A12EAR Week 7
Dr Sue Chan
[email protected]
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)
