Hypothyroidism

Hypothyroidism occurs due to low levels of thyroid hormone in the body.

Thyroid Gland Structure and Function

The thyroid gland is a butterfly shaped gland found anterior to the trachea in the neck. It produces thyroid hormone which has a widespread role in the body affecting multiple bodily functions including metabolism and growth.

Three main hormones are produced by the thyroid:

• Triiodothyronine (T3) – this is the active form of the hormone.
• Tetraiodothyronine (T4) - T4 is converted in the peripheries in certain tissues including kidney, liver and muscle tissues.
• Calcitonin

The vast majority of T3 and T4 hormone is bound to transport proteins in the serum, including thyroxine-binding globulin (TBG) and albumin. It is the amount of free (unbound) T3 hormone which is truly active.

Thyroid Hormonal Axis

Thyroid hormone homeostasis begins at the hypothalamus. The axis works in the following way:

1.    The periventricular nucleus (PVN) of the hypothalamus releases thyroid releasing hormone (TRH) into the hypothalamo-hypophyseal portal system to get to the anterior pituitary gland.

2.    TRH stimulates release of thyroid stimulating hormone (TSH) from the anterior pituitary gland.

3.    TSH binds to receptors on follicular cells of the thyroid gland, resulting in increased levels of serum T3 and T4.

4.    T3 and T4 work to increase metabolic and cellular activity. Some actions of their actions include:

• Increasing heart rate
• Increasing gut motility
• Increasing lipolysis
• Increasing metabolism of carbohydrates i.e., upregulation of glycogenolysis (breaking down of glycogen) and gluconeogenesis (synthesis of glucose)

5.    TRH also stimulates prolactin production from the anterior pituitary which can cause lactation and growth of breast tissues.

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Thyroid Hormonal Axis

Causes

Various causes exist for hypothyroidism. These include:

Primary Causes: The thyroid gland itself is dysfunctional

• Iodine deficiency: This is the most common cause worldwide but is less common in iodine-sufficient countries due to the introduction of iodised salt.
   
• Hashimoto’s Thyroiditis: An autoimmune condition affecting the thyroid gland. Individuals are thought to have autoantibodies such as anti-thyroid peroxidase, which destroys thyroid tissue and results in inadequate hormone production. Hashimoto’s is associated with development of thyroid lymphoma, as well as other autoimmune conditions including diabetes mellitus, coeliac disease, vitiligo and primary biliary cholangitis.
   
• Iatrogenic: For example, thyroidectomy or secondary to radioactive iodine for management of hyperthyroidism
   
• Radiotherapy to the Head/Neck
   
• Drug-Induced: Amiodarone, lithium, sulfonylureas
   
• Post-partum thyroidits: Inflammation of the thyroid gland usually around 6 months after giving birth. May be preceded by a hyperthyroid state.

Secondary/Tertiary Causes: The pituitary or hypothalamus is dysfunctional (respectively):

• Pituitary tumours
• Sheehan syndrome: Post-partum hypopituitarism secondary to hypovolaemic shock following childbirth. This means you don't get TSH from the pituitary to stimulate the T3/T4 release.
• Tumours which compress the hypothalamus

Clinical Features

You can think of the signs and symptoms of hypothyroidism indicating a ‘slowing down’ of bodily functions e.g.

• Fatigue
• Weight gain
• Bradycardia
• Constipation
• Cold sensitivity
• Reduced libido
• Dry skin and thinning of hair
• Loss of the lateral third of the eyebrow
• Depression
• Prolonged QT

Other features include:

• Cold hands
• Pleural and pericardial effusions
• Carpal tunnel syndrome
• Goitre: Usually from thyroiditis e.g. Hashimoto’s/Drug-induced/post-partum
• Hoarse voice
• Peri-orbital oedema

Menstruation can be a bit confusing with hypothyroidism. Although we commonly consider hypothyroidism as a ‘slowing down’ of functions, with menstruation, women tend to experience menorrhagia in hypothyroidism vs amenorrhoea in hyperthyroidism.

Differential Diagnosis

• Iron deficiency anaemia
• Major depressive disorder
   

Investigations

Bedside

• History and examination

Bloods

• Thyroid function tests

• Auto-antibody testing: Particularly looking for anti-TPO, anti-thyroglobulin, and anti-TSH which may suggest an autoimmune cause such as Hashimoto’s thyroiditis
   
• Screen for other autoimmune conditions: Hashimoto’s is associated with other autoimmune conditions so screening for the following can be done:
  • Type 1 Diabetes Mellitus: HbA1c
  • Coeliac screen
  • Pernicious anaemia: B12 and FBC
     
• Lipid panel: Hypercholesterolaemia

Management

Treatment is to replace the deficiency with levothyroxine. The dose is typically calculated by weight, and NICE recommend 1.6 micrograms per kilogram per day for individuals under 65 and no history of cardiovascular disease – patients with cardiovascular disease are typically started on lower doses of 25 micrograms which is then titrated up.

TSH is measured every 3 months until levels stabilise, and this is then reduced to once annually. Remember to check compliance in cases where thyroid hormone levels fail to improve.

Myxoedema Coma

A myxoedema coma is a potential complication of hypothyroidism and is a serious medical emergency. Various things may trigger a myxoedema coma such as hypothermia, infection, GI bleed, stroke, trauma, or drugs such as amiodarone. Ultimately, a particular stressor disrupts the body and without sufficient thyroid hormone, the body is unable to maintain sufficient homeostasis resulting in various signs and symptoms including:

• Hypothermia
• Altered mental state: Confusion, psychosis, lethargy, stupor
• Hypotension
• Bradycardia
• Hypoventilation and hypoxia

Patients should be managed in an A-E approach, usually in a HDU/ITU environment, with definitive management focused on replacing thyroid hormone (usually intravenously), alongside IV steroid treatment in case there is an underlying cortisol deficiency and warming of the body to correct hypothermia. Patients may also require mechanical ventilation due to hypoventilation. ECG monitoring is important due to the risk of a prolonged QT.

References

Barrett, EJ. The Thyroid Gland – Medical Physiology. Chapter 49, 1006-1017.e2

https://www.ncbi.nlm.nih.gov/books/NBK459262/

http://www.medicinabuenosaires.com/PMID/29044016.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980701/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818825/

https://www.nice.org.uk/guidance/ng145/chapter/recommendations#investigating-suspected-thyroid-dysfunction-or-thyroid-enlargement

https://cks.nice.org.uk/topics/hypothyroidism/diagnosis/assessment/

https://www.ncbi.nlm.nih.gov/books/NBK279007/

https://patient.info/doctor/myxoedema-coma