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 A 50 year old male came to the OPD
with the chief complaint of having
lump in front of the neck which
moves with swallowing. He also had
difficulty in breathing & change in
his voice for the past 4 months. In
addition to this physician elicit peri-
orbital oedema and his ENT report &
RFT was also normal…….
what’s the condition??????
BY V.P.KARTHIKEYAN
 One of the largest endocrine, butterfly
shaped organ
 Profoundly influence normal growth &
development.
 Essential for mental & psychological
development in infancy & childhood.
 Bilobed structure lobus dexter (right lobe)
and lobus sinister (left lobe) connected via
the isthmus.
 Anterior side of the neck, lying against the
larynx and trachea.
 Extra thyroidal tissue from thymus-pyramidal
lobe.
 Weight- 15-20 gms.
 Develops from the floor of the primitive
pharynx- 3rd week of gestation.
 With thyroglossal duct migrates from floor of
tongue to the neck.
 Thyroid hormone synthesis – 11th week.
 Thyroxine(T4)
Triiodothyronine(T3)
Reverse triiodothyronine(RT3)
 All thyroid hormones are iodine containig
aminoacids.
 T3 is the active form.
 RT3 is the inactive form.
 Calcitonin-calcium lowering hormone.
500µg of iodine
500 120
Intestine
40
60 80
bile
20µg-stool
ECF
Iˉ
THYROID
LIVERKIDNEY
480 µg
 Iodide trapping
 Conversion of iodide to iodine-organification
 Thyroglobulin synthesis
 Coupling
 Proteolysis of thyroglobulin
 Secretion of thyroid hormones
Dopamine, somatostatin & glucocorticoids also
inhibit TSH secretion.
 Available through certain foods
(eg, seafood, bread, dairy products), iodized
salt, or dietary supplements, as a trace
mineral
 The recommended minimum intake is 150
g/day
 Iodized salt & iodate-preservatives in flour &
bread.
 Soln of iodized poppy seed oil –i.m.
 Other tissues accumulate iodide salivary
gland,placenta,choroid plexus,gastric
mucosa,ciliary body.
 Disease states in synthesis:
congenital hypothyroidism
NIS deficiency: mutation of NIS
gene, AR, decreased iodide uptake.
 Pendred syndrome:
Pendrin – apical surface of the thyroid cells
regulation of iodide inflow
also present in cochlea of middle ear
Mutation leads to pendred syndrome.
Characterized by defective organification,
goiter, sensory neural deafness.
 Released hormones 99.9% - T4
99.6% - T3
binds to plasma proteins.
 TBG(70%T4 , 45%T3)
 TBPA-Transthyretin –(20%T4 ,<1%T3)
 TBA(10%T4,55%T3)
 Physiological effects depend on free form
level in plasma.
 Normal values:
 Total T4:4.8-10.4mg/dl(62-134nmol/L)
 Total T3:79-149ng/dl(1.2-2.3nmol/L)
 Free T4:0.7-1.86ng/dl(9-24pmol/L)
 Free T3:145-348pg/dl(2.2-5.4pmol/L)
 TSH :0.4-4µIu/L
 TSH also increases blood supply
increases the size & number of follicle-goiter.
 45% of T4 is converted to T3 by 5’ deiodinase
by peripheral metabolism.
 Ideal to measure total & free levels of
hormone in blood for diagnosing thyroid
dysfunction.
TARGET SYSTEM FUNCTION
Metabolism BMR
CVS -Tachycardia
-inc. contractility
-increased SBP
-dec.DBP
CNS Brain development
Bone inc.growth
Muscle inc.exp.MHC,pr. Cat
Adipose inc lipolysis
GIT inc motility,apetite
Reproduction fol.maturation
 Hypothyroidism is a disorder with
multiple causes in which the thyroid fails
to secrete an adequate amount of
hormone.
◦ The most common thyroid disorder.
◦ Usually caused by primary thyroid gland failure.
◦ Also may result from diminished stimulation of
the thyroid gland by TSH.
TSH T4 T3
Hypothyroidism High Low Low
Hyperthyroidism Low High High
• Primary hypothyroidism
– From thyroid destruction
• Central or secondary hypothyroidism
– From deficient TSH secretion, generally due to sellar lesions
such as pituitary tumor or craniopharyngioma
– Infrequently is congenital
• Central or tertiary hypothyroidism
– From deficient TSH stimulation above level of pituitary—
ie, lesions of pituitary stalk or hypothalamus
– Is much less common than secondary hypothyroidism
 Congenital hypothyroidism
◦ Agenesis of thyroid
◦ Defective thyroid hormone biosynthesis due to enzymatic
defect
 Thyroid tissue destruction as a result of
◦ Chronic autoimmune (Hashimoto) thyroiditis
◦ Radiation (usually radioactive iodine treatment for
thyrotoxicosis)
◦ Thyroidectomy
◦ Other infiltrative diseases of thyroid (eg, hemochromatosis)
 Drugs with antithyroid actions
(eg, lithium, iodine, iodine-containing
drugs, radiographic contrast agents, interferon
alpha)
TREATMENT
 LEVO THYROXINE(T4)
 LIOTHYRONINE(T3)
 LIOTRIX4:1(T4:T3)
 Thyroxine is absorbed best in the duodenum
and ileum.
 absorption is modified by intraluminal factors
such as food, drugs, gastric acidity, and
intestinal flora.
 Oral bioavailability of current preparations of
L-thyroxine averages 80%
 T3 is almost completely absorbed (95%).
 T4 and T3 absorption appears not to be
affected by mild hypothyroidism but may be
impaired in severe myxedema.
 These factors are important in switching
from oral to parenteral therapy. For
parenteral use, the intravenous route is
preferred for both hormones.
 synthetic (levothyroxine, liothyronine, liotrix
 animal origin (desiccated thyroid).
 Synthetic levothyroxine is the preparation of
choice for replacement because,
-stability,
-content uniformity,
-low cost,
-lack of allergenic foreign protein,
-easy laboratory measurement of
serum levels, and long half-life (7 days), which
permits once-daily administration.
 T3 is 4 times potent than T4
 Shorter half life(24 hours)
 Greater risk of cardiotoxicity
 Best used for short term suppression of TSH.
 The shelf life of synthetic hormones is about
2 years.
DRUG EFFECT DRUGS
Inhibition of TRH or TSH secretion
without induction of
hypothyroidism or
hyperthyroidism.
Dopamine, levodopa,
corticosteroids, somatostatin,
metformin, bexarotene.
Inhibition of thyroid hormone
synthesis or release with the
induction of hypothyroidism (or
occasionally hyperthyroidism).
Iodides (including amiodarone),
lithium, aminoglutethimide,
thioamides, ethionamide.
Change in thyroid hormone synthesis
 Alteration of thyroid hormone transport and serum
total T 3 and T4 levels, but usually no modification of
FT 4 or TSH.
DRUG EFFECT DRUGS
Increased TBG Estrogens, tamoxifen, heroin,
methadone, mitotane, fluorouracil
Decreased TBG Androgens, glucocorticoids
Displacement of T3 and T4 from
TBG with transient
hyperthyroxinemia
Salicylates, fenclofenac,
mefenamic acid, furosemide
DRUG EFFECTS DRUGS
Induction of increased hepatic
enzyme activity.
Nicardipine, imatinib, protease
inhibitors, phenytoin,
carbamazepine, phenobarbital,
rifampin, rifabutin.
Inhibition of 5'-deiodinase with
decreased T3, increased rT3.
Iopanoic acid, ipodate,
amiodarone, blockers,
corticosteroids,
propylthiouracil, flavonoids.
Alteration of T 4 and T 3 metabolism with modified serum T 3
and T 4 levels but not FT 4 or TSH levels
Drug effects drugs
Interference with T4 absorption. Cholestyramine, chromium
picolinate, colestipol,
ciprofloxacin, proton pump
inhibitors, sucralfate, sodium
polystyrene sulfonate, raloxifene,
sevelamer hydrochloride,
aluminum hydroxide, ferrous
sulfate, calcium carbonate, bran,
soy, coffee.
Induction of autoimmune thyroid
disease with hypothyroidism or
hyperthyroidism.
Interferon- , interleukin-2,
interferon- , lithium, amiodarone.
Other interactions
DRUG EFFECTS DRUGS
Anticoagulation Lower doses of warfarin required
in hyperthyroidism, higher doses
in hypothyroidism.
Glucose control Increased hepatic glucose
production and glucose
intolerance in hyperthyroidism;
impaired insulin action and
glucose disposal in
hypothyroidism.
Cardiac drugs Higher doses of digoxin required
in hyperthyroidism; lower doses in
hypothyroidism.
Effect of thyroid function on drug effects
 The average dosage for an infant 1–6 months of
age is 10–15 mcg/kg/d.
 whereas for an adult is about 1.7 mcg/kg/d.
Older adults (> 65 years of age) may require less
thyroxine for replacement.
 should be administered on an empty stomach.
 Serum TSH and free thyroxine should be
measured.
 takes 6–8 weeks after starting a given dose
of thyroxine to reach steady-state levels in
the bloodstream.
 dosage changes should be made slowly.
Reduced dosages in
-Older patients,
-patients with cardiac disease,
For such patients 12.5-25mcg/d for 2 weeks.
daily dose by 25mcg for every 2 weeks.Untill
euthyroid or drug toxicity.
 In children: restlessness, insomnia, and
accelerated bone maturation and growth may be
signs of thyroxine toxicity.
 In adults: increased nervousness, heat
intolerance, episodes of palpitation and
tachycardia, or unexplained weight loss may be
the presenting symptoms.
 Chronic overtreatment with T4 , particularly in
elderly patients, can increase the risk of atrial
fibrillation and accelerated osteoporosis.
 MYXOEDEMA COMA:
◦ Myxedema coma is an end state of untreated
hypothyroidism.
◦ It is associated with progressive weakness, stupor,
hypothermia, hypoventilation, hypoglycemia,
hyponatremia, water intoxication, shock, and
death.
◦ Medical emergency. treat with tracheal intubation
and mechanical ventilation.Associated illnesses
such as infection or heart failure must be treated
by appropriate therapy.
◦ It is important to give all preparations
intravenously, because patients with myxedema
coma absorb drugs poorly from other routes.
 Rx: loading dose of levothyroxine
intravenously— 300–400 mcg initially,
followed by 50–100 mcg daily.
 Intravenous hydrocortisone is indicated if the
patient has associated adrenal or pituitary
insufficiency. Opioids and sedatives must be
used with extreme caution.
 Hypothyroidism & pregnancy:
The daily dose of thyroxine be adequate because
early development of the fetal brain depends on
maternal thyroxine.
In many hypothyroid patients, an increase in the
thyroxine dose (about 30–50%) is required to
normalize the serum TSH level during pregnancy
because of the elevated maternal TBG.
 Sub clinical hypothyroidism:
 DRUG INDUCED HYPOTHYROIDISM:
◦ Managed with L thyroxine if offending agent cannot
be stopped.
◦ For amiodarone induced,T4 is necessary even after
the cessation because of long half life.
NON TOXIC GOITER:
Enlarge thyroid due to TSH stimulation due to
inadequate T4
Iodide def-managed by iodide intake about 150-
200 mcg
 THYROID NODULE:
 Benign functioning nodules regress when TSH is
suppressed by T4 therapy
 Therapy should be stopped if the nodule doesn’t
decrease in size within 6 mths and when it starts
regressing.
Papillary carcinoma of thyroid :
responsive to TSH
full doses to T4 suppress TSH secretion
 Empirical use:
 Refractory anaemias
 Menstural disorders
 Chronic/ non healing ulcers
 Obstinate constipation.
thyroid drugs

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thyroid drugs

  • 1.  A 50 year old male came to the OPD with the chief complaint of having lump in front of the neck which moves with swallowing. He also had difficulty in breathing & change in his voice for the past 4 months. In addition to this physician elicit peri- orbital oedema and his ENT report & RFT was also normal……. what’s the condition??????
  • 2.
  • 4.  One of the largest endocrine, butterfly shaped organ  Profoundly influence normal growth & development.  Essential for mental & psychological development in infancy & childhood.
  • 5.  Bilobed structure lobus dexter (right lobe) and lobus sinister (left lobe) connected via the isthmus.  Anterior side of the neck, lying against the larynx and trachea.  Extra thyroidal tissue from thymus-pyramidal lobe.  Weight- 15-20 gms.
  • 6.  Develops from the floor of the primitive pharynx- 3rd week of gestation.  With thyroglossal duct migrates from floor of tongue to the neck.  Thyroid hormone synthesis – 11th week.
  • 7.
  • 8.  Thyroxine(T4) Triiodothyronine(T3) Reverse triiodothyronine(RT3)  All thyroid hormones are iodine containig aminoacids.  T3 is the active form.  RT3 is the inactive form.  Calcitonin-calcium lowering hormone.
  • 9. 500µg of iodine 500 120 Intestine 40 60 80 bile 20µg-stool ECF Iˉ THYROID LIVERKIDNEY 480 µg
  • 10.  Iodide trapping  Conversion of iodide to iodine-organification  Thyroglobulin synthesis  Coupling  Proteolysis of thyroglobulin  Secretion of thyroid hormones
  • 11.
  • 12. Dopamine, somatostatin & glucocorticoids also inhibit TSH secretion.
  • 13.  Available through certain foods (eg, seafood, bread, dairy products), iodized salt, or dietary supplements, as a trace mineral  The recommended minimum intake is 150 g/day  Iodized salt & iodate-preservatives in flour & bread.  Soln of iodized poppy seed oil –i.m.
  • 14.  Other tissues accumulate iodide salivary gland,placenta,choroid plexus,gastric mucosa,ciliary body.  Disease states in synthesis: congenital hypothyroidism NIS deficiency: mutation of NIS gene, AR, decreased iodide uptake.
  • 15.  Pendred syndrome: Pendrin – apical surface of the thyroid cells regulation of iodide inflow also present in cochlea of middle ear Mutation leads to pendred syndrome. Characterized by defective organification, goiter, sensory neural deafness.
  • 16.  Released hormones 99.9% - T4 99.6% - T3 binds to plasma proteins.  TBG(70%T4 , 45%T3)  TBPA-Transthyretin –(20%T4 ,<1%T3)  TBA(10%T4,55%T3)
  • 17.  Physiological effects depend on free form level in plasma.  Normal values:  Total T4:4.8-10.4mg/dl(62-134nmol/L)  Total T3:79-149ng/dl(1.2-2.3nmol/L)  Free T4:0.7-1.86ng/dl(9-24pmol/L)  Free T3:145-348pg/dl(2.2-5.4pmol/L)  TSH :0.4-4µIu/L
  • 18.  TSH also increases blood supply increases the size & number of follicle-goiter.  45% of T4 is converted to T3 by 5’ deiodinase by peripheral metabolism.  Ideal to measure total & free levels of hormone in blood for diagnosing thyroid dysfunction.
  • 19.
  • 20. TARGET SYSTEM FUNCTION Metabolism BMR CVS -Tachycardia -inc. contractility -increased SBP -dec.DBP CNS Brain development Bone inc.growth Muscle inc.exp.MHC,pr. Cat Adipose inc lipolysis GIT inc motility,apetite Reproduction fol.maturation
  • 21.
  • 22.  Hypothyroidism is a disorder with multiple causes in which the thyroid fails to secrete an adequate amount of hormone. ◦ The most common thyroid disorder. ◦ Usually caused by primary thyroid gland failure. ◦ Also may result from diminished stimulation of the thyroid gland by TSH.
  • 23. TSH T4 T3 Hypothyroidism High Low Low Hyperthyroidism Low High High
  • 24. • Primary hypothyroidism – From thyroid destruction • Central or secondary hypothyroidism – From deficient TSH secretion, generally due to sellar lesions such as pituitary tumor or craniopharyngioma – Infrequently is congenital • Central or tertiary hypothyroidism – From deficient TSH stimulation above level of pituitary— ie, lesions of pituitary stalk or hypothalamus – Is much less common than secondary hypothyroidism
  • 25.  Congenital hypothyroidism ◦ Agenesis of thyroid ◦ Defective thyroid hormone biosynthesis due to enzymatic defect  Thyroid tissue destruction as a result of ◦ Chronic autoimmune (Hashimoto) thyroiditis ◦ Radiation (usually radioactive iodine treatment for thyrotoxicosis) ◦ Thyroidectomy ◦ Other infiltrative diseases of thyroid (eg, hemochromatosis)  Drugs with antithyroid actions (eg, lithium, iodine, iodine-containing drugs, radiographic contrast agents, interferon alpha)
  • 26.
  • 27.
  • 28.
  • 30.  LEVO THYROXINE(T4)  LIOTHYRONINE(T3)  LIOTRIX4:1(T4:T3)
  • 31.  Thyroxine is absorbed best in the duodenum and ileum.  absorption is modified by intraluminal factors such as food, drugs, gastric acidity, and intestinal flora.  Oral bioavailability of current preparations of L-thyroxine averages 80%
  • 32.  T3 is almost completely absorbed (95%).  T4 and T3 absorption appears not to be affected by mild hypothyroidism but may be impaired in severe myxedema.  These factors are important in switching from oral to parenteral therapy. For parenteral use, the intravenous route is preferred for both hormones.
  • 33.  synthetic (levothyroxine, liothyronine, liotrix  animal origin (desiccated thyroid).  Synthetic levothyroxine is the preparation of choice for replacement because, -stability, -content uniformity, -low cost, -lack of allergenic foreign protein, -easy laboratory measurement of serum levels, and long half-life (7 days), which permits once-daily administration.
  • 34.  T3 is 4 times potent than T4  Shorter half life(24 hours)  Greater risk of cardiotoxicity  Best used for short term suppression of TSH.  The shelf life of synthetic hormones is about 2 years.
  • 35. DRUG EFFECT DRUGS Inhibition of TRH or TSH secretion without induction of hypothyroidism or hyperthyroidism. Dopamine, levodopa, corticosteroids, somatostatin, metformin, bexarotene. Inhibition of thyroid hormone synthesis or release with the induction of hypothyroidism (or occasionally hyperthyroidism). Iodides (including amiodarone), lithium, aminoglutethimide, thioamides, ethionamide. Change in thyroid hormone synthesis
  • 36.  Alteration of thyroid hormone transport and serum total T 3 and T4 levels, but usually no modification of FT 4 or TSH. DRUG EFFECT DRUGS Increased TBG Estrogens, tamoxifen, heroin, methadone, mitotane, fluorouracil Decreased TBG Androgens, glucocorticoids Displacement of T3 and T4 from TBG with transient hyperthyroxinemia Salicylates, fenclofenac, mefenamic acid, furosemide
  • 37. DRUG EFFECTS DRUGS Induction of increased hepatic enzyme activity. Nicardipine, imatinib, protease inhibitors, phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin. Inhibition of 5'-deiodinase with decreased T3, increased rT3. Iopanoic acid, ipodate, amiodarone, blockers, corticosteroids, propylthiouracil, flavonoids. Alteration of T 4 and T 3 metabolism with modified serum T 3 and T 4 levels but not FT 4 or TSH levels
  • 38. Drug effects drugs Interference with T4 absorption. Cholestyramine, chromium picolinate, colestipol, ciprofloxacin, proton pump inhibitors, sucralfate, sodium polystyrene sulfonate, raloxifene, sevelamer hydrochloride, aluminum hydroxide, ferrous sulfate, calcium carbonate, bran, soy, coffee. Induction of autoimmune thyroid disease with hypothyroidism or hyperthyroidism. Interferon- , interleukin-2, interferon- , lithium, amiodarone. Other interactions
  • 39. DRUG EFFECTS DRUGS Anticoagulation Lower doses of warfarin required in hyperthyroidism, higher doses in hypothyroidism. Glucose control Increased hepatic glucose production and glucose intolerance in hyperthyroidism; impaired insulin action and glucose disposal in hypothyroidism. Cardiac drugs Higher doses of digoxin required in hyperthyroidism; lower doses in hypothyroidism. Effect of thyroid function on drug effects
  • 40.  The average dosage for an infant 1–6 months of age is 10–15 mcg/kg/d.  whereas for an adult is about 1.7 mcg/kg/d. Older adults (> 65 years of age) may require less thyroxine for replacement.  should be administered on an empty stomach.  Serum TSH and free thyroxine should be measured.
  • 41.  takes 6–8 weeks after starting a given dose of thyroxine to reach steady-state levels in the bloodstream.  dosage changes should be made slowly. Reduced dosages in -Older patients, -patients with cardiac disease, For such patients 12.5-25mcg/d for 2 weeks. daily dose by 25mcg for every 2 weeks.Untill euthyroid or drug toxicity.
  • 42.  In children: restlessness, insomnia, and accelerated bone maturation and growth may be signs of thyroxine toxicity.  In adults: increased nervousness, heat intolerance, episodes of palpitation and tachycardia, or unexplained weight loss may be the presenting symptoms.  Chronic overtreatment with T4 , particularly in elderly patients, can increase the risk of atrial fibrillation and accelerated osteoporosis.
  • 43.  MYXOEDEMA COMA: ◦ Myxedema coma is an end state of untreated hypothyroidism. ◦ It is associated with progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death. ◦ Medical emergency. treat with tracheal intubation and mechanical ventilation.Associated illnesses such as infection or heart failure must be treated by appropriate therapy. ◦ It is important to give all preparations intravenously, because patients with myxedema coma absorb drugs poorly from other routes.
  • 44.  Rx: loading dose of levothyroxine intravenously— 300–400 mcg initially, followed by 50–100 mcg daily.  Intravenous hydrocortisone is indicated if the patient has associated adrenal or pituitary insufficiency. Opioids and sedatives must be used with extreme caution.
  • 45.  Hypothyroidism & pregnancy: The daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, an increase in the thyroxine dose (about 30–50%) is required to normalize the serum TSH level during pregnancy because of the elevated maternal TBG.
  • 46.  Sub clinical hypothyroidism:
  • 47.  DRUG INDUCED HYPOTHYROIDISM: ◦ Managed with L thyroxine if offending agent cannot be stopped. ◦ For amiodarone induced,T4 is necessary even after the cessation because of long half life. NON TOXIC GOITER: Enlarge thyroid due to TSH stimulation due to inadequate T4 Iodide def-managed by iodide intake about 150- 200 mcg
  • 48.  THYROID NODULE:  Benign functioning nodules regress when TSH is suppressed by T4 therapy  Therapy should be stopped if the nodule doesn’t decrease in size within 6 mths and when it starts regressing. Papillary carcinoma of thyroid : responsive to TSH full doses to T4 suppress TSH secretion
  • 49.  Empirical use:  Refractory anaemias  Menstural disorders  Chronic/ non healing ulcers  Obstinate constipation.