2. THYROID GLAND
anatomy;-
The thyroid gland is one of the largest endocrine
glands.
The thyroid glans is located immediately below the
larynx and anterior part of the trachea .
It weights about 15-20g.
It consists of 2 lateral lobes connected by a narrow
band of thyroid tissue called the ‘ isthmus ‘.
The isthmus usually overlies the region from the 2nd to
4th tracheal cartilages .
4 tiny parathyroids glands located posteriorly at each
pole of thyroid gland .
Hormones secreted;-
1) Thyroxine (T4)
2) Tri iodothyronine(T3)
3) Reverse T3
4) Calcitonin
3. Synthesis of thyroid hormone
Steps ;-
Thyroglobulin synthesis
Iodide trapping
Oxidation of iodide
Transport of iodine into follicular cells
Iodination of tyrosine
Coupling reactions
11. Thyroid scintigraphy in the investigation of thyrotoxicosis;-
This teq. Analyses radioactive
iodine uptake by the thyroid gland
and can be used to differentiate
between ‘hot ‘ and ‘cold ‘ areas of
increased and decreased function
respectively .
In most hyperthyroid states uptake
will be at the higher end of the
normal or raised .
Specific scintigraphy appearance
asso. With different conditions ;-
12. Specific disorders of thyroid hormone excess;-
1) Grave’s Disease
Most common cause of thyrotoxicosis.
Graves’ disease is a syndrome consisting of hyperthyroidism , moderate diffuse
goiter , ophthalmopathy , and dermopathy .
Autoimmune etiology with familial predisposition .
F>M
30-60yrs
Thyroid receptors stimulating antibody (TSH-Ab) unique to graves’ disease
(antibodies which specially activate phospholipase A2 are specially
goitrogenic.); other autoantibodies present (TgAb , TPOAb).
13. Graves’ disease is well known to be associated with HLA-
DR3 and HLA-DQA1 while HLA-DRB1 is protective.
Graves’ disease has been associated With other
autoimmune diseases, including Type-1 DM , vitiligo ,
coeliac disease , pernicious anemia and addison’s disease.
Extrathyroidal manifestations such as ophthalmopathy(
with exophthalmos and conjunctival oedema ) and rarely ,
dermopathy and acropathy .
15. Thyroid eye disease;-
Also known as TRO / graves’ orbitopathy.
Self limiting autoimmune process
Mild to severe irreversible sight threatening disease
EPIDEMIOLOGY;-most common disease affecting the orbit
F>M
Severe cases more frequent in >50yr age group
TED associated more strongly with smoking .
16. PATHOPHYSIOLOGY OF TED
Fibroblast are the target cells in TAO; they are extremely sensitive to
stimulation by cytokines and immunoglobulins.
↓
stimulated fibroblasts secrete hyaluronic acid which is hydrophilic
and causes edema in extraocular muscles.
↓
doubling of hyaluronic acid content causes a 5 fold increase in
tissue osmotic load.
↓
proptosis
17. EYE SIGNS
1) PROPTOSIS;-proptosis is axial
Most common cause of both bilateral and unilateral proptosis in adults.
Proptosis is uninfluenced by RX of hyperthyroidism and is permanent in 70% of
cases.
2) DALRYMPLE;S SIGN;-Retraction of upper eyelid producing characteristic staring and
frightened appearance.
18. 3)Von graefe’s sign;-lid lag – when globe moves
downward , the upper eyelid lags behind.
4) kocher’s sign;- staring appearance of the eye
particularly marked on attentive fixation.
5)ENROTH SIGN;- FULLNESS OF THE EYELID DUE TO
PUFFY EDEMATOUS SWELLING.
6)GIFFORD’S SIGN;- DIFFICULTY IN EVERSION OF
UPPER LID .
7)STELLWAG’S SIGN ;- INFREQUENTLY BLINKING .
8)NAFFZIGER’S SIGN;- EXOPTHALAMOS
9)MOEBIUS SIGN;- LOSS OF CONVERGENCE (DUE TO
OPHTHALMOPLEGIA)
10)JOFFROY’S SIGN ;- ABSENCE OF WRINKLING OF
FOREHEAD ON LOOKING UP .
19.
20. Thyroid dermopathy / pretibial myxedema;-
Occur in <5% patients
Almost always in the presence of the
moderate or severe ophthalmopathy
Pretibial myxedema – most frequently
over the anterior and lateral aspect of
the lower leg .
21. Thyroid acropachy
Clubbing found in <1% patients with
grave’s disease .
Occur with ophthalmopathy or
dermopathy.
There is no treatment .
22. investigation
Thyroid function test;-
1)Serum TSH ↓es or undetectable .
2)↑es free T3 or T4
3)Measurement of TPO antibodies positive in 90% cases of grave’s
disease.
4)TG antibody positive in 49% pt. while TSH-R antibody only in 45%
pt.
Thyroid scan;- diffuse elevated iodine uptake.
23. Toxic multinodular goitre
Female – late 30s or 40s multiple palpable
nodules.
Occasionally a solitary nodule may be palpable
but there are multiple small nodules impalpable .
Nodules may be colloid or cellular , cystic
degeneration and hemorrhage .
Complications ;- tracheal stenosis ;- huge goitres
or substernal prolongation of goitre.
Carcinoma (usually follicular)
Cardiovascular symptoms(palpation , AF ,
tachycardia, predominate.
Investigation;-TFT
Iodine scan – to differentiate hot and cold
nodules .
USG
FNAC
CT , MRI
Thyroid autoantibody
CXR
24. TREATMENT;-
Most pts. Are asymptomatic and do not need
operation.
Operation may be indicated on cosmetic
ground , for pressure symptoms , or in response
to pt. anxiety .
Choice of surgery;- total thyroidectomy
Total lobectomy
Subtotal thyroidectomy.
25. SOLITARY TOXIC ADENOMA(PLUMMER’S DISEASE)
Isolated thyroid swelling.
Isolated , confined to one or other lateral lobe
or to isthmus .
Mostly they are SNG formed by inactive
colloid or apparently localized manifestations
of simple MNG.
Radionuclide scanning may be utilized to
distinguish a solitary toxic adenoma from toxic
MNG and grave’s disease.
26. INESTIGATION FOR HYPERTHYROIDISM
TFT ;- T4 AND T3 ↑; TSH undetectable
Radioisotope study
ECG ;- cardiac involvement
Total count and neutrophilic count
Thyroid antibody estimation
27. TREATMENT OF HYOERTHYROIDISM ;-
1)Relief of symptoms ;-
Beta blockers – control cardiovascular manifestations.
Calcium channels blockers –
Oral rehydration
2)Antithyroid drugs ;-
Methimazole 20-40mg od ( blocks thyroid hormone synthesis )
Carbimazole 5-10mg tds
PTU 200mg TDS (block thyroid hormone synthesis as well as block peripheral
conversion of T4 toT3.)
Iodides- reduce vascularity
Steroids.
30. Thyrotoxicosis in the absence of hyperthyroidism
Thyrotoxicosis may present in the absence of the
hyperthyroidism.
In these instances thyrotoxicosis results from thyroid hormone
excess originating either from the thyroid gland as a
consequence of a destructive lesion or from a source outside
the thyroid .
The absence of hyperthyroidism refers to thyrotoxicosis
occurring despite there being no ↑es synthesis of thyroid
hormones in the thyroid gland .
Consequently , a low uptake of RAI is seen on scintigraphy .
31. DESTRUCTIVE THYROIDITIS ;-
THYROIDITIS;- any inflammatory condition of the thyroid .
It may be associated with transient thyrotoxicosis during it’s acute phase as a
consequence of disruption to normal architecture of the thyroid gland , which
release of t4 and t3 from the colloid .
Classification of thyroiditis ;-
33. 1)Subacute granulomatous / De Quervain’s thyroiditis;-
Also k/a granulomatous thyroiditis and giant cell thyroiditis .
Caused by viral infection ( cox sackie virus , mumps ,and adenovirus )
F>M
40-60yrs
H/o URTI just prior to onset of thyroiditis .
Clinical features;-
pain ;- is a striking feature , radiate to the ear and worse on turning the head .
Fever
Malaise
Dysphagia
Signs of thyrotoxicosis may be present , such as tachycardia , tremors and
irritability .
Firm ,irregular enlargement of one or both thyroid lobes , extremely painful to
palpate.
34. Investigations of subacute thyroiditis;-
↑es inflammatory markers such as ESR , CRP,
Normocytic normochromic anemia .
Thyroid scintigraphy with Tc99 or I121/131 shows a complete absence of uptake
HPE;- multiple giants cells surrounding a central core of colloid .
FNAC
RAI uptake
Clinical course;-
At 12-16 weeks there may be a hypothyroid phase during which the damaged
tissues is unable to generate thyroid hormone .
Most pts. Do not require t/t with thyroxine and most are ultimately euthyroid.
35. Treatment of subacute granulomatous thyroiditis
Treatment is supportive.
NSAIDs such as aspirin, and indomethacin are effective
analgesics .
Beta blockers ; if symptomatic in the thyrotoxic phase .
steroids ( prednisolone 30-40mg daily ) in severe acute
cases
36. 2) Silent / painless thyroiditis
Occur in the early stages of autoimmune thyroiditis .
Mild biochemical hyperthyroidism and occasionally to symptomatic
thyrotoxicosis.
Thyroid is enlarged ( ~1/2 of all pts.) .
Not painful .
FNAC;- extensive lymphocytic infiltration with plasma cells .
Thyroid autoantibodies positive .
Thyrotoxic phase is around 8 weeks and symptomatic t/t with beta
blockers →then follows a hypothyroid phase last for more than 6 months
→restore euthyroidism
37. 3) Radiation induced thyroiditis
Cause ;1) follow t/t with RAI ( high dose ) for hyperthyroidism.
2) EBRT for certain CA.
C/F ;- 1)occasionally thyrotoxicosis
2)More frequently hypothyroidism .
t/t;- 1)self resolve within 2 weeks of its onset.
2)Simple analgesia
3)Oral glucocorticoids therapy for pain and swelling
38. 4) drugs induce thyroiditis
Drugs;- amiodarone , lithium , interferons , cytokines
Amiodarone may result in thyrotoxicosis by 1 of 2 ways;-
Amiodarone induce thyrotoxicosis (AIT) type 1;- in pts. With pre-existing thyroid
disease , the high iodine content of amiodarone may induce thyrotoxicosis .
AIT type -2 ;- when a destructive thyroiditis occur as a consequence of the
cytotoxic effect of amiodarone and its metabolite ( des-ethyl -amiodarone )
AIT is prevalent in iodine deficient areas whereas in areas which iodine replete ,
amiodarone – induced hypothyroidism (AIH) common .
t/t ;- withdrawal of amiodarone – improve in both AIT type 1 and AIT type 2.
Oral corticosteroids ;- restore euthyroidism in AIT type 2
Thionamides;- effective in AIT type 1.
Antithyroid drugs with potassium perchlorate ;- inhibits thyroidal iodide uptake and
consequently ↑es sensitivity to thionamide action .
39. 5) Iodine induced thyroiditis
Iodine induced thyroiditis ( IIT) results from genetic change that leads to
autonomous thyroid hormone production within sufficient numbers of
thyrocytes to cause hyperthyroidism in the presence of an ↑es supply of
iodine .
This “Jod Basedow” effect seen in pts. With toxic MNGs in areas of iodine
deficiency.
It may also occur in the absence of pre-existing thyroid disease
generally resolve within 6months .
40. 6)Acute suppurative thyroiditis
Most common cause;- staph. Aureus , hemolytic streptococcus , or
streptococcus pneumoniae .
This bacterial infection of the thyroid gland may be the result of trauma ,
hematologic seeding from a distant infected site or direct extension from a
deep cervical infection.
The infection is usually localized to a single lobe and most commonly develop
an abscess cavity that may rupture through the gland capsule and extend into
the mediastinum
Common in the children.
Referred pain to the I/L mandible and ear
Typically the child fixes the head and neck in a single position similar to
torticollis.
Localize tenderness over the gland and pain on head movement
TFT normal , ESR normal and TLC ↑es
41. Diagnosis ;- needle aspiration of the abscess and culture for organism
Mx;- high dose antibiotics
When an abscess has been shown on needle aspiration , surgical drainage
is usually required .
Drainage may involve a partial thyroidectomy to remove abscess and
necrotic tissues .
43. PATHOPHYSIOLOGY
Thyroid gland needs iodine to secrete thyroid hormone
↓
production of thyroid hormone depends upon the TSH, iodine
intake and also protein intake
↓
Enlargement of thyroid gland results goitre from increased secretion
of pituitary gland
↓
TSH stimulates the thyroid to secrete more level of T4
↓
In the blood ,T4 levels are low, the thyroid gland will be more large
and compress then neck and also the chest
↓
Causing in respiratory manifestation.
44. ETIOLOGY
The most common cause in areas replete with iodine is chronic autoimmune
hypothyroidism , Hashimoto thyroiditis.
49. Myxedema ( gull disease)
Hypothyroidism developing in adults , deposition of
excess mucoproteins in skin of forearm, leg , feet.
Features;-
Enlargement of thyroid gland ( goiter)
Slowing physical and mental activity .
Generalized fatigue and dull look.
apathy.
Overweight
↓es sympathetic activity –constipation
↓es sweating
50. Skin- dry , thicken ,yellow ( carotenemia) , cool ( ↓es blood flow).
Edema , puffy face, periorbital swelling.
Ptosis ( drooping of upper eyelid )
Coarse hair
Broadening of facial features
Enlarged tongue
Deepening of the voice ( telephonic voice)
Calorigenic action ;- BMR ↓es to 30-40%
cold intolerance
CNS ;- myxedema madness ( psychosis)
Memory loss
51. Menstrual irregularities.
Carbohydrate metabolism – low blood
sugar
Bone marrow – anemia
On left side , a euthyroid 6yr old girl
with the height of 105cm .
On the right , a 17yr old girl with a
height of 100cm , mental retardation ,
myxedema and a TSH of 288( normal
0.3-5.5)
53. Neonatal hypothyroidism
( cretinism)
Hypothyroidism developing in infancy/early
childhood , due to maternal iodine deficiency.
2types;-
1) endemic ;- due to dietary iodine
deficiency.
2) sporadic ;- due to either an
inborn error of thyroid metabolism or complete or
partial agenesis of the gland.
55. dwarfism and shunted growth
Often deaf and mute
Thick and coarse , dry skin.
Failure of sexual development .
Delayed milestones .
Occur in iodine deficient areas of world (i.e.
Himalayas , china , Africa)
56. THYROIDITIS
Inflammation of thyroid .
Types ;-
A) hashimoto’s thyroiditis( autoimmune )
b) Riedel’s thyroiditis .
57. Hashimoto’s thyroiditis
Gradual thyroid failure due to autoimmune destruction of
thyroid .
45-65yrs
10:1 female predominance
Genetic component –pts with ↑es circulating anti – thyroid
Ab.
Progressive depletion of thyroid epithelial cells replaced by
mononuclear cells and fibrosis.
Painless enlargement of gland with some degree of
hypothyroidism.
Hypothyroidism progresses slowly ( a slowly growing goitre
may have been found on examination)
Can be also asso. With papillary ca. and lymphoma .
↑es anti thyroid Ab in 85% cases.
58. Family H/O other autoimmune
diseases.
Diffuse or nodular goiter with
‘’bosselated’’ appearance.
HPE;- gland is infiltrated with
lymphocytes and areas of follicular
destruction and fibrosis.
Diagnosis;-↑es Sr. level of thyroid Ab
FNAC
T/T ;- oral thyroxine if
hypothyroidism.
59. RIEDEL’S THYROIDITIS
Very rare ( 0.5% of goitre)
Cellular fibrosis replacing thyroid follicles with
local infiltration of parathyroids , recurrent nerve,
carotid sheath , muscles etc.
Present as hard and fixed thyroid which clinically
is similar to CA.
Confirmed by biopsy.
T/T;- high dose steroids , tamoxifen , thyroxine
replacement.
62. THYROID DISEASE IN PREGNANCY
Thyroid dysfunction is common in pregnancy , during which both overt and
subclinical disease are associated with adverse outcomes.
Foetal development id depended on maternal thyroid hormone delivered via the
transplacental route until around 18weeks of gestation , although maternal thyroid
hormone transfer continues up to delivery.
Thyroid hormones are known to influence foetal size and maturation of tissues, in
addition to uteroplacental development.
Maternal TSH is seen to decline during the first trimester but resolve to pre-
pregnancy levels by the end of geststion.
Maternal ft4 concentrations decline throughout pregnancy.
63. HYPERTHYROID STATES IN PREGNANCY;-
Those with pre-existing disease may find symptoms are aggravated at
different times during the pregnancy.
Postpartum , around 5-10% of women develop thyroid dysfunction.
The risk is higher in those who have positive thyroid antibodies , Type-1
DM , a family H/O thyroid disease or other autoimmune conditions .
Of those who develop postpartum thyroid dysfunction , around 1/3rd have
postpartum thyroiditis .the remainder may present with either grave’s
disease or Hashimoto’s thyroiditis .
Radioisotope uptake measurements are the investigation of choice and
can help to distinguish between postpartum thyroiditis and grave’s
disease.
Postpartum thyroiditis will show ↓es uptake on scintigraphic scanning
whereas those with grave’s disease will show ↑es uptake .
Breastfeeding S/b avoided for 24hrs if Tc99 is used.
64. Radioisotope uptake measurements are the investigation of choice and
can help to distinguish between postpartum thyroiditis and grave’s
disease.
Postpartum thyroiditis will show ↓es uptake on scintigraphic scanning
whereas those with grave’s disease will show ↑es uptake .
Breastfeeding S/b avoided for 24hrs if Tc99 is used.
3 conditions may be present during pregnancy;-
1) postpartum thyroiditis
2)hyperemesis gravidarum
3) grave’s disease
65. 1) Postpartum thyroiditis;-
Pt. commonly present with symptoms of thyrotoxicosis at around 12weeks
post delivery , f/b a period of hypothyroidism at around 3-6 months .
In some women , only the hypothyroid phase is evident and eventually will
be return to a euthyroid state.
Long term , pts. Who have experienced postpartum thyroiditis are at risk of
further episodes in subsequent pregnancies .
Pts. May be managed symptomatically with propranolol during the
thyrotoxic phase .
Treatment of the hypothyroid phase may be needed in around a 1/3rd of
women and t4 may be necessary for up to 12 months.
66. 2)Hyperemesis gravidarum;-
Transient thyrotoxicosis may be seen in hyperemesis gravidarum.
B’coz Sharing of alpha subunit of beta-HCG and TSH, with levels of HCG
in hyperemesis gravidarum causing stimulation of the TSH receptor.
Around 60% of women with H.G . Have a raised serum ft4 with a ↓es
serum TSH.
Physical signs typically associated with grave’s disease , such as a diffuse
goitre , will also be absent.
Management is supportive and antithyroid medications S/b avoided.
67. 3) grave’s disease;-
This accounts for around 90% of cases of thyrotoxicosis observed in the
pregnancy.
Grave’s disease may contribute to menstrual irregularities , difficulties in
conception ,and a ↑es rate of miscarriage .
Grave’s disease may rarely develop de novo in pregnancy but diagnosis
may be delayed as signs and symptoms may be wrongly attributed to
physiological changes occurring in pregnancy , such as ↑es BMR ,↑es C.O
, heat intolerance and mood changes.
t/t;- beta – adrenergic blockers may be used as adjuncts but the main t/t is
antithyroid medications .
RAI contraindicated.
PTU is preferred to carbimazole in the first trimester ( as it is associated
with fewer teratogenic effects).
68. 2nd and 3rd trimester , the drug of choice is carbimazole in view
of fears of liver function abnormalities with PTU .
The presence of circulating anti-TSH-R Ab in pregnancy may
result in foetal thyrotoxicosis due to transplacental transfer .
Current guidance recommends the determination of TSH-R Ab
concentrations at 20weeks gestation and close monitoring of
those with significantly raised levels.
69. Hypothyroid states in pregnancy
There is additional data to link maternal hypothyroidism with an ↑es
incidence of neurodevelopmental defects.
2 forms of hypothyroidism may be present during pregnancy;-
1) overt hypothyroidism
2) subclinical hypothyroidism
70. 1) Overt hypothyroidism;-
Pre-conception thyroid hormone replacement may offer protection against
early pregnancy hypothyroidism.
During pregnancy the requirement of thyroid hormone ↑es due to weight
gain , transfer of T4 to the foetus and ↑es concentrations of TBG.
Dose adjustment of LT4 S/b based on serum TSH as it demonstrates less
interindividual variation than fT4 concentrations.
71. 2) Subclinical hypothyroidism;-
Subclinical hypothyroidism in pregnancy are dependent on the iodine
status of the population.
Subclinically hypothyroid populations have ↑es risk of pregnancy loss (
including miscarriage , stillbirths and perinatal deaths ) , pre-term delivery
, placental abruption , breech presentation at term.
t/t;- levothyroxine therapy , ideally prior to conception and regular
monitoring of TFT.
72. EUTHYROID GLANDULAR ENLARGEMENT( GOITRE)
GOITRE;- enlargement of the thyroid gland .
Thyroid enlargement may be diffuse or may result from the
presence of 1 or multiple thyroid nodules .
It may additionally occur in the context of Euthyroidism ,
hypothyroidism , or hyperthyroidism .
A discrete swelling ( nodule) in one lobe with no palpable
abnormality elsewhere is termed an isolated ( or solitary)
swelling.
Discrete swelling with evidence of abnormality elsewhere in the
gland are termed dominant nodule.
77. USG;-
The most widely used imaging modality in the detection of
thyroid nodules.
Painless , quick , no contrast material , no radiation .
Has capacity to detect non-palpable nodules, as small as
2-3mm .
Allowing accurate guidance of FNAB.
Can be used in pregnancy.
A number of specific USG changes are associated with
malignancy , including;-
1)Hypoechogenicity
2)Solid nodule
3)Microcalcification
4)Irregular margins
5)↑es intramodular flow
6)T>W
7)Presence of invasion of regional lymphadenopathy.
78.
79. Thyroid scintigraphy;-
Little value in differentiation between benign and malignant nodular disease due to both to it’s
poor sensitivity and specificity.
This teq. Permits differentiation between ‘hot’( functional ) and ‘cold’(non-functional ) nodules ,
most malignant nodules trap isotopes less well than normal thyroid tissue and thus appear cold.
In this investigation a traceable radioactive iodine or technetium is injected into the blood , the
thyroid gland concentrates radioactive iodine .
The concentrated radioactive iodine can be detected by gamma camera.
I123 has a shorter half life as compare to I131 and therefore preferred because it has less
exposure of the pt. to radiation.
Scintigraphy has no role in the routine management of thyroid nodule.
80. CT and MRI;-
CT and MRI provides high resolution three dimensional
imaging of the thyroid gland .
They additionally afford Little value in the differentiation
between benign and malignant lesions .
May be indicated if more detailed are needed before
surgery or there is suspicion of malignancy.
PET SCAN;- use of PET scan limited by both cost and
availability.
Follow up of thyroid CA.
Tumors that don’t concentrate radioactive iodine.
Metastatic thyroid ca.
81. Radiological investigations;-
Normal AP and lateral CXR may demonstrate retrosternal
extension of the goitre (retrosternal shadow)
Thoracic inlet x-rays may demonstrates compression or
deviation of the trachea , this important to anesthetist
(difficult intubation).
82. FNAB;-
FNAB is the gold standard investigation in the evaluations of pts. Presenting with
thyroid enlargement and provides both direct and specific information about the
pathology of nodules . (97-99%)
(1-4%)
(0-3%)
(5-15%)
(15-30%)
. (60-75%)
(97-99%)
83. Treatment of goitre;-
No t/t for euthyroid , small diffuse goiter
Medical ;-a) thyroxine → for large diffuse goiter; to depress TSH
stimulation and reduce hyperplasia.
b) iodine → for endemic goiter
Surgery;-
a)Compression symptoms
b)Suspicion for malignancy
c)Cosmetically acceptable
RAI ablation;- done in case of compressive symptoms.
