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Evaluating Hoarseness: Keeping Your Patient's Voice Healthy - June 1998 - American Academy of Family Physicians;
http://www.aafp.org/afp/980600ap/rosen.html

Age group
• Infants (0 -11mth)
• Children (12 mnth - 59 mnth)
• School age child (6-12 year)
• Adults (above 12 year)
• Pregnant & lactating women
Iodine requirement(μg)
50
90
120
150
200
WHO/UNICEF Recommended daily iodine

• Iodine essential for thyroid hormone
• Adult hypothyroidism and cretinism occurs in severe iodine deficiency
• Daily adult require 1 to 2 μg / Kg / day.
• Iodine used for iodine-deficiency goiter
• Iodine or iodate added to salt (iodized salt) 100 μg of iodine per gram
Relation of Iodine to Thyroid Function

Growth and development
• Normal growth and development of organism
• DNA transcription, critical control of protein synthesis and translation of
genetic code
• Brain development
• Irreversible mental retardation (cretinism) in absence of thyroid hormones
during active neurogenesis (upto 6 month postpartum)
- Severe morphological alteration in brain
-Supplementation during first 2 weeks of life prevent development of brain changes
Functions of Tyhroid Hormones

Metabolism:
• Lipid: Induce lipolysis (catecholamines), ↑ free plasma fatty acid and all phases
of cholesterol metabolism enhanced (bile acid more)
- Hyperthyroidism – hypercholesterolemia
• Carbohydrate: Stimulation of carbohydrate metabolism, glycogenolysis,
gluconeogenesis
- Hyperthyroidism – diabetes-like state
• Protein: Certain protein synthesis increased but overall catabolic action –
negative nitrogen balance
- Hyperthyroidism – Weight loss and wasting
Functions of Tyhroid Hormones

Calorigenic & CVS(Cardio Vascular System) Effects
• T3 and T4 increases basal metabolic rate (BMR) by stimulation of cellular metabolism –
maintenance of body temperature
• Hyperdynamic state of circulation - due to direct CVS action and ↑ peripheral demand
o Hyperthyroidism: tachycardia, ↑ Total Periferic Resistance(TPR)
o Hypothyrodism: bradycardia, ↓ cardic index, ↓ TPR
Others:
• Nervous system – mental retardation
• GIT – Increased gut motility
Functions of Tyhroid Hormones

16
Mechanism of actions of thyroid
hormones
T3, via its nuclear receptor, induces
new proteins generation

Differences between T3 and T4
T3 T4
Four time more potent thanT4 Less potent
Peak effect reaches with in 24-48hrs. Peak effect reaches in 6-8 hrs
Plasma protein binding capacity isless It bind more tightly to plasmaproteins
It is active in vitro It is inactive invitro
Thyroid gland produce 20%of T3 Thyroid gland produces 80%of T4
T3is the active form T4 is less active than T3
18

• Normal range:
• T4: 77- 155nmol/l
• T3 : 1.2- 2.8nmol/l
• TSH: 0.3- 4mU/L
• The levels of hormones above or below indicate hyperthyroidism or
hypothyroidism.

Definition andEpidemiology
• Hypothyroidism is traditionally defined
as deficient thyroidal production of
thyroid hormone
• Prevalence of overt hypothyroidism
varies from 0.1 to 2 percent.
• Hypothyroidism is five to eight times
more common in women than men.
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Manifestations ofHypothyroidism
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• Common symptoms: fatigue,cold intolerance,weightgain,
constipation, dry skin,myalgia,andmenstrualirregularities
• Physical examination: goiter
,bradycardia, diastolic hypertension,
andadelayed relaxation phaseof thedeep tendon reflexes
• Metabolic abnormalities: hypercholesterolemia, macrocytic
anemia,elevatedcreatine kinase,andhyponatremia

TSH (2)
 T4 & T3 are feed-back regulators of TSH
 TSH is stimulated by a-adrenergic agonists
 TSH secretion is inhibited by:
Dopamine
Bromocreptine
Somatostatin
Corticosteroids

THYROID HORMONES (3)
 Conversion of T4 to T3 is decreased by:
Acute & chronic illnesses
b-adrenergic receptor blockers
Starvation & severe PEM
Corticosteroids
Propylthiouracil
High iodine intake (Wolff-Chaikoff effect)

THYROXINE (2)
 Total T4 is decreased when the following drugs are used:
Steroids
Phenytoin
Salicylates
Sulfonamides
Testosterone
Maternal TBII

THYROXINE (3)
 Total T4 is increased with:
Acute thyroiditis
Acute hepatitis
Estrogen therapy
Clofibrate
iodides
Pregnancy
Maternal TSI

GOITROGENS
•DRUGS
Anti-thyroid
Cough medicines
Sulfonamides
Lithium
Phenylbutazone
PAS
Oral hypoglycemic agents

GOITROGENS
 FOOD
Soybeans
Millet
Cassava
Cabbage

Hypothyroidism
definition: Thyroid gland does not produce enough hormones
● affect People who are most at risk include those over age 50 & mainly in
females
● Diagnosed by low plasma levels of T3 & T4 and TSH
causes:
congenit
al
in children,
hypothyroidism leads to
delay in growth
(dwarfism),and
intellectual
development
(cretinism)
Primar
y
Iodine deficiency is the
most common cause of
primary hypothyroidism
and endemic
goiter worldwide
Autoimmune;
Hashimoto’s thyroiditis
Radioactive iodine
treatment of
hyperthyroidism
Post thyroidectomy
Anti-thyroid drugs (CMZ
, PTU)
Other drugs(lithium,
amioderone)
Sub-acute thyroiditis Thyroid carcinoma
Inadequat
e function
of the
gland
itself
seconda
ry
Hupothalamic
and pitutary
diseases

mind map
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23
Thyroid drugs
• Levothyroxine sodium: The synthetic Na salt of levo (L) isomer of
thyroxine (T4)
• Liothyronine (T3)
• Liotrix (T4 plus T3)
Pharmacokinetics
Orally easily absorbed; the bioavalibility of T4 is 80%, and T3 is 95%.
Drugs that induce hepatic microsomal enzymes (e.g., rifampin, phenbarbital,
phenytoin, and etc) improve their metabolism.

treatment of hypothyroidism: Thyroid preparation
Levothyroxine (T4) Liothyronine (T3) Liotex (mix T4 and
T3)
Pharmacokinatic
s
● A synthetic form of the
thyroxine (T4) , is the drug
of choice for replacement
therapy.
● Stable and has a long half life
( 7 days).
● Administered once daily.
● Restores normal thyroid
levels within 2-3 weeks.
● Absorption is increased
when hormone is given
on empty
stomac
h.● Oral preparations available
from
0.025 to 0.3 mg tablets.
● Parnteral preparation 200-
500μ.
★ in old patient and patient
with any cardiac problems,
start with reduced (12.5 –
25 μg/day) for two weeks
and then increased every
● More potent (3-4
times) and rapid
action than
levothyroxine .
● has a short half life,
not recommended
for routine
replacement therapy
(because it’s given
multiple daily doses).
● oral
preparation
available.
● parenteral use. (used
in life threatening
cases)
● Combination of
synthetic T4 & T3 in a
ratio 4:1 that
attempt to mimic
the natural
hormonal secretion
.
● The major limitations
of this product are
high cost and lack of
therapeutic rationale
because 35% of
T4 is peripherally
converted to T3, so
the drug is under the
study yet.

Levothyroxine
(T4) Liothyronine (T3) Liotex (mix T4 and
T3)
Clinical use
Any Hypothyroidism case ,regardless of
etiology ( including Congenital ,Hashimoto
thyroiditis , Pregnancy and Thyroid
carcinoma ) .
- -
ADR
Overdose in children:- restlessness ,
insomnia and accelerated bone maturation
Over dose in adult :-
-cardiac arrhythmias (Tachycardia, atrial
fib.) - tremor , restlessness ,headache
-heat intolerance
-muscle pain
-change in appetite, weight loss
Should be avoided in
cardiac patient
-

Levothyroxine sodium (T4)
Use: thyroid replacement and suppression therapy.
Advantages:
-high stability
-uniform
-low cost
-lack of allergenic foreign protein
-easy laboratory measurement of serum levels
-long half-life -7 days (once-daily administration)
-In addition, T4 is converted to T3 intracellularly; thus, administration of T4 produces both
hormones.

LEVOTHYROXINE :
• Individualize the dosage and adjust based upon the factors including patient age, body
weight, cardiovascular status, concomitant medical conditions (including pregnancy ).
• Primary hypothyroidism in adults who have been hypothyroid for a short time – initially ,
give full thyroid replacement dose – 1.6mcg/kg PO/ OD
• Adjust dose by 12.5 – 25mcg increments every 4 – 8 weeks until patient is clinically
euthyroid and TSH is normal.
• Doses >200 and 300mcg/day are rarely needed.
• Severe longlasting Hypothyroidism :
• initial dose – 12.5 – 25mcg PO/OD ; adjust in 11.5- 25mcg increments every 2-4 weeks.
• Hospitalized , not critically ill when enteral administration is not feasible, 75%of the oral dose
given IV.

Liothyronine (T3) is 3 to 4 times more potentthan
levothyroxine.
• Use:
short-term suppression of TSH.
• Disadv:
- Shorter half-life -24 hours (not recommended for routine replacement
therapy which requires multiple daily doses)
- Higher cost
- Difficulty of monitoring.
- Its greater hormone activity and consequent greater risk of cardiotoxicity-
avoided in patients with cardiac disease.

Liotrix - Mixture of thyroxine and liothyronine
- Expensive
Clinical use
• Hypothyroidism: cretinism & myxedema
• Cretinism: Decrease in the levels of thyroid hormone in infants or during foetal stage is known as
cretinism
• Myxedema: a condition in which hypothyroidism results in accumulation of
mucopolysaccharide in the intercellular spaces of muscle and skin
Adverse reactions
• Overmuch leads to thyrotoxicosis
• Angina or myocardial infarction usually appears in aged

Conditions RequiringDoseAdjustment
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Increased doserequirement
1
. Decreased intestinal absorption of T4
• Dietary fibersupplements
•Reducedgastric acid secretion:H.pylori infection, atrophic gastritis,proton-pump
inhibitors
•Malabsorption: coeliac disease, short bowel syndrome,lactose intolerance,
bariatricsurgery
• Bile-acid sequestrants
•Agentsthatbind L
-T4:sucralfate, aluminumhydroxide, ferrous sulfate, calcium
carbonate,sevelamer

Conditions RequiringDoseAdjustment
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Increased doserequirement
2.Increased need for T4
• Weightgain
• Estrogens
• Pregnancy
3.Increased metabolic clearance of T4
•Antiepileptic drugs(phenobarbital,
phenytoin,carbamazepine)
• Tuberculostatic drugs(rifampicin)

Conditions RequiringDoseAdjustment
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Decreased doserequirement
1
.Decreased need for T4
• Weightloss
• Androgens
2.Decreased metabolic clearance of T4
• Old age

CentralHypothyroidism
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• Decreased thyroidal secretion of hormonecaused by insufficient
stimulationof thyroid glandby TSH.
• Pituitary TSHrelease (secondary hypothyroidism)
• Hypothalamic TRHrelease (tertiaryhypothyroidism)
• Characterizedby Low T4concentration/TSHnot appropriately elevated
• Central hypothyroidism less common than primary hypothyroidism

CentralHypothyroidism
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• Shouldbe suspected inthefollowing circumstances:
• Thereis knownhypothalamic orpituitary disease
• A masslesion is present inthepituitary
• When symptoms/signsof hypothyroidism associated withpituitary
hormonaldeficiencies
• Goal of replacement therapyis to Titrate FT4/FT3to mid-upper normal.
• TSHnotmonitored asit is unreliable.

MyxedemaComa
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• Myxedema comarepresentsdecompensated stateof severeuntreated
hypothyroidism.
• The prognosis is poor withareported mortality between 20%and50%.
• Triad of hypothermia, hyponatremia, and hypercapnia.
• Commonprecipitating factors include cold exposure,infection, trauma,
oranesthesia.

MyxedemaComa
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• Physical manifestations include hypotension, bradycardia,
macroglossia,delayed deep-tendon reflexes. cold, clammy,anddryskin,
nonpitting edema,andperiorbital edema.
• Laboratory examination mayreveal anemia, hyponatremia,
hypoglycemia, hypercholesterolemia, andhighserumcreatine kinase
concentrations.
• Most patients havelow serumFT4andhighserumTSH.

MANAGEMENT OF MYXEDEMA COMA
Hypothyroidism Largeinitialivdose of 300-500μgT4,if noresponse add T3
Alternative-initialIVdose of 200-300μg T4plus10-25μg T3
Hypocortisolemia IV hydrocortisone200-400 mgdaily
Hypoventilation Don’tdelayintubation andmechanical ventilationtoo long
Hypothermia Blankets,noactiverewarming
Hyponatremia Mild fluidrestriction
Hypotension Cautiousvolumeexpansionwithcrystalloid orwholeblood
Hypoglycemia Glucoseadministration
Precipitatingevent Identificationandeliminationby specific treatment,liberal useof
antibiotics
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MyxedemaComa

MyxedemaComa
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Therapeutic endpoints inMyxedemacomashould be:
• Improved mentalstatus
• Improved cardiacfunction
• Improved pulmonaryfunction
Measurement of thyroid hormonesevery1-2daysto ensureafavorable
trajectory inthebiochemical parameters.

• MYXEDEMA COMA:
• Initial dose – 300 – 500mcg IV once ;F/B maintenance dose of 50 -100mcg IV/OD until patient can
tolerate oral therapy.
• Liothyronine – loading dose of 5- 20mcg IV f/b maintenance dose 2.5 – 10mcg IV every 8 hrs.
• Thyroid stimulating hormone suppression therapy , pituitary- doses > 2mcg/kg/day /PO are
usually required to suppress TSH below 0.1milli international units/L.
• PEDIATRIC DOSING:
• 0-3 months : 10 – 15mcg /kg/day po ( solution, tab)
• 3- 6 months : 8- 10mcg/kg/day po.
• 6- 12 months:6- 8 mcg /kg/day po
• 1 – 5 yrs : 5-6 mcg /kg/day po
• 6 – 12 yrs : 4 – 5mcg/kg/day po ( capsule, solution, tab)
• Older than 12 yrs : 1.6mcg/kg/day po

• As soon as pregnancy is confirmed add 2 additional doses per week of the current
dose given as 1 extra dose twice weekly with several days increase.
• If TSH is above normal range increase the dose by 12.5 to 25mcg daily and
measure TSH every 4 weeks until stable.
• Pregnant women with new onset of hypothyroidism-
• Normalize thyroid function as rapidly possible intiate 1mcg/kg ( mild
hypothyroidism TSH less than 10milli international units/L) to 1.6mcg/kg (
moderate to severe) if greater than 10MIU/L.
.

• GERIATRIC:
• Initial dose( <1.6mcg/kg/day), consider 12.5 – 25mcg PO/OD, adjust
dose every 6-8 weeks.( normal TSH ranges are higher in older
populations )
• Underlying cardiac disease or at risk for atrial fibrillation : initiate
orally at a lower starting dose ( <1.6mcg/kg/day) , consider 12.5-
25mcg PO/OD adjust dose to every 6-8 weeks.
• Large body weight change: adjust dosage based on thyrotropin, and
assess thyrotropin 4-6 weeks after dosage change.

LIOTHYRONINE:
• Initial dose – 25mcg PO/ OD, increase by 25mcg /day every 1- 2 weeks;
maintenance dose : 25- 75mcg od.
• Myxedema coma : 25- 50mcg IV .
• Patients with h/o of coronary artery disease or arrythmias – loading dose ,
5 -20mcg IV f/b 2.5- 10mcg IV every 8 hrs.
• Pediatrics:
• Initial dose- 5mcg po od ; infants to few months older may require
20mcg/day; pts 1 yr or older may require 50mcg/day , children older than
3 yrs to adult dose 25-75mcg/day.
• Geriatrics:
• Initiate 5mcg OD and increase by 5mcg increments every 1- 2 weeks if
neded.

PROPYLTHIOURACIL
• ADULTS:
• Initial dose 50- 150mg PO TID , based on severity or 300mg PO daily in 3 evenly divided doses at 8
hr intervals.
• May increase to 400mg/day for severe hyperthyroidism, very large goiters, or both; 600-
800mg/day (occasionally).
• Maintenance dose- 50mg PO 2-3 times daily or 100-150 mg PO TID every 8 hrs.
• Preganacy- Thyrotoxicosis due to graves disease:
• Use lowest dose to keep mothers total T3 and T4 levels slightly above normal range for
pregnancy, keep TSH suppressed , assess monthly and adjust dose as required.
• Switch to methimazole for 2nd and 3rd trimesters.
• THYROID STORM:
• 500-1000MG –loading dose PO F/B 250mg PO every 4 hours.
• Pediatric dosing:
• Initial (6yr or older) : 50mg PO daily carefully uptitrated.

METHIMAZOLE:
• Initial dose: mild- 15mg/day PO TID at 8hr intervals.
• Moderately severe condition: initial dose 30- 40mg/day PO TID -8hr intervals.
• Severe : initial dose 60mg/day PO TID -8hr intervals.
• Maintenance 5-15mg/day TID – 8hr intervals.
• Radioactive iodine therapy: discontinue methimazole 2-3 days prior to RAI and consider
resuming 3-7 days after RAI administration in patients who are at increased risk of
complications a/w worsening of hyperthyroidism.
• Thyroidectomy: treat until euthyroid and discontinue at the time of surgery.
• Thyroid storm: 60-80mg/kg PO
• Thyrotoxicosis, drug induced:
• Amiodarone induced- initially 40mg PO OD until the pt is euthyroid, generally 3-6
months.
• Iodine induced- 20-40mg PO as a single or divided doses.

• Pediatric dosing:
• Initial- 0.4mg/kg/day PO TID – 8 hrs intervals; maintenance dose
approx. 50% of initial dosage.
• infants: 1.25mg/day; 1-5yrs : 2.5- 5mg/day; 5-10yrs: 5-10mg/day;10-
18yrs : 10-20mg/day.

RADIOACTIVE IODINE ( RAI )
MOA Accumulates in the thyroid gland and destroys parenchymal cells, producing a long-
term decrease in thyroid hormone levels.
Pharmacokinetic
• Clinical improvement may take 2-3 months
• Half -life 5 days
• Cross placenta & excreted in breast milk
• Easy to administer ,effective , painless and less
expensive
• Available as a solution or in capsules
clinical uses
• Hyperthyroidism mainly in old patients
(above 40)
• Graves, disease
• Patients with toxic nodular goiter
• As a diagnostic
Disadvantages
• High incidence of delayed hypothyroidism
• Large doses have cytotoxic actions ( necrosis of the follicular cells followed
by fibrosis )
• May cause genetic damage

IODINE (Lugol's solution, potassium iodide)
Eamples
•Organic iodides as : iopanoic acid or
ipodate
•Potassium iodide
Mechanism of
action
•Inhibit thyroid hormone synthesis and release
•Block the peripheral conversion of T4 to T3
•The effect is not sustained ( produce a temporary remission of symptoms
)
Therapeutic
uses
& size of the gland
• Prior to thyroid surgery to decrease
vascularity
•Following radio-active iodine therapy
•Thyrotoxicosis
Precautions /
toxicity
- Iodism Symptoms:
skin rash , hypersalivation
•Should not be used as a single therapy
•Should not be used in pregnancy
•May produce iodism ( Rare, as iodine is not much used now) oral ulcers bad breath.

ADRENOCEPTOR BLOCKING AGENTS
Mechanism ofaction
Adjunctive therapy to relief the adrenergic symptoms of
hyperthyroidism such as tremor, palpitation, heat intolerance
and nervousness.
Examples Propranolol, Atenolol , Metoprolol
contraindication Propranolol is contraindicated in asthmatic
patients
Thyrotoxicosis during pregnancy:
Better to start therapy before
pregnancy with 131I or subtotal
thyroidectomy to avoid acute
exacerbation during
pregnancy
During pregnancy radioiodine
is contraindicated,
Propylthiouracil is the drug of
choice during pregnancy.
pregnanc
y

★ Thyroid storm:
● A sudden acute exacerbation of all
of the symptoms of thyrotoxicosis,
presenting as a life threatening
syndrome.
● There is hyper metabolism, and
excessive adrenergic activity,
death may occur due to heart
failure and shock.
● It is a medical emergency .
★ management ofthyroid
storm:
● should be treated in an ICU for close
monitoring of vital signs and for access to
invasive monitoring and inotropic support
● Correct electrolyte abnormalities, Treat cardiac
arrhythmia ( if present ) & Aggressively control
hyperthermia by applying ice packs
● Promptly administer antiadrenergic drugs (e.g.
propranolol) 1-2mg to minimize
sympathomimetic symptoms and if not
controlled tachycardia add diltiazem 60-120mg
twice a day orally.
● High-dose Propylthiouracil 200-300mg 6th
hourly (PTU) is preferred
because of its early onset of action ( risk of
severe liver injury and acute liver failure )
● Administer iodine compounds (Lugol's iodine
or potassium iodide) 6-10 dropsorally or via a
nasogastric tube
● Hydrocortisone 50 mg IV every 6 hours to
prevent shock.
● Rarely, plasmapheresis has been used to treat
thyroid storm

Management of Hyperthyroidism due to Graves’ disease
Severe Hyperthyroidism
[ markedly elevated serum T4 or T3
very large goiter, > 4 times normal ]
Definitive therapy with radioiodine preferred in
adults
Normalization of thyroid function with anti-thyroid
drugs before surgery in elderly patients and those
with heart disease
Mild/moderate hyperthyroidism
[ small or moderately enlarged thyroid; children or pregnant or lactating women ]
Primary anti-thyroid drug therapy
should be considered
Start methimazole, 5–30 mg/day,
(PTU preferred in pregnant women)
Monitor thyroid function every 4–6 wk
until euthyroid state achieved
Discontinue drug therapy after 12–18 mo
Monitor thyroid function every 2 mo for 6 mo then less frequently
Relapse Remission
Monitor thyroid function
every 12 mo indefinitely
Definitive radioiodine
therapy in adults
(Second course of anti-thyroid
drug therapy in children)

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