Hypothyroidism

Authored by , Reviewed by Dr Colin Tidy | Last edited | Meets Patient’s editorial guidelines

This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Underactive Thyroid Gland (Hypothyroidism) article more useful, or one of our other health articles.


Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

For congenital hypothyroidism see the separate Childhood and Congenital Hypothyroidism article.

Hypothyroidism often has an insidious onset but has a significant morbidity. The clinical features are often subtle and nonspecific and may be wrongly attributed to other illnesses, especially in postpartum women and in the elderly.

The earliest biochemical abnormality is an increase in serum thyroid‐stimulating hormone (TSH) concentration with normal serum fT4 and fT3 concentrations (subclinical hypothyroidism), followed by a decrease in serum fT4, at which stage most patients have symptoms and require treatment (overt hypothyroidism).

  • Incidence:
    • Overt form - 2% women, 0.2% men[1].
    • Subclinical - 6-8% women, 3% men.
    • 2.5% of pregnant women develop hypothyroidism.
  • Hypothyroidism increases with age and is most common around the age of 60 years.
  • Autoimmune hypothyroidism is more common in Japan.
  • The most common cause of hypothyroidism worldwide is iodine deficiency.
  • In areas where iodine deficiency is not a problem, autoimmune and iatrogenic hypothyroidism are more commonly the cause.

Hypothyroidism results from insufficient secretion of thyroid hormones and can be due to a variety of abnormalities. The severest form is myxoedema where there is accumulation of mucopolysaccharides in the skin and other tissues, causing thickening of the facial features and associated with ventilatory dysfunction and coma[2].

Primary hypothyroidism

  • Autoimmune hypothyroidism - Hashimoto's thyroiditis (associated with a goitre) and atrophic thyroiditis.
  • Iatrogenic - radio-iodine treatment, surgery, radiotherapy to the neck - eg, lymphoma (no goitre usually).
  • Iodine deficiency - the most common cause worldwide and goitre is present.
  • Drugs - amiodarone, contrast media, iodides, lithium and antithyroid medication.
  • Congenital defects - eg, absence of thyroid gland or dyshormonogenesis.
  • Infiltration of the thyroid - eg, amyloidosis, sarcoidosis and haemochromatosis.

Secondary hypothyroidism

  • Isolated TSH deficiency.
  • Hypopituitarism - neoplasm, infiltrative, infection and radiotherapy.
  • Hypothalamic disorders - neoplasms and trauma.

Transient hypothyroidism

  • Withdrawal of thyroid suppressive therapy.
  • Postpartum thyroiditis.
  • Subacute/chronic thyroiditis with transient hypothyroidism.

Often insidious onset with nonspecific symptoms[3].

Symptoms

  • Tiredness, lethargy, intolerance to cold.
  • Dry skin and hair loss.
    HYPOTHYROID
                
  • Slowing of intellectual activity - eg, poor memory and difficulty concentrating.
  • Constipation.
  • Decreased appetite with weight gain.
  • Deep hoarse voice.
  • Menorrhagia and later oligomenorrhoea or amenorrhoea.
  • Impaired hearing due to fluid in middle ear.
  • Reduced libido.

A relationship between hypothyroidism and depression has been assumed for many years. However, the true nature of this association has been difficult to define, with many conflicting studies. Large epidemiological studies generally suggest no association between thyroid function and depression in people without thyroid disease. Patients taking thyroxine have poorer psychological well-being than those with no thyroid disease, even if biochemically euthyroid[4].

Signs

  • Dry coarse skin, hair loss and cold peripheries.
  • Puffy face, hands and feet (myxoedema).
  • Bradycardia.
  • Delayed tendon reflex relaxation.
  • Carpal tunnel syndrome.
  • Serous cavity effusions - eg, pericarditis or pleural effusions.

In autoimmune hypothyroidism, patients may have features of other autoimmune diseases - such as, vitiligo, pernicious anaemia, Addison's disease and diabetes mellitus.

Although most people with hypothyroidism do not have any associated eye problems, hypothyroidism may cause swelling around the eyes, a loss of the hairs in the outer part of the eyebrows, eye discomfort, protruding eyeballs and visual disturbance[5].

Other presentations

  • Acute kidney injury[6].
  • Hypercholesterolaemia.

This can develop into myxoedema:

  • Expressionless dull face with peri-orbital puffiness, swollen tongue, sparse hair.
  • Pale, cool skin with rough, doughy texture.
  • Enlarged heart.
  • Megacolon/intestinal obstruction.
  • Cerebellar ataxia.
  • Psychosis.
  • Encephalopathy.

Patients can go on to develop myxoedema coma (see below).

Hashimoto's and atrophic thyroiditis

  • Subclinical autoimmune thyroiditis probably represents the early stages of chronic thyroiditis with a soft or firm thyroid gland which is usually normal in size or slightly enlarged.
  • Subclinical autoimmune thyroiditis is associated with normal thyroid function.
  • Hashimoto's thyroiditis and atrophic thyroiditis probably represent two ends of the same spectrum of chronic thyroiditis. In Hashimoto's thyroiditis there is a painless goitre of varying size with a rubber consistency and irregular surface. Thyroid function varies from normal to subclinical or overt hypothyroidism.
  • Atrophic thyroiditis represents the end stage of autoimmune hypothyroidism and patients are overtly hypothyroid.
  • Excessive iodine intake can lead to autoimmune hypothyroidism.
  • Autoimmune hypothyroidism is uncommon in children. It presents as delayed growth and facial maturation. Puberty may also be delayed. In very young children there may be intellectual impairment.

Postpartum thyroiditis

This occurs in 5-7% of pregnancies within the first six months postpartum[7]. Most women show complete remission but some may progress to permanent hypothyroidism.

Subacute thyroiditis

Also referred to as granulomatous, giant cell or de Quervain's thyroiditis - a viral infection produces local symptoms and exquisite tenderness of the thyroid gland with nodularity. Initially patients are thyrotoxic but later they become hypothyroid.

The symptoms of hypothyroidism are not specific to underactivity of the thyroid gland and it is therefore essential to diagnose hypothyroidism with TFTs because it can be dangerous to take levothyroxine or other thyroid hormones if they are not clinically indicated.

Offer tests for thyroid dysfunction to adults, children and young people with type 1 diabetes or other autoimmune diseases, or new-onset atrial fibrillation. Also consider tests for those with depression or unexplained anxiety. In addition for children and young people with abnormal growth, or unexplained change in behaviour or school performance.

Be aware that symptoms of thyroid dysfunction may be mistaken for menopause.

The National Institute for Health and Care Excellence (NICE) suggests measuring thyroid stimulating hormone (TSH) alone for adults and if the TSH is above the reference range, measure free thyroxine (FT4) in the same sample. If the TSH is below the reference range, measure FT4 and free tri-iodothyronine (FT3) in the same sample[8].

Condition
TSH
Free T4
Free T3
Thyroid hormone resistanceRaised or normalRaisedRaised
Primary hypothyroidismRaisedLoweredLowered or normal
Secondary hypothyroidismLowered or normalLoweredLowered of normal
  • Anti-thyroid peroxidase (anti-TPO) antibodies or anti-thyroglobulin antibodies are found in 90-95% of patients with autoimmune thyroiditis. NICE recommends measuring thyroid peroxidase antibodies (TPOAbs) for adults with TSH levels above the reference range, but not repeating TPOAbs testing[8].
  • Untreated hypothyroidism may be associated with a raised CK, raised cholesterol and triglycerides and anaemia (normocytic or macrocytic). These abnormalities usually resolve with treatment.
  • If the patient has an asymmetrical goitre then they may need imaging of their thyroid gland - eg, ultrasonography - to rule out neoplastic lesions.

Neonates - investigations include ultrasonography or 123I scintigraphy, serum thyroglobulin and low molecular weight iodopeptides to differentiate different types of defects. Total urinary iodine excretion will differentiate between inborn errors of metabolism and hypothyroidism due to iodine deficiency or excess. 

Clinical hypothyroidism[8]

  • When a sufficient dose of thyroid treatment is given to lower the TSH to within the normal reference range for the test method used, patients usually recover from the symptoms of hypothyroidism. Some patients may require fine-tuning of TSH levels inside the reference range.
  • Patients whose thyroid blood tests are within the reference ranges but who have continuing symptoms, whether on levothyroxine or not, should be further investigated for a non-thyroid cause of their symptoms.
  • Start levothyroxine at a dosage of 1.6 micrograms per kilogram of body weight per day (rounded to the nearest 25 micrograms) for adults under 65 with primary hypothyroidism and no history of cardiovascular disease (CVD).The usual maintenance dose is 100-200 micrograms once daily.
  • Start levothyroxine at a dosage of 25 to 50 micrograms per day with titration for adults aged 65 and over and adults with a history of CVD.
  • TSH should be measured every three months until the level has stabilised (two similar measurements within the reference range three months apart), and then once a year. The patient needs to be informed that symptom relief may take many months and even up to six months after TSH levels have normalised.
  • Drugs, such as ferrous sulfate, calcium supplements, rifampicin and amiodarone can interfere with T4 absorption.

In its guidance for CCGs on items which should not routinely be prescribed in primary care[9], NHS England advises that liothyronine (sometimes known as T3) should not be initiated in primary care for any new patient. Patients currently prescribed liothyronine should be reviewed by a consultant NHS endocrinologist with consideration given to switching to levothyroxine where clinically appropriate. In exceptional cases, a local decision, involving the Area Prescribing Committee (or equivalent), may be made regarding arrangements for ongoing prescribing of liothyronine for individual patients in whom an ongoing need has been established by an NHS endocrinoligist after a carefully audited trial of at least three months' duration of liothyronine.

Subclinical hypothyroidism[8]

Subclinical hypothyroidism occurs when a patient has a TSH level above the upper limit of the reference range (but usually less than 10 mU/L) and free T4 levels are within the reference range.

The population prevalence of subclinical hypothyroidism is approximately 5-10%. It is common and increases with age, affecting up to 18% of the elderly, with a higher prevalence in women compared to men.

Treat patients with a history of radio-iodine treatment or positive thyroid antibody test, as this subgroup will nearly always progress to overt hypothyroidism.

Levothyroxine treatment should be considered for adults with subclinical hypothyroidism who have a TSH of 10 mlU/L or higher on two separate occasions three months apart. A six-month trial of levothyroxine should also be considered for adults under 65 with subclinical hypothyroidism who have a TSH above the reference range but lower than 10 mlU/L on two separate occasions three months apart, and symptoms of hypothyroidism. If symptoms do not improve after starting levothyroxine, re-measure TSH and if the level remains raised, adjust the dose. If symptoms persist when serum TSH is within the reference range, consider stopping levothyroxine and follow the recommendations on monitoring untreated subclinical hypothyroidism and monitoring after stopping treatment.

If none of the above is present, then monitor TSH every 6-12 months. If symptoms begin then a trial of thyroxine may be warranted, as above.

Children

  • Very rarely, levothyroxine therapy can cause pseudotumour cerebri in children.
  • It is an idiosyncratic reaction and presents with raised intracranial pressure and can occur months after treatment.

Pregnancy

  • Women of childbearing age should be encouraged to wait until they are euthyroid before trying to conceive[10].
  • It is important to maintain a euthyroid state throughout pregnancy, especially during the first trimester[7].
  • Measure TFTs during the first, second and third trimesters for all pregnant women with known hypothyroidism.
  • TSH is a sensitive marker of thyroid dysfunction during pregnancy[11].
  • Treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes[12].
  • Levothyroxine dose may need to be increased by more than 50% during pregnancy. The dose can usually be reduced postpartum[13].

Older patients and comorbidity

There are certain patients for whom the recommended initial dose of levothyroxine is 25 micrograms once daily, adjusted in steps of 25 micrograms every four weeks according to response. These include:

  • Patients with cardiac disease.
  • Patients with severe hypothyroidism.
  • Patients aged over 50 years.
  • Myxoedema coma is seen mostly in elderly patients and is associated with a mortality rate between 20% and 50%.
  • Patients may be on treatment for hypothyroidism or be previously undiagnosed.
  • Infections and discontinuation of thyroid supplements are the major precipitating factors[15].
  • Patients present with[1]:
    • A reduced level of consciousness.
    • Seizures
    • Hypothermia
    • Features of hypothyroidism.
  • Precipitating factors include sedative drugs and anything that impairs the respiratory system - eg, pneumonia, cardiac failure and myocardial infarction[16].
  • Hypoventilation plays a major role with resulting hypoxia and hypercapnia.
  • Metabolic disturbances are also prominent, including hyponatraemia and hypoglycaemia.

Treatment[17]

  • Intravenous levothyroxine is used - usually start with a loading dose and then a lower dose for maintenance on a daily basis.
  • Other therapy is usually supportive - eg, correct metabolic disturbances, patient warming if hypothermic and treatment of precipitating factors.
  • Patients may need to be intubated and ventilated if respiratory impairment is severe.
  • Intravenous hydrocortisone is also required, as impaired adrenal function is present in profound hypothyroidism (but send a random blood cortisol first).

Further reading and references

  • Okosieme O, Gilbert J, Abraham P, et al; Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. Clin Endocrinol (Oxf). 2016 Jun84(6):799-808. doi: 10.1111/cen.12824. Epub 2015 Jun 25.

  1. Hypothyroidism; NICE CKS, June 2018 (UK access only)

  2. Skin problems associated with thyroid disease; DermNet NZ

  3. Gaitonde DY, Rowley KD, Sweeney LB; Hypothyroidism: an update. Am Fam Physician. 2012 Aug 186(3):244-51.

  4. Dayan CM, Panicker V; Hypothyroidism and depression. Eur Thyroid J. 2013 Sep2(3):168-79. doi: 10.1159/000353777. Epub 2013 Aug 27.

  5. Hiromatsu Y, Eguchi H, Tani J, et al; Graves' ophthalmopathy: epidemiology and natural history. Intern Med. 201453(5):353-60.

  6. Liakopoulos V, Dovas S, Simopoulou T, et al; Acute renal failure: a rare presentation of hypothyroidism. Ren Fail. 200931(4):323-6.

  7. Lazarus JH, Premawardhana LD; Screening for thyroid disease in pregnancy J Clin Pathol. 2005 May

  8. Thyroid disease: assessment and management; NICE (November 2019)

  9. Items which should not routinely be prescribed in primary care: Guidance for CCGs; NHS England

  10. Alexander EK, Pearce EN, Brent GA, et al; 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017 Mar27(3):315-389. doi: 10.1089/thy.2016.0457.

  11. Krassas G, Karras SN, Pontikides N; Thyroid diseases during pregnancy: a number of important issues. Hormones (Athens). 2015 Jan-Mar14(1):59-69.

  12. Lazarus J, Brown RS, Daumerie C, et al; 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014 Jun3(2):76-94. doi: 10.1159/000362597. Epub 2014 Jun 7.

  13. Bach-Huynh TG, Jonklaas J; Thyroid medications during pregnancy. Ther Drug Monit. 2006 Jun28(3):431-41.

  14. Wiersinga WM; Myxedema and Coma (Severe Hypothyroidism)

  15. Mathew V, Misgar RA, Ghosh S, et al; Myxedema coma: a new look into an old crisis. J Thyroid Res. 20112011:493462. doi: 10.4061/2011/493462. Epub 2011 Sep 15.

  16. Savage MW, Mah PM, Weetman AP, et al; Endocrine emergencies. Postgrad Med J. 2004 Sep80(947):506-15.

  17. Elshimy G, Correa R; Myxedema

I posted on here the other day, trying to find some answers! I recently found out I was over medicated! I went on a higher dose and my tsh went from 52 to .14 in 3 weeks! I was on that dose which was...

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