How Hypothyroidism Causes Hyperprolactinemia?

What Is Hypothyroidism?

The thyroid is a small gland that sits at the front of your neck. Its job is to produce two hormones, namely thyroxine (T4) and triiodothyronine (T3). These hormones help the body by regulating metabolism, body temperature, heart rate, and cellular energy use.

Normally, the brain regulates hormone secretion through the hypothalamus, which releases thyrotropin-releasing hormone (TRH). Now, the TRH tells the pituitary gland to release thyroid-stimulating hormone (TSH), which in turn signals the thyroid to produce adequate amounts of T3 and T4. This is a well-regulated hormonal pathway, and if things go wrong at either point, it will affect the body.

Hypothyroidism occurs when the thyroid gland fails to produce enough T3 and T4. There are multiple reasons why this may occur, including autoimmune damage, iodine deficiency, surgical removal, or radiation. When the thyroid hormone levels drop, the brain responds to the shortage by releasing more TRH, which eventually causes prolactin to rise as well.

What Is Hyperprolactinemia?

Prolactin hormone is produced and secreted by the anterior pituitary gland. The most well-known function of the hormone is the induction of breast milk production after childbirth. However, prolactin also plays a role in immune function, reproductive health, and metabolism, even in those who have never been pregnant.

Men also have the hormone prolactin, though it is present in much lower amounts than in women. The normal prolactin concentrations are less than 25 ng/mL in non-pregnant women and less than 17 ng/mL in men. Hyperprolactinemia, as the name suggests, simply means that prolactin is much higher in the blood than it should be.

Hyperprolactinemia suppresses reproduction by inhibiting GnRH (Gonadotropin-Releasing Hormone), leading to decreased LH and FSH secretion. This causes a drop in estrogen production in women and testosterone production in men. High prolactin can cause complications like irregular periods, sexual dysfunction, and infertility.

Core Mechanism Of How Hypothyroidism Causes Hyperprolactinemia

Once the hormonal pathway is understood, it becomes clear exactly how hypothyroidism causes hyperprolactinemia in people. When thyroid hormone levels fall, as seen in hypothyroidism, the hypothalamus in the brain releases more TRH to stimulate the pituitary to produce more TSH. The plan is to push the thyroid into producing more T3 and T4.

The catch is that TRH does not simply stimulate the release of TSH; it also stimulates prolactin release from the pituitary gland. In simpler words:

• Step 1: Failure of the thyroid glands → Reduction in levels of T3 and T4 levels
• Step 2: Sensing lack of thyroid hormones by the hypothalamus → Increase in the production of TRH
• Step 3: Increased level of TRH → stimulation of TSH and prolactin secretion from the pituitary gland
• Step 4: Increase in blood level of prolactin → Hyperprolactinemia TRH is synthesised in the paraventricular nucleus of the hypothalamus. Despite its small size, it performs two main functions in the pituitary:
• Primary: It stimulates the thyrotroph cells in the pituitary to create and release TSH, which then acts on the thyroid gland.
• Secondary: TRH also stimulates lactotroph cells in the pituitary gland to release prolactin directly into the circulation.

When a person is healthy, without any conditions, especially thyroid conditions, TRH is produced at a moderate, controlled level. Because of this, the prolactin also stays within the normal range, that is, if other factors aren’t causing an increase in the hormone. In hypothyroidism, though, the hypothalamus keeps producing more and more TRH in hopes of stimulating the thyroid. This excessive production stimulates lactotroph cells, increasing prolactin secretion.

Does Dopamine Play A Role In The Connection?

Produced by the hypothalamus, dopamine acts as the primary inhibitor of prolactin. It reaches the pituitary through the portal blood vessels and acts on D2 receptors on lactotroph cells, thereby acting as a brake and suppressing prolactin secretion.

In the case of hypothyroidism, low levels of T3 and T4 result in dopaminergic inhibition, which means that the prolactin “brake” is weakened. Since inhibition is weaker than before, prolactin is secreted more readily, leading to a rise in the hormone, especially with high TRH.

Therefore, in hypothyroidism, two processes are happening at the same time. One: the increased production of TRH, and two: the weakening of dopamine. As a result, prolactin levels increase.

Symptoms To Look Out For

When hypothyroidism and hyperprolactinemia occur at the same time, symptoms from both conditions can overlap. While some warning signs may be shared, others are specific to each.

Symptoms of hypothyroidism:

• Fatigue or sluggishness
• Unexplained weight gain
• Cold intolerance
• Dry skin
• Hair loss
• Constipation
• Depression
• Brain fog
• Slow heart rate

On the other hand, symptoms of hyperprolactinemia include:

• Irregular periods
• Absence of periods
• Galactorrhea or milky discharge from nipples
• Infertility
• Reduced sex drive
• Erectile dysfunction
• Breast tenderness
• Headaches

Galactorrhea can occur in both men and women. Milky discharge in a non-breastfeeding person should prompt testing if they notice milky discharge from their nipples.

Can Hypothyroidism Cause A Pituitary Tumour?

Typically, hypothyroidism results in hyperprolactinemia but without any abnormality in the structure of the pituitary gland. But in case of severe and long-term, untreated hypothyroidism, the overstimulation of the lactotrophs by the excess amount of TRH results in their hyperplasia. This means that the cells multiply abnormally.

As a consequence, the pituitary gland enlarges, resembling an adenoma on MRI scans. Such pituitary lesions are referred to as pituitary pseudotumors or hyperplasia, as opposed to pituitary adenomas.

If a patient with hypothyroidism and elevated prolactin is found to have an enlarged pituitary on MRI, the first and foremost thing that should be done is to treat the hypothyroidism, not the pituitary. In true hypothyroidism-induced hyperprolactinemia, the gland will shrink back to normal size once the thyroid hormones are replaced.

How Is Hypothyroidism-Induced Hyperprolactinemia Diagnosed?

How Is Hypothyroidism-Induced Hyperprolactinemia Diagnosed?

Blood tests play a vital role in the diagnosis of hypothyroidism-induced hyperprolactinemia. For every patient suspected to have a raised prolactin level, TSH and free T4 levels should be measured as part of the work-up. This is because untreated hypothyroidism is one of the most common reversible causes of high prolactin levels and must be excluded before attributing the finding to a pituitary tumour or a prolactinoma.

Typical findings in a blood test for hypothyroidism-induced hyperprolactinemia include high TSH, low free T4, and elevated prolactin levels. If TSH is elevated and thyroid treatment normalises prolactin, the diagnosis is confirmed. However, in the case that prolactin remains high despite treating thyroid issues, further investigation is required to rule out a coincidental prolactinoma.

Does Treating Hypothyroidism Normalise Prolactin Levels?

In the vast majority of cases, hypothyroidism-induced hyperprolactinemia is completely reversible. When synthetic T4 is prescribed by a healthcare professional and thyroid levels are restored to the normal range, TRH production returns to normal. In turn, the pituitary receives much less stimulation, and prolactin levels decline on their own.

Once hyperprolactinemia has been resolved by treating hypothyroidism, menstrual cycles typically resume, galactorrhea resolves, fertility improves, and, in men, testosterone levels return to normal, as LH and FSH normalise with the decrease in prolactin.

If prolactin levels remain high despite the treatment of hypothyroidism, it is best to consult a doctor for further investigation.

Conclusion

This interaction between low thyroid gland function and high prolactin levels is perhaps the clearest example of how interconnected the hormone functions of our bodies are. If the thyroid gland does not function as well as it should, the body responds by increasing TRH production, which inevitably results in elevated prolactin levels. Reduced dopamine inhibition only adds to this effect. The result? Two conditions that appear unrelated on the surface but share a single hormonal root cause.

Knowing this link is essential when diagnosing these conditions, as it means you will not have to undergo unnecessary investigations or be misdiagnosed with pituitary tumours. Therefore, patients will be spared unnecessary treatments. A simple blood test for TSH can explain elevated prolactin, and a simple tablet of levothyroxine could be sufficient to reverse hypothyroidism-induced hyperprolactinemia.

If you have been told that your prolactin is high, make sure to get your thyroid checked first and foremost. Only then should you reach any conclusions about your pituitary gland.