Thyroid Glands

Graves' Disease
A disorder with 3 major manifestations :

1. Hyperthyroidism
with diffuse
goiter
2. Opthalmopathy
3. Dermopathy
Acropachy

THYROID CRISIS
Life threatening clinical extreme of
hyperthyroidism
Female > Male
Mortality 10-20% with treatment
FT3 and FT4 correlate poorly with severity
of condition: condition is essentially an
inability of end-organs to modulate their
response to excess thyroid hormone
Aetiology
Usually occurs in patients with poorly
controlled-unrecognized hyperthyroidism
Precipitated by intercurrent illness : infection,
trauma, surgery, uncontrolled DM, labour,
eclampsia
Other precipitants include excessive palpation of
thyroid, incomplete pre-op preparation,
inadequate peri-operative dose of beta blockers,
use of radio-iodine in unprepared patients, drugs
such as iodides in patients with impaired
autoregulation, haloperidol, massive overdose of
thyroid hormone
Clinical features
Exacerbation of features of hyperthyroidism

The classic clinical presentation: fever, tachycardia, tremor,
nausea+vomiting, diarrhea, dehydration, delirium, coma

Hyperpyrexia. May be extreme (>41
o
C) and is
generally considered essential to diagnosis.
Confusion, coma, muscle weakness.
Arrhythmias, cardiac failure. Decreasing pulse rate
and BP with the development of shock are
associated with poor prognosis
Vomiting, diarrhoea. Occasionally jaundice:
associated with poor prognosis
Apathetic hyperthyroidism (elderly patients) may
present in crisis with features of profound
exhaustion, tachycardia, hyporeflexia, severe
myopathy, marked weight loss and hypotension

Differential diagnosis
1. Malignant hyperpyrexia
2. Sepsis

TREATMENT
1. Treat underlying cause
2. Decrease thyroid hormone
concentrations
3. Reduce peripheral action of thyroid
hormones
4. Supportive therapy
1. Iodide (I-)
trapping
2. Diffusion of
iodide
3. Transport of
iodide
4. Oxidation
inorganic
iodide
5. Combination
DIT
6. Uptake of
thyroglobulin
7. Release T4 -
T3
8. Deiodination
of DIT&MIT



X
Treatment to reduce thyroid hormone concentrations
1. Iodine: in large doses inhibits release of thyroid
hormones. Generally given > 1 h after
PTU/carbimazole/methimazole, - it may lead to
an increase in thyroid hormone synthesis.
Use Lugol's iodine (16 mg bd PO), potassium
iodide (50 mg bd PO) or sodium iodide (0.5 mg
bd IV).
Lithium carbonate (300 mg qds titrated to a serum
lithium level of 0.7-1.4 mmol/l) is an alternative
in patients who are allergic to iodine.
Inorganic Iodide

To decrease T3 & T4 synthesis
Inhibiting iodide transport, oxidation and
organification (Wolff-Chaikoff effect)
To block the release of T3 & T4 from thyroid
Rapid decrease in thyroid hormone levels
Preoperatively when other medications are
ineffective or contraindicated
During pregnancy when antithyroid drugs are
not tolerated
With antithyroid drugs to treat amiodarone-
(Cordarone-) induced hyperthyroidism


X
X
X
X
X
Treatment to reduce thyroid hormone concentrations
2. Propylthiouracil (inhibits conversion of T4 to T3
as well as blocking iodination of tyrosine and
hence secretion of T4). PO/NG 1 g loading
followed by 200-300 mg 4-6 hrly.
Rapid onset of action.
Alternatives are methimazole and carbimazole
Methimazole may be absorbed more slowly
than PTU but is longer acting. Does not affect
peripheral conversion of T4.
P T U & M M I
A c t i o n
1. Intrathyroidal
a. Inhibition of iodine oxidation & organification
b. Inhibition of iodotyrosine coupling
c. Possible alteration of structure of thyroglobulin
d. Possible inhibition of thyroglobulin
biosynthesis
2. Extrathyroidal : inhibition of conversion of T4 to
T3 (only by PTU)
3. On the immune system


X
X
X
X
X
Treatment to reduce peripheral action of thyroid
hormones
Beta blockade: IV propranolol - 0.5 mg to a total
of 10 mg. Give further doses 4-6 hrly.
Drug of choice: inhibits peripheral conversion of
T4 to T3.
Beta1 selective agents do not inhibit T4 to T3
conversion as effectively but may be preferred
in patients with reactive airways or heart failure.
Diltiazem, reserpine and guanethidine should be
considered in patients in whom beta blockade is
contraindicated
Supportive therapy
1. Glucose for nutrition.
2. Steroids: hydrocortisone 300 mg loading followed
by 100 mg tds. Relative hypoadrenalism occurs as a
result of increased metabolism of corticosteroids
3. Sedation
4. NG suction
5. Vitamins (especially thiamine).
6. Active cooling. Chlorpromazine 25-50 mg 4-6 hrly
to prevent shivering
7. Fluid replacement. Patients tend to be fluid
depleted because of increased insensible loss,
diarrhoea and vomiting and decreased ADH
secretion
Supportive therapy
Cooling should be attempted before specific
therapy is given for congestive cardiac failure.
However judicious use of inotropes and
diuretics may be necessary
Clearance of many drugs is increased and a
shortening of dose intervals may be necessary.
(Dose intervals will have to be increased again
once thyroid storm is controlled).
Avoid salicylates and frusemide both of which
cause abrupt increases in free thyroid
hormones

MYXEDEMA COMA
Is the ultimate stage of severe long-
standing hypothyroidsm, is an uncommon
but potentially lethal condition.
Physical Findings in Myxedema Coma
1. Altered mentation
2. Alopecia
3. Bladder dystonia &
distention
4. Cardiovascular
1. Elevated diastolic blood
pressure--early
2. Hypotension--late
3. Bradycardia
5. Delayed reflex relaxation
6. Dry, cool, doughy skin
7. Gastrointestinal
Decreased motility
Abdominal distension
Paralytic ileus
Fecal impaction
Myxedema megacolon-late
8. Hyperventilation
9. Hypothermia
10.Myxedematous face
Generalized swelling
Macroglossia
Ptosis
Periorbital edema
Coarse, sparse hair
11.Nonpitting edema


MYXEDEMA COMA
Often demonstrate classic symptoms of
hypothyroidism:
1. fatigue
2. constipation
3. weight gain
4. cold intolerance
5. a deep voice
6. coarse hair
7. dry, pale, cool skin.
Laboratory Abnormalities
in Myxedema Coma
Anemia
Elevated CPK
Elevated creatinine
Elevated transaminases
Hypercapnia
Hyperlipidemia
Hypoglycemia
Hyponatremia
Hypoxia
Leukopenia
Respiratory acidosis
MYXEDEMA COMA
Admitted to the intensive care unit,
hypovolemia and electrolyte abnormalities
corrected.
Mechanical ventilation may be necessary.
Patients with hypothermia should be covered
with regular blankets; the use of warming
blankets should be avoided because the
resulting peripheral dilatation may lead to
hypotension and cardiovascular collapse.

MYXEDEMA COMA
Cardiovascular status should be monitored
carefully, especially after intravenous
thyroid hormone replacement.
Myocardial infarction must be ruled out
and blood pressure stabilized.
If possible, pressors and ionotropes should
be avoided because of their tendency to
provoke arrhythmias in the setting of
intravenous thyroid replacement.

MYXEDEMA COMA
An initial levothyroxine dose of 100 to 500 g
administered intravenously should be followed by
75 to 100 g administered intravenously daily until
the patient is able to take oral replacement.
The lower initial dose should be administered to
patients who are frail or have other comorbidities,
particularly cardiovascular disease.
Elderly patients typically require 100 to 170 g of
oral levothyroxine daily.
MYXEDEMA COMA
Antibiotics
Infection is often the cause of the
patient's decompensation
An infectious etiology should be
sought with blood & urine cultures as
well as a chest radiograph.
Some authorities advocate empiric
therapy with broad-spectrum
intravenous antibiotics.

MYXEDEMA COMA
Steroids
Because of the possibility of secondary
hypothyroidism and associated
hypopituitarism, hydrocortisone should be
administered until adrenal insufficiency
has been ruled out.
Hydrocortisone should be administered
intravenously at a dosage of 100 mg every
8 hours.
Failure to treat with hydrocortisone in the
face of adrenal insufficiency may result in
the precipitation of adrenal crisis.
MYXEDEMA COMA
Factors associated with a poor prognosis in
patients with myxedema coma:
advanced age
bradycardia
persistent hypothermia.