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«‘Medical’ thyroid disease Issues for the GP Dr Simon Page Advice and Guidance • 90 A+G requests July-Dec 2014 • 41 related to thyroid disease ...»

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‘Medical’ thyroid disease

Issues for the GP

Dr Simon Page

Advice and Guidance

• 90 A+G requests July-Dec 2014

• 41 related to thyroid disease management

– Sub clinical hyperthyroidism 12

– Hyperthyroidism 3

– Thyroid and pregnancy 2

– Hypothyroidism 7

– Sub clinical hypothyroidism 6

– Positive TPO antibodies 2

– T4/T3 combination therapy 3

– Amiodarone 1

Case 1 - Hyperthyroid I would be grateful for your advice on this 46 year old lady who has been seen by my colleague for weight loss and tremors. She has also been finding that her periods have stopped but she has no change in bowel habits. Patients initial concern was around if she was suffering from cancer and on blood testing she has been found to be hyperthyroid. Her eyes have also become more prominent but I have asked her to check if this has always been the case by checking some previous photographs. She is fairly certain this a definitely a change. She also has a family history with her mum and siblings who have had thyroid problems. Her thyroid antibody results are positive.

I have given her the treatment options and currently she would prefer Carbimazole and I have started her on 15mgs daily with a repeat TFT to be done in one months time. She has been advised about implications for her blood counts and she will be having her FBC done at the same time as her TFT but is aware of the risk of sore throat.

Based on the investigations I believe that this is hyperthyroidism of autoimmune origin and I can not feel any goitre in the neck but I would like to ascertain whether there are any further investigations which need to be done. Do we need to give her any different treatment? She is not keen on radioiodine initially as she works as a carer and this would have implications I would value your advice on her management Case 2 - Hyperthyroid Thank you for your advice on this 32 year old lady who is previously known to Dr (Renee) Page with thyrotoxicosis. She was initially diagnosed in 2007, however she has defaulted several appointments.

Eventually she was discharged from your clinic after she did not attend an appointment in 2009. She has been fairly stable on a dose of Propylthiouracil 50mg a day which she has been on from at least 2011, prior to that she had taken 100mg a day for a short period as well.

Her most recent TSH in July 2012 was 3.6 and she is asymptomatic in herself.

I was wondering what the long term plan would be in terms of her monitoring and whether she is to stay on PTU? If you feel you need to see her in clinic to discuss more therapeutic options or whether we need to monitor her more carefully in primary care.

Please let me know.

Diagnosis–diseases to consider Causes Drug-induced

• Amiodarone

• The top thr

–  –  –

Wartofsky et al., Thyroid 1991, 1, 129-135 Hyperthyroid management - NICE

• Thionamide therapy (CBZ and PTU) with a confirmed biochemical diagnosis of hyperthyroidism. Not essential for mild disease if prompt definitive treatment with radioiodine is planned.

• PTU not recommended first line, (bd or tds dosing, risk of severe

liver injury, ANCA positive vasculitis), except in:

– First trimester of pregnancy.

– Thyroid storm.

– People with minor reactions to CBZ who refuse radioactive iodine or surgery.

• NICE CKS recommends seeking specialist advice before initiating thionamide therapy.

–  –  –

Abraham et al., Cochrane Library of Systematic Reviews. www.thecochranelibrary.com ATD: Titration vs B @ R 12 trials

• Relapse rates similar T 54% vs B@R 51%

–  –  –

I agree that Ms Bowen has autoimmune thyroid disease – likely Hashitoxicosis given the TPO titre of 1300. Starting carbimazole as you have done is the right thing to do since she needs to have her thyroid hormone levels lowered to the normal range as soon as possible to help with symptoms. You may consider treatment with propranolol 10-20mg tds if her symptoms are marked and she has no contraindication – this could be withdrawn once her TFT have improved.

I assume this is her 1st episode? If so then a 12 month course of carbimazole is reasonable, with TFT monitoring every 6-8 weeks and dose titration to deliver normal range T4 and T3 levels. After this the CBZ can be withdrawn to see if she has gone into remission – post treatment TFT bloods at 4 and 12 weeks after stopping CBZ are advised. Assuming she remains euthyroid, then further TFT would be required only if she developed further symptoms. Having said that an annual TFT to spot early hypothyroidism would be appropriate given the high TPO antibody level.

A scan of the thyroid is not required.

10th Oct 2014 fT4 40 fT3 17.2 TSH 0.1 15th Jan 2015 TSH 4.2 Case 2 - Hyperthyroid

• Thanks for this A+G request. She was seen by Dr Renee Page in

2009. She has a diagnosis of autoimmune thyroid disease with raised TPO antibodies. Therefore it is reasonable to consider that she might have gone into remission and her TSH is now detectable.

• I would suggest stopping the PTU and repeating her TFT in 4 weeks and 12 weeks time to look for any early signs of recurrent hyperthyroidism. If she remains euthyroid then no further monitoring is needed unless she develops recurrent symptoms.





• If her hyperthyroidism recurs then re-start PTU and arrange a referral to the endocrine service at the Treatment Centre.

• TSH – July 2014 3.3 – Jan 2015 2.6 Sub-clinical hyperthyroidism

• What is it?

– ‘Normal’ fT4 and fT3 – Suppressed TSH

• Does it matter?

– 3-5 fold increased risk of AF – Increased risk of osteoporosis Case – subclinical hyperthyroidism A&G Endocrinology Reason for referral - Subclinical hyperthyroidism I would value your opinion as to whether any further investigation is warranted for this 75 year old lady. She has had a suppressed TSH but normal T4 (current level 14.2) and T3 current level 6.2 since 2001. She has osteoporosis and review of her thyroid status has been requested by the Metabolic bone team prior to commencement of treatment. She is asymptomatic.

I would value your advice as to whether anything further is required. She is not keen to have an out-patient appointment unless this is absolutely necessary.

She is generally fit and healthy, aside from the osteoporosis. She takes Calcium and Vitamin D but no other regular medication. She has regular follow-ups for mild aortic regurgitation, which is not progressive and asymptomatic.

Yours sincerely Case – subclinical hyperthyroidism Thanks for this A+G request This patient has had sub-clinical hyperthyroidism since at least May 2000 – her T4 levels are mid range but her T3 is at the upper end of the range. Likely cause is nodular thyroid disease. This is acknowledged as a contributory factor in osteoporosis.

Reasonable to treat, although there are no clinical trials to support this recommendation – it is endorsed by 2011 American Thyroid Association Guidelines – I suggest starting Carbimazole 5mg daily and review TFT in 6 and 12 weeks – ideally you would want the TSH to return to the normal range but it may not do so for a while as it has been suppressed for so long.

If tolerated then low dose CBZ may be appropriate in the long term, but a dose of RAI is also an option which could be considered – perhaps try medical therapy 1st Case - SCH • 76 year old male

• Cognitive impairment

• PAF

–  –  –

• Recommendation 65 – When TSH is consistently ( 3 mths) 0.1 mU/l then treatment should be strongly considered in patients

• Over 65 yrs of age

• Post-menopausal women not on HRT or bisphosphonates

• Patients with cardiovascular risk factors

• Patients with cardiac disease

• Patients with osteoporosis

• Patients with symptoms of hyperthyroidism

• Recommendation 66 – When TSH is consistently ( 3 mths) below the lower limit of normal but 0.1 mU/l then treatment should be considered in patients

• Over 65 yrs of age

• Patients with cardiac disease

• Patients with symptoms of hyperthyroidism ATA Guidelines 2011 Thyroid disease and pregnancy Thyroid disease and pregnancy

• Key points – Positive TPO antibodies in 1st trimester predict:

• Post partum thyroiditis

• Increased risk of miscarriage – Mild hyperthyroidism in 1st trimester (HCG)

• Does not usually require treatment

• May be associated with hyperemesis – Increased TBG (and other binding proteins) lead to increased total T4 levels during pregnancy

• If on thyroxine dose adjustment 25-50% usually needed

• Pregnancy specific reference ranges A+G request – pre pregnancy M is trying for a second pregnancy…… TSH was normal at 2.8 mu/L. Saw a Dr whilst visiting Poland in April 14.

Repeat bloods TSH 7, TPO antibodies positive. She was started on thyroxine 50mcg od.

UK review May 2014; stop thyroxine for 3 weeks to repeat TFT to see if she was hypothyroid or not. 16th June TSH of 4.0, TPO antibody at 666.9 iu/mL.

Clearly she is not currently hypothyroid, but it would appear that she was borderline in Poland. She is aware that she is likely to develop hypothyroidism in the future. Keen to conceive, anxious that the thyroid may be contributing to her oligomenorrhoea. She would be keen to take low dose thyroxine if this returned her to a regular cycle.

A+G request - pre pregnancy

• My advice would be to re-commence low dose thyroxine therapy – initially 25 mcg daily with repeat TFT 4-6 weeks later – the objective would be to keep the TSH level in the range 0.3-2.5 mU/l which is considered optimal for women planning pregnancy.

The T4 dose may need to be titrated to achieve this.

• TSH – July 2014 4.0 – Oct 2014 3.3 – Dec 2014 2.0 fT4 16.4 fT3 5.2 BMJ 2011, May 9;342

• Association between thyroid autoantibodies and miscarriage and preterm birth: metaanalysis of evidence.

– The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.

T4 in Euthyroid Women with Positive TPO Antibodies

–  –  –

‘These will be appended to our reports but please note that these are only added if we are aware that the patient is pregnant’.

Pregnancy and Thyroxine

• Check thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels before conception if possible.

• At diagnosis of pregnancy, immediately increase the levothyroxine dose (25-50 mcg) and check TSH and FT4 levels while waiting for referral to a specialist.

• Monitor TSH and FT4 levels:

– Every 4 weeks during titration of levothyroxine.

– Every 4 weeks during the first trimester, and again at 16 weeks and at 28 weeks of gestation, in a woman who is on a stable dose of levothyroxine.

– More frequent tests may be appropriate on specialist advice.

–  –  –

I would be most grateful for your advice regarding the above named gentleman. He has been diagnosed with vitiligo a few months ago and he was seen in the skin clinic. He was given steroids for his vitiligo.

The skin clinic arranged some thyroid tests.

I have recently reviewed his results and his TSH has come back as 1.9. His thyroid peroxidase antibody level was 745.5 which is way above the upper normal limit.

Clinically this chap is euthyroid and he has got no complaints regarding thyroid dysfunction.

I was wondering about the significance of the elevated thyroid peroxidase antibody level or whether we should just monitor things.

I would be most grateful for your advice regarding this. Thank you.

Positive TPO antibodies Dear Dr X The positive TPO antibodies indicate Hashimoto’s thyroiditis, although currently his TSH is normal suggesting normal thyroid function.

He has a 2-3% annual risk of developing progressive hypothyroidism. Hence an annual monitoring set of thyroid function tests is recommended. If hypothyroidism develops then he would require treatment with an appropriate dose of thyroxine.

–  –  –

This lady was noted to have hypothyroidism in 2010 but was not taking her thyroxine in 2011 and was persuaded to start doing so in July 2011.

You will be able to see her results on NoTIS.

Essentially her TSH has gradually fallen as the dose of thyroxin has been increased. The latest dose was up to 225 and her TSH in November 2014 was 9.8.

She tells me she is still taking the same amount of drug but her TSH has risen to 65, T4 of 4.2 on a dose of 225.

I cannot believe that her requirements are so great to cause this change and it does look at though the poor adherence to agreed therapy. Can you advise if you do ever see cases where patients do require significantly high doses, and if so how one plays it so to minimise risk.

–  –  –

• There was no effect with H2 receptor antagonists or glucocorticoids.

Irving et al., Clin Endocrinol. 2015;82(1):136-141.

Other considerations

• Variation associated with brand of T4 used – Reassess 6-8 weeks post change

• Atrophic gastritis (Pernicious anaemia) – May require dose adjustment

• H Pylori gastritis – Reassess once treated

• Coeliac disease – Reassess once on GFD

• Short bowel syndrome – 1 mg T4 daily – personal experience ATA guidelines 2014 Thyroid 2014, 12, 1670-1751 Compliance – an option ■ Recommendation

• If prescription of daily levothyroxine is not successful in maintaining a normal serum thyrotropin, weekly oral administration of the full week's dose of levothyroxine should be considered in individuals in whom adherence cannot otherwise be sustained.

• Supraphysiological T4 levels for 24 hrs, fT3 and TSH remain stable

• Weak recommendation. Low-quality evidence.

ATA guidelines 2014 Thyroid 2014, 12, 1670-1751 Try not to Fiddle!

Recommendation



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