Thyroid Hormones


Levothyroxine, Liothyronine

 [Unlicensed preparations of desiccated thyroid (e.g. ERFA thyroid) are outside the scope of this monograph]

  Issues for Surgery


Hypothyroid patients undergoing surgery are predisposed to anaemia, hypotension (which can lead to cardiovascular collapse), reduced gastrointestinal motility (which can lead to post-operative ileus) and rarely life-threatening myxedema coma1.


  Advice in the Perioperative period


Elective Surgery

Continue.

Patients with known hypothyroidism or who are on treatment for hypothyroidism should have thyroid-stimulating hormone (TSH) checked pre-operatively to determine if treatment is adequate or if dose optimisation is needed before surgery1. NB: It can take 4-6 weeks for thyroid function tests (TFTs) to reach steady state after thyroid hormone dose adjustment.

If TSH is significantly outside the normal limits, it may be preferable to defer elective surgery until a euthyroid state is achieved1. Discuss with the patient’s Endocrinologist.

Emergency Surgery

Continue.

If TSH indicates patient is not euthyroid the risks of proceeding with surgery must be balanced against the risks of delaying the surgery. It is suggested that patients with mild or moderate hypothyroidism can proceed with urgent surgery provided the patient is monitored closely for signs of post-operative complications1.

Post-operative Advice

Patients undergoing Thyroidectomy
When starting thyroid hormones after thyroidectomy a baseline (electrocardiogram) ECG should be arranged2. Consult product literature for starting dose and titrate accordingly.

Patients undergoing Other Surgery
Continue usual dose.

If a long nil by mouth (NBM) period is anticipated or if there are concerns regarding enteral absorption see Further Information.


  Interaction(s) with Common Anaesthetic Agents


Liothyronine – none relevant2, 3, 4, 5.

Esketamine and Ketamine

There have been isolated reports of marked hypertension and tachycardia when ketamine is given to patients taking levothyroxine3, 6, 7. Hypertension may occur with concomitant use of esketamine – bear the interaction in mind in case of an usual response to treatment3.

Sympathomimetics

Levothyroxine may enhance the effects of sympathomimetics (e.g. adrenaline / epinephrine, phenylephrine). This is possibly due to increased catecholamine receptor sensitivity6, 7.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Liothyronine – none relevant2, 3, 4, 5.

Drug-disease interactions

Many drugs are known to alter thyroid function by altering protein binding and could therefore affect disease control, including3:-

  • corticosteroids (dexamethasone > 4mg is specifically mentioned)
  • diamorphine
  • dopamine
  • heparin

Effects on Absorption of Levothyroxine

H2 antagonists
Cimetidine, but not ranitidine or famotidine, causes a small reduction in the absorption of levothyroxine. As the effect is small it seems unlikely to be clinically relevant3.

Proton Pump inhibitors (PPIs)
Efficacy of levothyroxine may be decreased by lansoprazole and omeprazole; however, esomeprazole and pantoprazole appear not to interact. An interaction between levothyroxine and PPIs is not established, and any interaction appears to take months to develop. Bear in mind the possibility of an interaction if a patient starting a PPI shows signs of reduced levothyroxine efficacy3.

Iron Supplements
Ferrous sulphate is known to reduce the effects of levothyroxine to a clinically significant extent; this reaction is predicted to occur with any ferrous salt3. Doses of levothyroxine and iron compounds should be separated by at least 4 hours on the assumption to improve absorption2; however, this may not prevent the interaction3. Monitor thyroid function if an interaction is suspected and adjust the levothyroxine dose accordingly.

Other Medicines
There is potential for other medicines to affect the absorption of levothyroxine (e.g. calcium salts) and consideration should be given to separating administration. Consult current product literature where appropriate on commencing new medication for patients already taking levothyroxine or for those patients commencing levothyroxine during the perioperative period.


  Further Information


Risks Associated with Pre-operative Omission and Prolonged NBM period

There is a potential risk of exacerbation of hypothyroidism if thyroid hormones are omitted perioperatively. However, the actual risk is dependent on the patient’s TFTs on admission and the length of time that they are omitted. It takes 4 – 6 weeks from being euthyroid to the patient becoming hypothyroid once thyroid hormones are stopped. If there are any concerns regarding the omission or continuation of thyroid hormones during the perioperative period, the patient’s Endocrinologist should be consulted.

If oral medications cannot be given post-operatively thyroid hormones can be safely omitted for a few days1. The action of liothyronine is expected to persist for 1 to 2 days after it is stopped4, 5 and levothyroxine has a long half-life, approximately 6-7 days in euthyroid patients4, 5. If after this time oral medication still cannot be taken consideration should be given to prescribing an intravenous preparation if there are any concerns regarding the patient’s euthyroid state – consult product literature for preparation and dose.

Unlicensed indications e.g. Resistant Depression

Whilst this monograph relates to the use of thyroid hormones for endocrinology indications, perioperative continuation of thyroid hormones for other indications is not anticipated to be problematic.

 

  References


  1. Palace, M. Perioperative Management of Thyroid Dysfunction. Health Services Insights. 2017; 10: 1-5
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 26th June 2019]
  3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 26th June 2019]
  4. Summary of Product Characteristics – Eltroxin® (levothyroxine) 100mcg tablets. ADVANZ Pharma. Accessed via www.medicines.org.uk 26/06/2019 [date of revision of the text March 2019]
  5. Levothyroxine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com. [Accessed 26th June 2019]
  6. Liothyronine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com. [Accessed 26th June 2019]
  7. Summary of Product Characteristics – Liothyronine Sodium BP 20microgram Tablets. ADVANZ Pharma. Accessed via www.medicines.org.uk 26/06/2019 [date of revision of the text October 2018]