Thyroid-Brain Crosstalk-Part 1: The Microglia, Neuron and Thyroid Connection

The evidence clearly demonstrates that there is functional crosstalk between the brain and the thyroid.  Thyroid hormones have very powerful influence on microglia cells of the brain and neuronal neurotransmitter pathways.  Cytokine surges (which initiate inflammatory processes) turn on microglia cells causing neural inflammation.  Patients with thyroid disorders develop a vast list of neurological, mood, and cognitive symptoms.  These people may not have a neurological disease but they suffer from various brain disorders, such as anxiety, depression, mood disorders and memory loss.

There is clear evidence that neurotransmitters are important centrally for the modulation of the HPT axis.   Long-term hypothyroidism leads to neurodegeneration (degeneration of the brain).  The research shows when people have long-lasting hypothyroidism, they will have accelerated neurodegeneration.  People that are not diagnosed with hypothyroidism for a long period of time after onset will have increased neurodegeneration.

The brain is one of the main tissue/organ that degenerates in hypothyroidism.  When the brain degenerates, there are two common symptoms patients have:

  • Depression
  • Fatigue (with brain activity)

 Hypothyroidism leads to depression

People may think their depression and fatigue is thyroid-related and will focus their efforts into improving their thyroid but they will continue to have symptoms until they address their brain.  When the brain loses its health and integrity, they get depression.  Their brain fires less efficiently and has less endurance.  Their neurotransmitter activity is decreased and the brain is less efficient in its firing rate.  This leads to depression, decreased ability to motivate and concentrate.  Depression from a neurological perspective results from decreased firing of the frontal cortex of the brain.

Hypothyroidism leads to brain-based fatigue

Hypothyroid patients will have brain-based fatigue.  When hypothyroid patients perform activities that require mental activity, such as reading or driving for prolonged periods, they get tired.  Even after they start taking thyroid hormones, they will continue to have these symptoms and they will think their thyroid is not managed well.  Both neurons and glial cells of the brain are impacted by hypothyroidism.

Their brain also has less endurance so they get tired when they use their brain for extended periods of time.  If people have fatigue when they read, drive or have long conversations, this is brain-based fatigue.  You cannot get brain endurance back unless you support your brain.  These hypothyroid patients fail because their practitioners are not looking at the brain.

Thyroid hormones dampen glial activation and brain inflammation

The brain is composed of glial cells and neurons.  More than half the mass of the brain is glial cells.  There are 10 glial cells to every neuron.  The glial cells are part of the brain-immune response and prone to inflammation.  When patients become hypothyroid, the glial cells are prone to an inflammatory state.  Thyroid hormones dampen glial activation.  We all have some degree of brain inflammation but a person who is hypothyroid has increased brain inflammation.  In addition, systemic cytokine surges also turn on glial cells toward an inflammatory state.  When the brain gets inflamed, you get decreased neuron conductance.  The most common way people explain decreased neuron conductance is “brain fog”.  We see many brain-fog hypothyroid patients that have difficulty completing a thought.

“Thyroid hormones have powerful microglia-modulating properties that are very important for brain development as well as healthy adult brain aging and neuro-immune modulation”

Hypothyroidism in youth leads to developmental disorders

Kids that are hypothyroid that never get diagnosed have much lower IQ scores than kids that never develop a thyroid disorder.

“Congenital hypothyroidism leads to developmental disorders characterized by cognitive, sensory, and motor disorders that are correlated with the magnitude of the thyroid hormone deficiency.  This reflects a variety of alterations in CNS histogenesis, including impaired dendritic and axonal development, reduced number of synapses, hypomyelination and altered astroglial development”

 Hypothyroidism in pregnancy leads to brain developmental disorders

If the mother is hypothyroid during pregnancy, there is a very high chance of mental retardation in the child.  Thyroid hormone has very powerful influences on the brain.  When thyroid hormone is imbalanced, the brain is compromised.

Hypothyroidism in adults increases risk of all neurodegenerative disorders

People that are hypothyroid as an adult have increased risk of all neurodegenerative disorders: Alzheimer’s, vascular dementia, Parkinson’s, etc.

“T3 and T4 thyroid hormones have been demonstrated to favor basic processes of neurogenesis, including precursor cell proliferation, neuronal migration, dendritic and axonal growth, meylination an synaptogenesis.  In the adult brain, thyroid hormones have shown the ability to promote plasticity and promote healthy brain aging.  It is suggested that thyroid hormones might influence microglial reactions that accompany lesions or neurodegenerative diseases in the CNS and could regulate microglial functions”

 Microglial activation…now what?

One of the things we need to consider with these hypothyroid patients is the health of their brain.  We always look for depression or brain-based fatigue with these patients.  It is common for hypothyroid patients to have brain-based fatigue (ie: fatigue with driving, reading, etc.)  If someone has thyroid deficiency and the microglial cells get activated, even after they go on thyroid hormones, the glial cells remain activated.  Once the microglial cells get activated, they never completely shut off, even after going on thyroid hormone.  Thyroid hormone will dampen microglial activation, but not completely stop it.  The longer they have been hypothyroid, the more neurodegeneration they will have and the more microglial activation they will have.

Nutritional Strategies: Dampen Glial Activation

One of the strategies we use with these patients is to dampen the neural inflammation and glial activation of the brain.  There are very few natural substances which have the ability to dampen microglial activation.  There are only certain flavanoids that can cross the blood-brain-barrier and have an anti-glial inflammatory response.  We use these flavanoids to dampen glial activation in hypothyroid patients.


Article by Datis Kharrazzian, D.C., Mastering the Thyroid, Nov. 12, 2010