Transcript No Slide Title

BENIGN DISEASES OF THE
THYROID
Rivka Dresner Pollak M.D
Endocrinology.
Thyroid gland- anatomy
Thyroid gland- anatomy
sternocleidomastoid
thyroid
esophagus
vertebra
strap muscles
trachea
jugular v.
carotid a.
Recommended and Typical Values
for Dietary Iodine Intake
μg I/day
150
200
90-120
Recommended Daily Intake
Adults
During pregnancy
Children
Typical Iodine intakes
North America
Europe (Germany, Belgium)
Switzerland
Chile
75-300
50-70
130-160
<50-150
Serum thyroid hormone binding
Feedback control
Thyroid secretion
Free T4, T3
Tissue action
Hormone metabolism
Protein
Bound
Thyroid
hormone
P
Fecal excretion
THYROID HORMONES TRANSPORT AND METABOLISM
TRANSPORT
TBG = thyroxine binding globulin
TTR = transthyretin
% binding- mostly to TBG
T4 - 99.5
T3- 95
METABOLISM
THYROXINE BINDING GLOBULIN
DEIODINASE
TYPE 1 & 2
Estrogen
Androgen
Glucocorticoids
Acute illness
Chronic illness
Liver dis.

=
=
N


Serum protein binding of thyroid hormones
“Pill effect”
Total T4
Bound
T4
Free
T4
TBG T4
 synthesis
By liver
T4
T4
TBG
T4
T4
T4
Regulation of Thyroid hormone secretion
Hypothalamus
(-)
TRH
(+)
Pituitary
(+)
(-)
T4, T3
Thyroid
TSH
Assessment of bioactive thyroid
hormones
Check free hormone levels:
Free T4
Free T3
Check thyroid hormone “biosensor’:
TSH
Thyroid function tests
FT4
FT3
pmol/L
nmol/L
21
3.0
10
1.2
TSH
4
0.15
Hypo Hyper
Hypo Hyper
1o Hypo 1o Hyper
Laboratory tests in thyroid disease
Anti-thyroid antibodies:
Anti-thyroid peroxidase (TPO)
Thyroid stimulating antibodies:
TSI-Thyroid stimulating imunoglobulins
TSH receptor Antibody
Thyroglobulin
2. Thyroid scanning
Radioactive isotopes of I (131I, 123I)
Pertechnetate
Generates Data on:
- Anatomy
- Physiology
Normal thyroid scan
“Hot nodule”
“Cold” nodule
Multinodular goiter (MNG)
Pertechnetate scan
CHEST X-RAY
Radio Active Iodine Uptake
(RAIU)
50
Hyperthroidism
40
30
Normal
20
Hyperthyroidism with
Rapid turnover
10
Hypothroidism
0
0 2
6
12
Time (hours)
18
24
Thyroid abnormalities
Function
Structure
Thyroiditis
Hyperthyroidism
Hypothyroidism
Etiology
RX
Goiter
Nodular
Benign
Malignant
Diffuse
Function nl 
Hyperthyroidism-Etiology
• Diffuse toxic goiter (Graves’ disease)- most common in young people
• Toxic adenoma (Plummers’ diesease)
• Toxic mulitinodular goiter (MNG)
• Subacute thyroiditis-Hyperthyroid phase
• Hyperthyroid phase of Hashimotos’ thyroiditis
• (“Hashitoxicosis)
• Factitious hyperthyroidism
• Rare causes: -TSHoma
-Hydatidiform mole/choriocarcinoma
- Multiplex pregnancy
- Struma ovarii
Graves’ disease
• Diffuse
toxic goiter
• Opthalmopathy
• Dermopathy
•Acropathy (clubbing)
Etiology:
Autoimmune
Anti-TSH receptor antibodies (stimulating, blocking, neutral)
Anti-thyroid antibodies
 expression of HLA-DR3
 association with:
-diabetes mellitus-type 1
-Addison’s disease
- pernicious anemia
myasthenia gravis
lupus
Graves’ disease
• Epidemiology : incidence 0.3-1.5/1000
• Female: Male 5:1
• Most Common cause of hyperthyroidism
Thyroid and pituitary function in
Graves’ disease
T4, T3
(+)
(-)
TSH
(+)
Thyroid Stimulating
Immunoglobulins (TSI)
Graves’ diseaseClinical features
Signs:
Symptoms:
Fatigue
palpitations
Weight loss
Heat intolerance
Frequent bowel movements
Sweating
hyperkinesia
In the elderly:
Tachycardia
Muscle wasting
 pulse pressure
Eye signs
Diffuse goiter
Lymphadenopathy
Splenomegaly
Hyperreflexia
cardiovascular symptoms, myopathy
Graves’ Disease- Goiter
Graves diseaseOpthalmopathy
Extrathyroidal TSHR is present in retro-orbital
adipocytes, muscle cells and fibroblasts
Grave’s Opthalmopathy
• Class 0 — No symptoms or signs
• Class I — Only signs, no symptoms (eg, lid
retraction, stare, lid lag)
• Class II — Soft tissue involvement
• Class III — Proptosis
• Class IV — Extraocular muscle involvement
• Class V — Corneal involvement
• Class VI — Sight loss (optic nerve involvement)
Graves’ disease dermopathy
Graves disease- diagnosis
• Clinical hyperthyroidism
• Biochemistry:
FT4, TT3 , TSH
cholesterol 
• Serology:
anti-TSH receptor antibodies
anti-thyroid antibodies
Graves’ disease- therapy
1. Antithyroid drugs:
Thionamides-
3. Definitive therapy:
131I-
Propylthiouracil (PTU)
Methimazole (MMI)
b-blockers
Treat for 12 months
side effects:
hypothyroidism
Surgery-
subtotal thyroidectomy
side effects:
anesthesia morbidity
hypoparathyroidism
recurrent laryngeal nerve damage
hypothyroidism
70%
~30%
remission
Recurrence
Or non-remission
Follow-up
Anti-thyroid thionamide drugs
PTU (propylthiouracil)
MMI (methimazole)
Dosage:
TID
Once daily
Effect:
T4, T3  synthesis
inhibits T4→T3(high dose)
T4, T3  synthesis
(slow)
Agranulocytosis*:
Non-dose dependent
Dose dependent
(> 40 mg/day)
  > 40 yrs
Pregnancy:
 placental transfer
 placental
transfer
aplasia cutis
*occurrence 0.3-0.6%
Treatment of Graves' Orbitopathy
• Treatment of patients with Graves' orbitopathy has
three components:
• Reversal of hyperthyroidism, if present
• Symptomatic treatment
• Treatment with a glucocorticoid, orbital irradiation,
orbital decompression surgery to reduce
inflammation in the periorbital tissues
• Anti thyroid drugs and thyroidectomy are safe;
Radioactive iodine may worsen the situation.
The effect of high- dose PTU
Pulse rate:
FT3
FT4
140
50
45
120
40
Normal
range
100
35
30
80
25
Upper limit
of normal
20
0
1
2
3
4
5
Days
PTU dose mg/day:
1200
600
6
10
9
8
7
6
5
4
3
2
1
0
Subacute thyroiditis
Etiology:
(Post) viral inflammation
of thyroid
Symptoms & signs:
Hyperthyroidism
Painful swelling of thyroid
Pain irradiation to ear
Fever
Sometimes “silent”
Laboratory:
 ESR
 acute phase reactants
(CRP)
Subacute thyroiditis- therapy
A self limited disease
Therapy depends on symptoms/signs
Non-steroid anti-inflammatory agents (NSAIDS)
b-blockers
Corticosteroids
Outcome - in 6 months 90% euthytroid
Hypothyroidism- classification
Primary - TSH↑
1. Hashimoto’s thyroiditis
2. Post 131I therapy for Grave’s disease
3. Post thyroidectomy
4. Excessive I intake (amiodarone-procor)
Secondary TSH ↓ or normal:
Hypopituitarism due to adenoma, destructive lesion, ablation
TSH↓
Tertiary:
Hypothalamic dysfunction (rare)
Hypothyroidismclinical features
Signs:
Symptoms:
Fatigue
Weakness
Weight gain
Cold intolerance
Constipation
Cramps
Paresthesias (carpal tunnel)
Laboratory:
Coarse features
Bradycardia
Myxedema
Anemia
 serum thyroid hormones,  cholesterol
anemia (iron def., megaloblastic)
Hypothyroidism
Hypothyroidism- myxedema
Hypothyroidismdifferential diagnosis
Serum FT4 and
TSH
FT4, TSH normal/low
Secondary
hypothyroidism
FT4, TSH
TRH test
Excessive
response
Primary
hypothyroidism
Hypothyroidism- therapy
• Levothyroxine 0.05-0.3 mg/day
• Combined L-T4 and L-T3 may be beneficial with
respect to well-being
• In elderly patients (at high risk for CVD),
“go low, go slow”
Hypothyroidism- treatment
Before
After
Thyroid Storm and Myxedema Coma
– rare endocrine emergencies
THYROID STORM
Acute life threatening exacerbation of thyrotoxicosis
Clinical setting
History of Graves’ disease and discontinuation of medications/
previously undiagnosed hyperthyroidism.
Acute onset of hyperpyrexia (over 40 ˚C)
Sweating
Marked tachycardia, often with atrial fibrillation
Nausea, vomiting, diarrhea
Agitation, tremulousness, delirium
Occasionally “apathetic” – without restlessness and agitation, but with
weakness, confusion, and cardio-vascular dysfunction.
THYROID STORM
DIAGNOSIS:
Largely based on the clinical findings and clinical suspicion.
Elevated serum FT4, FT3.
Low TSH
MANAGEMENT
1. Supportive care
Fluids, Oxygen, Cooling blanket,cetaminophen
2. Specific measures
Propranolol, 40-80 mg every 6 hours.
Antithyroid drugs – PTU.
Glucocorticoids - Dexamethasone, 2 mg every 6 hours (due to reduction in
glucocorticoids half life)
Myxedema Coma
Extreme hypothyroidism:
• Coma
• Hypothermia
• Hypoventilation
• Hypoglycemia
• Hyponatremia
• Bradycardia
Laboratory:
FT4 , FT3, TSH
Co2 retention
Myxedema Coma- therapy
Ventilation
Treat:
Precipitating factors
T4 or T3 I.V.
Corticosteroids-50-100mg hydrocortisone
every 8 hours
Subclinical Hypothyroidism
Biochemical definition
TSH
FT4 AND FT3 NORMAL
WHEN TO TREAT?
WHEN TSH > 10
AND WHAT ABOUT 4.5<TSH<10????
Subclinical hyperthyroidism
• TSH below lower limit of normal (<0.3)
• Free T3 & Free T4 – normal
• Make sure not over treatment of
hypothyroidism
• Associated with increased risk of atrial
fibrillation in subjects > age 60 and accelerated
bone loss in postmenopausal women
Always repeat the
test before initiating
therapy!
Amiodarone (Procor)-induced thyroid
dysfunction
• Each Procor tablet (200 mg) has 75 mg Iodine
• Procor can cause:
hypothyroidism- does not require discontinue the
medication (thyroxine can be added)
Hyperthyroidism- anti thyroid drugs have limited
efficacy; radioactive iodine doesn’t work
Thyroiditis- may require steroids
»