The hypothalamic-pituitary-thyroid (HPT) axis consists of the hypothalamus, the pituitary gland, and the thyroid gland. The hormones involved are thyrotropin-releasing hormone (TRH) secreted by the hypothalamus, thyroid-stimulating hormone (TSH) released by the anterior pituitary, and T3 and T4 produced by the thyroid gland.
The HPT axis is essential for maintaining homeostasis of metabolic functions within the body. This article will discuss the function of the HPT axis, its regulation, and relevant clinical conditions.
Further information on the thyroid gland and thyroid hormone synthesis can be found here.
Hypothalamic-Pituitary-Thyroid Axis Function
Effects of T3 and T4
The actions of T3 and T4 are widespread. Some important functions include:
- Metabolic – increasing basal metabolic rate and promoting catabolism e.g. lipolysis, glycogenolysis, glycolysis and proteolysis
- Nervous system – important for speed of reflexes and mental activity
- Cardiovascular system – increases synthesis of cardiac muscle protein, increases cardiac output
- Bone – increases bone mineralisation
Hypothalamic-Pituitary-Thyroid Axis Regulation
Hypothalamic Control
The hypothalamus produces thyrotrophin-releasing hormone (TRH). TRH binds to TRH receptors on thyrotropic cell membranes in the anterior pituitary, stimulating the production of thyroid-stimulating hormone (TSH), also known as thyrotropin.
TSH enters the blood and binds to receptors on follicular cells of the thyroid gland, stimulating the production of thyroid hormones: triiodothyronine (T3) and tetraiodothyronine (T4), also known as thyroxine.
Regulation of Thyroid Hormones
Control of this system is via negative feedback: high levels of T3 and T4 inhibit TRH and TSH production by the hypothalamus and anterior pituitary gland, respectively. The mechanisms are as follows:
- T3 is found in thyrotropes either as a result of the deiodination of T4 or by entering from the bloodstream. This intracellular T3 decreases the number of TRH receptors of thyrotrope cells, leading to indirect inhibition of downstream T4/T3 synthesis.
- T3 also binds directly to response elements in TSH promotor elements of thyrotrophic cell DNA, inhibiting TSH synthesis.
Clinical Relevance – Abnormal Thyroid Function
A common presentation for a malfunctioning HPT axis is cardiac-related symptoms. The patient may complain of palpitations. This is because an overactive thyroid gland can cause sinus tachycardia or atrial fibrillation.
Patients may also present with acute heart failure. Take the example of a patient who has compensated heart failure secondary to a past myocardial infarction. Excess circulating thyroxine in this context can put extra strain on the heart, causing it to decompensate.
Other common presentations of an under or over-active thyroid gland include:
- Menorrhagia (heavy periods)
- Confusion
- Weight loss/gain
- Tremor
The function of the thyroid gland is measured using a blood test called thyroid function tests (TFTs).
Treatment for an overactive thyroid gland is by blocking the production of thyroxine, usually with a medication called carbimazole. Similarly, if a patient presents with proptosis and eye symptoms, corticosteroids can also help. It is important to treat symptoms, so palpitations may be treated using beta-blockers such as propanolol which slow down the heart.
Treatment for an underactive thyroid gland is by replacing inadequate thyroxine with levothyroxine tablets.