L6: Thyroid Disorders Flashcards
T4 has four ____ while T3 has three
Iodine residues
T4 means
Tetraiodothyronine or L-thyroxine
T3 means
L-triiodothyronine
glycoprotein synthesized
in the thyroid follicular cell, and acts as a precursor for the synthesis of thyroid
hormones
Thyroglobulin
Thyroglobulin contains large amount of ?
Tyrosine
Iodine from food is transported to the plasma and to the thyroid follicular cell. This process is called as?
Iodine trapping
Enzyme needed to activate inorganic iodide
thyroid oxidase or
peroxidase
Once activated, iodine will be transported
here, where it will be used for the
organification of thyroglobulin.
follicular lumen
iodine will be covalently
linked to the tyrosine residues located in
thyroglobulin
Organification
Organification forms iodotyrosine residues
DIT – diiodotyrosine (2 iodine
residues connected to tyrosine)
MIT – monoiodotyrosine (1 iodine)
will combine to form T4
DIT + DIT
will combine to form T3
DIT + MIT
Stimulates the release of thyroid hormones from thyroglobulin
Lysosomes
more abundant in the plasma; less
biologically active
T4
less abundant in the plasma; more
biologically active (acts on the peripheral
tissues)
T3
T4 can be converted into T3
through the process of
Deiodination
In deiodination, T4 can also be converted into?
Reverse T3
block transport of
iodide into the thyroid gland
Bromine, Fluroine, Lithium
These substances can impair
organification and coupling reaction
Amides (thionamides, sulfonamide,
salicylammide) and Antipyrine (an antipyretic)
Inhibit secretion of thyroid hormone
large doses of iodide and
lithium
The release of thyroid hormones is regulated by
the
hypothalamic, pituitary, and thyroid axis or the
HPT axis.
The primary point of regulation for this axis occurs
at the release of the _ by _
TSH by the anterior pituitary gland
Release of TSH is stimulated by the
release of the _ by _
TRH by the hypothalamus
TSH receptor is also called as?
Thyrotropin receptor
Activating TSH receptor activates what
activate adenylyl
cyclase, converting ATP into cAMP
An increased level of this increases the expression of the gene involved in the synthesis of thyroid hormones
cAMP
negative feedback control
mechanism
Once the body detects that the level of
thyroid hormones is too high, it will send a
negative feedback signal to the pituitary
gland, preventing release of TSH
test used
to measure how much radioactive iodine is
taken up by the thyroid gland.
RAIU (Radioactive Iodine Uptake)
THYROTOXICOSIS WITH
HYPERTHYROIDISM has high _
RAIU
THYROTOXICOSIS W/O HYPERTHYROIDISM has __ RAUI
One of the most common cause of
hyperthyroidism
GRAVE’S DISEASE
Immune system disorder resulting from
overproduction of thyroid hormones
GRAVE’S DISEASE
Thyroid-stimulating antibodies (TSAb)
directed against the thyrotropin receptor on the
surface of the thyroid cell.
Graves disease
Also known as Plummer’s disease
Toxic multinodular goiter
enlarged thyroid gland
Goiter
TH production is independent of TSH
Toxic multinodular goiter
Benign tumor that may be
active or inactive
Thyroid adenoma
Active tumor
Toxic adenoma
Function is independent of pituitary control
Thyroid adenoma
↑Human chorionic gonadotropin (hCG) → TSH
receptor → TH
Trophoblastic disease
Serum hCG levels usually exceed ____ U/mL
(kU/L) and always exceed ___ U/mL
300
100
Mean peak hCG level in Normal pregnancy:
50
U/mL
↑ or inappropriately “normal” serum
immunoreactive TSH concentrations
TSH-INDUCED HYPERTHYROIDISM
Evidence of peripheral hypermetabolism
TSH-INDUCED HYPERTHYROIDISM
Diffuse thyroid gland enlargement (goiter)
TSH-INDUCED HYPERTHYROIDISM
Characterized by the presence of tumors in the
anterior pituitary gland
TSH-SECRETING PITUITARY TUMORS
Tumors can secrete a TSH that is as biologically
active as the normal TSH, that is unresponsive
to normal feedback control.
TSH-SECRETING PITUITARY TUMORS
TSH-SECRETING PITUITARY TUMORS cosecretes what
prolactin and growth hormone
Prolactin cause
Amenorrhea/galactorrhea
Growth hormone causes
Signs of acromegaly
Selective resistance of the pituitary thyrotrophs to
thyroid hormone → ↑TSH → Hyperthyroidism
PITUITARY RESISTANCE TO THYROID
HORMONE
Thyrotoxicosis factitia
EXOGENOUS THYROID HORMONE
a physiological response where the thyroid gland temporarily reduces thyroid hormone synthesis in the presence of high iodine levels
Wolf-chaikoff effect
Thyroid tissue destruction, inflammation,
fibrosis
Type II-amiodarone induced thyrotoxicosis
↑Iodine delivery and uptake → ↑TH
Type I-amiodarone induced thyrotoxicosis
Common cause of thyrotoxicosis
PAINLESS THYROIDITIS
Autoimmunity underlies most cases
PAINLESS THYROIDITIS
Inflammation is caused by presence of anti-
thyroid antibodies that attack thyroid tissue
Painless thyroiditis
Is thyroid tenderness present in painless thyroiditis
No
(absent)
Similar to painless thyroiditis, except
inflammation is caused by a virus
Subacute thyroiditis
Patients complain of severe pain in the thyroid
region, which often extends to the ear on the
affected side
SUBACUTE THYROIDITIS
Teratoma of the ovary that contains differentiated
thyroid follicular cells and is capable of making
thyroid hormone.
STRUMA OVARII
Functioning metastatic differentiated papillary or
follicular carcinomas synthesize sufficient thyroid
hormones → thyrotoxicosis.
METASTATIC THYROID CANCER
Outstretched hands
hyperkinesia
Hyperactive deep tendon reflexes
hyperreflexia
unique sign of grave’s disease
Exophthalmos
swelling or redness of legs, especially in
the pretibial area or shin
Pretibial myxedema or thyroid dermopathy
Pretibial myxedema or thyroid dermopath is due to localized accumulation of?
hyaluronic acid and chondroitin sulfate in
the dermis of the skin
Sign of autoimmune disorder,
characterized by digital clubbing, swelling
of hands and feet
Thyroid acropachy
When you feel up the patient’s neck, you
will feel vibrations
Thyroid thrill and systolic bruit
Give false positive result in blood tests for diagnosing hyperthyroidism and thyrotoxicosis
Biotin
Normal RAIU
1p-30%
Black thyroid scan
Grave’s disease
Patchy white thyroid scan
Thyroiditis
Single black patch in thyroid scan
Hot nodule
Single white patch in thyroid scan
Cold nodule
Two types of thyroidectomy:
Total and subtotal
Thyroidectomy for graves disease
Total thyroidectomy
Indication for thyroidectomy
o Large thyroid gland (>80 g)
o Severe ophthalmopathy
o Lack of remission on antithyroid drug
Before conducting thyroidectomy, you
need to ensure that the patient is in _
Euthyroid state
given until the
patient is euthyroid (6-8 weeks) b4 thyroidectomy
Methimazole
given 10-14 days before surgery before thyroidectomy
Iodides 500 mg/day
given 10-14 days
combined pretreatment with propranolol before thyroidectomy
Potassium iodide
given several weeks
preoperatively and 7-10 days after
surgery. To maintain PR <90 bpm
Propranolol
Thionamide drugs
• Methimazole (MMI)
• Propylthiouracil (PTU)
PTU acts on the peripheral tissues,
preventing conversion of T4 into T3
Propylthiouracil
Inhibits peroxidase, which is responsible
for the oxidation of iodide into iodine
Thionamides
Can also inhibit coupling reactions of
iodotyrosine residues, which prevents
synthesis of thyroid hormones
Thionamides
Which thioanamide is more potent
Methimazole
safest thionamide for
pregnant patients in the 1st trimester
ONLY
Propylthiouracil
To induce long-term remission in
patients with Grave’s disease →
Continue antithyroid therapy for ___
12 - 24 mos
After remission monitor the patient every ___
6 to 12 mos
Tx when relapse occurs while using thionamides
Alternate therapy with RAI
Minor ADRs of thionamides
- pruritic maculopapular rashes
- arthralgia or joint pain
- fever
- benign transient leukopenia
When should u discontinue thionamides when it causes benign transient leukopenia
Since leukopenia is transient and if the WBC is not too low, you may continue the drug. Continue to
monitor, and if WBC continues to lower, it becomes reasonable to discontinue.
Major ADRs of thionamides
- agranulocytosis
- a plastic anemia
- arthralgia and lupus-like syndrome
- Polymyositis
- GI intolerance
- hypoprothrombinemiamia
- hepatotoxicity
Inhibit thyroid hormone biosynthesis by
interfering with intrathyroidal iodide
utilization
Iodides
Decrease the size and vascularity of the
gland
Iodide
Difference in improvement seen in thionamides and iodides
Thionamides - 4-8weeks
Iodides - 2-7 days
Adjunctive therapy to prepare patients
with Grave’s disease for surgery
(euthyroid state)
Iodides
Adrs of iodides
- hypersensitivity reactions
- salivary gland swelling
- iodism
- gynecomastia
- Contains 38 mg iodide per drop
- Contains 6.3 mg iodide per drop
- Saturated solution of potassium iodide
- Lugol’s solution
How many days is needed to prevent
interference of iodides with the
uptake of RAI
3 to 7 days
Used to ameliorate the symptoms such as
palpitations, tremors, anxiety, and heat
intolerance
B - blockers
block the conversion
of T4 to T3
Propranolol and Nadolol
Adjunctive therapy with antithyroid drugs,
RAI, or iodides in Grave’s disease and toxic nodules, in preparation for surgery, in
thyroid storm
Beta blockers
CI of beta blockers
o Decompensated heart failure
o Sinus bradycardia
o Concomitant therapy with MAOI/TCA
o Hypoglycemia
Initial dose of propranolol
Initial dose: 20-40 mg QID
Dose of propranolol for younger and severely toxic patients
** 240-480 mg/day**
Useful when contraindications to B-blocker exist
Centrally acting sympatholytics
For symptomatic treatment of hyperthyroidism
Centrally acting sympatholytics
Dose of clonidine
150 mcg twice daily
Diltiazem dose
120 mg every 8 hours
Agent of choice for Graves’ disease, toxic
autonomous nodules, and toxic MNGs.
SODIUM IODIDE 131 (131I)
mainstay adjunctive therapy to RAI
treatment.
b-blockers
given prior to RAI to patients with
cardiac disease and elderly
thionamides
thionamides should be withdrawn in __ days prior to RAI and reinstituted _ days after
4-6 days
4
increases cure rate and shortens time to cure
lithium
prevents post-therapy increase in thyroid hormones
lithium
has the same indication as thionamides
lithium
side effects of iodides
o Hypothyroidism (occurs years after RAI)
o Mild thyroidal tenderness
o Dysphagia
Preferred thionamide
propylthiouracil
does NOT have an effect on
the peripheral tissues (but has a longer
duration of action)
methimazole
can propylthiouracil be crushed into suspension with water or saline and be instilled via gastric or rectal tube
yes
Should be administered after thionamide is
initiated
iodide
Can be used in patients with pulmonary
disease (COPD or asthma) or at risk for
cardiac failure
esmolol
why are corticosteroids used for thyroid disorders
Benefits derived from steroids may be caused by
their antipyretic action and their effect of
stabilizing BP
should not be given
aspirin or NSAIDS
given to remove excess thyroid hormone
PLASMAPHERESIS & PERITONEAL
DIALYSIS
