Contents
Thyroid hormone deficiency.
- M/C disorder arising from hormone deficiency.
History:

Aetiology
Primary hypothyroidism:
Disorder of thyroid gland causing decreased synthesis and secretion of thyroid hormones.
- Chronic autoimmune thyroiditis (50% cases): ↑ Antithyroid antibodies (anti-TPO & antithyroglobulin antibodies)
- Silent thyroiditis: Mild, of recent onset hyperthyroidism due to secretion of thyroid hormones in circulation, due to cell lysis and subsides in 6-12 weeks or is transformed in 50% of the cases to transient hypothyroidism, which subsides in 2-12 weeks
- Iodine insufficiency: Presents with large goiter
- Iatrogenic causes:
- Partial thyroidectomy (for hyperthyroidism)
- External radiotherapy
- Drugs: Amiodarone and lithium
- Antithyroid drug therapy (in pregnant women): Hypothyroidism in newborn infants.
- Thyroid agenesis/dysgenesis: Children and infants

Secondary (central) hypothyroidism.
Caused by a disorder of the pituitary or the hypothalamus, leading to decreased TSH secretion and consequently to decreased synthesis and secretion of thyroid hormones. Secondary hypothyroidism is also reported as central and is divided in secondary and tertiary when the causes are in the pituitary and the hypothalamus, respectively.

Peripheral (ponsumptive) hypothyroidism (rare):
Caused by aberrant expression of the deiodinase 3 enzyme (which inactivates thyroid hormone) in tumour tissues resulting in peripheral resistance to thyroxine
- Infantile hepatic haemangiomatosis
- Vascular and fibrotic tumours
- Gastrointestinal stromal tumours (GIST)
- Rare genetic syndromes
Clinical features
Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms.

Mild/subclinical hypothyroidism:
Asymptomatic presentation
Overt/clinical primary hypothyroidism:
Defined as thyroid-stimulating hormone (TSH) concentrations above the reference range and free thyroxine concentrations below the reference range.
The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors

Complications
Myxedema coma/gull disease (rare):
Outcome of long-standing untreated and severe hypothyroidism
- Altered mental status, hypothermia, progressive lethargy, and bradycardia and can eventually result in multiple organ dysfunction syndrome and death.
Additional symptoms include swelling of the arms and legs and ascites. | By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m15004/latest/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=30826142 Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor | By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m15004/latest/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=30826141
Congenital hypothyroidism/cretinism:
Condition of severely stunted physical and mental growth owing to untreated congenital deficiency of thyroid hormone (congenital hypothyroidism) usually owing to maternal hypothyroidism.

Diagnosis
The diagnosis of hypothyroidism is made from the history, the clinical picture and the laboratory measurements.
Thyroid function test:
TSH and FT4 measurement are the laboratory examinations necessary for the diagnosis of hypothyroidism and the differential diagnosis between primary (clinical or subclinical) and secondary one.
- Primary hypothyroidism:
- ↑ TSH & ↓/N FT4
- ↑ Anti-TPO or anti-Tg antibodies (autoimmune thyroiditis)
- Clinical type: ↑ TSH & ↓ FT4
- Subclinical type: ↑ TSH & normal FT4
- Secondary (central) hypothyroidism:
- ↓/N TSH & ↓ FT4
- TRH test:
- Normal response: Pituitary cause
- Abnormal response: Hypothalamic cause

Radiological investigations:
To differentiate between central causes of hypothyroidism

Management
Thyroid hormone replacement therapy:
Levothyroxine monotherapy in solid formulation, taken on an empty stomach, is the treatment of choice

Myxedema coma/gull disease:
ICU management
- Thyroid replacement: 0.50mg T4 or 0.10 μg T3 IV/oral every 4-6 hours
- If temperature < 30°C:
- Broad-spectrum antibiotics IV
- Hydrocortisone (divided doses)
Thyroxine absorption test:
For individuals in whom high TSH concentrations persist after treatment and other causes have been excluded, the possibility of non-adherence, a common cause of therapy failure, should be considered and made to undergo a supervised thyroxine absorption test

Summary