Transcript the thyroid gland

THE THYROID GLAND
Anatomy, Histology, Physiology
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Situated in the anterior neck
Macroscopic : two lobes connected through the isthmus
Microscopic :-follicles which contain the colloid and are surrounded by a
single layer of thyroid epithelium
The follicle cells synthesize thyroglobulin (Tg) which is extruded into the
lumen of the follicle. The biosynthesis of T4, T3 occurs within Tg at the
cell-coloid interface.( Tg =large GP containing 140 tyrosyl residues)
! Sufficient iodide is necessary to allow the synthesis of TH
Thyroidal peroxidaze (TPO) is a membrane-bound GP, available at the cell
coloid interface for iodination and hormonogenesis in Tg.
Thyroid hormone synthesis and secretion
Involves several major steps:
1) active transport of I- across the BM into the thyroid cell (trapping of
iodide) → by an intrinsec membrane protein =Na+/I- symporter (NIS)
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The NIS is ●( +) by TSH and TSH rec- stimulating antibody (TRAb)
found in Grave’ s disease
●saturable with large amounts of iodide
● (-) by ions such as ClO4-( perchlorate), TcO4(pertechnetatea)
Physiology
2) oxidation of iodide:I-  I2 and iodination of thyrosyl residues in Tg to form
iodothyrosine (MIT, DIT) [ =I organification] ← catalyzed by TPO
3) coupling of iodotyrosine molecules within Tg to form iodothyronines (T3,T4) ← also
mediated by TPO
MIT+DIT=T3
DIT+DIT=T4
!!! Thiocarbamide drugs- particularly propylthiouracil, methimazole, carbimazole- are
potent inhibitors of TPO and will block thyroid hormone synthesis.
4) proteolysis of Tg, with release of free iodothyronines and iodotyrosines ( at the cellcolloid interface, colloid is engulfed into a colloid vesicle and is absorbed into the
thyroid cell → the lysosomes then fuse with the colloid vesicle and hydrolysis of Tg
occurs, releasing T4, T3, DIT, MIT; T4, T3 are released into circulation
THYROID HORMONE TRANSPORT
TH are transported in serum bound to carrier protein :TBG, TBPA, Albumin
Although only 0,04% of T4 and 0,4% of T3 are “free”, it is the free fraction that is
responsible for hormonal activity !!! The levels of free H are normal in states where
there are primary or secondary changes in plasma binding proteins, because TSH
release is controlled by the free thyroid hormone level and adjusts to normalize it
irrespectively of how much hormone is bound by the plasma proteins.
! The active form in peripheral tissues is T3
Most of the plasma pool of T3 is derived from peripheral metabolism (5’-deiodination ) of
T4
Iodide
Thyroid
hormones
biosynthesis
transport (the iodide
trap)
Iodination of thyrosil in
thyroglobulin →MIT, DIT
Coupling
of iodotyrosyl
residues in thyroglobulin→
Apical
Basement
microvilli
T3,
T4
membrane
NaI-
TPO
INa/I
Colloid
Tyr
Tg
symporter
TBG-carrier
Tissue
protein of TH
monodeiodinaze
NONTOXIC GOITER
 Goiter= enlargement of the thyroid gland
 Nontoxic goiter (ie, goiter not associated with hyperthyroidism)
can be diffuse or nodular.
Criteria –clinic : 4 grades in OMS classification
Grade 1= small goiter; it can’t be observed with the head in a
normal position( only with the head in hyperextension), but it
can be palpated
Grade 2=moderate goiter; physical examination: visible with the
head in normal position, palpable; it does not extend beyond the
external branch of sternocleidomastoid muscle
Grade 3=large goiter: one or both lobes extend beyond the external
branch of sternocleidomastoid muscle; it is visible from 10 m
distance; ± pressure symptoms in the neck
Grade 4= huge goiter; extend inferiorly to present as substernal
goiter and superiorly towards the mandible; it totally deforms the
neck and it can be “seen” from behind ; it is accompanied by
important pressure symptoms in the neck
Criteria- ultrasonographic: goiter volume
The upper normal limits in Women=16 ml
Men=18ml
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Etiology of nontoxic goiter:
Iodine deficiency
Hashimoto’s thyroiditis
Subacute thyroiditis
Inadequate hormone synthesis due to inherited defect in thyroidal
enzymes necessary for T4,T3 biosynthesis
Neoplasm, benign or malignant
! In some cases, nontoxic goiter results from TSH stimulation, which in turn results from
inadequate TH synthesis. Some goiters ← to mutations in genes involved in thyroid growth
and/or thyroid function. In many patients, however, the cause of the goiter is obscure, because
serum TSH levels are normal
ENDEMIC GOITER
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Worldwide, iodine deficiency remains the most common cause of nontoxic goiter
or endemic goiter
 Definition: any goiter occurring in a region where goiter is prevalent (>10% of
children in the population have a thyroid enlargement)
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Optimal iodine requirements for adults:100-150 g/day (200-300g/zi)( during
pregnancy and lactation: 200 g/day )
In endemic goiter areas the daily intake (and urinary excretion) of iodine falls <50
g/day→ the gland is unable to maintain adequate hormonal secretion, and
thyroid hypertrophy ( goiter) and hypothyroidism result.
PATHOGENESIS :
The development of nontoxic goiter in patients with severe iodine deficiency ( or with
dyshormonogenesis) involves impaired TH synthesis and, secondarily, ↑ in TSH
secretion, → diffuse thyroid hyperplasia ± focal or nodular hyperplasia
→ over an extended period of time a diffuse, nontoxic goiter may progress → to
multinodular nontoxic goiter → toxic multinodular goiter (with hyperthyroidism)
! The mechanism for the development of autonomous growth and function of thyroid
nodules may involve some activating mutations (Gs protein in the cell membrane)
which result in thyroid cell proliferation and hyperfunction even when TSH is
suppressed.
PATHOGENESIS
ENDEMIC GOITER
A DIET VERY
LOW IN IODINE
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↓ INTRATHYROIDAL IODINE CONTENT
T3 PREFERENTIAL SYNTHESIS
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↑ TSH
GOITER WITH A HIGH IODINE UPTAKE
MAINTAINACE OF NORMAL CONCENTRATIONS OF
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TH
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ENDEMIC CRETINISM
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Severe hypothyroidism in infancy is termed cretinism.
Retardation of mental development and growth are the
hallmark of cretinism.
Endemic cretinism is a development disorder that occurs
in regions of severe endemic goiter. Both parents of an
endemic cretin are usually goitrous. And in addition to the
features of sporadic cretinism, endemic cretins often have
deaf-mutism, spasticity, motor dysfunction, and
abnormalities in the basal gnglia.
3 types of cretins can be discerned :
Hypothyroid cretins
Neurologic cretins
Cretins with combined features of two
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CLINICAL PICTURES
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thyroid enlargement diffuse or multinodular
neck dicomfort
Pressure symptoms: large, huge goiter which may displace or
compress adjacent structures such as trachea, esophagus, neck
vessels → dyspnea, inspiratory stridor, dysphagia, chocking
sensation, facial flushing and dilatation of cervical veins on lifting
the arms over the head
compression of the recurrent laryngeal nerve, with hoarsenessrare
usually not associated with abnormal thyroid hormone secretion,
but endogenous subclinical thyrotoxicosis caused by
autonomously nodules may develop ; rarely hypothyroidism
PHYSICAL EXAMINATION
goiter size→ OMS classification
consistency: may be relatively firm, but it is often soft or rubbery
shape, structure : diffuse (smooth) or nodular
mobility with deglutition and sub adjacent structures
tenderness
the presence of latero- cervical adenopathy
Laboratory findings
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1. THYROID ULTRASONOGRAPHY : assesses both morphology and the
size of the goiter; useful for measuring the size of individual nodules and
for evaluating the results of therapy; for differentiating solid from cystic
lesion; is a simple way to follow the growth of the goiter and nodules ;
also used to guide the operator to a deep nodule during FNAB
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2. SCINTIGRAPHY (ISOTOPE SCANNING) → a patchy uptake, frequently
with focal areas of increased uptake corresponding to “hot” nodules and
areas of ↓ uptake → “cold” nodule ( !!!10% of surgically removed cold
nodule=malignant)
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3. RAIU – values N/( high iodine uptake- in endemic regions) ( =I avidity, not
hyperthyroidism !!!/↓ depending on the iodide pool and TSH levels
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4. HORMONAL DETERMINATIONS : TSH, FT4 –usually normal
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5. THYROID AUTOANTIBODIES : TPO Ab, Tg Ab- high titers in
autoimmune thyroid disease
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5. CONVENTIONAL RADIOGRAPHY OF THE NECK AND THE UPPER
MEDIASTINUM → tracheal compression
Laboratory findings
 6. NECK AND MEDIASTINAL CT/ MRI → in
the presence of intrathoracic goiter to define
the relationship with surrounding structures
 7. LARINGOSCOPHY – vocal cord paralysis
 8. FNAB of a thyroid nodule→ in malignity
suspicion; it has been proved to be the best
method for differentiation of benign from
malignant thyroid disease; it may have
therapeutically utility → draining a cyst
Treatment
 A. MEDICAL TREATEMENT :in diffuse goiter
and multinodular goiter ( after excluding
malignity)
a. IODIDE → diffuse goiter, youth
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KI 1 mg 2tb/week
JODID 100-200 g/day
b. L-T4 25-50 g/day → nontoxic multinodular goiter (=
suppressive therapy)
c. I+L-T4
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JODTHYROX (100 g I+ 100 g L-T4) /tb
½ tb/day
d. Treating the hyperthyroidism when a multinodular goiter
becomes toxic with one or more hyperfunctional nodules/
hypothyroidism
Treatment
 B. SURGICAL TREATMENT
 For goiter that continues to grow despite TSH suppression
with LT4
 for goiters that produce obstructive symptoms, with
substernal extension
C. PROPHYLAXI
IODIDE for risk groups : pregnancy, lactation, ages: 6-14
and 14-18
THYROIDITIS
THYROIDITIS CLASSIFICATIONCLASIFICAREA
TIROIDITELOR
 1. ACUTE thyroiditis
 2. SUBACUTE thyroiditis
 3. CHRONIC thyroiditis
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Autoimmune
Fibrous
ACUTE THYROIDITIS (THYROID ABSCESS )
=acute bacterial inflammation of thyroid gland which untreated →
abscess
 Etiology: staphilococ, streptococ, germeni gram negative bacteria, fungi
 rare; may appear in the context of septicemia or acute infective
endocarditis
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Acute onset
Clinic
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GENERAL signs : malaise, fever, sweating
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LOCAL signs : pain and tenderness, swelling and warmth and
redness of the underlying skin
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Satellite adenopathy
 LABORATORY FINDINGS
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↑↑ ESR
FBC- anemia, ↑ neutrophyls
Thyroid scintigraphy : no uptake corresponding to the
affected thyroid area
Thyroid ultrasonography : → the abscess or evidence of
swelling
Needle aspiration will confirm the diagnosis and identify
the organism
TREATMENT
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ANTIBIOTIC THEARPY ± occasionally EXCISION/
DRAINAGE (ABSCESS)
SUBACUTE THYROIDITIS (DE QUERVAIN’ S
THYROIDITIS)
 or granulomatous thyroiditis; = an acute inflammatory disorder
of the thyroid gland most likely due to viral infection : mumps,
adenoviruses…
 CLINIC
 Subacute onset ; usually- !an episode of upper respiratory tract
infection in the previous weeks
 Pain, soreness in the neck, which may extend up to the
angle of jaw or toward the ear lobes on one or both sides of
the neck
 Thyroid enlargement
 Initially, the patient may have symptoms of hyperthyroidism:
palpitation, agitation, sweats
 General signs: fever, malaise
 LABORATORY FINDINGS
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↑ ESR (sometimes =100mm/h)
Initially :↑ T3,T4 + ↓TSH + ↓↓ RAIU; as the disease progress –
T3,T4 will ↓ and TSH will ↑( and symptoms of hypothyroidism are
noted ); later RAIU ↑ (→ recovery of the gland from the acute
insult)
Thyroid scinthygraphy - no uptake “white”
Thyroid ultrasonography –hypoechogene aspect corresponding to
the affected area
 TREATMENT
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Prednisone 50-60 mg/day, decreasing progressively the dosage
-blocker
sedative
L-thyroxine – during the hypothyroid phase
CHRONIC THYROIDITIS (HASHIMOTO’S THYROIDITIS,
LYMPHOCYTIC THYROIDITIS )
  an immunological disorder in which lymphocytes become sensitized to
thyroidal antigens and autoantibodies are formed that react with these
antigens
Pathology : heavy infiltration of lymphocites totally destroiyng normal
thyroidal architecture
 CLINIC
 Firm goiter /small, atrophic thyroid gland
 Euthyroid / mild hypothyroidism →severe
 rarely- “HASHITOXICOSIS ”→ may go through periods of activity when
large amounts of T3,T4 are released or “ dumped”, resulting in transient
symptoms of thyrotoxicosis ( =“spontaneously resolving hyperthyroidism )
! One variant of Hashimoto’s thyroiditis has been termed “silent” or “painless” thyroiditis (→
predilection: the postpartum period) ; evolves with a triphasic course, similar to what is seen in
subacute thyroiditis :
mild hyperthyroidism (1-3 months)→ hypothyroid phase (several months) →recovery
! Reccurent episodes
CHRONIC THYROIDITIS (HASHIMOTO’S THYROIDITIS)
 COMPLICATIONS: progressive hypothyroidism
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COURSE : may develop other autoimmune diseases:
pernicious anemia, adrenal insufficiency, DM type1
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LABORATORY FINDINGS
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ESR=normal
TSH, T3, T4 vary with the course of disease; usually normal/
↑ TSH ± ↓ T3,T4 / ↓ TSH, ↑T3,T4
Thyroid ultrasonography: diffuse hypoechogene aspect ← Ly
infiltrate
TPO Abs , Tg Abs  =the most striking laboratory
findings
TREATMENT
 Replacement treatment with LT4 – overt hypothyroidism
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B-blocker –hyperthyroid phase of silent or postpartum
thyroiditis
RIEDEL’ THYROIDITIS
  rare
 → characterized by fibrosis of the thyroid gland and adjacent
structure
 CLINIC
 insidious onset
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goiter –usually as stony-hard mass with extensive fibrosis
extending outside the gland and involving overlying muscle
and surrounding tissue
compression signs of adjacent structure : TRACHEA,
ESOPHAGUS and LARYNGEAL NERVES
Euthyroid /mild hypothyroidism
 surgery may be required to preserve tracheal and
esophageal function
 ! Must be differentiated from thyroid cancer