Download 2_Thyroid and antithyroid drugs_ the whole lecture

Chapter 38
Thyroid & antithyroid drugs
Right Lobe
Left Lobe
Thyroglobulin
Thyroid gland
Structure:
• The thyroid gland consists of two lobes & is situated in
the lower neck
• The functional unit of the thyroid gland is the follicle
• Each follicle consists of a single layer of epithelial cells
(follicular cells) around a cavity, >>>
• the follicle lumen, which is filled with a thick colloid
containing thyroglobulin
– Thyroglobulin is a large glycoprotein,
– each molecule of which contains about 115 tyrosine
residues
Thyroid homones
• The thyroid gland secretes: triiodothyronine (T3)
thyroxine (T4)…iodothyronines
• The thyroid gland also secretes calcitonin
• T3 and T4 are critically important for:
– normal growth and development,
– normalize body temp.
– normalize energy levels
• Calcitonin is involved in the control of plasma Ca2+
(Ch. 42)
Synthesis, storage, release, and interconversion of
thyroid hormones
Iodine intake
 Iodide is ingested by food, water, medication…
 rapidly absorbed (best absorbed in the duodenum and
ileum)
 The daily intake is: 150mcg (200mcg during pregnancy)
 The thyroid gland removes 75mcg daily
Synthesis, storage, release, and interconversion of thyroid
hormones
1) Iodide ion (I-) is uptaken by the follicular cell (Na/Isymporter)…that incorporate it into active thyroid hormone.
2) Iodide is oxidized by thyroidal peroxidase into iodine
3) Iodine iodinates tyrosine residues of thyroglobulin to form
monoiodotyrosine (MIT) and diiodotyrosine (DIT)….iodine
organification
4) Two molecules of diiodotyrosine combine to form Lthyroxine (T4 ); one MIT and one DIT combine to form T3
(Coupling)
5. Proteolysis of thyroglobulin and the release of T4 and T3
into the blood
Na+/I- symporter
Thiocyanate /
Perchlorate
T3, T4
Extracellular space
Na+
K+
I-
Na+
Exocytosis
IT3, T4, DIT, MIT
Follicle cell
Proteolysis
colloid space
T
T
Pendrin
T
T
Thyroglobulin
T
DIT
T4
T
T4
DIT
T3
T
Io
peroxidase
I-
Organification
MIT
T
Coupling
T
MIT
T
MIT
Thyroglobulin with monoiodotyrosines (MIT) &
diiodotyrosines (DIT)
Synthesis, storage, release, and interconversion of
thyroid hormones
• In the blood thyroid hormones are 99% bound to plasma
protein,
– primarily thyroxin-binding globulin (TBG)
• T4
– is secreted solely from the thyroid gland
– and is produced in the greatest amounts
• T3:
– 20% of T3 is produced in the gland,
– the majority of T3 is formed from the breakdown of T4 in
peripheral tissues (liver) by 5-deiodinase
• T3 is 4X more potent in activity
1.
2.
3.
4.
5.
Amiodarone
Radiocontrast media
β-blockers
Corticosteroids
Starvation
T4
R
R
T3
Monodeiodination of
the
outer
ring,
producing
3,5,3'triiodothyronine (T3)
rT3
R=
Monodeiodination
in the inner ring
produces
3,3',5'triiodothyronine
(reverse T3, or rT3),
which
is
metabolically
inactive
Table 38-1.
T4 highly TGB bound
© The McGraw-Hill Companies, Inc., 2010
Table 38-2.
© The McGraw-Hill Companies, Inc., 2010
Control of thyroid function
Cold
Acute psychosis
Circardian & pulsatile rhythms
_
+
Stress
Hypothalamus
TRH
+
_
SST
_
-
Anterior pitutary
gland
-
TSH
Dopamine
Corticoids
+
_
Thyroid gland
+
T3 & T4
I (high)
I (low)
Pharmacokinetics
• Absorption of thyroid hormones is modified by
intraluminal factors such as food, drugs, gastric acidity,
and intestinal flora
– …change from oral to parenteral Tx. (I.V)
• T4..(80% absorbed), T3 (95%)
• Strict high regulation:
– Hyperthyroidism
• increase the metabolic clearances of T4 and T3;
• decreasing their half-lives; *
– (hypothyroidism opposite)
Pharmacokinetics
• Drugs that induce hepatic microsomal enzymes
–
–
increase T4 and T3 metabolism;
conc. remain normal in euthyroid patients….compensatory
increase in thyroid function
• Similarly, if TBG increase by pregnancy, estrogens, or oral
contraceptives
– ….initial shift of hormone from free to bound state
– and decrease in its rate of elimination
– until the normal hormone concentration is restored
Figure 38–4.
1
4
2
Active
transport
3
© The McGraw-Hill Companies, Inc., 2010
Mechanism of Hormone Action
• Most actions of thyroid hormones seem to be
mediated by nuclear receptors
– T3 binds to high-affinity nuclear receptors,
– which then bind to specific DNA sequences (thyroid
hormone
response
elements,
TREs)
in
the
promoter/regulatory regions of target genes,
– which may repress or promote the transcription of the
associated thyroid hormone-responsive genes
Effects of Thyroid Hormones
1. Growth & development
•
critical for the development and functioning of :
–
–
•
nervous, skeletal, and reproductive tissues
….directly by protein synthesis & indirectly by potentiation of
GH
Thyroid hormone plays a critical role in brain
development
–
The absence of thyroid hormone during the period of active
neurogenesis (up to 6 months postpartum) leads to
irreversible mental retardation and dwarfism (cretinism=
neonatal hypothyroidism)
Effects of Thyroid Hormones
2. Cardiovascular effects: thyroid hormone influences cardiac
function by direct and indirect actions:
• Thyroid hormones directly:
– increase the expression of genes of the sarcomeric myosin heavy
chains
– >>>…increase heart contraction
• Thyroid hormones indirectly:
– indirectly alter the sensitivity of the cardiac myocyte
responsiveness to catecholamines, possibly due to changes in
expression of myocardial β-adrenergic receptors
Effects of Thyroid Hormones
4. Metabolic effects
•
The thyroid hormones produce a general
increase in the metabolism of
–
–
–
–
•
carbohydrates,
fats,
proteins
and vitamins,
and regulate these processes in most tissues
Effects of Thyroid Hormones
5. Calorigenic effect
•
Most peripheral tissues (heart, skeletal muscle, liver, and kidney)
are stimulated markedly by thyroid hormone to
–
–
•
increased O2 consumption
& heat production
Several organs, including
–
–
–
–
brain,
gonads,
and spleen,
are unresponsive to the calorigenic effects of thyroid hormone
 Generally: hyperthyroidism cause:
 tremor,
 excessive sweating,
 Anxiety
 & nervousness
Thyroid preparations
• Thyroid preparations may be:
– synthetic (levothyroxine, liothyronine, liotrix)
– or of animal origin (desiccated thyroid)
• There is no significant difference in the qualitative response of
the patient with hypothyroidism to triiodothyronine, thyroxine,
or desiccated thyroid.
• However, there are obvious quantitative differences
Thyroid preparations
• Major indications:
1) hormone replacement therapy in patients with
hypothyroidism or cretinism
2) TSH suppression therapy in patients with thyroid
cancer and occasionally those with nontoxic goiter
Levothyroxine (T4) (oral & parenteral)
• It is the preparation of choice for maintenance of
plasma T4 and T3 concentrations for thyroid hormone
replacement therapy in hypothyroid patients
• Its long half-life (7 days) allows for convenient once
daily administration
• Since much of the T4 is deiodinated to T3; thus,
administration of T4 produces both hormones
Liothyronine (T3) (oral & parenteral)
• It is not used for maintenance thyroid hormone replacement
therapy because of:
1)
2)
3)
4)
shorter half-life and duration of action
Cost
Difficulty in monitoring by conventional lab methods
Hormone activity and consequent greater risk of cardiotoxicity
• Most appropriate use:
a. short-term suppression of TSH in patients undergoing surgery
for thyroid cancer
b. Initial therapy of myxedema and myxedema coma
(absorption and conversion impaired, T4 delayed onset)
Liotrix (oral)
• 4:1 mixture of levothyroxine sodium and liothyronine
sodium
• Based on the idea of combining T4 and T3 in replacement
therapy so as to mimic the normal ratio secreted by the
thyroid gland
• It does not appear that liotrix offers any therapeutic
advantage over levothyroxine alone
• Too expensive
Dessicated Thyroid (thyroid extracts) (oral)
• The use of desiccated thyroid rather than synthetic
preparations is never justified…..
– protein antigenicity,
– product instability,
– variable hormone concentrations,
– and difficulty in laboratory monitoring
>>>>>>> far outweigh the advantage of lower cost
• Shelf life of synthetic hormone preparations is ~2 years
(stored in dark bottles to minimize spontaneous deiodination)
• Shelf life of desiccated thyroid is not known with
certainty….its potency is better preserved if it is kept dry
Abnormalities of thyroid function
Hypothyroidism
• Hypothyroidism is manifested largely by a reversible
slowing down of all body functions…diagnosed by
elevated TSH in the serum and low free thyroxine
• In infants and children,
– striking retardation of growth and development that results in
dwarfism and irreversible mental retardation
Table 38-3.
© The McGraw-Hill Companies, Inc., 2010
Hypothyroidism
• The laboratory diagnosis of hypothyroidism
– the combination of a low free thyroxine and elevated serum TSH
• Subclinical hypothyroidism
– ….elevated TSH level
– and normal thyroid hormone levels??
– >>>>>> hormone therapy considered for patients with
very high TSH levels
– >>>>>>>….close TSH monitoring is appropriate for those with
lower TSH elevations
• Pituitary failure (2ry hypothyroidism)
– should be suspected in patients with low T4 and TSH levels
Hypothyroidism
• Hypothyroidism can occur with or without thyroid
enlargement (goiter)
• Tx goals:
– restore thyroid hormone conc.;
– provide symptomatic relief,
– prevent neurologic deficits in newborn & infants
– and reverse the biochemical abnormalities of hypothyroidism
Hypothyroidism
• NON-TOXIC GOITER:
• Syndrome of enlargement of the thyroid gland without
excessive thyroid hormone production
– Enlargement is often due to TSH stimulation from inadequate
thyroid hormone synthesis ….Hashimoto’s thyroiditis
– Goiter due to Iodide deficiency: Daily iodide intake is 150–200
mcg….iodized salt are excellent sources of iodine in the diet
1The
anemia of hyperthyroidism is usually caused by increased red blood cell turnover. The anemia of hypothyroidism may be due to
decreased production rate, decreased iron absorption, decreased folic acid absorption, or to autoimmune pernicious anemia.
LDH, lactic dehydrogenase; AST, aspartate aminotransferase.
Clinical Features of Hypothyroidism
Puffy Eyes
Lethargy
Forgetfulness/Slower Thinking
Mood irritability
Depression
Inability to Concentrate
Dry and brittle hair, brittle nails
Enlarged Thyroid (Goiter)
Deepening of Voice
Difficulty Swallowing
Decrease HR, CO, prolonged PR
interval
Dry, Patchy Skin
Menstrual Irregularities/
Heavy Period
Weight Gain
Cold Intolerance
Infertility/Impotence
Elevated Cholesterol & TG’s
Anemia: decreased erythropoiesis
Decrease drug metabolism
Increased warfarin requirements
Decrease appetite and bowel
movement/Constipation
Muscle Weakness/
Cramps
Decrease renal blood flow &
GFR..impaired water excretion
Management of Hypothyroidism
• There are no drugs that specifically augment the
synthesis or release of thyroid hormones
• The only effective treatment for hypothyroidism is to
administer the thyroid hormones themselves as
replacement therapy
• Combination levothyroxine plus liothyronine has not
been found to be superior to levothyroxine alone (once
daily)
Management of Hypothyroidism
• Drug-induced hypothyroidism
– can be treated by simply removing the depressant agent if
possible…..or levothyroxine (if can not stop it)
• amiodarone-induced hypothyroidism,
– levothyroxine
therapy
may
be
necessary
even
after
discontinuance because of amiodarone's very long half-life
Management of Hypothyroidism
 Infants and children
 require more T4 per kilogram of body weight than adults.
 Older adults (> 65 years of age)
 may require less thyroxine for replacement than younger adults.
 Thyroxine administration:
 should be administered on an empty stomach (eg, 30 minutes
before meals or 1 hour after meals)
 ….interactions with certain foods (eg, bran, soy, coffee) and drugs
can impair absorption
SPECIAL CASES: Myxedema and Coronary Artery
Disease
• Myxedema frequently occurs in older persons, often
associated with underlying coronary artery disease
• The low levels of circulating thyroid hormone actually:
– protect the heart against increasing demands (that may result in
angina pectoris or MI)
• So….correction of myxedema, in patients with coronary
artery diseae,
>>>>> must be done cautiously to avoid provoking arrhythmia, angina,
or acute MI
Management of Hypothyroidism
 In younger patients or those with very mild disease,
 full
replacement
therapy
may
be
started
immediately…..monitor for normal growth and development.
 Serum TSH and FT4 should be measured at regular
intervals
 It takes 6–8 weeks after starting a given dose of thyroxine to
reach steady-state levels in the bloodstream
Adverse effects
• The toxicity of thyroxine is directly related to the
hormone level (i.e., symptoms of hyperthyroidism)
• In children:
– restlessness,
– insomnia,
– and accelerated bone maturation and growth
• In adults:
–
–
–
–
increased nervousness,
heat intolerance,
episodes of palpitation and tachycardia,
or unexplained weight loss may be the presenting symptoms
Adverse effects
 Chronic overtreatment
 may develop osteoporosis ,especially in elderly, increased bone
turn over.
 In older patients,
 the heart is very sensitive to the level of circulating thyroxine, and
if angina pectoris or cardiac arrhythmia develops,
 >>>>>it is essential to stop or reduce the dose of thyroxine
immediately
Drug interactions
a. Drugs may interfere with thyroid hormones absorption
(e.g. cholestyramine, iron and calcium supplements,
aluminum hydroxide)
b. CYP450 enzyme inducer (eg, rifampin, phenobarbital,
carbamazepine, phenytoin, protease inhibitors)
c. Inhibition of 5'-deiodinase (e.g. Beta-blockers)
d. Changes in TBG concentration:
I.
II.
Increased TBG: Estrogens, tamoxifen, heroin, methadone,
fluorouracil
Decreased TBG: Androgens & glucocorticoids
Drug interactions
• Thyroid hormone & sympathomimetic agents
– increase the risk of coronary insufficiency in patients with CAD
• Thyroid hormones & coumarins
– increase the effect of the anticoagulant
– Because of ……increase catabolism of vit. K–dependent clotting factors
– (lower doses of coumarins are required)
• Initiation of thyroid hormone therapy in patients with DM
– ….increase the requirement for insulin or oral hypoglycemic agents
• Thyroid hormone & cardiac glycosides
– …..larger doses of digoxin may be required
SPECIAL CASES: Hypothyroidism and Pregnancy
• Hypothyroid women frequently have:
– anovulatory cycles
– and are therefore relatively infertile until restoration of the euthyroid
state
• Widespread use of thyroid hormone for infertility,
– although there is no evidence for its usefulness in infertile euthyroid
patients
• During pregnancy: Adequate daily dose of thyroxine because
of;
– early development of the fetal brain depends on maternal thyroxine
– and coz elevated TBG levels
SPECIAL CASES: Myxedema Coma
• is an end state of untreated hypothyroidism associated
with:
–
–
–
–
–
–
–
progressive weakness,
stupor,
hypothermia,
hypoventilation,
hypoglycemia,
hyponatremia, water intoxication,
shock, and death
• …mortality rate 60-70%
• Medical emergency….the patient is treated with:
– i.v loading dose of levothyroxine;
– tracheal intubation
– and mechanical ventilation may be required
Hyperthyroidism
• Hyperthyroidism refers to excess synthesis and secretion
of thyroid hormones by the thyroid gland
– ….T3, T4 , FT4, and FT3 are elevated
– while TSH is suppressed
– Radioiodine uptake is usually markedly elevated as well
• Thyrotoxicosis is the term applied to any condition
caused by elevated levels of circulating free thyroid
hormones
Hyperthyroidism
• It is associated with a number of disease states,
including:
– Graves’ disease,
– toxic adenoma,
– or toxic goiter
• Graves’ disease: autoimmune disorder in which the
– antibody (TSH-R [stim] Ab) is directed against the TSH receptor
site on the thyroid cell membrane
– and activate adenylate cyclase in the same manner as TSH
– Spontaneous remission occurs
– but some patients require years of antithyroid
therapy
Hyperthyroidism
• Toxic Uninodular Goiter & Toxic Multinodular
Goiter:
– occur often in older women with nodular goiters
– FT3 or T3 is strikingly elevated (FT4 may be normal)
– Single toxic adenomas can be managed with either
• surgical excision
• or with radioiodine therapy
– Toxic multinodular goiter is best treated with:
• methimazole or propylthiouracil
• followed by subtotal thyroidectomy
1The
anemia of hyperthyroidism is usually caused by increased red blood cell turnover. The anemia of hypothyroidism may be due to
decreased production rate, decreased iron absorption, decreased folic acid absorption, or to autoimmune pernicious anemia.
LDH, lactic dehydrogenase; AST, aspartate aminotransferase.
Signs and Symptoms of Hyperthyroidism
Mental Disturbances/ Irritability
Difficulty Sleeping
Nervousness/Tremor
Difficulty Swallowing
Bulging Eyes/ Vision Changes
Enlarged Thyroid (Goiter)
Palpitations/
Tachycardia, increase CO, SV,
angina, arrhythmias
Frequent Bowel Movements
Heat Intolerance
Menstrual Irregularities/
Light Period
Increased Sweating
Warm, Moist Palms
Impaired Fertility
First-Trimester Miscarriage/
Excessive Vomiting in Pregnancy
Increase erythropoiesis /
anemia
Sudden Paralysis
Weight loss / Increase appetite
Hyperglycemia, decrease
FA, TG’s, cholesterol
Increase drug metabolism,
decrease warfarin requirements
Hyperthyroidism
• The three primary methods for controlling Graves’
disease hyperthyroidism are:
– antithyroid drug therapy,
– surgical thyroidectomy,
– and destruction of the gland with radioactive iodine
Thyredectomy
• A near-total thyroidectomy is the treatment of choice for
patients with:
– very large glands
– or multinodular goiters
• Patients are treated with antithyroid drugs
– until euthyroid (about 6 weeks) before surgery
• About 80–90% of patients
– will
require
thyroidectomy
thyroid
supplementation
following
near-total
Hyperthyroidism
• Antithyroid Drug Therapy:
– the only Tx that leaves the thyroid gland intact (advantage)
– but require long period of Tx (12-18 months) (disadvantage)
– with 50-70% incidence of relapse (disadvantage)
1) Inhibit synthesis of the hormone
2) Inhibit iodide uptake
3) Block the release of the hormone
4) Remove/destroy part of the thyroid by surgery or radiation
Inhibition of thyroid hormone synthesis:
thioamides
• Agents: propylthiouracil and methimazole
• Thionamides are the primary and major drugs used to
decrease thyroid hormone production
• Methimazole:
– 10x more potent than propylthiouracil
– and can be given once daily
• Uses
– in the management of hyperthyroidism
– and thyrotoxic crisis
– and in the preparation of patients for surgical subtotal
thyroidectomy
Thioamides- MOA
1) Prevent hormone synthesis by inhibiting the thyroid
peroxidase-catalyzed reactions and blocking iodine
organification
2) Block coupling of the iodotyrosines
3) Inhibit the peripheral deiodination of T4 and T3 (mainly
propylthiouracil)
• Since the synthesis rather than the release of hormones is
affected, the onset of these agents is slow (3-4 weeks)
before stores of T4 are depleted
• They do not block uptake of iodide by the gland
Thioamides- ADRs
I.
Most common: maculopapular pruritic rash (antihistamine)
II. Most
serious:
agranulocytosis
(sore
throat,
high
fever….discontinue Tx)
III. Rare: urticarial rash, vasculitis, a lupus-like reaction,
lymphadenopathy, hypoprothrombinemia, exfoliative
dermatitis,
polyserositis,
cholestatic
jaundice
(methimazole), hepatitis
(propylthiouracil) and acute
arthralgia
• Thioamides cross the placental barrier, caution when using
these drugs in pregnancy
• (propylthiouracil is preferable in pregnancy…more protein bound)
ANION INHIBITORS
• Monovalent anions:
– perchlorate (ClO4–),
– pertechnetate(TcO4–),
– and thiocyanate (SCN–)
• MOA:
– can block uptake of iodide by the gland….competitive
inhibition of the iodide transport mechanism
• Effects may be overcome by large
iodides…..unpredictable effectiveness
doses
of
• N.B: rarely used clinically because it is associated with
aplastic anemia
Inhibition of hormone release: IODIDES
•
The effects of iodide on the thyroid gland are
complex:
1) Inhibit hormone release, possibly through inhibition
of thyroglobulin proteolysis (major)
2) Inhibit organification
3) Decrease the size and vascularity of the
hyperplastic gland
•
In susceptible individuals, iodides can:
•
•
induce hyperthyroidism
or precipitate hypothyroidism
Iodides
• Clinical Uses
1.
Treatment of severe thyrotoxicosis or thyroid crisis
when a rapid decrease in plasma T4 and T3 is
desirable
1.
2.
….Improvement in symptoms occurs rapidly—within 2–7
days
Preoperative preparation of patients about to
undergo total or subtotal surgical thyroidectomy
1.
…..decrease vascularity and size of the hyperplastic gland
Iodide
• Iodide should not be used alone coz over time, the
beneficial effects disappear, even with ongoing
therapy
– Hypersecretion of thyroid hormone and thyrotoxicosis may
return at the previous or a more severe intensity
• Iodide use should be initiated only after onset of
thioamide treatment & not used if radioactive iodine
therapy is planned
• Chronic use of iodides in pregnancy should be
avoided….cross the placenta….fetal goiter
Iodides- ADRs
• Iodism: are uncommon and reversible:
a. Acneiform rash (similar to that of bromism)
b. Swollen salivary glands
c. Mucous membrane ulcerations
d. Conjunctivitis
e. Rhinorrhea
f. Drug fever
g. Metallic taste
h. Bleeding disorders
i. Anaphylactoid reactions (rare)
Radioactive Iodine (131I)
• The only isotope used for treatment of thyrotoxicosis
–
–
–
–
•
131I
….orally in solution as sodium 131I,
it is rapidly absorbed,
concentrated by the thyroid,
and incorporated into storage follicles
is taken up and trapped in the same manner as I-.
• The ablative effect depends on emission of β rays, which
destroy thyroid tissue...T1/2 of 5 days
• Within few weeks, destruction
parenchyma is evidenced by:
–
–
–
–
epithelial swelling and necrosis,
follicular disruption,
edema,
and leukocyte infiltration
of
the
thyroid
Radioactive Iodine (131I)
• Advantages:
– easy administration,
– effectiveness,
– low expense,
– and absence of pain
• Major disadvantage
– is the development of hypothyroidism…replacement with T4
• Should not be administered to pregnant women or
nursing mothers…..crosses the placenta to destroy the fetal
thyroid gland and is excreted in breast milk
Adrenergic receptor blocking drugs
• Rationale: reduction of sympathetic manifestations of
thyrotoxicosis (thyroid storm)
• Applicable drugs:
 Beta adrenoceptor blockers without intrinsic
sympathomimetic activity (propranolol, metoprolol,
atenolol)
 Beta blocker cause improvement of symptoms but
do not alter thyroid hormone levels
 Patients suffering from asthma: CCB (diltiazem)
 At high doses propranolol inhibit conversion of T4 to T3
SPECIAL PROBLEM: thyroid storm
• Sudden acute exacerbation of all thyrotoxicosis symptoms; lifethreatening syndrome; vigorous management:
1. Propranolol (diltiazem) control severe CV manifestations
2.
Release of thyroid hormones from the gland is retarded by the
administration of potassium iodide solution
3.
Hormone synthesis is blocked by the administration
propylthiouracil or methimazole (orally or rectally)
4.
Hydrocortisone protect the patient against shock and block the
conversion of T4 to T3
5.
Supportive therapy essential to control fever, heart failure, and any
underlying disease that may have precipitated the acute storm
6.
Rarely: peritoneal dialysis to lower circulating thyroxine levels
of
SPECIAL PROBLEM: Subacute Thyroiditis
• Subacute thyroiditis:
– Destruction of thyroid parenchyma
– during acute viral infection of the thyroid gland
– with transient release of stored thyroid hormones
• These transient episodes of thyrotoxicosis
spontaneously resolving hyperthyroidism
are
called
• Supportive therapy:
– β-adrenoceptor blocking for tachycardia
– and NSAIDs to control local pain and fever
• Corticosteroids may be necessary in severe cases to control
the inflammation
SPECIAL PROBLEM: thyrotoxicosis & pregnancy
• Women in childbearing period with severe disease should
have
– definitive therapy with
pregnancy
131I
or subtotal thyroidectomy prior to
• If thyrotoxicosis develops during pregnancy, radioiodine is
contraindicated (crosses the placenta and may injure the fetal
thyroid)
– In the first trimester…propylthiouracil
– Mid trimester….subtotal thyroidectomy performed safely.
• Most patients are treated with propylthiouracil during the
pregnancy (lower dose)