Obtain a history and perform relevant general examination.



· Dryness of skin.

· Hair dryness or loss.

· Cold intolerance.

· Change in the voice (hoarse, husky).

· Lethargy, undue tiredness.

· Constipation.

· Moderate weight gain in spite of loss of appetite.

· Menstrual irregularity, especially menorrhagia.

· Infertility.

· Depression.

· Dementia.

· Muscle cramps.

· Oedema.

· Radioiodine therapy for previous Graves' disease (the patient may have associated eye signs of Graves' disease).

· Medications and other compounds such as lithium carbonate and iodine-containing compounds (e.g. amiodarone, radiocontrast agents, expectorants containing potassium iodide, and kelp).

· Family history of thyroid dysfunction, pernicious anaemia, diabetes mellitus, primary adrenal insufficiency.

· Obtain history of hypercholesterolaemia, angina pectoris and hypertension (remember, hypertension occurs in 10% of these patients and disappears with thyroxine replacement).


· Coarse, dry skin (look for yellowish tint of carotenaemia - 'peaches and cream' complexion).

· 'Dirty elbows and knees' sign (Ber A 1954 The sign of 'dirty' knees and elbows. Acta Endocrinol (Copenh) 16: 305).

· Puffy lower eyelids.

· Loss of outer third of eyebrows, xanthelasma.

Proceed as follows:

· Examine the neck for goitre and the scar of previous thyroidectomy. The typical Hashimoto gland is firm and lobulated.

· Slow pulse.

· Check the ankle jerks, looking for delayed relaxation.

· Look for:

-Proximal muscle weakness. - Cerebellar signs. -Carpal tunnel syndrome.


This patient has delayed ankle jerks, puffy lower eyelids, slow pulse and hoarse, husky voice (lesions) indicating that he has hypothyroidism (functional status); the cause needs to be determined (aetiology).


How is delayed relaxation best elicited in the ankle?

Get the patient to kneel on a chair with his hands holding the back of the chair and

then elicit the jerks on either side.

What are the causes of goitre?

· Idiopathic (majority).

· Hashimoto's thyroiditis.

· Graves' disease.

· Iodine deficiency (simple goitre).

· Puberty, pregnancy, subacute thyroiditis, goitrogens (lithium, phenylbutazone).

What is the thyroid status in Hashimoto's disease?

Hypothyroidism (usually).

What is the single best clinical indicator for hypothyroidism?

Delayed ankle jerks.

What is the best laboratory indicator for hypothyroidism?

Elevated serum TSH levels. When there is a suspicion of pituitary or hypothalamic

disease, the serum free T4 concentration should be measured in addition to serum

TSH levels. Serum triiodothyronine concentrations are a poor indicator of

hypo-thyroid state and should not be used.

What are the laboratory changes in hypothyroidism?

· Hypercholesterolaemia.

· Hyponatraemia.

· Anaemia.

· Elevations of creatinine phosphokinase and lactate dehydrogenase.

· Hyperprolactinaemia.

What are the causes of isolated TSH elevation?

· Mild (subclinical) hypothyroidism.

· Recovery from hypothyroxinaemia of non-thyroidal illnesses.

· Medications such as amiodarone or lithium (Arch Intern Med 2000; 160: 1573-5).

What are the causes of isolated TSH suppression?

· Mild (subclinical) hyperthyroidism.

· Recovery from overt hyperthyroidism.

· Non-thyroidal illness which cause low serum free thyroxine concentration.

· Pregnancy during first trimester.

· Medications such as dopamine and glucocorticoids.

How would you investigate a simple goitre?

Estimation of serum T3, T4, TSH and thyroid antibodies.

What is the cause for delayed relaxation in hypothyroidism?

The exact cause is not known. It is probably due to decreased muscle metabolism.

How would you manage this patient with hypothyroidism?

Oral thyroxine replacement therapy for life. The therapeutic dose varies between 100

and 200 gg per day taken as a single dose. Dose adjustments are made once in 3

weeks. The dose is adjusted depending on the clinical response and suppression

of raised serum TSH levels. Lack of response to thyroxine suggests:

· Non-thyroid related disease.

· Poor compliance.

· Underlying psychiatric abnormalities.

· Presence of pernicious anaemia.

· Associated autoimmune disease such as Addison's disease.

What is the hazard in treating the elderly?

Rapid T4 replacement may precipitate angina and myocardial infarction. The starting

dose in the elderly is 50/ag per day.

What are the cardiovascular manifestations of hypothyroidism?

· Bradycardia.

· Mild hypertension.

· Pericarditis and pericardial effusion.

· High low-density lipoprotein, low high-density lipoprotein levels,


· Diminished cardiac output and cardiac failure.

· Coronary artery disease.

· ECG changes: low-voltage T and P waves, prolongation of QT interval.

What are the neurological manifestations of hypothyroidism?

· Delayed deep tendon reflexes (Woltman's sign). · Carpal tunnel syndrome, peripheral

neuropathy. · Myxoedema madness. · Myxoedema coma. · Pseudodementia.

· Deafness to high tones (Trotter's syndrome) (Trotter WR 1960 The association of

deafness with thyroid dysfunction. Br Med Bull 16: 92).

· In Pendred's syndrome, babies are born with a goitre, deafness and mental


· Cerebellar syndrome (Lancet 1960; ii: 225).

· Hoffmann's syndrome, i.e. muscle aches with myotonia in myxoedema. In infants,

muscle involvement may result in Kocher-Debr6-S6mdlaigne syndrome or 'infant


What do you understand by subclinical hypothyroidism?

This is a condition in which serum thyroxine levels are low normal, and serum TSH is

moderately raised (grade 1: 5-10, grade 2: 10.1-20, grade 3: >20). All these

patients should be treated.

What other conditions are associated with Hashimoto's thyroiditis?

· Addison's disease.

· Diabetes mellitus.

· Graves' disease.

· Hypoparathyroidism.

· Premature ovarian failure.

· Pernicious anaemia.

· Rheumatoid arthritis.

· Sj6gren's syndrome.

· Ulcerative colitis.

· SLE.

· Haemolytic anaemia.

What do you understand by the term 'sick euthyroid syndrome'?

In severe acute non-thyroidal illness or following surgery, changes in l~ituitary-thyroid

function result in altered thyroid indices but, despite this, patients remain

euthyroid. On recovery from the illness, the indices of thyroid function return to

normal (N Engl J Med 1995; 333: 1562-3). The changes in thyroidal indices


· Decrease in extrathyroidal conversion of thyroxine T4 to triiodothyronine (T3), the

active form of the thyroid hormone.

· A decrease in thyrotrophin secretion, which causes decreased thyroidal secretion

and, in time, decreases in serum T4 concentrations and further decreases in

serum T3 concentrations - the latter due to both decreased secretion of T3 by the

thyroid and diminished availability of T4 for peripheral conversion to T3.

· Decreased production or diminished affinity for thyroidal hormones of one or more

major serum thyroid hormone-binding proteins - thyroxine-binding globulin,

transthyretin and albumin. These decreases can result in decreased serum total

thyroxine levels but not in free T4 or T3. Serum concentrations of reverse T3

(which is inactive) are increased because its deiodination is impaired.

What is the prevalence of hypothyroidism?

The prevalence is 2% of the adult population, whereas that of mild (subclinical)

hypothyroidism is 5-17% (subclinical hypothyroidism is when serum TSH is

elevated with a normal free T4 concentration).

The complete clinical description of myxoedema was first given by Gull in 1873, but it

was Ord in 1878 who coined the word myxoedema when, at autopsy, he found

extensive deposits of mucin in the skin of the feet (Ord WM. On myxoedema, a

term proposed to be applied to an essential condition in the 'cretinoid' affection

occasionally observed in middle-aged women. Med Chir Trans 1878; 61: 57).

W.W. Gull (1816-1890), FRS, graduated from Guy's Hospital in London and was

created a Baronet when he treated the then Prince of Wales, who had typhoid. He

was a good teacher and said that 'Savages explain, science investigates' (Gull

WW. On a cretinoid state supervening in adult life in women. Trans Clin Soc

London 1873; 7: 180-5).

Emil Theodor Kocher (1841-1917), Swiss Professor of Surgery in Berne, was

awarded the Nobel Prize in 1909 for his work on the physiology, pathology and

surgery of the thyroid gland. He was the first to excise the thyroid gland for goitre

and described myxoedema following thyroidectomy - 'cachexia strumipriva'. His

name is associated with: (1) Kocher forceps; (2) Kocher's transverse cervical

incision for thyroidectomy; (3) Kocher's operation for the wrist; (4) Kocher's oblique

right subcostal incision for gallbladder surgery; (5) Kocher manoeuvre for reduction

of a dislocated shoulder; and (6) Kocher syndrome describing splenomegaly and

lymphadenopathy with thyrotoxicosis.

R. Debr~ and G. S~m~laigne were both French physicians (Debre R, S~m~laigne G.

Syndrome of diffuse muscular hypertrophy in infants causing athletic appearance.

Its connection with congenital myxoedema. Am J Dis Child 1935; 50: 1351).

H. Hashimoto (1881-1934), a Japanese surgeon.

Johann Hoffmann (1857-1919), a German neurologist.

in 1948, H.E.W. Roberton, a general practitioner in New Zealand, was the first to

recognize post-partum thyroid disease - he successfully treated lassitude and

other symptoms of hypothyroidism related to the post-partum period with thyroid