Download Causes of thyroiditis

‫בלוטת התריס‬
‫פיזיולוגיה ומחלות‬
‫ד"ר סמיר קאסם‬
‫השרות לאנדוקרינולוגיה ומטבוליזם‬
Thyroid gland- anatomy
Thyroid anatomy
Thyroid histology
Thyroid Hormones
Thyroglobuline
Calcitonine
THYROID HORMONES
T4
T3
rT3
-The thyroid production rate of T4 is 80 to 100 µg (100 to 130 nmoles) / day.
-T4 is degraded at a rate of about 10 % / day. –
•80 % is deiodinated, 40 % to form T3 and 40 % to form rT3. The remaining 20 % is
conjugated with glucuronide and sulfate.
Thyroid hormone biosynthesis
TPO
(1)iodide (I-)trapping by the thyroid follicular cells; (2) diffusion of iodide to the apex of the
cells; (3)
transport of iodide into the colloid; (4) oxidation of inorganic iodide to iodine and incorporation
of
iodine into tyrosine residues within thyroglobulin molecules in the colloid; (5) combination of
two
diiodotyrosine (DIT) molecules to form tetraiodothyronine (thyroxine, T4) or of
monoiodotyrosine
(MIT) with DIT to form triiodothyronine (T3); (6) uptake of thyroglobulin from the colloid into
the
Regulation of Thyroid hormone
secretion
Thyrotropin-releasing hormone (TRH) increases the secretion of thyrotropin (TSH), which
stimulates the synthesis and secretion of trioiodothyronine (T3) and thyroxine (T4) by the
thyroid gland. T3 and T4 inhibit the secretion of TSH, both directly and indirectly by
suppressing the release of TRH. T4 is converted to T3 in the liver and many other tissues by the
action of T4 monodeiodinases. Some T4 and T3 is conjugated with glucuronide and sulfate in
the liver, excreted in the bile, and partially hydrolyzed in the intestine. Some T4 and T3 formed
in the intestine may be reabsorbed. Drug interactions may occur at any of these sites.
Regulation of transcription by thyroid hormones
Thyroid investigations
Blood –
Imaging : –
Scan
U/S
CT
PET
•
•
•
•
Assessment of bioactive thyroid
hormones
Check free hormone levels:
Free T4
(Free T3)
Check thyroid hormone “biosensor’:
TSH
TT3
Thyroid function tests
FT4
TT3
TSH
(“sensitive”, mIU/L)
nmol/L
nmol/L
pmol/L
21
3.0
10
1.2
4
0.15
Hypo Hyper
Hypo Hyper
Hypo Hyper
Serum factors in thyroid disease
1-Anti-thyroid antibodies:
Anti- microsomal or thyroid peroxidase (TPO)
Anti- thyroglobulin
2-Thyroid stimulating antibodies:
Thyroid Stimulating Immunoglobulin (TSI)
=
TSH receptor Stimulating antibody
TSI- growth promoting
TSI- hormone secretion stimulation
TSI- block
3-Thyroglobulin
4-Sex hormone binding globulin (SHBG)
5-Cholesterol
6- Calcitonine (Medullary Thyroid carcinoma)
Thyroid ultrasound
Fine Needle Aspiration
Nl thyroid scan - Hot nodule – Cold
Nodule
Thyroid diseases – Part II
(clinical)
Hyperthyroidism
Hypothyroidism
Thyroiditis
Nodules and Goiter
•
•
•
•
Thyroid abnormalities
Function
Structure
Thyroiditis
Hyperthyroidism
Hypothyroidism
Etiolog
y
RX
Goiter
Nodular
Benign
Diffuse
Malignant Function ? ()
‫סימטומים של תירוטוקסיקוזים‬
Hyperactivity / nervousness
Heat Intolerance / increased sweating
Fatigue / weakness
Weight loss WITH increased appetite
Palpitations
Dyspnea
Diarrhea
Oligomenorhea-amenorrhea- loss of libido
Eye complaints EXCLUSIVELY in Grave’s disease
–
–
–
–
–
–
–
–
–
‫סימנים בבדיקה גופנית‬
Sinus tachycardia, Atrial Fibrillation (10%)
Eye-lid retraction and staring
Goiter (multinodular / diffuse)
Fine tremor / hyperreflexia
Warm – moist skin
Hair loss
Muscle weakness and wasting
Palmar erythema – Onycholysis
Psychosis
Congestive (high output) heart failure / IHD
Thrill over thyroid
Grave’s disease exclusively
Exophtalmy
•
•
•
•
•
•
•
•
•
•
•
•
Thyrotoxicosis- Causes
Primary hyperthyroidism
Graves' disease
Toxic multinodular goiter
Toxic adenoma
Functioning thyroid carcinoma metastases
Activating mutation of the TSH receptor
Activating mutation of Gsα (McCune-Albright syndrome)
Struma ovarii
Drugs: iodine excess (Jod-Basedow phenomenon)
Thyrotoxicosis without hyperthyroidism
Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma
Ingestion of excess thyroid hormone (thyrotoxicosis factitia) or thyroid tissue
Secondary hyperthyroidism
TSH-secreting pituitary adenoma
Thyroid hormone resistance syndrome: occasional patients may have features of
thyrotoxicosis
Chorionic gonadotropin-secreting tumors a
Gestational thyrotoxicosisa
a
Circulating TSH levels are low in these forms of secondary hyperthyroidism.
Note: TSH, thyroid-stimulating hormone.
Graves’ disease
• Diffuse toxic goiter
• Opthalmopathy
• Dermopathy
Etiology:
Autoimmune
Anti-TSH receptor antibodies
Anti-thyroid antibodies
expression of HLA-DR3
association with:
-diabetes mellitus
-Addison’s disease
-pernicious anemia
Graves disease- goiter
Graves diseaseopthalmopathy - Exophtalmus
Graves’ disease dermopathy
The effect of high- dose PTU
Pulse rate:
TT3
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
Causes of Hypothyroidism
Primary
Autoimmune hypothyroidism: Hashimoto's thyroiditis, atrophic thyroiditis –
Iatrogenic: 131I treatment, subtotal or total thyroidectomy, external –
irradiation of neck for lymphoma or cancer
Drugs: iodine excess (including iodine-containing contrast media and –
amiodarone), lithium, antithyroid drugs, p-aminosalicyclic acid, interferon-α
and other cytokines
Congenital hypothyroidism: absent or ectopic thyroid gland, –
dyshormonogenesis, TSH-R mutation
Iodine deficiency –
Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis, –
scleroderma, cystinosis, Riedel's thyroiditis
Transient Silent thyroiditis, including postpartum thyroiditis –
Subacute thyroiditis –
Withdrawal of thyroxine treatment in individuals with an intact thyroid –
•
Secondary Hypopituitarism:
tumors, pituitary surgery or irradiation, infiltrative disorders, Sheehan's –
syndrome, trauma, genetic forms of combined pituitary hormone
deficiencies
Isolated TSH deficiency or inactivity –
Hypothalamic disease: tumors, trauma, infiltrative disorders, idiopathic –
•
TSH, thyroid-stimulating hormone; TSH-R, TSH receptor.
Signs and Symptoms of Hypothyroidism
(Descending Order of Frequency)
Symptoms • •Signs
Dry coarse skin;
Tiredness, weakness
Dry skin
cool peripheral extremities
Feeling cold
Puffy face, hands, and feet
Hair loss
(myxedema)
Difficulty concentrating and poor memory
Diffuse alopecia
Constipation
Bradycardia
Weight gain with poor appetite
Peripheral edema
Dyspnea
Delayed tendon reflex relaxation
Hoarse voice
Carpal tunnel syndrome
Menorrhagia (later oligomenorrhea or
Serous cavity effusions
amenorrhea)
Paresthesia
Impaired hearing
Laboratory:
serum thyroid hormones, cholesterol
anemia (iron def., megaloblastic)
Hypothyroidism- therapy
• Levothyroxine (1.7 mcg/kg/d) 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”
Myxedema Coma
Extreme hypothyroidism:
• Coma
• Hypothermia
• Hypoventilation
• Hypoglycemia
• Hyponatremia
• Bradycardia
Laboratory:
FT4 , TT3, TSH
Lactascent serum
Co2 retention
Myxedema Coma- therapy
Ventilation
Treat:
Hypoglycemia
Precipitating factors
Give:
T4 or T3 I.V.
Corticosteroids
Causes of thyroiditis
Acute •
-Bacterial infection: especially Staphylcoccus Streptococcus and
Enterobacter
-Fungal infection: Aspergillus Candida Coccidioides Histoplasma and
Pneumocystis
-Radiation thyroiditis after 131I treatment
-Amiodarone (may also be subacute or chronic)
Subacute
Viral (or granulomatous) thyroiditis –
Silent thyroiditis (including postpartum thyroiditis) –
Mycobacterial infection –
Chronic
- Autoimmunity: focal thyroiditis, Hashimoto's thyroiditis, atrophic
thyroiditis Riedel's thyroiditis
- Parasitic thyroiditis: echinococcosis, strongyloidiasis, cysticercosis
- Traumatic: after palpation
•
•
Clinical course of subacute thyroiditis. The release of thyroid hormones is
initially associated with a thyrotoxic phase and suppressed thyroid-stimulating hormone (TSH). A
hypothyroid phase then ensues, with low T4 and TSH levels that are initially low but gradually
increase. During the recovery phase, increased TSH levels combined with resolution of thyroid
follicular injury leads to normalization of thyroid function, often several months after the beginning
of the illness. ESR, erythrocyte sedimentation rate; UT4, unbound T4
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, fibrinogen)
Subacute thyroiditis- therapy
Non-steroid anti-inflammatory agents (NSAIDS)
β-blockers
Corticosteroids
Goiter and nodules