The document discusses hypothyroidism, its prevalence, causes, and symptoms, highlighting primary and secondary forms, such as autoimmune atrophic hypothyroidism and Hashimoto's thyroiditis, which are more common in women. It emphasizes the need for proper diagnosis and management, including the use of levothyroxine replacement therapy and considerations for special populations like children and the elderly. Screening for congenital hypothyroidism in newborns is crucial to prevent severe intellectual and neurological damage.

1. Hypothyroidism
Dr Waqar A Qureshi
Prof of Med

2. • Primary hypothyroidism
• Secondary hypothyroidism

3. prevalence
In UK
• over 2 % women
• Under 0.1 % men
Worldwide subclinical hypothyroidism
1 % - 10 %

4. Causes of primary hypothyroidism
• Autoimmune
Atrophic hypothyroidism
The most common cause of hypothyroidism and is associated
with antithyroid autoantibodies leading to lymphoid
infiltration of the gland and eventual atrophy and fibrosis. It is
six times more common in females and the incidence
increases with age. The condition is associated with other
autoimmune disease such as pernicious anaemia, vitiligo and
other endocrine deficiencies. Occasionally intermittent
hypothyroidism occurs with subsequent recovery; antibodies
which block the TSH receptor may sometimes be involved in
the aetiology.

5. Hashimoto's thyroiditis. This form of autoimmune
thyroiditis, again more common in women and most
common in late middle age, produces atrophic
changes with regeneration, leading to goitre
formation. The gland is usually firm and rubbery but
may range from soft to hard.

6. TPO antibodies are present, often
in very high titres (>1000 IU/L).
Patients may be hypothyroid or
euthyroid, though they may go
through an initial toxic phase,
'Hashi-toxicity'. Levothyroxine
therapy may shrink the goitre even
when the patient is not hypothyroid.

7. Postpartum thyroiditis. This is usually a
transient phenomenon observed following
pregnancy. It may cause hyperthyroidism,
hypothyroidism or the two sequentially. It is
believed to result from the modifications to the
immune system necessary in pregnancy, and
histologically is a lymphocytic thyroiditis. The
process is normally self-limiting, but when
conventional antibodies are found there is a high
chance of this proceeding to permanent
hypothyroidism. Postpartum thyroiditis may be
misdiagnosed as postnatal depression,
emphasizing the need for thyroid function tests in
this situation.

8. Defects of hormone synthesis
• Iodine deficiency. Dietary iodine deficiency exists in
some areas as 'endemic goitre'. The patients may be
euthyroid or hypothyroid depending on the severity
of iodine deficiency. The mechanism is thought to be
borderline hypothyroidism leading to TSH stimulation
and thyroid enlargement. Efforts to prevent
deficiency by providing iodine in salt continue
worldwide but often with incomplete success. Even
in the late 20th century of the 500 million with iodine
deficiency in India, about 2 million had cretinism (see
below).

9. Dyshormonogenesis. This rare
condition is due to genetic defects in
the synthesis of thyroid hormones;
patients develop hypothyroidism with
a goitre. One particular familial form
is associated with sensorineural
deafness due to a deletion mutation
in chromosome 7, causing a defect of
the transporter pendrin (Pendred's
syndrome).

10. Clinical features
‘Myxoedema' refers to the accumulation of
mucopolysaccharide in subcutaneous tissues.
The classic picture of the slow, dry-haired,
thick-skinned, deep-voiced patient with weight
gain, cold intolerance, bradycardia and
constipation makes the diagnosis easy. Milder
symptoms are, however, more common and
hard to distinguish from other causes of
nonspecific tiredness.

11. Special situations
• Children with hypothyroidism may not show classic
features but often have a slow growth velocity, poor
school performance and sometimes arrest of pubertal
development.
• Young women with hypothyroidism may not show
obvious signs. Hypothyroidism should be excluded in
all people with oligomenorrhoea/amenorrhoea,
menorrhagia, infertility or hyperprolactinaemia.
• The elderly show many clinical features that are
difficult to differentiate from normal ageing.

12. Investigations
In primary hypothyroidismSerum TSH is the
investigation of choice; a high TSH level
confirms primary hypothyroidism. A low
free T4 level confirms the hypothyroid
state (and is also essential to exclude TSH
deficiency if clinical hypothyroidism is
strongly suspected and TSH is normal or
low).

13. Investigations
• Thyroid and other organ-specific antibodies may be present.
• :Anaemia, usually normochromic and normocytic in type but may
be macrocytic (sometimes this is due to associated pernicious
anaemia) or microcytic (in women, due to menorrhagia)
• Increased serum aspartate transferase levels, from muscle and/or
liver
• Increased serum creatine kinase levels, with associated myopathy
• Hypercholesterolaemia and hypertriglyceridaemia
• Hyponatraemia due to an increase in ADH and impaired free
water clearance.

14. Treatment
• Replacement therapy with levothyroxine (thyroxine, i.e. T4) is given
for life.
• The usual starting dose is 100 μg daily for the young and fit, 50 μg
(increasing to 100 μg after 2-4 weeks) for the small, old or frail.
• People with ischaemic heart disease require even lower initial doses,
especially if the hypothyroidism is severe and longstanding. Most
physicians would then begin with 25 μg daily and perform serial ECGs,
increasing the dose at 3- to 4-week intervals.
• Occasional patients develop 'thyrotoxic' (hyperthyroid) symptoms
despite normal fT4 levels if dose is increased too rapidly.

15. Borderline hypothyroidism or 'compensated
euthyroidism
• 'Patients are frequently seen with low-normal serum T4 levels
and slightly raised TSH levels. Treatment with levothyroxine is
normally recommended where the TSH is consistently above
10 mU/L, or when possible symptoms, high-titre thyroid
antibodies, or lipid abnormalities are present.
• Where the TSH is only marginally raised, the tests should be
repeated 3-6 months later.
• Vague symptoms in people with marginally elevated TSH
(below 10 mU/L) rarely respond to treatment, but a
'therapeutic trial' of replacement may be needed to confirm
that symptoms are unrelated to the thyroid.

16. Myxoedema coma
• Severe hypothyroidism, especially in the elderly, may present with
confusion or even coma. Myxoedema coma is very rare: hypothermia is
often present and the patient may have severe cardiac failure, pericardial
effusions, hypoventilation, hypoglycaemia and hyponatraemia. The
mortality was previously at least 50% and patients require full intensive
care.
• Most physicians would advise T3 orally or intravenously in doses of 2.5-5
μg every 8 hours, then increasing as above. Large intravenous doses
should not be used. Additional measures, though unproven, should
include:Oxygen (by ventilation if necessary)
• Monitoring of cardiac output and pressures
• Gradual rewarming
• Hydrocortisone 100 mg i.v. 8-hourly
• Glucose infusion to prevent hypoglycaemia.

17. Screening for hypothyroidism
• The incidence of congenital hypothyroidism is approximately 1 in
3500 births. Untreated, severe hypothyroidism produces
permanent neurological and intellectual damage ('cretinism').
Routine screening of the newborn using a blood spot, as in the
Guthrie test, to detect a high TSH level as an indicator of primary
hypothyroidism is efficient and cost-effective; cretinism is
prevented if T4 is started within the first few months of life.
• Screening of elderly patients for thyroid dysfunction has a low
pick-up rate and is controversial and not currently recommended.
However, patients who have undergone thyroid surgery or
received radioiodine should have regular thyroid function tests, as
should those receiving lithium or amiodarone therapy.