Where is the thyroid gland located?
- located in the neck
- anterior to the lower larynx and upper trachea.
- inferior to the thyroid cartilage.
Describe the embryological development
1st endocrine gland to develop
1) 3/4 weeks gestation, appears as epithelial proliferation in floor of pharynx at base of tongue
2) spends several weeks migrating. first descends as diverticulum through thyroglossal duct and then migrates downwards passing in front go hyoid bone
3) during migration, remains connected to tongue via thyroglossal duct which eventually degenerates
4) detached thyroid then continues to its final position our following two weeks
What are the two major cell types found in the thyroid gland?
Follicular cells: arranged in units called follicles separated by connective tissue. The follicles are spherical and are lined with epithelial (follicular) cells surrounding a central space (lumen) containing colloid (protein)
Parafollicular (C-cells)-found in the connective tissue
Describe how T3 and T4 are synthesised
1) iodide transported into the epithelial (follicular) cells against a concentration gradient (coupled with 2 Na+ ions – Sodium Iodide Symporter protein is utilised).
2) tyrosine rich protein (thyroglobulin) synthesised in the epithelial cells
3) Secretion (exocytosis) of thyroglobulin into the lumen of the follicle
4) Oxidation of iodide to produce an iodinating species
5) Iodination of the side chains of tyrosine residues in thyroglobulin to form MIT (monoiodotyrosine) and DIT (di-iodotyrosine)
Coupling of DIT with MIT to form T3
Coupling of DIT with DIT to form T4 within the thyroglobulin
What are some sources of dietary iodine?
dietary iodine reduced to iodide and then absorbed in the small intestine. I- then taken up by thyroid epithelial cells via symporter.
essential as it is used in thyroid hormone synthesis. found in:
- dairy
- grains
- meat
- veg
- iodised salt
How are T3 and T4 secreted?
- Thyroglobulin endocytosis to enter epithelial cells from lumen
- Proteolytic cleavage of thyroglobulin occurs to release T3 & T4, which diffuse from the epithelial cells into circulation.
How are thyroid hormones transported?
T3 & T4 are hydrophobic molecules, therefore are bound to proteins:
- Thyroxine binding globulin (TBG)
- pre-albumin
- albumin
less than 1% of T3/T4 is free in circulation (biologically active).
-T3 has less affinity to transport proteins, therefore greater free % and a lower half-life (T3 half-life is around 2 days whereas T4 half-life is around 8 days.)
Note T4 isn’t biologically active and it is cleaved in the liver and kidneys.
How is the thyroid regulated?
- T3 & T4 Secretion is controlled by the hypothalamus and anterior pituitary gland
- Thyrotrophin-Releasing Hormone (TRH) is released from cells in the dorsomedial nucleus of the hypothalamus. This is influenced by:
- T3 & T4 (negative feedback).
- Stress
- TRH
- Temperature
-TRH travels in the hypothalamic/pituitary portal system to stimulate secretion of Thyroid Stimulating Hormone (TSH) from the thyrotrophs in the anterior pituitary. TSH travels in the blood to affect the follicular cells
-TSH interacts with receptors on the surface of the follicle cells and stimulates (all aspects of the) synthesis
and secretion of T3/T4. TSH has trophic effects on the gland that result in vascularity, size/number of follicle cells.
What is the effect of thyroid hormones in the body?
- increased metabolic rate (exceptions are brain, spleen, testis)
- stimulates glucose uptake and metabolism
- stimulates protein metabolism
- stimulates mobilisation and oxidation of fatty acids
- catabolic effects lead to increased heat production and increased oxygen consumption
- increases target cell response to catecholamines in the body (heart)
- increases myelination and neutron development in the nervous system
How do thyroid hormone receptors work?
- bind DNA in absence of hormone causing transcriptional repression
- comformational change on thyroid binding
What substances are used in thyroid scanning?
- radioactive iodine rarely used
- technetium99 used
What are the main causes of metabolic thyroid disease?
- extremely rare for pituitary adenoma to produce TSH and thyrotoxicosis
- pituitary failure only rarely presents with isolated hypothyroidism
- 99% of dysfunction is due to the gland itself
TSH is top screen for assessing thyroid function due to negative feedback loop
What is goitre and what is it caused by?
- enlargement of thyroid gland which can be diffuse, multi nodular or affecting a single node
- affects females more potentially due to oestrogen progesterone ratio
- commeonest causes globally are due to iodine deficiency (hypothyroid risk) and multionodular goitre (hyperthyroid risk)
note, retrosternal multi nodular goitre can lead to respiratory issues due to compression of trachea
What is the risk of iodine deficiency during pregnancy?
- mental retardation
- abnormal gait
- deaf mutism
- short stature
- goitre
- hypothyroidism
cretinism
What are the signs and symptoms of hypothyroidism?
Signs and symptoms of hypothyroidism in adults:
- Cold intolerance and reduced BMR
- Weight gain
- Tiredness and lethargy
- Bradycardia (abnormally slow HR)
- Neuromuscular system – weakness, muscle cramps and cerebellar ataxia (clumsiness)
- Skin dry and flaky
- Alopecia (hair loss)
- Voice is deep and husky
- loss of outer third of eyebrow
- non pitting oedema due to mucopolysaccharide deposition
- constipation
- menorrhagea
treat with thyroxine
What are the signs and symptoms of hyperthyroidism?
- Heat intolerance- increased oxygen consumption and increased BMR
- Weight loss
- Physical and mental hyperactivity
- Tachycardia (increased HR >100)
- Intestinal hyper-mobility
- amenorrhea
- Skeletal and cardiac myopathy giving rise to tiredness, weakness and breathlessness
- Osteoporosis due to increased bone turnover and preferential resorption
- bounding pulse
- lid lag and staring eyes to to levator muscle
treat with carbimazole, thyroidectomy, radioactive iodine
What are Graves and Hashimoto’s disease?
Graves= TSI binding TSH receptor causing hyperthyroidism. Also causes exophthalmus and pretibial myxoedema
Hashimotos= Autoimmune destruction of thyroid leading to hypothyroidism.
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Appetite12
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Nutrition24
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Endocrinology Intro10
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Drug Metabolism14
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Oxidative Stress17
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Calcium20
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Energy Reactions in Cells14
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Glycolysis23
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TCA Cycle + Oxidative Phosphorylation12
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Lipids36
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Amino Acids17
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Energy Storage9
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Thyroid Gland17
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Pituitary Gland/ Growth Hormone14
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Adrenal Glands17
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Diabetes18
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Haemopoiesis+Iron22
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Anaemia16
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Spleen+White Cells17
