Hyperthyroidism

Endocrinology series

Dr Azeem Alam, MBBS BSc (Hons)Surgical AFPGuy’s and St. Thomas’ HospitalContent reviewed on the 26/04/2020.

Pathophysiology, differentials, investigations and management.

Cases Quiz

History

A 45-year-old lady presents to the GP with a 1-month history of ‘hot flushes’. She is very anxious and on occasion feels her chest thumping. Her clothes no longer fit, and she wonders if her symptoms could be due to menopause.

On examination, she has a 2 cm diffuse neck swelling.

Observations

HR 101, BP 138/98, RR 18, SpO2 99%, Temp 37.8°C.

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Case 1

History

A 45-year-old lady presents to the GP with a 1-month history of ‘hot flushes’. She is very anxious and on occasion feels her chest thumping. Her clothes no longer fit, and she wonders if her symptoms could be due to menopause.

On examination, she has a 2 cm diffuse neck swelling.

Observations

HR 101, BP 138/98, RR 18, SpO2 99%, Temp 37.8°C.

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Case 1

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Pathophysiology

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Definition: hyperthyroidism reflects an increased level of circulating thyroid hormones, leading to raised metabolic rate and sympathetic nervous system activation.

Pathophysiology

(1)

Pathophysiology

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Pathophysiology

Pathophysiology

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Primary hyperthyroidism• Excessive production of T3/T4 by the thyroid gland • Thyroid gland pathology• Most common subtype

Secondary hyperthyroidism• Stimulation of the thyroid gland by excessive TSH • Originates due to pathology of the pituitary or hypothalamus • May also be secondary to a TSH-secreting tumour

Pathophysiology

(1)

Pathophysiology

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Graves’ disease• Anti-TSH receptor antibodies• Most common cause of hyperthyroidism

(75%)• Diffuse goitre and thyroid eye signs

Primary hyperthyroidism

Toxic multinodular goitre• Iodine deficiency• Compensatory TSH secretion • Nodular goitre formation• Nodules become TSH-independent and

thyroid hormones

(2)

Pathophysiology

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Primary hyperthyroidism

Toxic adenoma Thyroiditis• Single autonomous functional

nodule• Initial stage will include transient

hyperthyroidism • Hypothyroidism is the final stage• Hashimoto’s and De Quervain’s

thyroiditis

Subclinical hyperthyroidism Drugs• Normal T3/T4, low TSH• May be due to any of the above

causes• Typically due to toxic multinodular

goitre or Graves’ disease

• Amiodarone: causes both hyperthyroidism and hypothyroidism

Pathophysiology

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Pituitary adenoma Ectopic tumour Hypothalamic tumour• TSH-secreting pituitary

adenoma• hCG-secreting tumours (e.g.

choriocarcinoma)• Excessive TRH secretion• Rare cause of

hyperthyroidism

Secondary hyperthyroidism

Choriocarcinoma(3)

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Risk factors

• Female gender: particularly for Graves’ disease

• Family history

• Other autoimmune conditions

• Smoking: increases risk of Graves’ eye disease

• Trauma to the thyroid: including surgery

• Drugs: e.g. amiodarone

Pathophysiology

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Clinical features

Symptoms SignsWeight loss Postural tremorHeat intolerance and sweating

Palmar erythema

Palpitations Graves’ disease• Thyroid acropachy• Pretibial myxedema• Eye signs

• Exophthalmos• Ophthalmoplegia

Menstrual irregularity Lid lag and retraction Anxiety Goitre

Hyperreflexia

THYROIDISM Mnemonic

TremorHeart rate increaseYawningRestlessOligomenorrhoeaIrritabilityDiarrhoeaIntolerance to heatSweatingMuscle wasting (weight loss)

Pathophysiology

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Clinical features: general

(4) Goitre

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Clinical features: Graves’ disease

No signs

Only signs no symptoms

Soft tissue involvement

Proptosis

Extraocular muscle involvement (ophthalmoplegia)

Corneal involvement

Sight loss

Pretibial myxedema

Exophthalmos

Thyroid acropachy

(5)

(5)

(6)

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Investigations: stable patient

Thyroid autoantibodiesAutoantibody Condition PrevalenceAnti-TSH receptor Graves’ disease 90-100%

Hashimoto’s thyroiditis 0-5%

Anti-TPO Graves’ disease 70-80%

Hashimoto’s thyroiditis 90-95%

Anti-thyroglobulin Graves’ disease 20-40%

Hashimoto’s thyroiditis 30-50%

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Investigations: stable patient

Primary investigations:• Thyroid function tests (TFTs): first-line investigation• Antibodies: anti-TSH receptor antibodies (95%) and anti-TPO most often raised in

Graves’ disease

Investigations to consider:• Ultrasound: if thyrotoxic with have a palpable thyroid nodule• Technetium radionuclide scan: performed if anti-TSH antibodies are negative• Glucose: hyperthyroidism is associated with hyperglycaemia• ECG: hyperthyroidism is associated with atrial fibrillation

TSH T4 Cause↓ ↑ Primary hyperthyroidism: e.g. Graves’ disease↓ ↔ Subclinical hyperthyroidism↑ ↑ Secondary hyperthyroidism: e.g. TSH-secreting pituitary

adenoma↔ ↑

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Investigations: stable patient

(7)

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Management

Antithyroid medication:• Carbimazole: usually first-line• Propylthiouracil: first-line pre-pregnancy or in the first trimester• Titration regime: titrate down to lowest effective dose

• Please note that there was a discrepancy previously regarding the titration regimen. This has now been rectified.

• Block and replace regimen: levothyroxine is added as needed

Radioiodine:• First-line definitive management in Graves' and toxic multinodular goitre• Contraindicated in pregnancy and breastfeeding• Offer patient advice

Surgery: total or hemithyroidectomy• Requires pre-operative optimisation• Be aware of the risks

Other: consider propranolol for symptomatic relief

Pathophysiology

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Thyroid storm

Aetiology• Untreated hyperthyroidism • Often provoked by infection

Clinical features• Tachycardia: often > 140 BPM, with or without AF• High temperature: often > 40°C• Diarrhoea and vomiting• Jaundice• Confusion or mental agitation

Mortality rate• With treatment, 20-40% • Untreated, up to 75%

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Investigations: thyroid storm

Primary investigations• TFTs: elevated T3 and T4, suppressed TSH• Screen for the cause: e.g. an infection screen• Full set of bloods: FBC, U&Es, LFTs, bone profile, blood glucose• CXR• Arterial blood gases

TSH T4 Cause↓ ↑ Primary hyperthyroidism: e.g. Graves’ disease↓ ↔ Subclinical hyperthyroidism↑ ↑ Secondary hyperthyroidism: e.g. TSH-secreting pituitary

adenoma↔ ↑

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Management: thyroid storm

Emergency• IV fluids: replace losses• NG tube insertion: if vomiting• Cooling: sponging and paracetamol

• Antithyroid drugs: propylthiouracil is often preferred• Corticosteroid: IV hydrocortisone• Beta-blocker: propranolol PO or IV over 10 minutes• Oral iodine: Lugol’s iodine offered >1 hour after propylthiouracil

• Sedation: if required, use chlorpromazine• Plasma exchange or thyroidectomy: in refractory patients

Pathophysiology

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Recap

• Graves’ disease is the most common cause of hyperthyroidism

• Graves’ disease occurs due to anti-TSH receptor antibodies

• Patients often present with palpitations, weight loss and height intolerance

• Graves’ may present with eye disease

• Initial investigations are TFTs and autoantibodies

• Additional investigations include ultrasound and Technetium radionuclide scanning

• Thyroid storm is a life-threatening manifestation of thyrotoxicosis

History

A 55-year-old lady is currently on chemotherapy for ovarian cancer. She presents to the GP with an ongoing history of palpitations that are particularly worse at night. Her friends have told her she has lost weight and her clothes are loose.

The GP checks her TFTs: low TSH and raised T3/T4.

Observations

HR 99, BP 148/98, RR 18, SpO2 99%, Temp 37.5°C.

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Case 2

History

A 55-year-old lady is currently on chemotherapy for ovarian cancer. She presents to the GP with an ongoing history of palpitations that are particularly worse at night. Her friends have told her she has lost weight and her clothes are loose.

The GP checks her TFTs: low TSH and raised T3/T4.

Observations

HR 99, BP 148/98, RR 18, SpO2 99%, Temp 37.5°C.

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Case 2

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Top decile question

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References

1. Mikael Häggström / Public domain2. Blausen.com staff (2014). Medical gallery of Blausen Medical 2014;. WikiJournal of Medicine 1 (2).

DOI:10.15347/wjm/2014.010. ISSN 2002-4436. / CC BY (https://creativecommons.org/licenses/by/3.0)3. Nephron / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)4. Drahreg01 / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)5. Herbert L. Fred, MD and Hendrik A. van Dijk / CC BY (https://creativecommons.org/licenses/by/2.0)6. Jonathan Trobe, M.D. - University of Michigan Kellogg Eye Center / CC BY

(https://creativecommons.org/licenses/by/3.0)7. Petros Perros / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)