Hypothyroidism/Hyperthyroidism

Rashmy Amuthan16/04/2014

Hypothyroidsim

• is the clinical consequence of deficient secretion by the thyroid gland. It is a common condition that often presents with non-specific symptoms.

• It may be classified on the basis of:-The time of onset — congenital or acquired.-The level of endocrine dysfunction — primary

(thyroid gland) or secondary (central — pituitary or hypothalamic dysfunction).

-Severity — overt or subclinical.

Overt/Subclinical• Overt hypothyroidism is diagnosed by a serum thyroid-

stimulating hormone (TSH) concentration above the normal reference range (the TSH concentration is almost always greater than 10 mU/L in overt hypothyroidism) and a serum free thyroxine (FT4) concentration below the reference range. Clinical features of hypothyroidism may be absent or present.

• Subclinical hypothyroidism is diagnosed by a TSH concentration above the reference range with an FT4 concentration within the reference range, confirmed on repeat testing after at least 3 months. Clinical features of hypothyroidism are usually absent.

Causes of Hypothyroidism

• Worldwide, iodine deficiency is the most common cause of hypothyroidism, but is a rare cause in the UK/Ireland.

• In the UK, hypothyroidism is usually due to autoimmune hypothyroidism or thyroid damage after surgery or radioactive iodine therapy

Causes of 1’ hypothyroidism

• Autoimmune thyroiditis: most common cause of acquired HypoT

• Injury to thyroid gland• Drug adverse effects: iodine and iodine-

containing medication such as amiodarone, lithium, interferon, Tamoxifen, etc

• Thyroid Infiltration: amyloidosis, sarcoidosis, Haemochromatosis

• Congenital HypoT

Causes of 2’ Hypothyroidism

• Pituitary underactivity: pituitary tumour, surger/radiotherapy/trauma to pituitary, Sheehan’s syndrom (postpartum pituitary necrosis)

• Isolated TSH def or inactivity• Hypothalamic disease: Tumors,

surgery/radiotherapy/trauma, infiltrative disease• Drugs: Bexarotene (an antineoplastic drug, used to

treat skin manifestations of cutaneous T-cell lymphoma) and other retinoids

Prevalence• Overt hypothyroidism:• 1.9% in women and 0.1% in men .• 0.5–5.0% in men and women older than 60 years of age, being more

prevalent in women.• Subclinical hypothyroidism:• 8% in women and 3% in men in an iodine-replete population, such as the UK

.• 10% in women older than 55–60 years of age.• In pregnancy:• The incidence of overt hypothyroidism is approximately 0.3–0.5.• The incidence of subclinical hypothyroidism is approximately 3–5.• Congenital hypothyroidism:• Occurs in 1 per 4000 live births

Symptoms• Current or increased constipation.• Current or increasingly hoarse voice.• Current deep voice.• Feeling colder.• Puffier eyes.• Weaker muscles.• Ask about other symptoms:• Deeper voice.• Drier skin.• Increasing tiredness.• More muscle cramps.• Slower thinking, poor concentration (some elderly people may present with symptoms of dementia).• Poorer memory.• Weight gain with poor appetite.• Hair loss.• Menstrual disturbance, including amenorrhoea, oligomenorrhoea, polymenorrhoea, and menorrhagia.• Paraesthesia in hands and arms (due to carpal tunnel syndrome).• Depression.• Infertility.• Decreased libido.• Hearing loss.• Prior symptoms of hyperthyroidism — thyroiditis (subacute and postpartum) commonly presents with transient symptoms of

hyperthyroidism lasting for 1–4 weeks, followed by a phase of hypothyroidism lasting 4–12 weeks before thyroid function normalizes.• Thyroid pain.• Subacute (de Quervain's) thyroiditis commonly presents with thyroid pain, which often radiates to the ears.• Silent thyroiditis (usually seen as postpartum thyroiditis) presents with an absence of thyroid pain.

Unusual Symptoms• Unusual presentations of hypothyroidism• Hypothermia.• Congestive cardiac failure.• Pericardial and pleural effusions.• Ileus and intestinal pseudo-obstruction.• Psychosis.• Ataxia.• Coma.• Have a heightened suspicion for investigation in pregnancy — if

such symptoms as constipation, weight gain, or fatigue predate the pregnancy, or are particularly troublesome, have a low threshold for investigation of thyroid function.

Clinical signs• Clinical signs may be absent.

Look for:

• Deep voice or hoarseness.• Slowed movements.• Slowly relaxing tendon reflexes, such as prolonged ankle reflex time, and sometimes ataxia.• Dry, coarse, pale, or yellowish skin (due to carotene accumulation).• Periorbital oedema, proptosis, conjunctival injection and oedema, restrictive extraocular myopathy, and exposure keratitis. These signs are more

common in Graves' disease, but can occur in 4–9% of people with chronic autoimmune thyroiditis.

• Sparse coarse hair.• Generalized myxoedema (non-pitting oedema).• Hypothermia.• Bradycardia, heart failure, pleural effusion.• Galactorrhoea (due to increased prolactin levels).• Enlarged salivary glands (very rare).

• Goitre. The causes of goitre are manifold. Those associated with hypothyroidism include autoimmune thyroiditis (Hashimoto's thyroiditis), thyroid hormone biosynthetic defect (for example Pendred's syndrome), destructive thyroiditis (postpartum thyroiditis, silent thyroiditis, and subacute thyroiditis), and infiltration (Riedel's thyroiditis, amyloidosis, and sarcoidosis). For further information on goitre, see the CKS topic on Neck lump.

• The goitre of Hashimoto's thyroiditis is of variable size, is often firm and irregular, and may rarely be painful.• The goitre of subacute (de Quervain's) thyroiditis is usually tender to touch and diffuse, but may be hard or asymmetrical.

• Systemic upset with fever:May be present in subacute (de Quervain's) thyroiditis, but is absent in postpartum (silent) thyroiditis.

Investigations

• To make a diagnosis of hypothyroidism measure both thyroid-stimulating hormone (TSH) and free thyroxine (FT4).

• Do not routinely check for thyroid peroxidase antibodies (TPO-Ab).

• Indications for checking for TPO-Ab include:-Subclinical hypothyroidism where the TSH level is less than 10 mU/L.-Prior to commencement of amiodarone, interferon alfa, or lithium.

• Do not routinely measure thyroglobulin antibodies (TgAb) or thyroid-stimulating hormone receptor antibodies (TSH-RAb).

Reference RangeSerum measure Reference range

Thyroid-stimulating hormone (TSH) 0.4-4.5 mU/L

Free thyroxine (FT4) 9.0-25 picomol/L

Free triiodothyronine (FT3) 3.5-7.8 picomol/L

Total thyroxine (TT4) 60-160 nanomol/L

Toral triiodothyronine (TT3) 1.2-2.6 nanomol/L

Interpreting • In overt hypothyroidism: TSH is above the reference range and

FT4 is below the reference range.• In subclinical hypothyroidism: TSH is raised and FT4 is normal.

Make the diagnosis only after a confirmatory result on repeat testing within 3–6 months, except in pregnancy where treatment should be started immediately and the woman referred to a specialist.

• In secondary hypothyroidism (pituitary or hypothalamic disease): TSH level is low or 'normal' and FT4 is low.

• It can be difficult to interpret test results in people on amiodarone or lithium.

• In the transient hypothyroid stage of subacute or postpartum thyroiditis, the TSH level is raised and FT4 is low.

Misleading TSH results• TSH results may be misleading:

-during stabilization of treatment-pregnancy-non-thyroidal illness-post-thyroiditis-hypopituitarism-during treatment with drugs that affect the function or action of thyroid hormones.

• In the first trimester of pregnancy, a TSH concentration less than 0.10 mU/L may be found in up to 3% of women.-Trimester-related reference ranges should be applied for TSH and for total and free thyroxine (FT4).

• During the early weeks of levothyroxine therapy. It may take 3 months or more for the TSH concentration to normalize after prolonged hypothyroidism.

• Discussion with an endocrinologist may be appropriate in these circumstances.

Other laboratory tests

Some other laboratory tests may be abnormal in people with hypothyroidism

• Normocytic normochromic anaemia or mild macrocytosis.

• Increased cholesterol.• Low sodium.• Increased serum prolactin.• Elevated creatine phosphokinase.• Abnormal clotting screen (if hypothyroidism has caused

von Willebrand syndrome).

Subacute or Postpartum Thyroiditis

• Suspect thyroiditis in someone who presents with transient thyroid dysfunction — the most common sequence is a brief thyrotoxic phase (1–4 weeks) followed by a hypothyroid phase (4–12 weeks), which usually resolves spontaneously.

Subacute (de Quervain's) thyroiditis:• Thyroid pain.• Systemic upset with fever.• A small, tender goitre which may be diffuse or asymmetrical.• A history of prodromal viral infection symptoms several weeks earlier.Postpartum (silent) thyroiditis• May present within 2–6 months after delivery, with:• Non-specific symptoms, such as tiredness, anxiety, or depression.• Painless thyroid, often with no goitre.• No systemic upset or fever.

• When should I suspect secondary hypothyroidism?

• Thyroid function tests are suggestive of secondary hypothyroidism.

• There are features of hypopituitarism (such as hypogonadism or adrenal failure).

• The person is taking bexarotene.

Screening of asymptomatic people• Routine testing of asymptomatic people for hypothyroidism is not

recommended, but targeted testing is recommended for certain groups with the following conditions.

Goitre:• At initial presentation.• At the earliest opportunity in women who are pregnant or planning

pregnancy.• At 6–8 weeks postpartum (or after miscarriage or termination of

pregnancy).Type 1 diabetes• At initial presentation, then annually.• At the earliest opportunity in women who are pregnant or planning

pregnancy — measure TSH, free thyroxine (FT4), and thyroid peroxidase antibody (TPO-Ab) prior to conception, at booking when pregnant, and at 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).

Who to screen• Type 2 diabetes: At initial presentation.• Atrial fibrillation: At initial presentation.• Osteoporosis: At initial presentation.• Dyslipidaemia: At initial presentation.• Radioactive iodine or surgery for hyperthyroidism: At 4–8 weeks post-treatment, then every

3 months for up to 1 year, and annually thereafter.• Previous neck irradiation/surgery of thyroid gland for head and neck cancer, including lymphoma:

Annually.• FHx of thyroid disease: At the earliest opportunity in women who are pregnant or planning

pregnancy.• Personal Hx of thyroid disease: At the earliest opportunity in women who are pregnant or planning

pregnancy.• Hx of thyroid lobectomy: At the earliest opportunity in women who are pregnant or planning a

pregnancy.• Hx of autoimmune thyroid disease: At the earliest opportunity in women who are pregnant or

planning pregnancy. At 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).• Women with other autoimmune disorders• At the earliest opportunity in women who are pregnant or planning a pregnancy.• At baseline and annually in Addison's disease.• Have a low threshold for testing in other autoimmune disorders.

Who to screenKnown to be thyroid antibody positive• At the earliest opportunity in women who are pregnant or planning pregnancy.• During pregnancy.• At 6–8 weeks and 6 months postpartum (or after miscarriage or termination of pregnancy).Down's or Turner's syndrome • Annually.Non-specific symptoms that may suggest thyroiditis• At 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).

History of postpartum thyroiditis• At the earliest opportunity in women who are pregnant or planning pregnancy.• At 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).• Annually.Subfertility, abnormal menstrual cycle, or miscarriage• At initial presentation.Personal history of preterm birth or recurrent miscarriage• Consider measuring TSH, FT4, and TPO-Ab.Taking amiodarone, lithium, sunitinib, sorafenib, or interferon alpha• At baseline and every 6 months.• If amiodarone is stopped, monitoring should continue for a further 12 months.Postpartum depression• At presentation.

Subclinical Hypothyroidism• TSH 10 mU/L or less• How should I manage someone with subclinical hypothyroidism who has a TSH of 10 mU/L or less?• Confirm by repeat testing of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels, with the

addition of measurement of thyroid peroxidase antibodies (TPO-Ab), 3–6 months after the original result.

Levothyroxine treatment is not routinely recommended.Consider offering levothyroxine treatment if:• The person has a goitre.• Their TSH level is rising.• The woman is pregnant or planning pregnancy .

Consider offering a trial of treatment if the person has symptoms compatible with hypothyroidism.• Only continue treatment if there is a clear improvement in symptoms.• If treatment is continued, once stable, measure TSH annually and alter the levothyroxine dose to maintain

the TSH level within the reference range.

If treatment is not offered, it is still necessary to monitor thyroid function to detect progression to overt hypothyroidism.

• If the person has serum TPO-Abs, measure serum TSH and FT4 annually, or earlier if symptoms develop.• Otherwise, measure serum TSH and FT4 approximately every 3 years, or earlier if symptoms develop.

• In women with raised serum TSH and positive antithyroid antibodies, the annual risk of developing overt hypothyroidism is approximately 5%.

• Treatment is not generally recommended because:• A significant number of people with subclinical hypothyroidism will not progress to overt hypothyroidism. • When TSH is elevated but less than 10 mU/L, no consistent evidence supports an association with symptoms,

secondary biochemical abnormalities (hyperlipidaemia), cardiac dysfunction, or other cardiac events.• Evidence from relatively small studies indicates that levothyroxine replacement therapy for subclinical

hypothyroidism does not result in improved survival or decreased cardiovascular morbidity, improved health-related quality of life, or improved symptoms.

• No evidence supports the benefit of routine early treatment with levothyroxine in non-pregnant adults with a serum TSH concentration above the reference range but less than 10 mU/L.

• It is recognized, however, that some people with TSH levels between 4.5 mU/L and 10 mU/L have symptoms compatible with hypothyroidism. Therefore, clinicians and patients may decide on a trial of levothyroxine while monitoring for an improvement in symptoms.

• There is no clear guidance available on the dose and duration of levothyroxine to use in this situation.• The dose of levothyroxine should be titrated until the TSH level is within the reference range, and given for a

sufficient length of time to judge whether or not there is any clinical benefit (usually several months).• Continuation of treatment should be dependent on clear symptomatic benefit, but this may be very difficult to

judge as some people may have a placebo effect.