What are the Causes of Thyrotoxicosis?

Thyrotoxicosis is defined as the state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excessive thyroid function.

Causes of Thyrotoxicosis

Regulation of thyroid hormone synthesis. Left. Thyroid hormones T4 and T3 feed back to inhibit hypothalamic production of thyrotropin-releasing hormone (TRH) and pituitary production of thyroid-stimulating hormone (TSH). TSH stimulates thyroid gland production of T4 and T3. Right. Thyroid follicles are formed by thyroid epithelial cells surrounding proteinaceous colloid, which contains thyroglobulin. Follicular cells, which are polarized, synthesize thyroglobulin and carry out thyroid hormone biosynthesis (see text for details). TSH-R, thyroid-stimulating hormone receptor; Tg, thyroglobulin; NIS, sodium-iodide symporter; TPO, thyroid peroxidase; DIT, diiodotyrosine; MIT, monoiodotyrosine.

Signs and Symptoms of Thyrotoxicosis (Descending Order of Frequency)

Hyperactivity, irritability, dysphoria
Heat intolerance and sweating
Fatigue and weakness
Weight loss with increased appetite
Oligomenorrhea or amenorrhea, loss of libido
Typical features indicative of Grave’s disease may also be present.

Tachycardia; atrial fibrillation in the elderly
Warm, moist skin
Muscle weakness, proximal myopathy without fasciculation
hyperreflexia, muscle wasting
Lid retraction or lag
Osteopenia in long-standing thyrotoxicosis
Lid retraction, causing a staring appearance, can occur in any form of thyrotoxicosis and is the result of sympathetic overactivity.


Thyroid function test:
Serum TSH is suppressed in hyperthyroidism (< 0.05 mU/L), except for the very rare instances of TSH hypersecretion.
Diagnosis is confirmed with a raised free T4 or T3; T4 is almost always raised but T3 is more sensitive as there are occasional cases of isolated 'T3 toxicosis'.
TSH receptor antibodies are present in the Grave’s disease.
Radio-iodine uptake test: but have been superseded by 99m technetium scintigraphy scans.

Non-specific laboratory abnormalities
Serum enzymes: raised ALT, gamma-glutamyl transferase and alkaline phosphatase from liver and bone.
Raised bilirubin
Mild hypercalcaemia
Glycosuria; associated diabetes mellitus, ‘Lag storage’ glycosuria (rapid gastric emptying and hence increased absorption of glucose)

Definitive treatment of thyrotoxicosis depends on the underlying cause.
Treatment option includes: antithyroid drugs, radioactive iodine or surgery.
In all: a beta blocker (propanolol 160mg daily or nadolol 48-80mg daily) will alleviate the symptoms within 24-48 hours. Only useful as short term.
Atrail fibrillation: common in thyrotoxicosis; little influenced by Digoxin,  but responds with beta blocker.
Thrombo-embolic vascular complication also common in thyrotoxic atrial fibrillation; warfarin given usless contraindicated.

Thyrotoxic crisis (‘thyroid storm’)
It is a medical emergency.
The mortality rate is 10%
A rare and life-threatening increase in the severity of the clinical features of thyrotoxicosis.
Fever, agitation, confusion, tachycardia or atrail fibrillation and cardiac failure in older patients are prominent features.
Most commonly precipitated by infection in patients with unrecognized or inadequately treated thyrotoxicosis.
Also precipitated by stress, surgery in an unprepared patient, or radioiodine therapy (acute irradiation may lead to a transient rise in serum thyroid hormone levels).
A broad spectrum antibiotics (aminopenicillins)
Propanolol (80mg 6 hourly orally or IV 1-5mg 6 hourly)
Sodium ipodate; a radiographic contrast medium which inhibits the release of thyroid hormones, but also reduces the conversion of T4 to T3, 500mg per day orally will restore serum T3 levels to normal in 48-72 hours.
It is more effective then potassium iodide or Lugol’s solution.
Dexamethasone (2mg 6 hourly) and amiodarone have similar effects.
Carbimazole 40-60mg daily orally inhibits the synthesis of new hormome. Can be administered rectally as well but no IV preparation is available.

Essentials of diagnosis
Sweating, weight loss or gain, anxiety, loose stools, heat intolerance, irritability, fatigue, weakness, menstrual irregularity.
Tachycardia; warm, moist skin; stare; tremor.
In Graves disease: goiter (often with bruit); ophthalmopathy.
Suppressed TSH in primary hyperthyroidism; increased T4, FT4, T3, FT3.