1. THE THYROID GLAND
HYPOTHYROIDISM

2. MEASUREMENT OF THYROID HORMONES
DIRECT METHODS
Circulating levels of total hormones
total thyroxine (TT4)
total triiodothyronine (TT3)
protein bound iodine (PBI)
Circulating levels of free hormones
free thyroxine (fT4)
free triiodothyronine (fT3)
Thyroid hormone binding proteins
Thyroxine binding globulin (TBG)
INDIRECT METHODS
Thyroid hormone binding tests
resin uptake of 125I-T3
Free thyroxine index (FTI)
FTI=
T4 x patient 125I-T3 resin uptake
Control 125I-T3 resin uptake

3. OTHER TESTS OF THYROID FUNCTION
Dynamic tests of thyroid activity
Thyroid uptake of 123I or 131I (and scan)
Thyroid uptake of 99mTc
T3 suppression test
TSH stmulation test
Tests of the thyroid-pituitary axis
Basal serum TSH
Serum TSH response to exogenous TRH
exaggerated response - hypothyroid
normal response - euthyroid
impaired response - hyperthyroid

4. HYPOTHYROIDISM
Hypothyroidism is a disease caused by a level of thyroid hormone insufficient for normal body function.
It affects every cell of human body.
An enlarged thyroid gland is the abnormality present in most cases.

5. Causes of hypothyroidism
PRIMARY
/thyroid gland/
Causes of hypothyroidism
SECONDARY
/pituitary/
TERTIARY
/hypothalamus/

6. Primary hypothyroidism
CONGENITAL
Athyreosis
Ectopic thyroid
Dyshormonogenesis
Iodide deficiency
Antithyroid immunity
(transient due to illness)
ACQUIRED
Iodine deficiency
Autoimmunity
Post-radioactive iodine therapy
Post-thyroidectomy
Antithyroid drugs
(e.g. Carbimazole)
Iodine excess
Subacute thyroiditis
Thyroid irradiation

7. Secondary hypothyroidism
pituitary tumours
pituitary granulomas (e.g. sarcoid) or injury
„empty sella” syndrome
Tertiary hypothyroidism
hypothalamic disorders (e.g. craniopharyngioma)
Isolated TRH deficiency

8. CAUSES OF HYPOTHYROIDISM
Iodine deficiency is the most common cause of goitre and bordeline hypothyroidism worldwide.
In noniodine-deficient areas autoimmunity is the common cause of hypothyroidism

9. EFFECTS OF IODINE DEFICIENCY EXCESS, ACUTE EXCESS, CHRONIC
Goitre, rarely hypothyroidism
EXCESS,
ACUTE
Temporary inhibition
of thyroid hormone synthesis
(Wolff-Chaikoff effect)
Induction of thyrotoxicosis
(Jod-Basedow phenomenon)
EXCESS,
CHRONIC
Goitre, hypothyroidism

10. IODINE DEFICIENCY REDUCTION OF DIETARY IODINE INTAKE
 thyroid hormone production
(preferential secretion of T3 rather than T4)
compensatory  TSH secretion

11. Urinary iodide excretion: Urinary iodide excretion:
IODINE DEFICIENCY
MODERATE
Urinary iodide excretion:
25 -50μ/g creatinine
Prevalence of goitre:
20 -50%
Hypothyroidism:
rarely
SEVERE
Urinary iodide excretion:
<25μ/g creatinine
Prevalence of goitre:
>50%
Hypothyroidism:
frequently

12. EXCESS OF IODINE
Acute increase in intracellular iodine concentrations 
Temporal inhibition of thyroid hormone synthesis and release
(Wolff-Chaikoff effect)
Decrease in intracellular iodine concentration
(escape from Wolff-Chaikoff effect)

13. EXCESS OF IODINE
Introduction of iodine therapy in areas of iodine deficiency 
Increase in the frequency of thyrotoxicosis
(Jod-Basedow phenomenon)
unmasking thyroid autonomy
(previously protected by iodine deficiency)

14. Permanent hypothyroidism No excape from Wolff-Chaikoff effect
EXCESS OF IODINE
Prolonged iodine ingestion in patients with autoimmune thyroiditis (Hashimoto’s disease) and in fetal and neonatal period (maternal ingestion of excess iodine) 
Permanent hypothyroidism
and goitre formation
No excape from Wolff-Chaikoff effect

15. CLINICAL PICTURE OF HYPOTHYROIDISM DEPENDS ON TIME OF THE ONSET OF DISEASE

16. CONGENITAL HYPOTHYROIDISM
The prevalence:
1 : ~4,000 live births
Usually no signs at birth
Untreated congenital hypothyroidism 
Non-reversible retardation of physical and mental development

17. Clinical features of congenital hypothyroidism
Delayed passage of meconium N
Constipation
Feeding problems
Prolonged icterus N
Hoarse, grunting cry
Goiter
Placidity, lethargy
Growth retardation and immature body proportions
Mental retardation
Typical face
Macroglossia
Enlarged posterior fontanelle (>0.5 cm) N
Hypotonia
Hypoactivity
Mottled skin
Cold extremities
Dry skin
Umbilical hernia (>0.5cm) N
N – symptoms only observed in the neonatal period
All signs are facultative and frequently are not seen in the neonatal phase.

18. CONGENITAL HYPOTHYROIDISM
May be detected biochemically by screening all neonates 3 – 5 days after birth.
T4 screening
TSH screening
Prematurity
Low TBG
Laboratory error
False positive
Laboratory error
Hypopituitarism
Laboratory error
Ectopic thyroid
Laboratory error
False negative

19. ACQUIRED HYPOTHYROIDISM
In noniodine-deficient areas 
primary hypothyroidism
women : men = 10 : 1
The prevalence in women of all ages:
2 - 4%
(one-third of this cases  iatrogenic hypothyroidism)

20. ACQUIRED HYPOTHYROIDISM
CLINICAL FEATURES IN HYPOTHYROIDISM
The symptoms of hypothyroidism are nonspecific and may be attributed by both patient and doctor to ageing, the onset usually being insidious.

21. Symptoms of hypothyroidism
USUAL
Lethargy
Increased sleep
Constipation
Mild weight gain
Cold intolerance
Facial puffiness
Dry skin
Hair loss
Hoarsensess
Abnormal menses
Acroparaesthesiae
Snoring
RARE
Deafness
Psychosis
Cerebellar disturbance
Myotonia

22. SIGNS OF HYPOTHYROIDISM
Change in appearance (e.g. face puffy and pale)
Periorbital oedema
Dry, flaking, cool, pasty skin
Diffuse hair loss
Bradycardia
Signs of median nerve compression
(carpal tunnel syndrome)
Effusions in body cavities
(e.g. ascites, pericardial effusion)
Delayed relaxation of reflexes
Croaky voice
Goitre
Rarely stupor or coma

23. MYXOEDEMA
Myxoedema is a severe form of hypothyroidism causing complete exhaustion of all bodily functions.
All the organs are infiltrated with mucopolysaccharides that interfere with proper cell metabolism.
Myxoedema patients have all the symptoms and signs described for hypothyroidism, as well as low brain center reserve, low cardiac reserve, low respiratory reserve, low adrenal reserve, and low thermoregulatory reserve. In addition, they may show hyponatremia, hypercapnia, hypoxia, and anemia.

24. HYPOTHYROIDISM- DIAGNOSTIC PROCEDURES
TSH level
(second or third generation assays = the lower detection limit: mU/l)
FT4 level
(the measurement of T3 is not a good diagnostic test for hypothyroidism)
TSH response to exogenous TRH
(secondary and tertiary hypothyroidism; subclinical hypothyroidism)

25. Hypothyroidism- summary of diagnostic tests
Primary
Hypothyroidism
Secondary
Tertiary
Non-thyroid
illness T4
low
Basal
TSH
raised
low or normal
low, normal
or elevated
normal or low
TRH
response
exaggerated
reduced
or absent
sluggish
or delayed
normal or low

26. Subclinical hypothyroidism (diminished thyroid reserve)
Serum T4 : normal (lower half of the normal range)
Serum T3: normal or sometimes even slightly elevated
Basal TSH: slightly raised
TSH/TRH: exaggerated
Definition: „subclinical”  no symptoms and signs (?)
Patients with subclinical hypothyroidism are at increased risk for coronary heart disease
HOWEVER

27. IMAGING STUDIES  Rapidly growing large goiter;
Goiter with a dominant nodule;
Hashimoto’s disease 
ultrasonography examination and fine needle aspiration biopsy

28. Cardiac function shoud be assessed before treatment is started.
IMAGING STUDIES
Cardiac function shoud be assessed before treatment is started.
The presence of other associated autoimmune endocrinopathies must be ascertained.

29. HYPOTHYROIDISM – TREATMENT
Hypothyroidismis treated with replacement T4 therapy (sodium L-thyroxine)
Replacement doses usually start at 50 μg/d being increased in a stepwise fashion at monthly intervals to μg/d as the response is assessed clinically and biochemically.

30. HYPOTHYROIDISM – TREATMENT
There is considerable variation in patient response to T4 because of differential thyroid hormone receptor isoform tissue concentration.

31. HYPOTHYROIDISM – TREATMENT
During T4 therapy:
Serum T3 concentration must be in the normal range, as should that of TSH
Serum T4 may exceed the upper limit of normal.

32. HYPOTHYROIDISM – TREATMENT
During T4 therapy:
Clinically satisfactory response:
normal pulse rate
and complete resolution of presenting symptoms and signs.
Occasionally cardiac symptoms such as palpitations may occur; in this case a β-adrenergic blocker drug is indicated.

33. HYPOTHYROIDISM – TREATMENT
In patients with ischemic heart disease:
Replacement therapy should be introduced cautiously, with started doses of 25μg/d; increments should also be small.

34. Protocol for the management of myxoedema coma
Take blood for diagnostic tests: T4, TSH and plasma cortisol
Give 300 μg T4 i.v. and repeat approximately 100 μg q.d; give via nasogastric tube if i.v. preparation is unaviable
Treat hypothermia with gradual rewarming using blankets
Give i.m. hydrocortisone 75 mg immediately and repeat mg 8-hourly
Give T3 20 μg i.v., i.m. or by nasogastric tube 12-hourly, if possible
Treat any heart failure with diuretics
Correct any electrolyte disturbances
Carefully exclude or treat infection
Use sedative drugs and fluids sparingly
Measure serum T4, T3 and TSH frequently