Clinical syndrome characterized by hypermetabolic state due to the increased free serum thyroxine (T4) and/or free triiodothyronine (T3).
- M/C cause of hyperthyroidism: Graves’ disease > toxic nodular goitre
Epidemiology
Graves disease is typically seen in younger patients and is the most common cause of hyperthyroidism in that demographic. Toxic multifocal goiter is typically seen in older individuals and is the most common cause of hyperthyroidism in this respective demographic.
Both Graves disease and toxic multifocal goiter have a female predilection and are typically seen in patients with pertinent family and personal medical histories.

Etiology
Hyperthyroidism is defined as elevated Thyroid Hormones (TH) in circulation. Thyroid hormones are important hormones in fetal development and also metabolism. So high thyroid hormone levels as you can imagine will amp up metabolism to a point where it becomes pathological. Hyperthyroidism and thyrotoxicosis refers to the same thing really. However some define hyperthyroidism specifically as increased synthesis of thyroid hormones where as thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. In this video hyperthyroidism will mean high levels of thyroid hormones in circulation causing the signs and symptoms of hyperthyroidism.

Pathophysiology
- Thyrotoxicosis: Clinical syndrome of excess circulating thyroid hormones, irrespective of the source
Thyrotoxicosis with hyperthyroidism “true hyperthyroidism”:
Normal/high radioactive iodine uptake
Effect of increased thyroid stimulators: | |
TSH-receptor antibody | Graves’ disease |
Inappropriate TSH secretion | TSH-secreting pituitary adenoma; pituitary resistance to thyroid hormone |
Excess hCG secretion | Trophoblastic tumours (choriocarcinoma or hydatidiform mole); hyperemesis gravidarum |
Autonomous thyroid function: | |
Activating mutations in TSH receptor or Gsα protein | Solitary hyperfunctioning adenoma; multinodular goitre; familial non-autoimmune hyperthyroidism |
Thyrotoxicosis without hyperthyroidism:
Low radioactive iodine uptake
Inflammation and release of stored hormone: | |
Autoimmune destruction of thyroid gland | Silent (painless) thyroiditis; post-partum thyroiditis |
Viral infection | Subacute (painful) thyroiditis (De Quervain thyroiditis) |
Toxic drug effects | Drug-induced thyroiditis (amiodarone, lithium, interferon α) |
Bacterial or fungal infection | Acute suppurative thyroiditis |
Radiation | Radiation thyroiditis |
Extrathyroidal source of hormone: | |
Excess intake of thyroid hormone | Excess exogenous thyroid hormone (iatrogenic or factitious) |
Ectopic hyperthyroidism (thyroid hormone produced outside the thyroid gland) | Struma ovarii; functional thyroid cancer metastases |
Ingestion of contaminated food | Hamburger thyrotoxicosis |
Exposure to excessive iodine: | |
Jod-Basedow effect | Iodine-induced hyperthyroidism (iodine, iodine-containing drugs, radiographic contrast agents) |
Presentation

Adrenergic:
- Palpitations, tachycardia
- Anxiety, tremor, jitteriness
- Diaphoresis, heat intolerance
- Stare, lid lag
- Hyperdefecation (not diarrhoea)
Cardiovascular:
- Tachycardia (atrial fibrillation in thyroid storm)
- Irregular pulse (in atrial fibrillation)
- Dyspnoea, orthopnoea
- Peripheral oedema (heart failure)
Cutaneous:
- Onycholysis (Plummer’s nails)
- Patchy/generalised hyperpigmentation (esp on face & neck)
- Pathognomic of Grave’s disease:
- Pretibial myxedema (thyroid dermopathy) & thyroid acropachy (clubbing of fingers & toes + soft-tissue swelling of hands & feet)



Hypermetabolism:
- Weight loss in spite of increased appetite
- Fever (in thyroid storm)
Neuromuscular:
- Brisk peripheral reflexes with accelerated relaxation
- Proximal muscle weakness
Neuropsychiatric:
- Anxiety, rapid & pressured speech, insomnia,
- Psychosis (severe cases)
Ocular:
- Increased lacrimation
- Incomplete closure of eyelids during sleep
- Photophobia
- Increased sensitivity to wind/smoke
- Grittiness/foreign-body sensation in eyes
- Pathognomic for Grave’s disease: Exophthalmos, periorbital oedema, diplopia, blurred vision, reduced colour perception


Complications
Congestive heart failure:

Osteoporosis
Thyroid storm:
Most commonly seen in the context of underlying Graves’ hyperthyroidism but can complicate thyrotoxicosis of any aetiology.
- Occurs when hyperthyroid patient stops treatment/develops infection/has surgery
- Clinical features represent manifestations of organ decompensation, with fever seen almost universally.

Diagnosis

Thyroid function tests:
Hormone | Reference Range |
---|---|
TSH | 0.4 – 4.5 µU/ml |
Total thyroxine (total T4) | 4.0 – 12.0 µg/dl |
Free thyroxine (free T4) | 0.7 – 1.8 ng/dl |
Total triiodothyronine (total T3) | 100 – 200 ng/dl |
Free triiodothyronine (free T3) | 208 – 596 pg/dl |
Condition | TSH | Total T4 | Free T4 | Total T3 |
---|---|---|---|---|
Overt hyperthyroidism |
Suppressed |
Elevated |
Elevated |
Elevated |
Subclinical hyperthyroidism* |
Suppressed or low |
Normal |
Normal |
Normal |
TSH-secreting pituitary adenoma |
Normal or elevated |
Elevated |
Elevated |
Elevated |
Estrogen excess |
Normal |
Elevated |
Normal |
Elevated |
Nonthyroidal illness syndrome |
Low |
Normal or mildly decreased |
Normal |
Low (and reverse T3 is elevated) |
Glucocorticoid and/or dopamine therapy |
Low |
Normal |
Normal |
Normal |
Radioactive Iodine Uptake and Scan:
Condition | Radioactive iodine uptake (normal = 15% to 25%) | Radiotracer distribution in the thyroid gland |
---|---|---|
Graves disease |
High |
Homogeneous |
Toxic adenoma |
High |
Iodine 123 is concentrated in one spot |
Toxic multinodular goiter |
High |
Iodine 123 is concentrated in multiple spots |
Thyroiditis |
Low |
Not applicable |

Management

Antithyroid drugs (ATDs):
Not effective in toxic adenoma or toxic multinodular goitre. In toxic nodular goitre, ATDs are generally used to restore euthyroidism before definitive treatment with surgery/radioactive iodine, and infrequently used as long-term treatment when the other two therapies are contraindicated or the patient has a short life expectancy.
- Propylthiouracil
- Thiamazole (DOC in Grave’s disease)
- Methimazole (DOC for initial treatment in Grave’s disease in children): As use of propylthiouracil in children associated with fetal hepatotoxicity
- Carbimazole
Radioactive iodine ablation:
First-line treatment for Graves’ disease, toxic adenoma, and toxic multinodular goitre
- Absolute contraindications:
- Pregnancy, breastfeeding, planning pregnancy
- Inability to comply with radiation safety recommendations
- Side effects: Acute thyroiditis (1% cases)
Thyroidectomy:
M/successful treatment for Graves’ hyperthyroidism.
- Recommended in:
- Large goitres or low uptake of radioactive iodine (or both)
- Suspected/documented thyroid cancer
- Moderate-to-severe ophthalmopathy (radioactive iodine therapy contraindicated)
- Preference for surgery
Summary