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??????
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.
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.
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)
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.
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
