This document summarizes information about hyperthyroidism and hypothyroidism, including their common causes, symptoms, signs, investigations, and treatment approaches. The most common causes are Graves' disease, multinodular goiter, and solitary thyroid adenomas. Common symptoms include weight loss, heat intolerance, palpitations, and tremors. Diagnostic testing involves measuring T3, T4, and TSH levels. Treatment depends on the underlying cause, and may include antithyroid drugs, radioactive iodine, surgery, or beta-blockers to control symptoms.

2.  Hyperthyroidism(thyrotoxicosis)
 Hypothyroidism
 Enlargement of thyroid (goitre or thyroid nodule)

3. The most common causes are
 Graves’ disease
 Multinodular goitre
 Solitary thyroid adenoma
 Iodide-induced
Drugs (amiodarone)
Radiographic contrast media
Iodine prophylaxis programme2

4.  Extrathyroidal source of thyroid hormone
Factitious thyrotoxicosis
Struma ovarii
 TSH-induced
TSH-secreting pituitary adenoma Choriocarcinoma and
hydatidiform mole
 Follicular carcinoma ± metastases

5. COMMON
Symptoms
 Weight loss despite normal or increased appetite
 Heat intolerance, sweating
 Palpitations, tremor
 Dyspnoea, fatigue
 Irritability, emotional lability
Signs
 Weight loss
 Tremor
 Palmar erythema
 Sinus tachycardia
 Lid retraction, lid lag

6. Less common
Symptoms
 Osteoporosis (fracture, loss of height)
 Diarrhoea, steatorrhoea
 Angina
 Ankle swelling
 Anxiety, psychosis
 Muscle weakness
 Periodic paralysis (predominantly in Chinese)
 Pruritus, alopecia
 Amenorrhoea/oligomenorrhoea
 Infertility, spontaneous abortion
 Loss of libido, impotence

7. SIGNS
 Excessive lacrimation
 Goitre with bruit
 Atrial fibrillation
 Systolic hypertension/increased pulse pressure
 Cardiac failure
 Hyper-reflexia
 Ill-sustained clonus
 Proximal myopathy
 Bulbar myopathy

8.  The first-line investigations are
serum T3, T4 and TSH
 In most patients, serum T3 and T4 are both
elevated
 Serum TSH is undetectable in primary
thyrotoxicosis, but values can be raised in the
very rare syndrome of secondary thyrotoxicosis
caused by a TSH-producing pituitary adenoma.

9.  When biochemical thyrotoxicosis has been confirmed,
further investigations should be undertaken to
determine the underlying cause, including
 Measurement of TSH receptor antibodies (TRAb,
elevated in Graves’ disease)
 isotope scanning

10. Non-specific laboratory abnormalities in
thyrotoxicosis:
 Serum enzymes: raised alanine aminotransferase, γ-
glutamyl transferase (GGT), and alkaline phosphatase
from liver and bone
 Raised bilirubin
 Mild hypercalcaemia
 Glycosuria: associated diabetes mellitus, ‘lag storage’
glycosuria
An ECG may demonstrate sinus tachycardia or atrial
fibrillation.

11. Occasionally, patients induce ‘factitious
thyrotoxicosis’ by consuming excessive amounts of a
thyroid hormone preparation, most often
levothyroxine. The exogenous thyroxine suppresses
pituitary TSH secretion and hence iodine uptake,
serum thyroglobulin and release of endogenous
thyroid hormones. The T4:T3 ratio (typically 30 : 1 in
conventional thyrotoxicosis) is increased to above 70 : 1
because circulating T3 . The combination of negligible
iodine uptake, high T4:T3 ratio and a low or
undetectable thyroglobulin is diagnostic.

12. Definitive treatment of thyrotoxicosis depends
on the underlying cause and may include
antithyroid drugs, radioactive iodine or surgery.
A non-selective β-adrenoceptor antagonist (β-
blocker), such as propranolol (160 mg daily) or
nadolol (40–80 mg daily), will alleviate but not
abolish symptoms in most patients within 24–48
hours. Beta-blockers should not be used for long-
term treatment of thyrotoxicosis

13. Graves’ disease can occur at any age but is
unusual before puberty and most commonly
affects women aged 30–50 years

14. Pathophysiology
The thyrotoxicosis results from the production of
IgG antibodies directed against the TSH receptor
on the thyroid follicular cell, which stimulate
thyroid hormone production and proliferation of
follicular cells, leading to goitre in the majority
of patients. These antibodies are termed
thyroid-stimulating immunoglobulins or TSH
receptor antibodies (TRAb) and can be detected
in the serum of 80–95% of patients with Graves’
disease.

15. For patients under 40 years of age, most
clinicians adopt the empirical approach of
prescribing a course of carbimazole and
recommending surgery if relapse occurs,
while 131I is employed as first- or second-line
treatment in those aged over 40.

16. Antithyroid drugs:should be introduced at high
doses (carbimazole 40–60 mg daily or propylthiouracil
400–600 mg daily). Usually, this results in subjective
improvement within 10–14 days and renders the patient
clinically and biochemically euthyroid at 3–4 weeks. At
this point, the dose can be reduced and titrated to
maintain T4 and TSH within their reference range. In
most patients, carbimazole is continued at 5–20 mg per
day for 12–18 months in the hope that remission will
occur. Patients with thyrotoxicosis relapse in at least
50% of cases, usually within 2 years of stopping
treatment. Rarely, T4 and TSH levels fluctuate between
those of thyrotoxicosis and hypothyroidism at successive
review appointments, despite good drug compliance,
presumably due to rapidly changing concentrations of
TRAb. In these patients, satisfactory control can be
achieved by blocking thyroid hormone synthesis with
carbimazole 30–40 mg daily and adding levothyroxine
100–150 µg daily as replacement therapy

17. Thyroid surgery:
Patients should be rendered euthyroid with
antithyroid drugs before operation. Potassium
iodide, 60 mg 3 times daily orally, is often added
for 2 weeks before surgery to inhibit thyroid
hormone release and reduce the size and
vascularity of the gland, making surgery
technically easier.

18. Radioactive iodine:
131I is administered orally as a single dose, and is
trapped and organified in the thyroid. Although 131I
decays within a few weeks, it has long-lasting inhibitory
effects on survival and replication of follicular cells.
This regimen is effective in 75% of patients within 4–12
weeks. During the lag period, symptoms can be
controlled by a β-blocker or, in more severe cases, by
carbimazole. However, carbimazole reduces the
efficacy of 131I therapy because it prevents
organification of 131I in the gland, and so should be
avoided until 48 hours after radio-iodine administration.
If thyrotoxicosis persists after 6 months, a further dose
of 131I can be given.

19. This condition is immunologically mediated but the
autoantigen has not been identified. Within the
orbit (and the dermis) there is cytokine-mediated
proliferation of fibroblasts which secrete
hydrophilic glycosaminoglycans. The resulting
increase in interstitial fluid content, combined with
a chronic inflammatory cell infiltrate, causes
marked swelling and ultimately fibrosis of the
extraocular muscles and a rise in retrobulbar
pressure. The eye is displaced forwards (proptosis,
exophthalmos and in severe cases there is optic
nerve compression.

20. The most frequent presenting symptoms are related
to increased exposure of the cornea, resulting from
proptosis and lid retraction. There may be
excessive lacrimation made worse by wind and
bright light, a ‘gritty’ sensation in the eye

22. Severe inflammatory episodes are treated with
glucocorticoids (e.g. daily oral prednisolone or pulsed IV
methylprednisolone) and sometimes orbital
radiotherapy.Loss of visual acuity is an indication for
urgent surgical decompression of the orbit. In ‘burnt-
out’ disease, surgery to the eyelids and/or ocular
muscles may improve conjunctival exposure, cosmetic
appearance and diplopia.

23. Atrial fibrillation occurs in about 10% of patients
with thyrotoxicosis. The incidence increases with
age, so that almost half of all males with
thyrotoxicosis over the age of 60 are affected.
Moreover, subclinical thyrotoxicosis is a risk factor for
atrial fibrillation. Characteristically, the ventricular
rate is little influenced by digoxin, but responds to
the addition of a β-blocker. Thromboembolic vascular
complications are particularly common in thyrotoxic
atrial fibrillation so that anticoagulation with
warfarin is required, unless contraindicated. Once
thyroid hormone and TSH concentrations have been
returned to normal, atrial fibrillation will
spontaneously revert to sinus rhythm in about 50% of
patients, but cardioversion may be required in the
remainder.

24. This is a rare but life-threatening complication
of thyrotoxicosis. The most prominent signs are
fever, agitation, confusion, tachycardia or atrial
fibrillation and, in the older patient, cardiac
failure. It is a medical emergency, which has a
mortality of 10% despite early recognition and
treatment. Thyrotoxic crisis is most commonly
precipitated by infection in a patient with
previously unrecognised or inadequately treated
thyrotoxicosis. It may also develop shortly after
subtotal thyroidectomy in an ill-prepared patient
or within a few days of 131I therapy, when acute
irradiation damage may lead to a transient rise
in serum thyroid hormone levels.

25. Patients should be rehydrated and given
propranolol, either orally (80 mg 4 times daily) or
intravenously (1–5 mg 4 times daily). Sodium
ipodate (500 mg per day orally) will restore serum
T3 levels to normal in 48–72 hours. This is a
radiographic contrast medium which not only
inhibits the release of thyroid hormones, but also
reduces the conversion of T4 to T3 and is, therefore,
more effective than potassium iodide or Lugol’s
solution.Oral carbimazole 40–60 mg daily should be
given to inhibit the synthesis of new thyroid
hormone.After 10–14 days the patient can usually
be maintained on carbimazole alone.