Thyroid func-on tests

Dr Jagadish R
11-05-2017
 Specific learning objec0ves
At the end of this lecture one should be able to

1. Explain the importance of pituitary gland and

hypothalamus in thyroid hormone synthesis

2. List the various disorders of thyroid gland and their

manifesta0ons

3. Enumerate the thyroid func0on tests and discuss their

interpreta0on
 Introduc0on
• Thyroid gland - is responsible for produc0on of:

① Thyroid hormones (Follicular cells)

② Calcitonin (Para-follicular or C cells) – minor

role in calcium metabolism

• Disorders of thyroid gland – hypofunc-on or

hyperfunc-on – primarily manifests with abnormality in
thyroid hormone levels
 Thyroid hormone synthesis
• Thyroid hormones – synthesized and stored in follicles

• Lumen of follicles – filled with colloid which contains a

protein called thyroglobulin

• Iodine and thyroglobulin are essen0al components

involved in thyroid hormone synthesis
Schema-c diagram showing steps involved in thyroid hormone
synthesis

Tyr Tyr

Iodine I- I- I- I- Tyr
Thyroglobulin

(I-) (I-) (I-) (Tg)

I- I- Tyr
Tyr

MIT
DIT
Thyroglobulin
DIT
Lysosome (Tg) DIT

T4 DIT MIT
T4
T3
T3
T4 T4
T4 T4
Thyroglobulin Thyroglobulin
T3 T3
(Tg) (Tg)
T4 T4

Tg Tg
(recycled)
 Major forms of thyroid hormones

T4 T3
20 %
80 %

Though T4 is major frac;on produced by thyroid gland, it gets converted to

T3 at the periphery
h"p://www.downsyndrometreatment.net/thyroid
Majority of T3 is derived from T4 by deiodina@on, catalyzed by
deiodinases

T4
Outer ring deiodina-on Inner ring deiodina-on

T3 rT3
T3 is metabolically ac-ve Reverse T3 is
metabolically inac-ve
Responsible for majority of
ac-ons of thyroid hormone at
cellular level
 Hypothalamo-pituitary thyroid axis
Hypothalamus

TRH
Anterior pituitary

TSH

Thyroid gland

h"p://drhayleenye.com
T3/T4
TRH- Thyrotrophin releasing hormone and TSH – Thyroid s0mula0ng hormone
 Thyroid hormones in circula@on

Protein Free form

bound form (i.e. unbound
form)

T4 – 99.96% T4 – 0.04%
T3 – 99.6% T3 – 0.4%

Binding proteins include

1. Thyroxine binding globulin (TBG)
2. Thyroxine binding prealbumin
(transthyre-n)
3. Albumin
 Free hormone vs. Bound hormone
Free hormones

Metabolically ac0ve (potency)

“Free T3 (FT3)” is metabolically ac-ve

Free hormone levels in circula0on - 0ghtly regulated

and maintained at “rela-vely constant levels”
 Total hormone = Free form+ Bound form

TBG é TBG ê

Total hormone é Total hormone ê

In both these situa-ons, free hormone levels remains constant

Bound hormone levels in circula0on tend to vary with levels
of binding proteins especially thyroxine binding globulin

TBG levels are

Increased in
• Pregnancy

Decreased in
• Liver dysfunc-on
• Nephro-c syndrome
Thyroid func0on tests
 Disorders of thyroid gland

Common clinical disorders associated with thyroid

hormones:
1. Hypothyroidism
2. Hyperthyroidism

Goiter – refers to enlargement of thyroid gland –

can be either with hypo- or hyperthyroidism
 Lab inves0ga0ons to assess thyroid
status
1.Measurement of thyroid s-mula-ng hormone (TSH)

2. Measurement of thyroid hormone levels

– Free T4
– Total T3
– Total T4

Rarely done: Free T3

 Measurement of serum TSH
Serum TSH is a sensi0ve indicator of thyroid dysfunc0on

It is the first test done to evaluate thyroid func0on

Serum TSH levels reveals the extent of nega0ve feedback by

thyroid hormones

“Small altera@ons in free T4 levels reflects large changes in

serum TSH levels”

Normal range of serum TSH: 0.6-5 mIU/L

 Measurement of thyroid hormones
• Es0ma0on of Free T4 levels aids in determining the
actual thyroid status

• Normal ranges:

Parameter Normal levels

Total T4 6-12 μg/dL
Free T4 0.8-2.7 ng/dL
Total T3 70-200 ng/dL
Free T3 200-400 pg/dL
Disorders of thyroid gland and their diagnosis
 Hypothyroidism
Primary hypothyroidism
1. Iodine deficiency

2. Auto-immune diseases – causing destruc0on of thyroid gland

3. Congenital hypothyroidism
Secondary hypothyroidism
1.Diseases of pituitary gland
• Trauma
• Tumor
• Infec0on
 Signs and symptoms - hypothyroidism

Hypothyroidism:
1. Cre-nism (children) 2. Myxedema (adults)
Primary hypothyroidism

Anterior pituitary

TSH é

Primary

Free T4 ê
h"p://drhayleenye.com

TSH – Thyroid s0mula0ng hormone

Secondary hypothyroidism

Anterior pituitary

TSH ê Secondary

Free T4 ê
h"p://drhayleenye.com

TSH – Thyroid s0mula0ng hormone

 Hyperthyroidism

Primary hyperthyroidism
1.Grave’s disease (thyrotoxicosis)
2.Thyroid cancers – producing func0onal thyroid hormones

3. Congenital hyperthyroidism
Secondary hyperthyroidism
1. Diseases of pituitary gland
• Tumor secre0ng TSH
Signs and symptoms of hyperthyroidism

mayoclinic.com/gravesdisease
Primary hyperthyroidism

Anterior pituitary

TSH ê

Primary

Free T4 é
h"p://drhayleenye.com

TSH – Thyroid s0mula0ng hormone

Secondary hyperthyroidism

Anterior pituitary

TSH é Secondary

Free T4 é
h"p://drhayleenye.com

TSH – Thyroid s0mula0ng hormone

 Interpreta-on of thyroid func-on tests

TSH High TSH low

Free T4 high Secondary Primary
hyperthyroidism hyperthyroidism
Free T4 low Primary Secondary
hypothyroidism hypothyroidism
 Other tests of thyroid func-on

1. Thyroid scin-graphy

2. Thyroid autoan-bodies
 Thyroid scin-graphy

• This is a scanning technique used to visualize and iden0fy

the func0onal thyroid 0ssue within the gland
• Done prior to surgery
• Techne0um (99mTc), a radioac0ve isotope is given
intravenously.
• This isotope will be taken up by the thyroid gland
• Then the images are obtained using a detector
Thyroid scin0graphy scans

Diffuse uptake
 Thyroid autoan-bodies
Disease An-bodies

Associated with An0- TSH receptor an0body

hyperthyroidism (ac0va0ng type)
Eg. Grave’s disease

Associated with An0-Thyroglobulin an0body

hypothyroidism (thyroglobulin)
 Summary
• Iodine, an essen0al trace element for thyroid
hormone synthesis

• Disorders of thyroid gland – hypofunc-on or

hyperfunc-on – primarily manifests with
abnormality in thyroid hormone levels

• Measurement of TSH, the primary test done to

evaluate thyroid dysfunc0on
• Primary disorders – indicates defect in thyroid
gland

• Secondary disorders – indicates defect in

pituitary gland

• Addi0onal inves0ga0ons include thyroid

scin0graphy and auto an0bodies
 References
Vasudevan’s Textbook of Biochemistry for Medical
Students, 8th edi0on, 2016, pages 621-647

Bishop’s Clinical chemistry : Techniques, principles,

correla0on, 8th Edi0on, pages 489-500

Williams Textbook of Endocrinology.,11th edi0on, Pages

327-350, Sec0on –III Thyroid