[PPT] - Hyperthyroidism Pathophysiology, differentials, investigations and PowerPoint Presentation

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Hyperthyroidism

Endocrinology series

Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital

Content reviewed on the 26/04/2020.

Pathophysiology, differentials, investigations and management.

Cases Quiz

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History A 45-year-old lady presents to the GP with a 1-month history

f ‘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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History A 45-year-old lady presents to the GP with a 1-month history

f ‘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)

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Pathophysiology

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Pathophysiology

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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)

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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)

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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

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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

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Pathophysiology

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Clinical features

Symptoms Signs Weight loss Postural tremor Heat 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

Tremor Heart rate increase Yawning Restless Oligomenorrhoea Irritability Diarrhoea Intolerance to heat Sweating Muscle wasting (weight loss)

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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 autoantibodies Autoantibody Condition Prevalence Anti-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

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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

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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

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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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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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