Dr Chris Sinclair-Wilson, Dr James Law, Dr Vikram Baicher
Although we don’t come across it every day, thyroid disease is relatively common in the paediatric population, occurring in up to 15 per 1000 children – and is more often seen in teenagers and young girls. HyPOthyroidism is more common than hyPERthyroidism. With non-specific symptoms like weight change, lack of energy and behavioural or mood changes, it can be tricky to diagnose unless you think carefully.
In this article we will take you through a case which highlights some of the challenges that come up when thyroid disease overlaps with an acute illness.
Towards the end of the article we’ll discuss management in the longer term and some ‘Top Tips’ to incorporate into your own practice. Let’s go!
Rebecca’s story
You’re on a day shift in the Paediatric Emergency department. The next patient to be seen is 14-year-old Rebecca, who’s here with her mum. She has been feeling generally unwell, and her current symptoms are two days of abdominal discomfort and fever, and an episode of diarrhoea & vomiting.
Mum says Rebecca has not been quite right for the last 4 weeks and she is worried that Rebecca’s latest symptoms are a sign of an underlying problem that is worsening.
A month ago, Rebecca had a sore throat and fever, and was diagnosed with Scarlet Fever by her GP. She completed a ten-day course of oral antibiotics and improved, however according to her mum ‘Rebecca has never quite got better’ and has since had increased lethargy, weight loss, palpitations, dizziness & headaches. She shows you a picture of Rebecca prior to the last month on her mobile and you agree she has had significant weight loss.
Rebecca used to enjoy sports at school but is now barely able to take part. Rebecca went back to her GP due to ongoing symptoms who arranged blood tests. The results were phoned through to the family in the last 24hr and were told Rebecca has a problem with her thyroid gland. Sadly, you don’t have access to Rebecca’s blood results.
There have been no new rashes or swellings, no current respiratory or urinary tract symptoms. She has no ear, nose, or throat symptoms. Headaches are mild, generalised and intermittent with no photophobia or neck stiffness. It’s been difficult for Rebecca to concentrate at school. She is currently on day four of her period. Rebecca has not had any bilious vomiting or PR bleeding. Her abdominal pains are generalised, cramping with no clear alleviating or exacerbating factors. She developed a fever this morning and had some paracetamol but vomited it back up 10mins later.
Rebecca’s past medical history is unremarkable, apart from mild asthma for which she takes Salbutamol and Clenil inhalers. There are no other medications currently and she is allergic to cow’s milk and egg whites.
Rebecca’s younger brother currently has upper respiratory tract symptoms but otherwise there is nothing to note from her social or family history.
You move on to the examination…
General: Rebecca is alert and orientated but appears slightly pale with a slim build. There is no respiratory distress and is well perfused. She is on the quiet side and she lets Mum do most of the talking.
A: Patent, own. No stridor/wheeze.
B: Clear – no cough, wheeze, crepitations or significant use of accessory muscles.
C: Heart sounds normal. CRT<2 seconds with warm peripheries and wet membranes. Radials are equal, regular and of increased rate & volume. Rebecca’s calves are soft, non-tender and have no oedema.
D: GCS 15, pupils equal & reactive to light with 4mm diameter in both. There is no exophthalmos, neck stiffness or photophobia.
E: Abdomen is soft but with some mild tenderness in right iliac fossa. There is no guarding, jaundice, masses, or distension. There is no rebound tenderness and there is no evidence of peritonism.
No abnormalities detected to ears, nose, throat, nails.
No concerning rashes observed including to shins.
No cervical lymphadenopathy.
Unfortunately, despite her previous use of paracetamol she is still scoring highly on PEWS.
RR: 38
Sats: 100% room air
HR: 152 bpm
BP: 122/78
Temperature: 38.9°C
AVPU: Alert
Respiratory effort: Mild
Appearance: Pale
PEWS Total: 12
You pause to think about differentials…
Differential Diagnosis | Symptoms which support potential diagnosis | Symptoms making diagnosis less likely |
Hyperthyroidism | Inattention Palpitations Weight loss Fatigue Bowel changes Tachycardia Vomiting | Fever (unless thyrotoxic storm – rare)RIF tenderness |
Appendicitis | RIF tenderness Fever 1-day history of D&V | 1 month history of constitutional symptoms |
UTI | Fever Vomiting RIF tenderness | 1 month history of constitutional symptoms |
Ruptured ectopic pregnancy | RIF tenderness | GI upset Fever 1 month history of constitutional symptoms Current menstruation |
Sepsis (of unknown source) | Fever GI upset Headache RIF tenderness | 1 month history of constitutional symptoms |
Anaemia | Fatigue Inattention Palpitations Dizziness | Fever GI upset Weight loss |
Eating disorder | Weight loss Inattention Palpitations Dizziness Fatigue Tachycardia | Fever RIF tenderness |
Influenza | Fever GI upset RIF tenderness | 1 month history of constitutional symptoms |
PLAN
Given the broad spread of potential diagnosis you chat to your consultant and decide to investigate with the following tests:
- Send routine sepsis bloods including venous blood gas, cultures, CRP, thyroid function tests, thyroid antibodies (TPO and TSH-R)
- Urinalysis including β-HCG
- ECG
- Lying/Standing BP
- IV fluid bolus
- IV broad-spectrum antibiotics
- Antipyretics & Antiemetics
Rebecca remains stable and is chatting to her mum whilst the results arrive
Blood Gas
Lab bloods
With some results now available you return to your differentials…
Diagnosis | Likelihood | Reasons |
Appendicitis | Low | CRP, WCC & Lactate all normal |
UTI | Low | Normal urinalysis, CRP & WCC |
Ruptured ectopic pregnancy | Low | Negative β-HCG & normal Lactate |
Sepsis (of unknown source) | Low | Normal CRP, WCC & Lactate |
Anaemia | Low | Normal Hb |
Hypothyroidism | Low | Circulating levels of T4 & T3 hormone levels are raised with a suppressed TSH level through negative feedback. In hypothyroidism you would expect the opposite. |
Hyperthyroidism | Strong | Raised T4 & T3, reduced TSH. This tells you the thyroid is overactive, but doesn’t tell you why. For that, you need the antibody levels. In Rebecca’s case her Thyroid Peroxidase Antibodies were 454 (range 0-6) and Thyroid Antibodies were 6.0 (range 0-0.9) |
Eating disorder | Low | Normal levels of electrolytes & glucose. Tachycardia on ECG rather than bradycardia. |
Influenza | Moderate | Mild lymphopenia |
You discuss the results and history with your hospital’s Paediatric Endocrinologist who advises:
- Start Carbimazole 20mg OD orally as tolerated
- Consider adding oral Propranolol TDS with caution, given her history of asthma
- Carbimazole will not correct thyroid function immediately but instead take 4-6 weeks to achieve euthyroid status. Whereas the Propanolol will have a more immediate effect on the patient’s clinical state/symptoms.
- Remember that Carbimazole’s most concerning side effect is agranulocytosis – which is rare – but will usually happen in the first 3 months of treatment if at all. Your teenage patients may need contraception – carbimazole can be teratogenic particularly when used in the first trimester at doses of >15mg.
- Avoid physical exertion until advised safe by endocrinology team.
Rebecca was admitted to the ward where she had repeat blood tests for infection. Cultures were negative but she was positive for Influenza A.
While on the ward, Rebecca met saw the Paediatric Endocrinology team who continued Carbimazole and arranged monthly thyroid function tests as well as a follow-up review in clinic. She was also given a low dose of propranolol for short term control of her thyroid symptoms. Her antibiotics were stopped on day 3, and by day 4 her symptoms of fever and GI upset had settled and she was discharged home.
Two months later Rebecca’s blood tests show normal levels of T4 & T3 and she is back to doing all her normal activities.
Rebecca’s final diagnoses:
- Flu A
- Grave’s disease – untreated
You reflect on Rebecca’s case and wonder when, as an A&E doctor, you might need to consider Hyperthyroidism as a diagnosis. This is what the helpful endocrinologist has to say…
Incidence
Thyrotoxicosis is rare, and is even less common in children, only occurring in 0.9 patients per 100,000 children aged under fifteen – a real ‘unicorn’ to spot. There are only about 85 cases per year in England (so you can be pretty satisfied if you make this tricky diagnosis!) Girls are much more likely to be affected than boys, particularly between the ages of 10-14 years of age. The most common type is Graves’ disease (84%) where the TSH receptor is activated by auto-antibodies.
Clinical presentation
The main features you will commonly see in a patient with thyrotoxicosis are weight loss, fatigue/lethargy and changes to behaviour (other symptoms detailed in the table below). The median length of time from onset to diagnosis for these symptoms is 3 months.
The most common clinical feature in children with thyrotoxicosis is goitre followed by tremor and lid retraction (see more in the table below). You can ask if handwriting has changed recently – this is a good way of picking up a fine tremor.
Figures A-C : Exophthalmos and Goitre in a paediatric patient (Image credit: https://www.researchgate.net/figure/A-A-3-year-old-girl-with-Graves-disease-A-C-Clinical-features-include-a-goiter-and_fig1_267743723).
Initial investigations in children (https://www.nice.org.uk/guidance/ng145)
*TPOAbs are found in 90% of people with Hashimoto’s disease and 75% of people with Graves’ disease. They are produced by lymphocytes that infiltrate the thyroid gland and are directly responsible for Hashimoto’s disease which may have a hyperthyroid phase. They are easier to measure than TRAb and so are often measured first in adults; in children TPO antibodies and TRAb should both be measured once the diagnosis of hyperthyroidism is made.
Treatments
- Offer children or young people at least 2 years of antithyroid drugs as a first line treatment, with latest guidance recommending 3 years
- 1st line: Carbimazole 0.5-0.75mg/kg/day orally once per day ()
- FBC & LFTs should be checked first
- Dose will need to be titrated according to thyroid hormone levels for first 4 months
- Euthyroid state usually achieved after 4-8 weeks of treatment
- Thyroid storm (thyrotoxic crisis) is vanishingly rare but is a possibility and is life threatening. If suspected should be managed as follows:
- IV fluids, Propranolol, Hydrocortisone, Antithyroid medication – both Carbimazole & Propylthiouracil are oral so you may need to consider IV iodide (radiographic dyes) or use both.
- Treat precipitating factor: Surgery, abrupt withdrawal, infection.
Key Learning Points
- Thyrotoxicosis is rare but symptoms can be vague and non-specific – meaning alternative diagnoses may need to be considered; in this case, how much was flu A and how much was hyperthyroidism? If in doubt, it may be necessary to treat for both whilst awaiting further results.
- Young people most commonly present in the early teens and girls are much more likely than boys to have it.
- The main complaints are usually weight loss, fatigue & changes in behaviour, typically over a period of months. These may be confused with symptoms of anorexia nervosa and you will need a good history/examination with thyroid function bloods to help differentiate.
- Most children will have a goitre and/or tremor.
- Antithyroid drugs generally take weeks to months to correct the hormone imbalance, but adrenergic symptoms can be treated straight away with beta-blockers.
- Cases should be discussed promptly with a local endocrinologist.
Authors
Dr Chris Sinclair-Wilson, Registrar in Accident and Emergency; Dr James Law, Consultant in Paediatric Endocrinology; Dr Vikram Baicher, Consultant in Paediatric Emergency Medicine. All authors affiliated to Queens Medical Centre, Nottingham, UK