A12EAR Week 7

Dr Sue Chan
sue.chan@nottingham.ac.uk

Thyroid function & disorders

Thyroid hormones
• synthesis, regulation, action
• Disorders & treatment – goals and
management
 Learning objectives
After this lecture, you will be able to:
• Name the major classes of thyroid disease, explaining briefly what is
meant by autoimmune disease further examples of autoimmune
endocrine disorders will be described in later lectures
• State the main causes, signs and symptoms of hyperthyroidism and
hypothyroidism, and how these thyroid disease conditions can be
treated
• Hypothyroidism
- under-activity

• Hyperthyroidism (thyrotoxicosis)
- over-activity
 Types of thyroid dysfunctions
Thyroid dysfunction Cause Plasma [ ] of hormones Goitre
present?

Hypothyroidism Primary failure of thyroid gland T3 and T4, TSH Yes
(Hashimoto’s thyroiditis ~ 90% of all
hypothyroidism)

Secondary to hypothalamic or ant.

T3 and T4, TSH No
pituitary failure

Lack of dietary iodine (simple non-toxic

goitre) T3 and T4, TSH Yes

Drug-induced (e.g. anti-thyroid drugs,

lithium, amiodarone)
Radioactive iodine therapy, surgery
Thyroid hormone resistance

Hyperthyroidism Abnormal levels of thyroid-stimulating T3 and T4, TSH Yes

immunoglobulins (Graves’ disease)

Secondary to excess hypothalamic or ant. T3 and T4, TSH Yes

pituitary secretion

Hyper-secreting thyroid tumour T3 and T4, TSH Yes

(Toxic multinodular goitre, toxic adenoma)

Iatrogenic causes (e.g. amiodarone,

lithium)
 Goitre – enlarged thyroid gland
 is a non-specific term for any enlargement of the thyroid gland

 may be diffuse OR nodular

- Occur when there is over-stimulation - a discrete area that is clearly different
of the thyroid gland by either TSH from surrounding thyroid gland
or TSI (Graves’ Disease) e.g. a thyroid tumour
 Hypth
Types of thyroid dysfunctions: TRH

Hypothyroidism Ant. pit

TSH
Autoimmune disease thyroid
- arise from an overactive immune response against
T3/ T4
substances / tissues normally present in the body
Thyroid Cause Plasma [ ] of hormones Goitre
dysfunction present?
Hypothyroidism Primary failure of thyroid gland T3 and T4, TSH Yes
(Hashimoto’s thyroiditis ~ 90% of
all hypothyroidism)

Secondary to hypothalamic or T3 and T4, TSH No

ant. pituitary failure

Lack of dietary iodine (simple T3 and T4, TSH Yes

non-toxic goitre)

Drug-induced (e.g. anti-thyroid drugs,

lithium, amiodarone)
Radioactive iodine therapy, surgery
Thyroid hormone resistance
 Hypothyroidism

• Signs & symptoms

o Weight gain MYXOEDEMA - puffy appearance,
o Dry skin part. face, hands and feet
o Hoarse voice, slow speech
o Menstrual changes
o Cold intolerance-once BMR slowed down= cold
o Constipation
o Lowered HR/ BP
o Depression, confusion, poor memory

Reduction in BMR & overall metabolic activity

Facial myxoedema – round, “moon-like”
• Puffy, pale, oedematous eye-lids
• Skin is thickened and dry

Patient 1 Patient 2
 Hypothyroidism

• Signs & symptoms

o Weight gain MYXOEDEMA - puffy appearance,
o Dry skin part. face, hands and feet
o Hoarse voice, slow speech
CRETINISM (neonate)
o Menstrual changes – dwarfism & mental retardation
o Cold intolerance • Every newborn is tested for TSH & T4
o Constipation
o Lowered HR/ BP
o Depression, confusion, poor memory

Reduction in BMR, overall metabolic activity

• Diagnosis: Thyroid function test
 Primary T3 and T4, TSH
 Secondary (hypo. or pit. disease) T3 and T4, TSH

 If suspect Hashimoto’s, test for thyroid antibodies

– anti-microsomal (TPO), anti-thyroglobulin antibodies
(approximately 10-15% may be antibody-negative)

• Goal: Euthyroid state

• Management: synthetic thyroid hormones

- Levo-thyroxine (T4) – treatment of choice
- Liothyronine (T3)
Levo-thyroxine (T4)

• Drug of choice
• Orally active, once a day (long t1/2)

Caution: May worsen or uncover angina

If angina, b-blocker may be prescribed

Baseline ECG with initial dosage

Liothyronine (T3)

• Max. effect 24h, disappear 24 - 48h

• Not used routinely, rapid onset can induce heart
failure

• Used in severe hypothyroid states when

rapid response is desired (i.v.)
 Hypth
Types of thyroid dysfunctions: TRH
Ant. pit
Hyperthyroidism TSH
(thyrotoxicosis) thyroid
T3/ T4

Thyroid Cause Plasma [ ] of hormones Goitre

dysfunction present?
Hyperthyroidism Abnormal levels of thyroid- T3 and T4, TSH Yes
stimulating immunoglobulins
(Graves’ disease)

Secondary to excess hypothalamic T3 and T4,  TSH Yes

or ant. pituitary secretion

Hyper-secreting thyroid tumour

T3 and T4, TSH Yes
(Toxic multinodular goitre, toxic
adenoma)

Iatrogenic causes (e.g. amiodarone,

lithium)
 Most common cause of hyperthyroidism =
Graves’ disease
• Accounts for 70-80% of all cases

• Autoimmune; Thyroid Stimulating Immunoglobulins (TSI) activate

t the thyroid gland to produce and release thyroid hormones
 _ _
hypothalamus

TRH Thyrotropin-releasing hormone

_ +
Anterior pituitary

TSH Thyroid-stimulating hormone

(thyrotropin)
Long feedback loop
+
Thyroid gland

T3/ T4
Regulation of thyroid
hormone secretion
Target cell response
 _ Role of thyroid-stimulating
hypothalamus
immunoglobulin (TSI) in
Graves’ disease
↓ TRH
_ +
Anterior pituitary

Thyroid-stimulating
↓ TSH Immunoglobulins (TSI)
Long feedback loop
+ + TSI bind to TSH receptors on
Thyroid gland thyroid gland, stimulating thyroid
hormone production/ release

↑ T3/ T4
Goitre
Hyperthyroidism
Target cell response
 Most common cause of hyperthyroidism =
Graves’ disease
• Accounts for 70-80% of cases

• Autoimmune; Thyroid Stimulating Immunoglobulins (TSI) activate

the thyroid gland to produce and release thyroid hormones

• Classic signs & symptoms: weight loss, sweating, heat intolerance,

palpitations, tremor, nervousness. Also, goitre and exophthalmos
(30%)
 Hyperthyroidism
• Signs & symptoms
o Weight loss
o Sweating
o Heat intolerance
o Diarrhoea
o Palpitations
o Tremor
o Anxiety, emotional, irritable
o Restlessness

 Increased cellular/ tissue metabolism due to

excessive thyroid hormone action

 Also, enhancement of b-adrenoceptor responses

• Diagnosis: Thyroid function test
 Primary  T3 and T4, TSH
 Secondary (hypo or pit. disease)  T3 and T4,  TSH

 If suspect Graves’ disease, test for thyroid-stimulating antibodies

 Perform thyroid uptake test (123I) for thyroid tumour(s)

1= fall in TSH as activate negative feedback loop

2= elevation in TSH that causes T3 and T4 to rise!!!

Thyroid uptake test- uptake of iodine by Na/I simporter

 Long exposure times

Two examples
of normal
thyroid scans

Graves' disease Multinodular goitre

(toxic diffuse goitre)
Shorter exposure times
• Diagnosis: Thyroid function test
 Primary  T3 and T4, TSH
 Secondary (hypo or pit. disease)  T3 and T4,  TSH

 If suspect Graves’ disease, test for thyroid-stimulating antibodies

 Perform thyroid uptake test (123I) for thyroid tumour(s)

• Goal: Euthyroid state & symptomatic relief

from increased sympathetic activity

• Management:
- Anti-thyroid drugs
- Radioiodine (131I)
- Surgery
 Pharmacological basis of management
Anti-thyroid drugs (thionamides)
– Carbimazole & propylthiouracil (PTU)
• Decrease production of thyroid hormones, by inhibiting iodination
and coupling processes (via TPO)

• Thyroid hormones have long plasma t½ (~ 1 week)

• Several weeks for clinical response to occur (colloid stores)

• Usually for 12 – 18 months, but ~50% relapse rate

 Pharmacological basis of management
Anti-thyroid drugs (thionamides)
– Carbimazole & propylthiouracil (PTU)
• Decrease production of thyroid hormones, by inhibiting iodination
and coupling processes (via TPO). PTU
also block T4 to T3 deiodination.

• Several weeks for clinical response to occur (colloid stores)

• Usually for 12 – 18 months, but ~50% relapse rate

If sensitivity to carbimazole,
Carbimazole, drug of choice BUT: use propylthiouracil
• Rashes & pruritus are common (2-25%)
• RARE complication (0.1-1.2%) – neutropenia and agranulocytosis
(bone marrow suppression). Reversible
 Pharmacological basis of management
Anti-thyroid drugs (thionamides)
– Carbimazole & propylthiouracil (PTU)
• Decrease production of thyroid hormones, by inhibiting iodination
and coupling processes (via TPO). PTU
also block T4 to T3 deiodination.

• Several weeks for clinical response to occur (colloid stores)

• Usually for 12 – 18 months, but ~50% relapse rate

Non-selective b-blockers
• Reduce actions of catecholamines  rapid
symptomatic relief of tremor, palpitations, anxiety
(within 4 days)
 Two approaches used with
anti-thyroid drugs
“dose titration”
- where only anti-thyroid drugs are used
- doses are adjusted to achieve normalisation of
thyroid hormone production

“block and replace”

- where anti-thyroid drugs are given with thyroxine
replacement

• both types of methods are equally effective

• dose titration method associated with a lower rate
of side-effects –less risky but slower…
 Radioactive iodine 131I

• First-line for older patients with nodular goitres

and hyperthyroidism

• Used when thyrotoxicosis recurs after anti-

thyroid drug therapy

• Given as single drink or capsule

Max effect 2-4 months after

Hypothyroidism may result

 Thyroidectomy

• Not frequently used

• Used when severe thyrotoxicosis associated

with a large goitre or concern about tumour
development

• Also, when there are obstructive symptoms

Hypothyroidism may result

 Useful websites and its links

http://www.btf-thyroid.org/

http://www.british-thyroid-association.org/
 Summary
• Thyroid hormones – primary determinant of overall metabolic
rate of the body. Also essential for normal growth, as well as
development & function of CNS
• Abnormalities of thyroid function include hypothyroidism and
hyperthyroidism
• A goitre (enlarged thyroid gland) develops when the thyroid
gland is over-stimulated (or tumour)
(elevated TSH, or presence of TSI in Graves’ disease).
• Hypothyroidism – hormone replacement
• Hyperthyroidism – anti-thyroid drugs, surgery or 131I
(b-blockers for symptomatic relief)