2. SLOS
SLO#1: Briefly describe the physiology of thyroid hormone synthesis and actions.
SLO#2: List the causes of hypothyroidism.
SLO#3: List the investigations to be done in a case of suspected thyroid disease and
how to interpret them.
SLO#4: Briefly describe Hashimoto’s thyroiditis, sick euthyroidism, subclinical
hypothyroidism, subclinical hyperthyroidism., thyrotoxic crisis, and myxedema coma.
SLO#5: Describe briefly the management of hypothyroidism, thyrotoxic crises, and
myxedema coma.
3. CASE
Khadeeja Nasser, a 35-year-old schoolteacher presented to the endocrinology clinic with a
complaint of persistent fatigue, unexplained weight gain, cold intolerance, and dry skin.
She reported that these symptoms had been progressively worsening over the past six months.
Additionally, she mentioned experiencing constipation and irregular menstrual periods.
Khadeeja expressed concern about her inability to lose weight despite dietary modifications and
regular exercise, which had previously been effective for her.
Khadeeja had no history of any illnesses or surgeries in the past. She had no family history of
thyroid disorders or autoimmune diseases. Her only medication at the time was an oral
contraceptive for birth control, which she had been taking for several years.
On examination, Khadeeja appeared tired and reported feeling fatigued throughout the day. Mild
puffiness was noted on her face. Her pulse was 58/min, and her BP was 130/84 mmHg. Her skin
was dry and her nails brittle. Her hair was thin. There was no palpable goiter or nodules in the
thyroid gland. Heart and lung sounds were heard normally. Her deep tendon reflexes were
sluggish.
6. The parafollicular C cells secrete calcitonin, which is of no apparent physiological significance in
humans.
The follicular epithelial cells synthesise thyroid hormones by incorporating iodine into the amino acid
tyrosine on the surface of thyroglobulin (Tg).
a protein secreted into the colloid of the follicle.
Iodide is a key substrate for thyroid hormone synthesis; a dietary intake in excess of 100 µg/day is
required to maintain thyroid function in adults.
The thyroid secretes predominantly thyroxine (T4) and only a small amount of triiodothyronine (T3).
approximately 85% ofT3 in blood is produced fromT4 by a family of monodeiodinase enzymes which
are active in many tissues, including liver, muscle, heart and kidney.
T4 can be regarded as a pro-hormone, since it has a longer half-life in blood thanT3 (approximately 1
week compared with approximately 18 hours), and binds and activates thyroid hormone receptors
less effectively thanT3.T4 can also be converted to the inactive metabolite, reverseT3.
THYROID PHYSIOLOGY
7. T3 andT4 circulate in plasma almost entirely (> 99%) bound to transport
proteins, mainly thyroxine-binding globulin (TBG).
Production ofT3 andT4 in the thyroid is stimulated by (thyroid-
stimulating hormone,TSH),
TSH released from the anterior pituitary in response to the
hypothalamic tripeptide, thyrotrophin-releasing hormone (TRH).
There is a negative feedback of thyroid hormones on the hypothalamus
and pituitary such that in thyrotoxicosis, when plasma concentrations of
T3 andT4 are raised,TSH secretion is suppressed. Conversely, in
hypothyroidism due to disease of the thyroid gland, lowT3 andT4 are
associated with high circulatingTSH levels.
THYROID PHYSIOLOGY
8. HYPOTHYROIDISM
Definition: It is when the thyroid gland doesn’t
make enough thyroid hormone to meet the body
demands.
Causes:
1) Autoimmune disease ( Hashimoto’s thyroiditis )
2) Thyroid failure following 131I
3) Surgical treatment of thyrotoxicosis
4) Iodine deficiency
9. Common:
less Common:
Rare:
Clinical feature:
- The clinical presentation depends on the duration and severity of the
hypothyroidism.
- Due to prolonged hypothyroidism :
infiltration of many body tissues by mucopolysaccharides, hyaluronic
acid and chondroitin sulphate, resulting in:
a low-pitched voice
poor hearing
slurred speech due to a large tongue
compression of the median nerve at the wrist (carpal
tunnel syndrome)
Infiltration of the dermis gives rise to:
nonpitting oedema (myxoedema) in the skin of the hands,
feet and eyelids
facial pallor due to vasoconstriction and anaemia,
lemon-yellow tint to the skin caused by carotenaemia,
purplish lips and malar flush
10. Investigation:
1. Primary hypothyroidism:T4 is low &TSH is elevated
2. Secondary hypothyroidism (rare):T4 & TSH are low.
3. Thyroid peroxidase antibodies
4. ECG : shows sinus bradycardia with low voltage complexes and ST segment andT wave abnormalities
Management:
levothyroxine replacement:
start with a low dose of 50 µg per day for 3 weeks, increasing thereafter to 100 µg per day for a further 3
weeks and finally to a maintenance dose of 100–150 µg per day.
In younger patients, it is safe to initiate levothyroxine at a higher dose (for example, 100 µg per day), to allow
a more rapid normalization of thyroid hormone levels.
Levothyroxine has a half-life of 7 days so it should always be taken as a single daily dose and at least 10
weeks should pass before repeating thyroid function tests and adjusting the dose, usually by 25 µg per day.
Patients feel better within 2–3 weeks.
Reduction in weight and periorbital puffiness occurs quickly unlike skin and hair that take 3-6 months
The dose of levothyroxine should be adjusted to maintain serumTSH within the reference range.To achieve
this, serumT4 often needs to be in the upper part of the reference range or even slightly raised, because the
T3 required for receptor activation is derived exclusively from conversion ofT4 within the target tissues,
without the usual contribution from thyroid secretion.
11. Levothyroxine replacement in ischaemic heart disease:
Hypothyroidism and ischaemic heart disease are common conditions that often occur
together.
In patients with known ischaemic heart disease, thyroid hormone replacement should
be introduced at low dose and increased very slowly under specialist supervision.
Coronary intervention may be required if angina is exuberated by levothyroxine
replacement therapy.
Hypothyroidism in pregnancy:
Most pregnant women with primary hypothyroidism require an increase in the
dose of levothyroxine .
Inadequately treated hypothyroidism in pregnancy has been associated with
impaired cognitive development in the fetus.
12. Myxoedema coma:
Rare presentation of hypothyroidism, It is a medical emergency.
Begin treatment before biochemical confirmation of the diagnosis
Presents with :
There is a depressed level of consciousness (elderly patients).
Body temperature may be as low as 25°C
convulsions
cerebrospinal fluid (CSF) pressure and protein content are raised.
Treatment:
1. IV 20 µg liothyronine followed by further injections of 20 µg 3 times daily until there is
sustained clinical improvement. In survivors, there is a rise in body temperature within 24 hours.
2. Oral levothyroxine ( for coma survivors ) After 48–72, 50 µg daily.
3. Hydrocortisone 100 mg IM 3 times daily the patient has primary hypothyroidism, the
thyroid failure should also be assumed to be secondary to hypothalamic or pituitary disease,
pending the results of T4,TSH and cortisol measurement.
4. Rewarming IV fluids
5. Broad spectrum antibiotics
6. High flow O2
13. Thyrotoxic crisis (‘thyroid storm’)
This is a rare but life-threatening complication of thyrotoxicosis, It is a medical emergency (mortality of
10%).
• Signs:
Fever
Agitation
Confusion
Tachycardia or atrial fibrillation
Cardiac failure in old patients
• Treatment:
Rehydrate patient
propranolol, orally (80 mg 4 times daily) or intravenously (1–5 mg 4 times daily).
Both glucocorticoids (hydrocortisone 100 mgIV every 8 hours) & iodine important to reduce
the conversion ofT4 toT3.
Sodium ipodate (500 mg per day orally) (restores serumT3 level to normalise in 48–72 hours.
Oral prophylthiouracil (PTU) (200 mg every day) to inhibit the synthesis of new thyroid
hormone.
PTU is preferred to carbimazole (20mg every 6 hours) as it also inhibit the conversion ofT4 toT3.
Unconcious patient PTU & propranolol can be administered by nasogastric tube.
After 10-14 days patient can be maintained on carbimazole alone.
• Precipitated by:
– infection
– shortly after subtotal thyroidectomy in an ill-
prepared patient
– within a few days of 131I therapy when acute
radiation damage may lead to a transient rise in
serum thyroid hormone level.
15. SUBCLINICAL THYROTOXICOSIS
Definition: Serum TSH is undetectable, and serum T3 and T4 are at the upper end
of the reference range.
This combination is most often found in older patients with multinodular goiter.
Complications: atrial fibrillation and osteoporosis.
Treatment: Iodine – 131 or low dose thionamide
16. SUBCLINICAL HYPOTHYROIDISM
Definition: Serum TSH is raised, and serum T3 andT4 concentrations are at the
lower end of the reference range.
Complication: Risk of progression to thyroid failure especially if thyroid peroxidase
antibodies present or TSH rises above 10 mlU/L.
Treatment:
Levothyroxine In patients with non-specific symptoms.
In those with positive autoantibodies or TSH greater than 10 mU/L, it is better to
treat the thyroid failure early rather than risk loss to follow-up and subsequent
presentation with profound hypothyroidism.
17. NON-THYROIDAL ILLNESS (SICK EUTHYROIDISM)
Definition: low serumTSH, raisedT4 and normal or lowT3, in a patient with systemic illness who
does not have clinical evidence of thyroid disease.
Causes:
decreased peripheral conversion ofT4 toT3.
altered levels of binding proteins and their affinity for thyroid hormones.
reduced secretion of TSH.
During convalescence, serumTSH concentrations may increase to the level found in primary
hypothyroidism.
Thyroid function test is difficult to interpret in patient with non thyroidal illness ,thus it is better not
to do the test unless there is a clinical evidence of thyroid disease.
If an abnormal result is found, treatment should only be given with specialist advice and the diagnosis
should be re-evaluated after recovery.
18. HASHIMOTO’S THYROIDITIS
Definition: destructive lymphoid infiltration of the thyroid, ultimately leading to a varying degree of fibrosis and
thyroid enlargement.
There is an increased risk of thyroid lymphoma.
Clinical examination finding: Patients present with a small or moderately sized diffuse goitre, which is
characteristically firm or rubbery in consistency,The goitre may be soft, however, and impossible to differentiate
from simple goitre by palpation alone.
25% of patients are hypothyroid at presentation.
Investigation:
1. Anti thyroid peroxidase antibodies : present
2. TSH : normal or high
3. T4 : normal
Management:
Levothyroxine therapy for hypothyroidism and also to
shrink an associated goitre.
19. CASE
Khadeeja Nasser, a 35-year-old schoolteacher presented to the endocrinology clinic with a complaint of
persistent fatigue, unexplained weight gain, cold intolerance, and dry skin. She reported that these
symptoms had been progressively worsening over the past six months. Additionally, she mentioned
experiencing constipation and irregular menstrual periods.
Khadeeja expressed concern about her inability to lose weight despite dietary modifications and regular
exercise, which had previously been effective for her.
Khadeeja had no history of any illnesses or surgeries in the past. She had no family history of thyroid
disorders or autoimmune diseases. Her only medication at the time was an oral contraceptive for birth
control, which she had been taking for several years.
On examination, Khadeeja appeared tired and reported feeling fatigued throughout the day. Mild puffiness
was noted on her face. Her pulse was 58/min, and her BP was 130/84 mmHg. Her skin was dry and her
nails brittle. Her hair was thin. There was no palpable goiter or nodules in the thyroid gland. Heart and lung
sounds were heard normally. Her deep tendon reflexes were sluggish.
21. MCQ:
60 years old patient admitted with depressed level of consciousness, convulsions, body temperature
< 25C, CSF pressure and protein are high, what is the diagnosis:
A. Myxoedema coma
B. Thyrotoxicosis crisis
C. Hashimoto thyroiditis
D. sick euthyroidism
Which of the following is not a symptom of hypothyroidism:
A. Cold intolerance
B. Hair loss
C. Weight loss
D. Menorrhagia
