Thyroid function tests

1

THYROID FUNCTION
TESTS
Notes on Renal function tests. . By Dr. Ashish Jawarkar
Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

2

OVERVIEW
1.
2.
3.
4.
5.

6.

7.

8.
9.

Biosynthesis of thyroid hormones
Regulation thyroid hormone production
What happens to thyroid hormones after release
Concept of FT3 and FT4
Hypothyroidism
a. Causes
b. Clinical features
c. Laboratory features
Hyperthyroidism
a. causes
b. Clinical features
c. Laboratory features
Thyroid function tests in detail
a. TSH
b. Total T4 and Free T4
c. Total T3 and Free T3
d. TRH Stimulation test
e. Anti thyroid antibodies
f. RAIU test
g. Thyroid scintigraphy
Summary and result interpretation
Neonatal hypothyroidism screening


3

*Biosynthesis of thyroid hormones:-

Steps:
Iodide (I-) enters the thryroid cell via sodium iodide symporter
It enters the colloid through pendrin receptor
It is oxidized into Iodine (I0) by peroxidase enzyme
Then it is organified into MIT and DIT (mono and di iodo thyronine)
Then after coupling it forms T3 (Tri iodo thyronine) and T4 (Thyroxine)
T3 and T4 conjugate with TBG (thyroid binding globulin)
conjugated TBG is stored in colloid till required
While releasing into blood stream, it is first endocytosed into thyroid cell and then de coupled to form, T3 and T4 with MIT and DIT
9. MIT and DIT can be reutilized for coupling
10. T3 and T4 are released into the blood stream
1.
2.
3.
4.
5.
6.
7.
8.


4

*Regulation of thyroid hormone production


5

*What happens to thyroid hormones after release

Action of thyroid hormone on the body:


6

*Concept of FT3 and FT4
1. Out of the total T3 and T4 in circulation, most of it remains bound to thyroid binding
globulin *, thyroid binding prealbumina nd Thyroid binding albumin. (*note – this is not
thyroglobulin)
2. Only about 0.05% of each T3 and T4 remains free in circulation. This is FT3 and FT4.
3. These are better indicators for thyroid function than total T3 and Total T4.
(total=bound+free)
4. For example in pregnancy, level of thyroid binding globulin rises; hence though total T3
and total T4 remains same, level of FT3 and FT4 decreases.


7

*Hypothyroidism
Causes:
Primary Hypothyroidism
High TSH
In response to low T3 and T4
thyroid problem
1. Iodine deficiency
2. Goitrogens
3. Hashimoto’s
(antimicrosomal
antibodies)
4. Iatrogenic – surgery,
antithyroid drugs,
radiation
Exaggerated response to TSHRH stimulation

Secondary hypothyroidism
Low TSH with normal TSH-RH
i.e. pituitary problem
1. diseases of pituitary

No response to TSH-RH
stimulation

Tertiary hypothyroidism
LOW TSH, Low TSH-RH
i.e. hypothalamic problem
1. diseases of the
hypothalamus

Rise and Delayed response to
TSH-RH stimulation

Clinical Features:
1. Lethargy
2. Weight gain
3. Cold intolerance
4. Menstrual disturbances
5. Dry skin
6. myopathy
7. myxedema coma


8

Laboratory features:
Clinical Features of hypothyroidism

Measure TSH and FT4

High TSH
Low FT4

High TSH
Normal FT4

Low TSH

Primary hypothyroidism

Subclinical hypothyroidism

Sec or Tertiary
Hypothroidism

Check for antimicrosomal
Antibody

a/w
1. Bad obstetric outcome
2. hypercholesterolemia risk
3. Poor cognitive development
4. Risk of progression to overt
Hypothroidism

Increased

Normal

Little or no response

Hashimoto’s

iodine def
Congenital T4 synth def

Secondary
hypothyroidism

TRH Stimulatn
test
Check TSH
FT4

Delayed but
Present TSH
response

Tertiary
hypothyroidism


9

*Hyperthyroidism
Causes:
Primary hyperthyroidism
Low TSH, High T4

1. Grave’s disease
2. Toxicity in
multinodular goiter
3. toxicity in adenoma
4. subacute thyroiditis

Secondary Hyperthyroidism
High TSH, High T4
Pituitary/Paraneoplastic
syndrome
1. TSH secreting
pituitary adenoma
2. Trophoblastic tumors
that secrete TSH
(choriocarcinoma, H.
mole)

Factitious Hyperthyroidism

Clinical Features:
1. anxiety
2. insomnia
3. fine tremors
4. weight loss
5. heat intolerance
6. amenorrhoea and infertility
7. palpitations and tachycardia
8. cardiac arrythmias
9. muscle weakness
10. proximal myopathy
11. osteoporosis
Triad of Grave’s Ophthalmopathy
1. Hyperthyroidism
2. Ophthalmopathy
a. exophthalmos
b. lid retraction
c. lid lag
d. corneal ulceration
e. impaired eye muscle function
3. Pretibial myxedema (dermopathy)


10

Laboratory Features:
Clinical features of hyperthyroidism

Measure TSH and FT4

High FT4, Low TSH
Primary Hyperthyroidism

Normal FT4, Low TSH

Isotope thyroid scan

Measure FT3

Diffuse
Uptake

Grave’s

Nodular
Uptake

Irregular
uptake

Toxic
Toxic
Adenoma multinodular
Goiter

Normal

High FT4, High TSH
Secondary Hyperthyr

TRH test

High

Subclinical
T3 Thyrotoxicosis
Hyperthyroid

a/w
1. atrail fibrillation
2. osteoporosis
3. progression to overt
hyperthyroidism

Increased response
i.e. TRH – inc TSH – inc FT4

No response i.e
self controlled

Resistance to thyroid hormone

Pituitary
Adenoma/
Paraneoplastic


11

*Thyroid function tests in detail
Rider:
Thyroid levels can be affected by various non thyroidal diseases mentioned below. Hence
thyroid function tests should not be carried out during active diseases.
1. infections
2. liver diseases
3. malignancies
4. trauma
5. surgery
6. renal failure
7. cardiac failure


12

(a) Thyroid stimulating hormone (TSH)
Method: (Radioimmunoassay)(RIA)
The technique was introduced in 1960 by Berson and Yalow as an assay for the
concentration of insulin in plasma. It represented the first time that hormone levels in the blood
could be detected by an in vitro assay.

(known concentration of
I /I131 labelled TSH)
125

(anti TSH antibody)

(Known concentration of
unlabelled TSH)





A mixture is prepared of
o radioactive antigen
 Because of the ease with which iodine atoms can be introduced into
tyrosine residues in a protein (TSH here), the radioactive isotopes 125I or
131
I are often used.
o antibodies ("First" antibody) against that antigen.
Known amounts of unlabeled ("cold") antigen (known unlabelled TSH) are added to
samples of the mixture. These compete for the binding sites of the antibodies.


13









At increasing concentrations of unlabeled antigen, an increasing amount of radioactive
antigen is displaced from the antibody molecules.
The antibody-bound antigen (assay sample TSH) is separated from the free antigen
(radioactive TSH) in the supernatant fluid, and
the radioactivity of each is measured.
From these data, a standard binding curve, like this one shown in red, can be drawn.

The samples to be assayed (the unknowns) are run in parallel.
After determining the ratio of bound to free antigen ("cpm Bound/cpm Free") in each
unknown, the antigen concentrations can be read directly from the standard curve (as
shown above).

This method is used for assaying all thyroid function tests.
Normal levels:
Adults

Normal
Borderline
High
Low

0.5 to 5 mU/L
5 to 10 mU/L
>10 mU/L
<0.1 mU/L

Abnormal values:
Low TSH
1. primary hyperthyroidism
2. T3 thyrotoxicosis
3. Secondary and tertiary hypothyroidism

High TSH
1. Primary hypothyroidism
2. Secondary hyperthyroidism (pituitary
adenoma/paraneoplastic syndromes)


14

(b) Total T4 and Free T4
TSH combined with FT4 gives best assessment of thyroid function
Method: Competititve immunoassay
Principle same as for TSH
Free T4:
1. Free T4 constitutes around 0.05% of total T4
2. Levels co relate better with metabolic state than total, because free levels are not affected
by TBG levels –
TBG levels are affected in
a. pregnancy
b. OCP use
c. Nephrotic syndrome
Normals:
Total T4
Free T4

5-12 µg/dL
0.7-1.9 ng/dL

Abnormals:
Causes of increased T4 (Total)
1. Primary hyperthyroidism
2. Increased thyroid binding globulin
Decreased FT4

1.
2.
3.
4.

Causes of decreased T4 (total)
Secondary and tertiary hypothyroidism
Anti thyroid Drugs, estrogen, danazol
Decreased thyroid binding globulin

Increased TSH
Increased FT4
Increased T4
Decreased TSH
Normal FT4, Elevated total T4
Decreased T4
3. Factitious hyperthyroidism
4. Secondary hyperthyroidism (pituitary
adenoma/paraneoplastic syndromes)

Normal FT4, decreased total T4


15

(c) Total T3 and Free T3
For routine assessment, TSH and T4 are enough, T3 levels are very low compared to T4 hence may
not be used.
Method:
Same as for TSH
Free T3:
1. Free T3 constitutes around 0.5% of total T3
2. Levels co relate better with metabolic state than total, because free levels are not affected
by TBG levels –
TBG levels are affected in
a. pregnancy
b. OCP use
c. Nephrotic syndrome
Normals:
T3
Free T3

80-180 ng/dL
0.5% of T3 ie 2.3 to 4.2 pg/ml

Uses:
1. For early diagnosis of hyperthyroidism – in early stages T4 is normal but T3 is elevated
2. For measurement of T3 thyrotoxicosis


16

(d) TRH Stimulation test
Method:
Baseline sample collected for estimation of basal serum TSH levels

Inject TRH (200 to 500 mU/L)

Measure TSH at 20 & 60 mins
Uses:
1. Confirmation of secondary (pituitary/hypothalamic) hypothyroidism
2. suspected hyperthyroidism
Interpretation:
interpretation
normal

Small decline
-

Low

rise

elevated

rise

Further rise
(delayed)
-

elevated

Hyperthyroidism

20 min TSH
Rise of
>2mU/L
Further rise
No rise

60 min TSH
Small decline

Elevated
Low

Hypothyroidism

Baseline TSH
Normal

No rise

-

Secondary
hypothyroidism
(pituitary)
Hypothalamic
hypothyroidism
Thyroid hormone
resistance
Pituitary
adenoma/paraneoplastic


17

(v) Antithyroid antibodies
Antibodies used:
Anti microsomal antibody
Anti thyroid peroxidase antibody (anti TPO)
Anti TSH receptor antibody

Hashimoto
Grave’s

Uses:
For diagnosis and monitoring of autoimmune thyroid disorders


18

(vi) Radioactive Iodine Uptake (RAIU)
Principle:
Radioactive iodine uptake co relates with functional activity of thyroid gland
Method:
Patient is administered tracer dose of I123 or I131 orally
The I123 or I131 is taken up through Iodine symporters in follicular cells

Radioactivity over thyroid gland is measured at 2 to 6 hours and again at 24 hours

Normals:
RAIU @ 24 hrs

10-30%

Causes:
RAIU separates causes of hyperthyroidism into-

1.
2.
3.
4.

Increased uptake
Grave’s disease
Toxic multinodular goiter
Toxic adenoma
TSH secreting tumor

Decreased uptake
1. Cryptogenic hyperthyroidism
(exogenous hormone administration)
2. Subacute thyroiditis


19

(vii) Thyroid Scintigraphy
Method:
99m

Tc pertechnate is administered

A gamma counter is used to assess its distribution within the thyroid gland
Interpretation and uses:
1. EVALUATION OF CAUSES OF THYROTOXICOSIS WITH INCREASED RAIU

Uniform/diffuse uptake

Grave’s

multiple discrete areas uptake

Toxic multinodular goiter

single area of uptake

Adenoma

2. EVALUATION OF A SOLITARY THYROID NODULE

Hot nodule

Cold nodule

Hyperfunctioning

Non functioning
(20% malignant)


20

*summary and result interpretation
Sr. No.
1
2.
3
4
5

TSH
Normal
Low
High
High
Low

6

Low

7

Low

FT4
Normal
Low
Normal
Low
Normal with
normal ft3
Normal with
raised ft3
High

RESULT
Euthyroid
Secondary hypothyroidism
Subclinical hypothyroidism
Subclinical hyperthyroidism
T3 thyrotoxicosis
Primary hyperthyroidism


21

*Neonatal Hypothyroidism Screening
Rationale:
1. Thyroid hormone deficiency can cause cretinism that can be prevented by early detection
and treatment
Method:
Take dry blood spots on filter paper (3rd to 5th day of life) OR Cord serum

Test for TSH

If elevated, diagnostic of hypothyroidism
To confirm do I123 RAIU

Increased uptake

No uptake

Dyshormonogenesis

thyroid agenesis

Normals:
Neonatal TSH

<20 mU/L


Thyroid function tests

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Was ist angesagt?

Was ist angesagt? (20)

Ähnlich wie Thyroid function tests

Ähnlich wie Thyroid function tests (20)

Mehr von Ashish Jawarkar

Mehr von Ashish Jawarkar (20)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

Thyroid function tests