms of hepatitis, and hepatic function tests should be obtained if appropriate.
• Patients should be instructed to immediately report rash, fever, sore throat, or any flulike symptoms.
• All patients receiving thioamide therapy should be well educated about the signs and symptoms of
agranulocytosis.
 Treatment of hyperthyroidism Beta-Adrenergic Receptor Blockade in the
Treatment of Thyrotoxicosis (ATA Guidelines)
Adjunctive therapies
Drug Dosage and Considerations
• β-blockers such as atenolol, metoprolol, propranolol are effective in alleviating frequency
the hyperthyroid symptoms, but propranolol is the only β-blocker that
significantly inhibits peripheral conversion of T4 to T3.
Propranolol i a
10–40 mg 3 to 4
times/day
Nonselective β-adrenergic receptor blockade;
Longest experience

D Bam
May block T4 to T3 conversion at high doses;
• Pts. With Hx of DM metoprolol 25-50mg initiated and maintain heart rate
Lao
pregnancy
Preferred agent for nursing, pregnant mothers
<90 BPM. and thyroid storm.
• (a) β-blockers are effective adjuncts in the management of thyroid storm, (b) Atenolol 25–100 mg 1–2 Relative β-1 selectivity; Increased compliance
times per day Avoid during pregnancy
useful to prepare patients for surgery, (c) useful in the short-term management
of thyrotoxicosis during pregnancy (only propranolol). Metoprolol 25–50 mg 2–3 t Relative β-1 selectivity

• Diltiazem or verapamil are effective alternatives when β-blockers are su

Nadolol
omg times per day
40–160 mg 1 time Nonselective b-adrenergic receptor blockade.
contraindicated. per day Once daily. Least experience to date.
May block T4 to T3 conversion at high doses

Esmolol
O
IV pump 50–100
lg/kg/min
In intensive care unit setting of severe
Thyrotoxicosis or storm

Surgery Treatment with Radioactive iodine

RAI, is the preferred treatment for
Surgery is considered the treatment of choice for Graves- related
hypothyroidism when (a) debilitated, cardiac, or older patients who are poor surgical candidates.

(a) malignancy is suspected (b) Patients who fail to respond to drug therapy or who experience adverse drug reactions
(b) esophageal obstruction is present (c) patients who experience recurrent hyperthyroidism after surgery.
(c) respiratory difficulties are present • Increasingly used in children.
(d) contraindications to the use of thioamides (e.g., allergy) or RAI (e.g., pregnancy) • Pretreatment with corticosteroids is indicated in patients with ophthalmopathy.
exist • Pregnancy is an absolute contraindication to RAI therapy.

(e) a large goiter that regresses poorly on RAI or thioamide therapy is present Education about radiation safety
(f) it is the patient’s preference. Pts with palliative thyroid cancer and
• In general, after the dose of RAI administered patient should avoid close contact with children for 5 days, with
thyroidectomy still levothyroxine recommended to maintain TSH level and it pregnant women for 10 days, and intimate contact with body fluids for 5 days.
reduces recurrence of such cancers. Use the same brand to avoid fluctuation of
• Patient should avoid airplane travel, public transportation.
thyroid levels.
• Other recommendations include sole use of bathroom facilities, sitting while urinating to avoid splashing, and
flushing the toilet twice with the lid down