LMP301 Lecture 8: Thyroid Disease Flashcards
Thyroid diseases
What is symptom of goiter?
Enlarged thyroid gland
Is goiter due to hypo, hyper, or eu-thyroid?
Can be anything
Goiter is due to…
Lack of iodine
Thyroid gland secretes…
T3 and T4
What is more abundant in the blood, T3 or T4?
T4
What makes 2/3 of the circulating T3?
Peripheral tissues (liver, kidney) deiodinate T4
What stimulates the production of thyroid hormones?
TSH
What is more biologically active, T3 or T4?
T3
What is the inactive form of T3?
rT3 (reverse)
How is rT3 produced
metabolised from T4
T4 can make both T3 and rT3
How can local thyroid status be modulated?
Balance production of T3 and rT3
Thyroid hormones are needed for…
all tissue maturation and metabolism
Precursor for thyroid hormones
tyrosine
MIT structure
1 iodide attached to tyrosine
DIT structure
2 iodides attached to tyrosine
T4 is made up of
DIT + DIT
T3 is made up of…
MIT + DIT
T4 - 1 iodine (at first benzene)
rT3 is made up of…
T4 - 1 iodine (at second benzene)
T4 is also called…
thyroxine
Hypothalamus-pituitary-thyroid axis for T3, T4 control
Hypothalamus: TRH
a. pituitary: TSH
Thyroid: TSH binds on TSH receptor -> T4 and T3 production
Feedback of thyroid hormones
TSH neg feedback on hypothalamus (short loop feedback)
T4 + T3 neg feedback on hypothalamus, a. pituitary (long loop feedback)
How do thyroid hormones travel? Give some examples.
Bound to carrier proteins in plasma (e.g. albumin, TBG)
TBG
T4-binding globulin
Which thyroid hormones are active?
The ones not bounded to carrier proteins in the plasma
% of free T3 + T4
T3: 0.3% of all T3
T4: 0.03% of all T4
What may change the concentration of free thyroid hormones?
Changes in the [ ] or affinity of carrier proteins
Are FT3 + FT4 better or worse markers of thyroid function? Why?
Better
Effects of increasing TBG
More T4 + T3
Same FT4
Same TSH
What compounds increase TBG?
- estrogen
- oral contraceptives
Effects of decreasing TBG
Less T4 + T3
Same FT4
Same TSH
Effect of inhibiting binding of thyroid hormones to TBG
Less T4
Same FT4
What compounds decrease TBG?
- androgens
- glucocorticoids
What compounds inhibit thyroid hormones from binding to TBG?
Salicylates
Myxedema
Dry, waxy swelling of the skin with abnormal deposits of glucosaminoglycans
Glucosaminoglycans
unbranched polysaccharides
What is myxedema a strong indication of?
hypothyroidism
key symptoms of hypothyroidism
- Weight gain
- fatigue
- myxedema
- high cholesterol
- slow HR
Hypothyroidism is a _____ syndrome
hypometabolic
What do thyroid hormones control in the body?
metabolism
Why is a symptom of hypothyroidisms high cholesterol?
Less LDL receptors produced, so less liver uptake
Types of hypothyroidism
- Primary hypothyroidism
- Secondary hypothyroidism
- Tertiary hypothyroidism
Primary hypothyroidism
Problem at thyroid gland
Examples of problems at the thyroid gland
- autoimmune destruction (Hashimoto’s disease)
- iodine deficiency
- treatment of hyperthyrodism
- congenital defects in hormone
- antithyroid drugs (side effect of some drug therapy)
Secondary hypothyroidism
Problems at pituitary gland (TSH)
Tertiary hypothyroidism
Problems at the hypothalamus (TRH)
Diagnosis for hypothyroidism:
High/normal TSH
High fT4
not hypothyroidism
Diagnosis for hypothyroidism:
High TSH
Low fT4
Primary hypothyroidism
What feature must be present for actual hypothyrodism to be diagnosed?
low fT4
Diagnosis for hypothyroidism:
High TSH
Normal fT4
subclinical hypothyrodism (high risk, but not yet hypo)
Diagnosis for hypothyroidism:
Low/normal TSH
Low fT4
Secondary hypothyrodism
Complications of hypothyroidism vary depending on…
When during the lifetime patient has the disease
Complications of hypothyroidism:
Pregnancy
Affect fetal development (irreversible)
Complications of hypothyroidism:
Infancy, childhood
- bad brain development
- can’t grow tall
- low IQ
- bad psychomotor development
- cretinism (if severe)
Complications of hypothyroidism:
Adult
- death from myxedema coma (if severe)
Myxedema coma
- long-term hypothyrodism + another factor
- cold body (<80 F)
- loss of consciousness
Creatinism is ____ ___thyroidism
congenital
hypo-
Creatinism can be caused by…
- absence of thyroid gland
- thyroid hormone synthesis defects
Is creatinism fatal?
No
- Creatinism happens if diagnosed too late
- Early diagnosis can completely reverse effect
Symptoms of creatinism
- mental retardation
- short
- deaf
- neurological problems
- tongue sticking out
- flat nose bridge
How to treat creatinism?
replacement thyroid hormone
Diagnosis of creatinism
screening tests for newborns (can’t usually tell from clinical symptoms)
- Screen TSH (should be high if T3 + T4 is low)
- High TSH = creatinism
Treatment for primary hypothyrodism
Replacement therapy with synthetic T3 + T4
- Monitor by observing TSH levels after a few weeks (should be normal)
Key symptoms of hyperthyrodism
- Weight loss
- Fatigue
- Glucose intolerance
- Tremor
- Infected eye
- Sweating
- Rapid heart rate
- High BP
Why is weight loss a symptom of hyperthyroidism?
Too much metabolic activity
Why is fatigue a symptom of hyperthyroidism? Why is it a symptom of hypothyrodism?
Hyper: high metabolic activity cause muscle overwork
Hypo: hormones not available, so no stimulation for metabolism
Causes of hyperthyrodism
- Graves’ disease
- Plummer’s disease
- Thyroid tumour
- Thyroiditis
- Pituitary tumour
- HCG secreting trophoblastic tumour
- Iodine / iodine drugs
- Excessive T4 + T3
Plummer’s disease
toxic multinodular goiter:
excess production of thyroid hormones from functionally autonomous thyroid nodules
Graves’ disease
Diffuse toxic hyperplasia:
- Autoimmune disease that affects the thyroid
- Antibodies bind to TSH receptor
Thyroiditis
inflammation of thyroid gland
HCG secreting trophoblastic tumour
HCG has same a-unit as TSH, so during prenancy, the excess HCG might bind to TSH receptor and stimulate T3 + T4 production
Why might high iodine cause hyperthyroidism
Iodine is a substrate needed to make T3 and T4
Symptoms of Grave’s disease
- retracted eyelids
Diagnosis of Graves’ disease
- Very low TSH
- Very high fT4
- Anti-TSH receptor antibodies
- Radionucleotide uptake and scan (will accumulate in the thyroid)
Treatment for Graves’ disease
- Antithyroid drugs
- radioiodine / radiosodium (destroy thyroid gland)
- surgery to remove thyroid gland
Antithyroid drugs
- Block iodide uptake
- inhibit T4 synthesis
- inhibit T4 -> T3 conversion
Diagnosis for hyperthyroidism:
Normal TSH
Normal fT4
not thyrotoxicosis
Diagnosis for hyperthyroidism:
High / normal TSH
High fT4
Pituitary tumour
Thyroid hormone resistance syndrome
Diagnosis for hyperthyroidism:
Low TSH
Normal fT4
Normal fT3
subclinical thyrotoxicosis
Diagnosis for hyperthyroidism:
Low TSH
Normal fT4
High fT3
T3 toxicosis
Diagnosis for hyperthyroidism:
Low TSH
High fT4
T3 toxicosis
Primary thyrotoxicosis
thyrotoxicosis
hyperthyroidism
Why is glucose intolerance a symptom of hyperthyroidism?
Insulin is quickly cleared due to high metabolic rate
