Thyroid & the Brain

Question 1

What is the Thyroid Gland and what does it do

Answer 1

Small (25g) butterfly shaped organ found at the front of the neck.
Secretes Calcitonin (bone growth) and T3 & T4 (growth, development and healthy metabolism)
Pituitary gland and Hypothalamus are involved along with thyroid gland in the healthy secretion of the thyroid hormones
Helps with Glucose metabolism by stimulating digestive tract motility (hence uptake of glucose).
Important for normal sleep and sexual function

Question 2

Excess of Thyroid hormone (Hyperthyroidism)

Answer 2

Weight loss/Increased appetite
Increased heart rate
Palpitation
Hyperventilation
Tremor
Heat intolerance
Angina

(More on this later….)

Question 3

Deficiency (Hypothyroidism)

Answer 3

Weight gain/Constipation
Tiredness
Reduced heart rate
Cold intolerance

(More on this later….)

Question 4

Thyroid gland in early development

Answer 4

The fetal thyroid gland develops from an anterior region of the embryonic gut and reaches maturity by week 11–12, close to the end of the first trimester and begins to secrete thyroid hormones by about week 16

However, TH is important for ● Neurogenesis ● Neuronal migration ● Neuronal and glial cell differentiation ● Myelination ● Synaptogenesis

So, in early development embryo relies on maternal source of TH

Question 5

TH role in adults

Answer 5

T3 & T4 regulate:

• Basal and nutrient metabolism
• Oxygen use and production of ATP
• Calcium homeostasis
• Protein synthesis
• Growth of body tissue and NS
• Neurocognitive function
• Neural stem cell homeostasis

Calcitonin regulates:
- Blood calcium concentration

Question 6

TH Synthesis and Release

Answer 6

Thyroid Stimulating Hormone (TSH), released by the anterior pituitary, binds to cells in the gland, causing active transport of iodide ions
● Iodides form iodine and iodine bonds with tyrosine amino acid
○ T3: thyroid hormone with 3 iodines
○ T4: thyroid hormone with 4 iodines
● When TSH stimulates the glands, the hormones are released
● Release of hormones is mediated by a negative feedback loop:
○ Low T3 and T4 in the blood trigger Thyrotropin Releasing Hormone (TRH) from hypothalamus, which triggers TSH
○ T3 and T4 are released from the gland, which decreases TRH and TSH levels

Question 7

Hyperthyroidism

Answer 7

• Elevated triiodothyronine (T3) and thyroxine (T4), suppressed thyroid stimulating hormone (TSH)
• Graves’ disease - overproduction of thyroid-stimulating immunoglobulin (TSI) → attaches to healthy thyroid cells, causing overproduction of thyroid hormones.
• Excessive thyroid hormones, particularly free triiodothyronine (T3), can induce oxidative stress and damage to neurons which modulate emotion and cognition
• Neuropsychiatric symptoms include lack of concentration, memory impairment, depression, anxiety, nervousness, irritability and stress intolerance

Question 8

Hypothyroidism

Answer 8

● Affects brain development cell maturation, proliferation and neurogenesis
● Deficit in thyroid hormones triiodothyronine (T3) and thyroxine (T4), leads to high thyroid stimulating hormone (TSH) release from anterior pituitary gland → growth effects on thyroid follicular cells and slower cell metabolism
● Can be caused by iodide deficiency or autoimmune dysfunction (e.g. Hashimoto)
● Treatment: administration of levothyroxine, which will be transformed in T3 and can then regulate TSH level
● Hypothyroidism during pregnancy, at week 17→ lower IQ, lower scores on tests of attention and
visuomotor performance at ages 7 – 9
● Lower maternal T4 (Thyroxine) concentration at the end of the first trimester was associated with reduced performance in a simple reaction time task at age 5–6 years

Question 9

Administration of PTU (propylthiouracil) to pregnant rats

Answer 9

PTU a thiomide derivate inhibits synthesis of thyroid hormone and easily crosses the placenta
○ targets genes of TH in development → i.e. cerebral cortex, corpus callosum, dentate gyrus, and cerebellar vermis → (causes) changes in genes involved in neuronal differentiation, development, cell migration, synaptic function, and axonogenesis
○ impacts genes modulating ephrine signaling and ionotropic glutamate receptor AMPA (neuronal migration)
○ electrophysiological recordings: reductions in synaptic transmission and impairment of short and long term plasticity in the dentate gyrus
○ decrease of the cognitive performance in the hippocampus
○ changes in the DNA hypermethylation of some important genes for brain functions → e.g. BDNF gene → critical for development of neuroplasticity related to the process of memory and learning in the hippocampus

Can be concluded that TH is crucial for health fetal brain development