Hyperthyroidism - DRAFT

Overview

Definition

Primary hyperthyroidism is biochemically defined as a suppressed TSH, usually accompanied by a raised free T4 and/or T3.

It is caused by excess synthesis and secretion of thyroid hormones from the thyroid gland.

Thyrotoxicosis describes excess circulating thyroid hormones due to release of preformed thyroid hormones into the circulation e.g. commonly seen in transient thyroiditis.

Hyperthyroidism can be:

• Overt - characterised by a low serum TSH and raised T4 and/or T3.
• Subclinical - characterised by a low serum TSH, but normal serum T4 and T3 concentrations – see separate guidance.

Important points

• The most common causes of hyperthyroidism in clinical practice include Graves’ disease, toxic multinodular goitre (MNG) and a toxic adenoma.
• It is important to consider the most likely underlying diagnosis as it will guide further investigation and management.
• These guidelines accept that local endocrinology services are not currently NICE compliant therefore these recommendations have been agreed with local stakeholders and published on REMEDY to support patients and their GPs to manage hyperthyroidism pending expert assessment.

Referral

Urgent Referral 

• Pregnancy - urgently refer any patient who is pregnant with biochemical hyperthyroidism, to the joint Endocrine Antenatal Clinic (JEANC) at the trust where the patient is booked or wishes to deliver.  See the Maternity Services page for referral details.
• If the free T4 > 60 (pmol/L) and/or free T3>20 (pmol/L) or if the patient is significantly symptomatic then refer to endocrinology via eRS marked urgent (also consider thyrotoxic storm - see Red Flags below)

Routine Referral

Refer all other patients with hyperthyroidism routinely to endocrinology via eRS and follow the guidance regarding treatment below.

Advice and Guidance

Consider requesting Advice and Guidance (Endocrinology) via eRS in the following scenarios:

• If a patient is taking amiodarone please request advice and guidance as well as making a referral.
• If advice regarding titration of anti-thyroid medication is required while awaiting a secondary care appointment.

Eye Hospital Referral

See the Thyroid eye disease page for advice on management of eye symptoms and when to refer to the eye hospital. 

Red Flags

Thyrotoxic crisis/ storm

This is a rare and life-threatening condition characterised by severe clinical features of hyperthyroidism. Clinical features can include (but are not limited to) fever, severe tachycardia, congestive cardiac failure and delirium. See also Complications | Hyperthyroidism | CKS | NICE (1).

If you have clinical concerns about a patient with hyperthyroidism and the above symptoms, please ring the Endocrinology SpR mobile at NBT (via switch),or bleep the Endocrine SpR at UHBW (via switch).

Thyrotoxicosis in pregnancy

If thyrotoxicosis is identified in pregnancy (1) please refer urgently to ante-natal clinic - see 'Referra'l section above.

Suspected Malignancy

If thyroid cancer is suspected please refer directly using the Head & Neck incl Thyroid - USC (2WW) pathway. Note thyrotoxicosis is very uncommon with thyroid malignancy.

Management - previously diagnosed hyperthyroidism

Please review previous thyroid function tests and any clinic letters.

If the patient is already known to Endocrinology at NBT/UHBW please email either team directly:

• NBT - diabetesandendocrinologyadmin@nbt.nhs.uk
• UHBW - diabetesendomedicalsecretaries@uhbw.nhs.uk

If the patient has relapsed Graves’ disease, please re-refer to Endocrinology (ideally the same Endocrinology team for continuity) and follow treatment advice below.

Ensure a history is taken regarding the severity of symptoms, chance of pregnancy and relevant medications e.g. amiodarone. ·

Examine for signs of Thyroid eye disease.

Management - First Presentation

For newly diagnosed patients then refer as appropriate and use the following advice on treatment while awaiting clinic appointment:

• If the patient is well with minimal symptoms, repeat the TFTs in 2 weeks with a TSH receptor antibody level (in case of transient thyroiditis).  In addition, request a full blood count to determine the neutrophil count prior to initiation of anti-thyroid medications.
• If the patient is well but moderately symptomatic, commence propranolol 10 - 40mg TDS with repeat TFTs and a TSH receptor antibody level in 2 weeks as above.
• If the patient cannot take B-blockers, diltiazem 60mg TDS can be used as an alternative.
• USS thyroid – is not routinely indicated unless there are concerns about a large goitre e.g. compressive symptoms, or possible malignancy (although hyperthyroidism in this case is rare).
• If the patient is planning a pregnancy, please counsel against conception until seen in the Endocrine clinic. Thyrotoxicosis and anti-thyroid medications carry some increased risks in pregnancy and full counselling should be offered.

Carbimazole

If the patient is severely symptomatic and/or the free T4 is > 60pmol/L and/or free T3 is >20 pmol/L, send an urgent referral AND commence treatment immediately (see dosing below) without repeating the blood test at 2 weeks.

For those in the minimally or moderately symptomatic category, if there is persistent biochemical hyperthyroidism after 2 weeks, commence Carbimazole using the following dosing advice:

NB. Prescribe Carbimazole at the higher dose if falls between the T4 and T3 value.

Once treatment has commenced, repeat thyroid function tests should be carried out every 4-6 weeks until a steady maintenance dose has been achieved.

As general guidance, it is recommended halving the dose of carbimazole/propylthiouracil once the free T4 and T3 fall into the normal range (the TSH may remain suppressed for some time).

Advice regarding titration of anti-thyroid medications can be gained using Advice and Guidance (Endocrinology) via eRS if the patient is waiting for a secondary care appointment.

If not done on the initial blood test, please ensure that a TSH receptor antibody level is taken on a subsequent sample.

Propylthiouracil

If there is any risk or consideration of pregnancy, please prescribe propylthiouracil instead of carbimazole at the following dose:

Block and replace regime

Block and replace is an alternative treatment approach but please discuss directly using Advice and Guidance (Endocrinology) via eRS prior to commencing.

This is an alternative treatment approach which can be used to achieve thyroid function test stability in certain patient groups. The main possible advantage of this regime is the need for fewer blood tests and a shorter duration of treatment.

Possible reasons for using block and replace regimes: severe thyroid eye disease (and the need to maintain biochemical stability), variable compliance/control on dose titration, to maintain stability prior to definitive treatment e.g. surgery.

After achieving a T3 and T4 in the normal range (TSH can still be suppressed) with high dose carbimazole (40mg OD) or propylthiouracil (200mg BD) alone, thyroxine is commenced at 100 micrograms once daily.

Thyroid function tests should be repeated six weeks later (or in the interim if symptoms consistent with thyroid dysfunction are present). Typically, the same Carbimazole dose is continued, and Thyroxine is amended in 25mcg increments to maintain biochemical control.

Block and replace regimes should not be used in pregnancy or patients of childbearing age unless the patient is using an effective method of contraception.

Safety Information

Agranulocytosis

Counsel ALL patients commenced on anti-thyroid medications regarding the risk of agranulocytosis/neutropaenia,and provide patients with an anti-thyroid safety card. (See Appendix 1).

Perform a full blood count to determine the neutrophil count prior to initiation of anti-thyroid medication.

The risk of agranulocytosis is 0.1-0.3% and is most likely to occur in the first 3 months after starting treatment.

In patients who develop a severe sore throat, fever, or mouth ulcers on anti-thyroid medications:

• Stop carbimazole/PTU immediately.
• Arrange a same day/urgent full blood count.
• If the neutrophil count is < 1.0, do not recommence treatment and discuss urgently with Endocrinology (Endocrine SpR mobile via NBT switchboard/Endocrine SpR bleep via UHBW switchboard)
• If the neutrophil count is 1.0-2.0, repeat the FBC the next day.
• If level is >2.0, it is safe to continue treatment.

Acute pancreatitis

In the UK, no Yellow Card reports of acute pancreatitis associated with Carbimazole treatment have been received over a period of 55 years; however, a small number of reports have been received in other countries. Although the mechanism for development of acute pancreatitis is poorly understood, the presence of cases reporting recurrent acute pancreatitis with a decreased time to onset after re-exposure to Carbimazole suggests a possible immunological mechanism.

Do not use Carbimazole in patients with a history of acute pancreatitis in association with previous treatment.

If acute pancreatitis occurs, stop Carbimazole treatment immediately. Re-exposure may result in life-threatening acute pancreatitis with a decreased time to onset.

Report suspected adverse drug reactions to the Yellow Card Scheme immediately.

Resources

References

(1) Hyperthyroidism | Health topics A to Z | CKS | NICE

(2) Thyroid disease: assessment and management | Guidance | NICE -NG 145

(3) BNSSG Formulary Chapter 6.9 Thyroid disorders

(4) Carbimazole | Drugs | BNF | NICE

Appendix 1

Information leaflet for patients taking Carbimazole or Propylthiouracil

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

Information provided through Remedy is continually updated so please be aware any printed copies may quickly become out of date.