Published June 23 2014
Most people reading this know that the thyroid gland is part of the endocrine system. The endocrine system consists of numerous glands, and these in turn produce hormones. In addition to the thyroid gland, some of the other glands of the endocrine system include the adrenals, the pituitary, the pancreas, and the pineal. Plus of course the testes and ovaries are responsible for producing hormones. But how do neurotransmitters relate to the endocrine system, and more specifically, to thyroid health?
Let’s begin by differentiating between hormones and neurotransmitters. Both hormones and neurotransmitters can be considered to be types of chemical messengers. As I mentioned before, hormones are secreted by certain glands of the endocrine system. They then get transported by the circulatory system until they reach its target organ. So for example, the thyroid gland secretes thyroid hormone, and every cell in the body has receptor sites for this hormone.
On the other hand, neurotransmitters are used by neurons to communicate with one another. The presynaptic cells of a neuron is what contains the neurotransmitters, and then when it’s released it binds to a receptor site on the postsynaptic cell.
What I’d like to do is briefly talk about the functions of some of the more well known neurotransmitters:
Serotonin. This is probably the most well known neurotransmitter. The amino acid tryptophan is a precursor of serotonin. Tryptophan in turn gets converted into 5-hydroxytryptophan, also known as 5-HTP, and this in turn gets converted into serotonin. As a result, to increase serotonin levels one can take tryptophan, or they can take 5-HTP. It is important to understand that certain nutrients are responsible for the enzymatic reactions which result in these conversions. For example, iron is necessary to convert tryptophan into 5-HTP. As a result, if someone is trying to take tryptophan in order to increase serotonin levels, but if they have an iron deficiency, then this very well might affect the conversion to 5-HTP. Obviously you can just take 5-HTP to increase serotonin levels, although you also need certain nutrients for this conversion as well.
What is the function of serotonin? Well, serotonin is produced in both the peripheral nervous system and central nervous system. The main function of serotonin in the peripheral nervous system is to regulate gastrointestinal tract motility. In the central nervous system it has other roles, such as the regulation of mood, appetite, and sleep. With regards to mood, low levels of serotonin are associated with depression, and certain drugs have been created to either prevent the breakdown of serotonin, or inhibit the reuptake of this neurotransmitter. Of course there are also natural alternatives to increasing serotonin levels, such as using the herb St. John’s Wort.
Serotonin is a precursor to the hormone melatonin. As a result, low serotonin levels will result in low melatonin levels, which can in turn interfere with sleep. Serotonin also goes through a few steps to convert to melatonin, and so even if there is sufficient amounts of serotonin, someone can have low melatonin levels if there is a problem with the conversion process.
GABA (gamma-aminobutyric acid). This is the main inhibitory neurotransmitter of the nervous system. Glutamate is a direct precursor to GABA, and is converted to GABA with the help of the enzyme glutamic acid decarboxylase, which is also known as GAD. GAD65 is the most well known form of this enzyme. It is possible to have antibodies against this enzyme, and if this is the case then someone can have depressed GABA levels. The company Cyrex Labs has a multiple autoimmune reactivity screen which tests for these antibodies.
What is the function of GABA? As I just mentioned, GABA is an inhibitory neurotransmitter, and low levels of GABA can lead to anxiety, depression, and insomnia. It’s important to understand that GABA can’t cross the blood brain barrier. As a result, taking GABA orally normally wouldn’t increase the levels of this neurotransmitter in the CNS. However, eating foods rich in glutamic acid such as walnuts, almonds, rice, spinach, and beans can increase the GABA levels.
I just mentioned how taking GABA orally “normally” shouldn’t increase the levels of this neurotransmitter in the CNS, and thus shouldn’t result in any changes in symptoms upon taking GABA. However, if someone does experience any changes in symptoms upon taking GABA then this means they have a compromised blood brain barrier. In fact, there is something called the “GABA challenge”, which involves taking some GABA, and if the person experiences any change then this indicates a “leaky” blood brain barrier.
Dopamine. This is a neurotransmitter that has important roles in both the peripheral nervous system and the brain. The amino acid tyrosine is a precursor of dopamine. What happens is that the amino acid phenylalanine converts to tyrosine, and then tyrosine crosses the blood-brain barrier and gets converted into L-DOPA, and this in turn gets converted into dopamine. Of course certain nutrients are involved in the conversion process, specifically iron, folate, and vitamin B6. And so a deficiency in any of these nutrients can result in a dopamine deficiency.
In the peripheral nervous system dopamine helps to increase heart rate and blood pressure. In the brain it is involved in a number of different functions, such as motor coordination, cognition, reward, and regulation of prolactin. Many reading this are aware that Parkinson’s disease is associated with a dopamine deficiency. However, in an article I wrote entitled “Can Estrogen and Prolactin Be The Main Triggers Of Graves’ Disease and Hashimoto’s Thyroiditis [1]?”, I discussed how dopamine agonists are commonly used for hyperprolactinemia, which is a potential trigger for autoimmunity. Getting back to Parkinson’s disease, I mentioned how tyrosine is first converted to L-DOPA, and this is then converted to dopamine. L-DOPA is given to those people with Parkinson’s disease, but why not just give them dopamine? The reason is because L-DOPA can cross the blood-brain barrier, but just as is the case with the other neurotransmitters, dopamine is unable to do this.
Acetylcholine. This neurotransmitter is also produced in both the peripheral and central nervous system. Choline is necessary for the synthesis of acetylcholine. Choline can cross the blood-brain barrier, and acetyl groups combine with it to form acetylcholine. Although dietary intake of choline is important, pantothenic acid is necessary for the conversion process. As a result, a deficiency of dietary choline or pantothenic acid can result in a deficiency of acetylcholine. Some of the nutrients high in choline include eggs, nuts, beef, and liver.
In the peripheral nervous system acetylcholine helps to regulate the autonomic nervous system. In the central nervous system this neurotransmitter plays an important role in cognition, memory, and arousal. Both Alzheimer’s disease and Myasthenia Gravis are associated with imbalances of acetylcholine. Alzheimer’s disease involves lower levels of acetylcholine, and as a result, some medications given are used to help prevent the breakdown of this neurotransmitter. With Myasthenia Gravis, there are antibodies which block or destroy the receptors for acetylcholine.
There are other neurotransmitters besides the ones I discussed here. Some additional neurotransmitters I didn’t discuss include epinephrine and norepinephrine, histamine, glutamate, and aspartate. Epinephrine and norepinephrine are considered to be both hormones and neurotransmitters. The reason for this is because these can be produced by the adrenal glands, and they are also produced by some neurons.
What Role Do These Neurotransmitters Play In Thyroid Health?
Thyroid hormone plays a role in the release of neurotransmitters (1) [2]. As a result, if someone has low levels of thyroid hormones then this can result in low neurotransmitters. Let’s specifically take a look at the four neurotransmitters I discussed above and see how each one relates to thyroid health. Some of this information is admittedly a little complex to understand, and so if you find it too advanced I would just skip ahead to the section below entitled “Other Reasons For Neurotransmitter Imbalances”, as I think most people will find this to be very interesting.
Serotonin and Thyroid Health. One study looked at thyroid hormone control and found that hypothyroidism led to a significant increase of serotonin, whereas induced hyperthyroidism resulted in no changes in serotonin levels (2) [3]. Another study looked at thyroid axis activity and serotonin function in major depression, and found that serotonin function is reduced in some depressed patients, and hypothalamic-pituitary-thyroid (HPT) axis dysregulation may be a compensatory mechanism for diminished central serotonin activity (3) [4]. Another study examined the relationship between baseline measurements of thyroid function and response to selective serotonin reuptake inhibitors (SSRIs) and to consider the effect of these antidepressants on thyroid hormone levels (4) [5]. The study showed that optimal thyroid function may be necessary for an optimal response to antidepressants. As a result, if you are taking antidepressants but have a thyroid hormone imbalance then you might not respond well to the medication.
GABA and Thyroid Health. Earlier I spoke about how glutamic acid decarboxylase (GAD) is important in the conversion of glutamate to GABA. I mentioned GAD65, but there are numerous forms of this enzyme, as there is also GAD67, GAD25, and GAD44. These different forms synthesize GABA in different locations, and a recent study showed that GAD65 was decreased in hypothyroidism, whereas GAD67 was not affected by thyroid hormone status (5) [6]. Another study looked at the interactions between thyroid hormone and GABA (6) [7], and found that in the developing brain, hypothyroidism generally decreases enzyme activities and GABA levels whereas in the adult brain, hypothyroidism generally increases enzyme activities and GABA levels. Hyperthyroidism does not always have the opposite effect. The same study showed that in rats and humans, GABA inhibits thyroid stimulating hormone (TSH) release from the pituitary.
Dopamine and Thyroid Health. There is evidence that thyroid hormone plays a role in the output of dopamine (7) [8]. One study showed that dopamine suppresses the secretion of TSH in newborns with primary hypothyroidism (8) [9]. The reason why this might be a problem is because dopamine is sometimes administered in neonatal intensive care, but this can cause problems when screening for neonatal hypothyroidism. Another study also showed that L-DOPA can inhibit TSH release (9) [10]. However, another study looked at thyroid function in people with Parkinson’s Disease, and this study showed that treatment with l- DOPA and/or dopaminergic drugs did not affect thyroid function (10) [11]. Yet another study suggested that an imbalance between thyroid hormones and the dopaminergic system might be responsible for the development of restless legs syndrome (11) [12].
Acetylcholine and Thyroid Health. Thyrotrophic-releasing hormone (TRH) increases acetylcholine synthesis (12) [13]. A recent study looked at the effects of thyroid hormone on hippocampal acetylcholine, and found that the amount of acetylcholine in the hippocampi was significantly decreased in rats with hypothyroidism, and that taking synthetic T4 restored the acetylcholine levels back to normal (13) [14]. Earlier I spoke about myasthenia gravis, and a study showed that mild myasthenia gravis is commonly associated with autoimmune thyroid disease (14) [15]. A few studies have demonstrated a relationship between Graves’ Disease and myasthenia gravis (15) [16] (16) [17].
Other Reasons For Neurotransmitter Imbalances
While thyroid conditions can result in neurotransmitter imbalances, there are other factors which can affect the production of neurotransmitters as well. As I have mentioned numerous times in this article, certain nutrient deficiencies can interfere with the enzymatic reactions which produce these neurotransmitters. For example, iron is required for the production of serotonin and dopamine. As a result, if someone has an iron deficiency anemia then this can result in low levels of these neurotransmitters. So for example, if someone is suffering from depression, before giving them an SSRI, or even St. John’s Wort, it would be a good idea to first do an iron panel to determine if the person has an iron deficiency. Or if they drink alcohol on a frequent basis then this can affect the absorption of certain nutrients which are responsible for the production of neurotransmitters.
The liver is responsible for the conversion of phenylalanine into tyrosine, which in turn is required for the synthesis of dopamine. And so problems with the liver can interfere with the production of dopamine. Glucose is necessary for the formation of GABA, and so if someone has a condition such as hypoglycemia then this can lead to a reduction in GABA. Blood sugar imbalances can also affect the production of serotonin and acetylcholine.
Testing For Neurotransmitters
There are a few different labs which conduct neurotransmitter testing through the urine. However, it’s important to understand that these tests do not measure the levels of neurotransmitters in the CNS. And having an imbalance of serotonin in the gut, for example, doesn’t necessarily mean that one has the same imbalance of serotonin in the CNS. And the same is true with the other neurotransmitters. This doesn’t mean that these tests have no value, as I know some healthcare professionals find them useful, but I personally don’t use this type of testing in my practice.
So hopefully you have a better understanding of the functions of neurotransmitters, and how certain nutrient deficiencies can affect the production of them. Conventional medicine of course focuses on correcting neurotransmitter imbalances with drugs, but they rarely take into consideration that certain nutrient deficiencies can cause these imbalances, and therefore it might make sense to correct these deficiencies first before giving medication. You also learned that thyroid hormone plays a role in the release of neurotransmitters, and so thyroid hormone imbalances can in turn cause neurotransmitter imbalances.