- Clinical science
Hypothyroidism is a condition in which the thyroid gland is underactive, resulting in a deficiency of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). In rare cases, it is not the production of hormones, but rather the peripheral effects of thyroid hormones that are insufficient. Hypothyroidism may be acquired or congenital. If congenital, it is usually the result of thyroid dysplasia or aplasia. The etiology of acquired hypothyroidism is commonly autoimmune (Hashimoto's thyroiditis) or iatrogenic. The pathophysiology in hypothyroidism is characterized mainly by a reduction of the basal metabolic rate as well as generalized myxedema. These two principles are reflected in the typical clinical findings, which include fatigue, cold intolerance, weight gain, and periorbital edema. More severe manifestations may include myxedematous heart disease and myxedema coma, which may be fatal if left untreated. Children with congenital hypothyroidism often have umbilical hernias and, without early treatment, develop cretinism (intellectual disability, stunted growth). Accordingly, neonatal screening for hypothyroidism between 24 and 48 hours after birth is required by law in most states. In adults, the diagnosis is established based on serum TSH and FT4 levels. Therapy of both acquired and congenital hypothyroidism consists of lifelong treatment with levothyroxine (L-thyroxine) and regular check-ups to monitor disease activity.
- Sporadic (∼ 85% of cases)
- Hereditary (∼15% of cases)
Primary hypothyroidism: insufficient thyroid hormone production
- Autoimmune etiology (Hashimoto's thyroiditis)
- Lymphocytic thyroiditis (or postpartum thyroiditis)
- Subacute granulomatous thyroiditis (or )
- Iatrogenic (e.g., surgery, radioiodine therapy, medication )
- Nutritional (insufficient intake of iodine)
- Secondary hypothyroidism: pituitary disorders → thyroid-stimulating hormone (TSH) deficiency
- Tertiary hypothyroidism: hypothalamic disorders → thyrotropin-releasing hormone (TRH) deficiency (very rare)
- Physiological: See “thyroid gland” in .
Effects of hypothyroidism
- Generalized decrease of the basal metabolic rate: oxygen and substrate consumption decreased throughout the body
- Generalized myxedema: caused by increased deposition of glycosaminoglycans (and thus fluid) in the dermis and mucous membranes (e.g., of the pharynx)
- Hyperprolactinemia: production is stimulated by TRH → ↑ prolactin suppresses LH, FSH, and testosterone secretion; also stimulates breast tissue growth
General signs and symptoms
As changes in thyroid metabolism have very complex and far-reaching consequences, not all of the symptoms have been directly or unambiguously connected to one of the principal pathophysiological phenomena.
- Symptoms related to decreased metabolic rate
- Symptoms related to generalized myxedema
- Symptoms of hyperprolactinemia
- Further symptoms
Older patients may not display typical symptoms of hypothyroidism. Instead, they may appear to suffer from dementia or depression!
- Cretinism; : impaired development; of the brain and skeleton, resulting in skeletal abnormalities; and intellectual disabilities
Most children with congenital hypothyroidism do not display symptoms at the time of birth, as the placenta supplies the fetus with maternal thyroid hormone → neonatal screening is vital even if children are asymptomatic! Irreversible intellectual disabilities can be avoided through early initiation of adequate therapy!
Overview of changes in hormone levels
|Central hormones||Peripheral hormones|
|Overt hypothyroidism||Primary hypothyroidism|| |
|Secondary hypothyroidism|| |
| || |
Basic diagnostic strategy
The initial step is to determine TSH levels, which may be followed by FT4 levels to confirm or rule out the suspected diagnosis.
- TSH levels
- FT4 levels
- FT3 levels
Further diagnostic considerations
- thyroglobulin) and (thyroid peroxidase): detectable in most patients with autoimmune hypothyroidism (
Thyrotropin-binding inhibitory immunoglobulin assay (TBII assay)
- Can detect the presence of antibodies against the TSH receptor, but cannot determine the type of the antibodies (blocking, neutral, or stimulating)
- However, if a patient displays symptoms of hypothyroidism and antibodies are detected via the assay, it is highly likely that these are blocking antibodies.
- Thyrotropin-binding inhibitory immunoglobulin assay (TBII assay)
- Radioactive iodine uptake test
- Associated conditions
Normal TSH levels very likely rule out both the possibility of hypothyroidism and hyperthyroidism and are therefore the decisive parameter in screening for both conditions!
Sick euthyroid syndrome (SES) (euthyroid sick syndrome (ESS), non-thyroidal illness syndrome (NTI))
- Occurs in severe illness or under severe physical stress (especially in intensive care patients)
- n/↓ TSH, ↓ FT3
- FT4 levels may be normal or, in prolonged courses of illness, low.
- Treatment: usually not recommended as thyroid function is normal; insufficient evidence that thyroid hormone substitution is beneficial to the patient
Thyroid hormone resistance
- Definition: insufficient end-organ sensitivity to thyroid hormones
- Etiology: deficits in thyroid hormone metabolism, transport, or receptor interaction as a result of genetic mutations
- Clinical features: Symptoms of both hypothyroidism and hyperthyroidism are possible.
- Laboratory: commonly persistently elevated FT4 and FT3, absent TSH suppression
- Therapy: no causative therapy available
The differential diagnoses listed here are not exhaustive.
- L-thyroxine: synthetic form of T4 → peripherally converted to T3 (biologically active) and rT3 (biologically inactive)
- General principles: lifelong replacement ; prompt initiation; gradual increase in elderly patients or those with preexisting cardiovascular conditions
- L-thyroxine interactions
- Follow-ups with laboratory controls of thyroid function (TSH) at regular intervals; adjustment of dosage if necessary
- Children: with congenital hypothyroidism: Normalization of thyroid hormone levels within 2–3 weeks is vital.
- L-thyroxine replacement in subclinical hypothyroidism
This extremely rare condition is caused by decompensation of an existing thyroid hormone deficiency and can be triggered by infections, surgery, and trauma. Myxedema coma is a potentially life-threatening condition and, if left untreated, is fatal in up to ∼ 40% of cases.
- Clinical presentation
We list the most important complications. The selection is not exhaustive.