Background Information

Definition

2 commonly confusing terms:

• Thyrotoxicosis: clinical manifestation of excess circulating thyroid hormones, irrespective of the cause (i.e. hyperthyroidism can cause thyrotoxicosis)
• Hyperthyroidism: overproduction of thyroid hormone by the thyroid gland

There are 3 main types of hyperthyroidism:

Causes

Thyrotoxicosis with Hyperthyroidism

Primary causes:

• Graves’ disease – most common
• Toxic multinodular goitre – 2nd most common
• Toxic adenoma
• Excess iodine
• Amiodarone-induced thyrotoxicosis
• Struma ovarii (ectopic thyroid hormone secretion in an ovarian teratoma)
• Causes of high hCG levels (can stimulate TSH receptors on the thyroid gland)
  • Gestational thyrotoxicosis
  • Hyperemesis gravidarum
  • hCG-secreting tumours (e.g. choriocarcinoma or hydatidiform mole)

Secondary causes:

• TSH-secreting pituitary adenoma
• Pituitary thyroid hormone resistance syndrome (rare)
• Hypothalamic disease (excess TRH production) (extremely rare)

Thyrotoxicosis without Hyperthyroidism

• Excess levothyroxine intake
• Acute phase of transient thyroiditis
  • De Quervain’s (subacute) thyroiditis
  • Postpartum thyroiditis

Diagnosis Guidelines

Clinical Features

Shared / Non-Specific Features

The clinical features of thyrotoxicosis are mapped to a thyroid examination (starting from the periphery, then top to bottom).

Body system	Clinical features
General (screening questions)	Heat intolerance (patient would be underdressed e.g. wearing a T-shirt when it’s winter) Weight loss, despite increased appetite Anxious, irritability Reproductive system Female: oligomenorrhoea / hypoamenorrhoea / amenorrhoea, decreased libido, infertility Male: decreased libido, infertility
Hands	Warm, moist palms Fine tremor Onycholysis (thickened nails with white discolouration + separation of the nail plates)
Pulse and BP	Atrial fibrillation Tachycardia / tachyarrhythmias Systolic hypertension
Skin changes	Warm, moist skin
Neck	Goitre / thyroid lump (seen in Graves’ disease, toxic multinodular goitre, toxic adenoma – see below for more details) *NB that a goitre can be seen in both hyperthyroidism and hypothyroidism (mainly Hashimoto’s thyroiditis and iodine deficiency)
Abdomen	Diarrhoea
Lower limb	Hyper-reflexia Proximal myopathy (NB this can be seen in both hypothyroidism and hyperthyroidism, but is more common and severe in hypothyroidism)

Cause-Specific Features

Graves’ Disease

Graves’ disease presents with a diffuse goitre (diffusely enlarged thyroid gland with no nodules) +/- bruit (on palpation / auscultation)

 

Classic Graves’ triad: ^[Ref1][Ref2]

Graves’ orbitopathy (Graves’ eye disease)	Upper eyelid retraction (seen in >90% cases) – results in visible sclera between the upper eyelid and corneal limbus, gives a ‘staring look’ Proptosis / exophthalmos (seen in~60% cases) – anterior displacement of the globe Lid lag – upper eyelid remains elevated in downgaze Ocular surface symptoms (due to exposure keratopathy from lid retraction and incomplete eyelid closure) – dryness, grittiness, photophobia, excessive tearing Periorbital oedema and erythema Conjunctival chemosis and injection Extraocular muscle dysfunction
Pretibial myxoedema	Bilateral and asymmetrical lesions on the anterior shin Non-pitting oedema, waxy or peau d’orange appearance Firm, indurated plaques or nodules
Thyroid acropachy	Triad of: Digital clubbing Soft tissue swelling of the fingers and toes Periosteal bone formation (in the hands and feet)

Toxic Multinodular Goitre

Toxic multinodular goitre presents with an irregular nodular thyroid enlargement

• Not a diffusely enlarged goitre that is seen in Graves’
• Typically, an asymmetrically enlarged goitre with multiple palpable nodules

Toxic Adenoma

Toxic adenoma presents as a single, palpable thyroid nodule

Investigation and Diagnosis

NICE recommends testing for thyroid dysfunction in:

• Clinically suspected cases
• Type 1 diabetes or other autoimmune disease
• New-onset atrial fibrillation

Thyroid Function Test Interpretation

Type	Free T4	TSH
Primary overt hyperthyroidism	↑	↓
Secondary overt hyperthyroidism	↑	↑
Subclinical hyperthyroidism	Normal	↓

Further Testing

Imaging:

• Consider technetium scanning of the thyroid gland if antibodies are -ve
• If there is palpable thyroid enlargement or focal nodularity → ultrasound neck

Summary Table

Comparison of Common Thyroid Disorders (Test Interpretation)

Condition	Antibody serology	Ultrasound findings	Technetium / radioiodine uptake scan
Graves’ disease	Anti-TSH receptor antibodies +ve in >90% Anti-TPO can be +ve	Diffuse enlargement ↑ Vascularity ↑ Doppler	Diffuse ↑ uptake
Toxic multinodular goitre	-ve	Multiple nodules of varying size Heterogeneous echotexture	Multifocal (patchy) ↑ uptake
Toxic adenoma	-ve	Solitary, well-defined nodule	Focal ↑ uptake (hot nodule) ↓ Uptake of remaining areas
Hashimoto’s thyroiditis	Anti-TPO +ve in >90%	Diffuse enlargement Heterogeneous hypoechoic echotexture	Diffuse ↓ uptake
Subacute (De Quervain’s) thyroiditis	-ve	Diffuse enlargement Hypoechoic areas ↓ Vascularity	Diffuse ↓ uptake
Thyroid cancer	-ve	Solid hypoechoic nodule +/- microcalcifications	Focal ↓ uptake

Management Guidelines

Thyrotoxicosis without Hyperthyroidism

This section refers mainly to transient thyroiditis like De Quervain’s thyroiditis and postpartum thyroiditis

Mainstay of treatment → Supportive / Symptomatic

• Hyperadrenergic/thyrotoxicosis symptoms→ beta blockers (propranolol / metoprolol / nadolol) usually sufficient

Anti-thyroid drugs / radioactive iodine are NOT used, as the thyrotoxicosis occurs due to hormone release from damaged thyroid tissue rather than increased synthesis

NB: the typically self-limited hypothyroid phase in De Quervain’s thyroiditis / postpratum thyroiditis does NOT routinely require levothyroxine unless persistent / severely symptomatic

Thyrotoxicosis with Hyperthyroidism

Primary Care Management

Offer a beta blocker (propranolol / metoprolol / nadolol) for symptomatic control +/- anti-thyroid drugs while awaiting specialist assessment and further treatment

Secondary Care Management

Offer a beta blocker (propranolol / metoprolol / nadolol) for symptomatic control

 

Definitive management depends on the underlying cause.

Graves’ Disease

It is not feasible to structure NICE’s recommendations into a stepwise algorithm; therefore the author has chosen to organise them by indications and contraindications

Treatment	Indication	Contraindication
Radioactive iodine	1st line in most patients, unless contraindicated	Pregnancy and breastfeeding Planning to conceive within the 4-6 months (both male and female) Active thyroid eye disease   Children and young people (not a contraindication but typically avoided)
Anti-thyroid drug 1st line: carbimazole 2nd line: propylthiouracil	1st line in: Mild uncomplicated disease (either anti-thyroid drug or radioactive iodine is suitable), or Radioactive iodine contraindicated	Carbimazole contraindications: Women of childbearing potential (unless on effective contraception) Severe blood disorders Severe hepatic impairment History of pancreatitis (not exactly a contraindication but NICE recommends considering propylthiouracil instead) Propylthiouracil contraindications: Severe hepatic impairment
Total thyroidectomy	Typically as a last resort or if anti-thyroid drugs and radioactive iodine are ​​​​​​contraindicated

Toxic Nodular Goitre

Toxic multinodular goitre:

• 1st line: radioactive iodine
• 2nd line: surgery (total thyroidectomy) or anti-thyroid drug therapy (1st line: carbimazole, 2nd line: propylthiouracil)

 

Toxic adenoma:

• 1st line: radioactive iodine OR surgery (hemithyroidectomy)
• 2nd line: anti-thyroid drug therapy

Follow-Up and Monitoring after Treatment

TSH +/- free T4 and free T3 should be monitored.

After total thyroidectomy:

• Offer levothyroxine replacement routinely (otherwise the patient goes into iatrogenic hypothyroidism)

After radioactive iodine:

• Offer levothyroxine replacement only if hypothyroidism develops

Subclinical Hyperthyroidism

Consider seeking specialist advice on treating subclinical hyperthyroidism if:

• TSH <0.1 on 2 separate occasions, 3 months apart, or
• Symptomatic, or
• Evidence of thyroid disease (e.g. goitre, +ve thyroid antibodies)

If treatment is not indicated:

• Monitor TSH +/- free T4 and T3 regularly

Hyperthyroidism in Pregnancy

See this article.

References

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