Thyroid Hormones & Drugs

8/14/2019 Thyroid Hormones & Drugs

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Dr. Eduardo D. RosasDr. Eduardo D. Rosas

BlumBlumDepartment ofDepartment of

PharmacologyPharmacology


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A 29 YO female complains of restlessness andA 29 YO female complains of restlessness and

increasing anxiety. HR 135bmp, PE: Tremors.increasing anxiety. HR 135bmp, PE: Tremors.Palpation on the neck reveals a 3cm nodule onPalpation on the neck reveals a 3cm nodule on

her thyroid gland. Laboratory test are sent toher thyroid gland. Laboratory test are sent to

confirm the diagnosis. In the meantime, withconfirm the diagnosis. In the meantime, with

drug could be given to acutely reduce herdrug could be given to acutely reduce herphysical symptoms?physical symptoms?

a)a) Propylthiouracil.Propylthiouracil.

b)b) Furosemide.Furosemide.

c)c) Prednisone.Prednisone.

d)d) Iodine.Iodine.

e)e) Propanolol.Propanolol.


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ThyroidThyroid

Secretes three hormones:Secretes three hormones:

Calcitonin, important in calciumCalcitonin, important in calcium

homeostasis.homeostasis.

Triiodothyronine (T3) and thyroxine (T4),Triiodothyronine (T3) and thyroxine (T4),

important in growth and metabolicimportant in growth and metabolic

function.function.


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Thyroid drugsThyroid drugs


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Thyroid HormonesThyroid Hormones

T4 and T3 are iodine-containing hormonesT4 and T3 are iodine-containing hormonesthat are analogs of tyrosine.that are analogs of tyrosine.

Regulated by TSH, which increases theRegulated by TSH, which increases the

Synthesis and secretion of theseSynthesis and secretion of thesehormones.hormones.

TSH secretion is regulated by negativeTSH secretion is regulated by negative

feed-back of the thyroid hormones; it isfeed-back of the thyroid hormones; it ispositively influenced by TRH from thepositively influenced by TRH from thehypothalamus.hypothalamus.


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lodide is necessary for thyroid hormonelodide is necessary for thyroid hormone

synthesis.synthesis.

Iodide is obtained from the diet and is absorbedIodide is obtained from the diet and is absorbed

from the gastrointestinal tract.from the gastrointestinal tract. Once in the gland iodide is oxidized to an activeOnce in the gland iodide is oxidized to an active

iodine intermediate, which iodinates tyrosineiodine intermediate, which iodinates tyrosine

residues of thyroglobulin.residues of thyroglobulin.

An aerobic condensation of iodinated tyrosineAn aerobic condensation of iodinated tyrosine

molecules results in production of T3 and T4.molecules results in production of T3 and T4.


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99% of T3 and T4 are bound to plasma99% of T3 and T4 are bound to plasma

proteins (thyroid-binding globulin).proteins (thyroid-binding globulin).

They are excreted in the bile and urine.They are excreted in the bile and urine.

T4 has a half-life of 6-7 days; T3 has aT4 has a half-life of 6-7 days; T3 has a

half-life of 1-2 days.half-life of 1-2 days.

Some of the circulating T4 is deiodinatedSome of the circulating T4 is deiodinatedto T3, the more potent and rapidly actingto T3, the more potent and rapidly acting

form.form.


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Activation of nuclear nonhistone proteinActivation of nuclear nonhistone proteinreceptors attached to DNA.receptors attached to DNA.

Binding leads to increased transcription ofBinding leads to increased transcription of

messenger RNA (mRNA).messenger RNA (mRNA). Increasing the synthesis of specific proteins. (T3Increasing the synthesis of specific proteins. (T3

x 10 potent).x 10 potent). Cell membranes receptors: increase amino acidCell membranes receptors: increase amino acid

and glucose uptake.and glucose uptake. Inner mitochondrial membrane receptors:Inner mitochondrial membrane receptors:

regulate energy metabolism.regulate energy metabolism.


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Effects in most major systems, including normalEffects in most major systems, including normal

growth and development.growth and development.

Increased basal metabolic rate and activation ofIncreased basal metabolic rate and activation of

oxygen consumption.oxygen consumption.

Thermogenic effect (increased heat production).Thermogenic effect (increased heat production).

Increased plasma glucose and free fatty acids,Increased plasma glucose and free fatty acids,

reduction in plasma cholesterol and triglycerides.reduction in plasma cholesterol and triglycerides. Increased HR, maturation of the CNS.Increased HR, maturation of the CNS.


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Thyroid DrugsThyroid Drugs

Replacement therapy.Replacement therapy.

Treatment for hypothyroidism.Treatment for hypothyroidism.

Suppress TSH secretion.Suppress TSH secretion. Levo isomers are more potent inLevo isomers are more potent in

increasing basal metabolic rate.increasing basal metabolic rate.

Once absorbed, their pharmacokinetic andOnce absorbed, their pharmacokinetic anddynamic properties are identical todynamic properties are identical to

endogenous thyroid hormones.endogenous thyroid hormones.


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Thyroid DrugsThyroid Drugs

Advers e reac tionsdvers e reac tions

Hyperthyroidism (or symptoms ofHyperthyroidism (or symptoms ofhyperthyroidism).hyperthyroidism).

Cardiovascular toxicity (tachyarrhythmias,Cardiovascular toxicity (tachyarrhythmias,

angina, and infarction)angina, and infarction) CNS stimulation, insomnia.CNS stimulation, insomnia.


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LevothyroxineLevothyroxine

Synthetic levo isomer of T4.Synthetic levo isomer of T4.

PO and IV available.PO and IV available.

Preferred drug for hypothyroidism.Preferred drug for hypothyroidism. Better standardization and stability andBetter standardization and stability and

long duration.long duration.

Long half-life of T4.Long half-life of T4. Facilitates maintenance of a steadyFacilitates maintenance of a steady

physiologic replacement.physiologic replacement.


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LiothyronineLiothyronine

Synthetic L-T3.Synthetic L-T3.

More difficult to monitor than T4.More difficult to monitor than T4.

More expensive.More expensive. Shorter duration of action.Shorter duration of action.

Treatment of choice for Mixedema coma.Treatment of choice for Mixedema coma.


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LiotrixLiotrix

Combination of levothyroxine andCombination of levothyroxine and

liothyronine.liothyronine.

Ratio of 4:1.Ratio of 4:1.

No advantage over levothyroxine.No advantage over levothyroxine.


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Antithyroid DrugsAntithyroid Drugs


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Antithyroid DrugsAntithyroid Drugs

Inhibit the formation of thyroidInhibit the formation of thyroid

hormones.hormones.

Used in the treatment ofUsed in the treatment of

hyperthyroidism.hyperthyroidism.


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lodidelodide

Small amounts of iodine (75-100 ng/day)Small amounts of iodine (75-100 ng/day)

are required for hormone synthesis.are required for hormone synthesis.

But high concentrations (+ 50 mg/day)But high concentrations (+ 50 mg/day)

produce autoinhibition.produce autoinhibition.

lodide blocks the uptake of iodide,lodide blocks the uptake of iodide,

inhibiting synthesis and release of thyroidinhibiting synthesis and release of thyroid

hormones.hormones.

Diminishes vascularity of the gland.Diminishes vascularity of the gland.


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lodidelodide

Used only preoperatively to shrink theUsed only preoperatively to shrink the

gland. (prior to surgical removal of thegland. (prior to surgical removal of the

gland).gland).

Treatment of thyroid storm.Treatment of thyroid storm.

It is given as Lugol's solution (iodine andIt is given as Lugol's solution (iodine and

potassium iodide).potassium iodide).

Effects are visible within 24 hours. It is noEffects are visible within 24 hours. It is no

longer used in long-term therapy.longer used in long-term therapy.


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lodidelodide

Adverse reactionsAdverse reactions

Hypersensitivity reaction .Hypersensitivity reaction .

Drug fevers, metallic taste, bleeding disordes.Drug fevers, metallic taste, bleeding disordes.

Gastric irritation.Gastric irritation.

Long-term use can lead to sudden disinhibitionLong-term use can lead to sudden disinhibition

of hormone synthesis, producing acuteof hormone synthesis, producing acutehyperthyroidism.hyperthyroidism.


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ThioamidesThioamides

Propyithiouracil (PTU), methimazole.Propyithiouracil (PTU), methimazole.

Inhibit the peroxidase enzymes catalyzingInhibit the peroxidase enzymes catalyzing

the oxidation of iodide, thus reducing thethe oxidation of iodide, thus reducing the

synthesis of thyroid hormones.synthesis of thyroid hormones.

PTU also inhibits the peripheralPTU also inhibits the peripheral

deiodination of T4 to T3.deiodination of T4 to T3.

Delay in onset (until preformed hormonesDelay in onset (until preformed hormones

have been metabolized).have been metabolized).


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Used for control of hyperthyroidism untilUsed for control of hyperthyroidism until

surgery.surgery.

Suppression of thyroid hormone synthesisSuppression of thyroid hormone synthesis

until the effect of radioactive iodide begins.until the effect of radioactive iodide begins.

Long-term therapy of mild-to-moderateLong-term therapy of mild-to-moderate

hyperthyroidism.hyperthyroidism.

The drugs are given PO.The drugs are given PO.


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Adverse reactions.Adverse reactions.

Mild maculopapular rash, joint pain, headache,Mild maculopapular rash, joint pain, headache,

nausea, and loss of hair.nausea, and loss of hair.

Rare: agranulocytosis.Rare: agranulocytosis.

Crosses the placenta and enter breast milk,Crosses the placenta and enter breast milk,

which can lead to hypothyroidism in the fetuswhich can lead to hypothyroidism in the fetusand nursing infant.and nursing infant.

Pregnancy ?Pregnancy ?


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Radioactive iodine (131I)Radioactive iodine (131I)

PO or IV.PO or IV.

Rapidly taken, then is incorporated intoRapidly taken, then is incorporated into

thyroglobulin.thyroglobulin.

Leads to partial or total destruction of theLeads to partial or total destruction of the

gland by emission of beta particles.gland by emission of beta particles.

Damage to surrounding tissue is minimal.Damage to surrounding tissue is minimal.


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Radioactive iodine (131I)Radioactive iodine (131I)

Used in the treatment of hyperthyroidism.Used in the treatment of hyperthyroidism.

Side effects and toxicity.Side effects and toxicity.

Mayor: hypothyroidismMayor: hypothyroidism..

Should be avoided during pregnancy.Should be avoided during pregnancy.


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Well be starting in 10min sharply


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Cli nical Ca seli nical Ca se A 52 years-old male comes to your officeA 52 years-old male comes to your office

with a 1-month-old annoying pain onwith a 1-month-old annoying pain on

arms and legs.arms and legs.

HPIHPI

The pain is referred as tingling sensation,The pain is referred as tingling sensation,

located or hands and feet, that increases atlocated or hands and feet, that increases at

night and has disturbs his sleep. Nothingnight and has disturbs his sleep. Nothing

reduces the pain.reduces the pain.

Also states that he has been feeling fatiguedAlso states that he has been feeling fatigued

for the past 2 months.for the past 2 months.


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Cli nical Ca seli nical Ca se PMIPMI

Hypothyroidism for the last 4 months (Euthyrox).Hypothyroidism for the last 4 months (Euthyrox).Loss of appetite for the last year.Loss of appetite for the last year.

Essential Hypertension for the last 3 years (LosartanEssential Hypertension for the last 3 years (Losartan

+ Hydroclorothiazide).+ Hydroclorothiazide). SHSH

Alcohol (+) every day, up to 20-30oz.Alcohol (+) every day, up to 20-30oz.

PEPE

HR 100 RR 18 BP 139/89 BMI 40.HR 100 RR 18 BP 139/89 BMI 40. Slight pale coloration of the skin and mucousSlight pale coloration of the skin and mucous

membranes.membranes. Neurological test unremarkable.Neurological test unremarkable. Rest of the examination unremarkable.Rest of the examination unremarkable.


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High-Yield Slides.High-Yield Slides.

Dr. Rosas BlumDr. Rosas Blum


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Crucial for normal development.Crucial for normal development.

Maintains metabolic homeostasis.Maintains metabolic homeostasis.

Affects every organ system.Affects every organ system. Cretinism: diminish thyroid hormones.Cretinism: diminish thyroid hormones.


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HypothyroidismHypothyroidism

Cold intolerance, hair changes, weightCold intolerance, hair changes, weightgain.gain.

Treatment thyroid hormone replacement.Treatment thyroid hormone replacement.


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HyperthyroidismHyperthyroidism

Array of treatmentsArray of treatments

PTU or methimazole.PTU or methimazole.

IodineIodine Radioactive Iodine.Radioactive Iodine.

Surgery.Surgery.


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MyxedemaMyxedema

Both hypo or hyperthyroidism.Both hypo or hyperthyroidism.

Refer different things.Refer different things.

Myxedema w/hypothyroidismMyxedema w/hypothyroidism

Apathy, listlessness, edema accumulates inApathy, listlessness, edema accumulates inskin and other tissues.skin and other tissues.

Broadening of facial features.Broadening of facial features.


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MyxedemaMyxedema

Myxedema w/hyperthyroidism.Myxedema w/hyperthyroidism.

Localized areas of hyperpigmentation.Localized areas of hyperpigmentation. Usually in feet and lower legs.Usually in feet and lower legs.


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B-BlockersB-Blockers

Excess thyroid hormones, upregulation ofExcess thyroid hormones, upregulation ofB-adrenergic receptors.B-adrenergic receptors.

Tachycardia, tremors, anxiety.Tachycardia, tremors, anxiety. Propranolol.Propranolol.

Inhibits peripheral conversion of T4 to T3.Inhibits peripheral conversion of T4 to T3.


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PTU, methimazol.PTU, methimazol.

Interfere in the incorporation of iodine toInterfere in the incorporation of iodine to

thyroglobulin.thyroglobulin. Slow onset.Slow onset.

Main therapy or used prior surgery.Main therapy or used prior surgery.

PTU inhibits conversion of T4 to T3.PTU inhibits conversion of T4 to T3.


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Adverse effects.Adverse effects.

Low incidence of side effects.Low incidence of side effects. Agranulocytosis.Agranulocytosis.

Rash (common).Rash (common).

Both crosses the placenta, but PTU is saferBoth crosses the placenta, but PTU is saferbecause its high protein binding.because its high protein binding.

Much safer that iodine or radioactive iodine.Much safer that iodine or radioactive iodine.


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Radioactive IodineRadioactive Iodine

Highly Effective.Highly Effective.

Contraindicated in pregnancy (destroysContraindicated in pregnancy (destroys

fetal gland).fetal gland). Low incidence of side effects.Low incidence of side effects.


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IodineIodine

Oldest drug.Oldest drug. Reduce gland size, vascularity and fragility.Reduce gland size, vascularity and fragility.

Temporal treatment (prior to surgery).Temporal treatment (prior to surgery). Contraindicated in pregnancy (neonatalContraindicated in pregnancy (neonatal

goiter).goiter).

Adverse: hypersensibility reaction, brassyAdverse: hypersensibility reaction, brassytaste, burning of mouth and gums.taste, burning of mouth and gums.


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InteractionsInteractionsw/receptorsw/receptors

Amiodarone.Amiodarone.

Structurally resembles thyroid hormones.Structurally resembles thyroid hormones.

May cause hypo or hyperthyroidism.May cause hypo or hyperthyroidism.

LithiumLithium

L-DopaL-Dopa

EstrogensEstrogens

A 29 YO f l l i f tlA 29 YO f l l i f tl


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A 29 YO female complains of restlessnessA 29 YO female complains of restlessness

and increasing anxiety. HR 135bmp, PE:and increasing anxiety. HR 135bmp, PE:

Tremors. Palpation on the neck reveals aTremors. Palpation on the neck reveals a3cm nodule on her thyroid gland.3cm nodule on her thyroid gland.

Laboratory test are sent to confirm theLaboratory test are sent to confirm the

diagnosis. In the meantime, with drugdiagnosis. In the meantime, with drug

could be given to acutely reduce hercould be given to acutely reduce herphysical symptoms?physical symptoms?

Propylthiouracil.Propylthiouracil.

Furosemide.Furosemide. Prednisone.Prednisone. Iodine.Iodine.

Propanolol.Propanolol.


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