Thyroid Flashcards
Describe the regulation of thyroid hormone production.
Hypothalamus > TRH --> Ant Pit > TSH --> Thyroid gland > T3/T4
T3/T4 inhibits secretion of TRH
T4 converted to T3 in liver
T3/T4 can be conjugated with glucuronide and sulfate in liver and excreted in the bile
What secretes TSH?
thyrotrope cells in the ant pit
Describe the structure of TSH
Glycoprotein with an alpha and beta subunit
Alpha subunit of TSH is identical to subunits for
hCG
LH
FSH
only variability is in glycosylation
What is unique to SH and determines its receptor specificity
beta subunit
what is the receptor for TSH
thyroid follicular cells
What are the steps in thyroid hormone biosynthesis?
NaCL symporter to absorb I-> Thyroglobulin secretion> exocytosis> Iodine gets oxidated> Iodination with TPO> conjugation> endocytosis> proteolysis to make tyroxine and triodothyronine> transported to blood
What percent of thyroid hormone is synthesized as T4 vs T3?
T4 90%
T3 9%
rT3 1 %
How is 80% of T3 made?
peripheral deiodination of T4
how is rT3 made?
periophaeral deiodination of T4
What % of T4 is bound to TBG/TTR/Alb?
TBG + T4 = 75%
T4-TTr = 10%
T4-albumine = 12%
What % of T3 is bound to TBG/TTR/Alb?
TBG + T3 = 80%
T3-TTr = 5%
T3-albumine = 15%
A 47 year old female presents to her primary care physician complaining of palpitations and diaphoresis.
What is the best test for screening for thyroid disease?
Thyrotropin(TSH) is the SINGLE BEST TEST for assessing thyroid function
– Very SMALL changes in free T4 induce large reciprocal changes in TSH
Why is it recommended to measure free T4, rather than total T4, total T3 or free T3 to initially assess active hormone levels?
• Measurement of T4 is preferred over T3 due to the excess of T4
– 100 times as much total T4 as total T3 – 10 times as much free T4 as free T3
• >99.9% of T4 is bound to protein and biologically inactive
– A variety of conditions can alter thyroid hormone‐ binding protein levels
– This causes changes in total T4 but free T4 remains the same
Is there a rationale for measuring total T3 or free T3? If you did want to measure T3 would it be preferable to order total or free T3?
In most cases of hyperthyroidism, patients have elevated T4 and T3, so free T4 measurement is sufficient
There are occasional patients who have T3 toxicosis:
– Low TSH, normal FT4, elevated free T3 and total T3
– Thought to represent early stages of hyperthyroidism or be due to an autonomous nodule
- If a patient appears hyperthyroid clinically, but FT4 is normal, consider assessing T3
Is total T3 preferred or FT3?
Total T3 is preferred over FT3, as assays for FT3 are less widely validated
However, if the patient has a known altered distribution of binding proteins that would affect total T3, free T3 should be measured instead
What are causes of hyperthyroidism with NORMAL or HIGH radioidodine uptake??
Graves Hashitoxicosis Toxic adenoma/toxic multinodular goiter Iodine induced Secondary to trophoblastic dz or GCT TSH producing pituitary adenoma
What are causes of hyperthyroidism with near ABSENT radioiodine uptake?
thyroiditis
exogenous hyperthyrodism
ectopic hyperthyroidism (struma ovarii, metatstic thryoid cancer)
What is the typical presentation of a
patient with hyperthyroidism?
Anxiety, emotional lability, tremor, palpitations, weakness, heat intolerance, diaphoresis, weight loss, hyperdefecation, urinary frequency, oligo‐ or amenorrhea
What features should one look for on physical exam to help with the differential diagnosis?
– Hyperactivity and rapid speech
– Lid retraction and lid lag from sympathetic hyperactivity
– Thyroid exam
– Look for evidence of Graves’:
• Exophthalmos (proptosis – forward displacement of eye)
• Periorbital/conjunctival edema
• Pretibial myxedema
What tests could be ordered next to determine the cause of hyperthyroidism?
- If patient has an enlarged thyroid, ophthalmopathy and severe hyperthyroidism, further evaluation is unnecessary (Graves)
- Thyroid uptake and scan
- Thyroid ultrasound
- Measurement of Graves’‐related autoantibodies
- Repeat TSH, free T4
What does the ATA/AACE recommend as the first line test if clinical presentation is not diagnostic of Graves?
Thyroid uptake
Thyroid scan can be added if nodularity