Clin Path - Thyroid Function

Front 1

Thyroglobulin
-define

Back 1

-protein containing thyroid hormone precursors (thyroxine T4; triiodothyronine T3)

Front 2

Thyroglobulin
-produced where

Back 2

-follicular cells of thyroid glands

Front 3

Most potent form of thyroglobulin

Back 3

-T3

Front 4

Describe hormonal control of thyroglobulin

Back 4

-TRH released from hypothalamus
-stimulates TSH release from pituitary
-stimulation of production and release of T4 and T3 from thyroid glands
-most T4 & T4 protein bound in blood
-fT4 & fT3 can enter peripheral cells
-T4 in peripheral cells converted to T3 (more potent)
-fT3 and fT4 in blood cause negative feedback to TSH secretion

Front 5

How is most T3 & T4 in blood

Back 5

-protein bound

Front 6

Clinical assays for measuring Thyroid function

Back 6

-Total Thyroxine ---> [tT4] (most protein bound)
-Free Thyroxine --> [fT4]
-Thyroid Stimulating Hormone --> [TSH]
-Thyroglobulin Autoantibody --> TgAA

Front 7

Goals for Interpreting thyroid diagnostic assays

Back 7

-hyperthyroidism
-hypothyroidism
-thyroiditis
-sick euthyroidism

Front 8

[tT4] assay
-gold standard
-dogs
-cats

Back 8

-Radioimmunoassay (RIA)

-dogs: 95% values +1 to -2 ug/dL different from SNAP

-cats: positive proportional bias (higher SNAP)

Front 9

[tT4]
-common canine reference interval

Back 9

-1-4 ug/dL

Front 10

Hyperthyroxemia
-causes

Back 10

Increased production by thyroid neoplasm
-Thyroid adenoma (cats)
-Positive interference by T4AA (dogs)

Front 11

Hypothyroxemia
-causes

Back 11

Decreased T4 production:
-Primary hypothryroidism
-Secondary hypothyroidism

Multifactorial mechanisms:
-Nonthyroidal disease
-Drugs

Front 12

Nonthyroidal diseases that may cause hypothyroxemia

Back 12

-hyperadrenocorticism
-inflammatory disease

Front 13

Drugs that may cause hypothyroxemia

Back 13

-glucocorticoids
-phenobarbital
-sulfmethoxazole/trimethoprim
-phenylbutazone

Front 14

Primary Hypothyroidism
-common disease in what spp.

Back 14

-dogs

Front 15

Primary hypothyroidism
-presenting signs

Back 15

-weight gain
-lethargy
-alopecia

Front 16

Secondary hypothyroidism
-cause

Back 16

-TSH deficiency from pituitary gland malfunction or destruction

Front 17

Sick Euthyroid
-defintion

Back 17

-dec. [T4] but not due to hypothyroidism

Front 18

Sick Euthyroidism
-cause

Back 18

-dec. in protein bound T4
-fT4 at normal levels

Front 19

How to figure out equilibrium and protein bound portions of thyroxine

Back 19

Equilibrium Dialysis
-place in dialysis chamber with a membrane not permeable to proteins
-fT4 crosses through membrane until it reaches equilibrium
-use RIA to measure [fT4] from protein poor side of membrane
-calculate the original [fT4]

Front 20

What are the results of canine samples that are measured using human nondialysis assays for [T4]

Back 20

-falsely low
different RIs

Front 21

[fT4]
-gold standard assay

Back 21

-Equilibrium dialysis

Front 22

Do T4AAs interfere with the fT4 equilibrium dialysis assay?

Back 22

-no

Front 23

Reasons [fT4] may not mirror [tT4]

Back 23

-horse with clinical hyperthyroidism can have normal [tT4] but increased [fT4]ed

-sick euthyroid state in cats suggested by dec. [tT4] and inc. [fT4]ed

Front 24

T4AA interference with tT4 assay in dog
-results

Back 24

-dec. [fT4]ed
-normal [tT4]

Front 25

Nonthyroidal disorders that cause dec. [tT4] & dec. [fT4]ed

Back 25

-inhibited TSH secretion
-inhibited T4 production

Front 26

Reason for inc. [TSH]

Back 26

-Primary hypothyroidism --> dec. [tT4]

Front 27

Can dec. [TSH] be reliably measured?

Back 27

-no
-detection limit of assay

Front 28

Assay results to differentiate Primary hypothyroidism and Sick euthyroidism

Back 28

-Primary hypothyroidism: dec. [tT4] & inc. [TSH]

-Sick Euthyroidism: dec. [tT4] & dec. [TSH]

Front 29

Formation of TgAA

Back 29

-lymphocytic thyroiditis
--damaged cells release thyroglobulin
---reaction to foreign protein
----formation of TgAA

Front 30

Is there an inc. in TgAA when the thyroid glands are destroyed?
-why?

Back 30

-no

-thyroglobulin does not leave the thyroid and get detected by the immune system

Front 31

Hyperthyroid cat
-effect

Back 31

-Thyroid produces too much T4

Front 32

Hyperthyroid Cat
-causes

Back 32

-thyroid adenoma
-adenomatous thyroid hyperplasia

Front 33

T3 Suppression Test
-mechanism

Back 33

-Give T3
--suppress release of TSH
---dec. release of T4
----dec. [tT4] (in health)

Front 34

What is critical for an accurate T3 suppression test

Back 34

-owner compliance in giving the 7 doses of T3 over the course of 3.5 days

Front 35

Expected results for a T3 suppression test in a hyperthyroid cat
-why

Back 35

-no dec. [tT4] because T4 production continues despite T3 administration

Front 36

What should also be measured besides [tT4] in a T3 suppression test
-why

Back 36

-[tT3] to check owner compliance

Front 37

Solid Phase RIA
-key concept

Back 37

-lower bound *T4 --> higher [T4]

Front 38

Solid phase RIA
-effect of T4AA on results

Back 38

-falsely increased T4

-low measured *T4 from binding to T4AA