Thyroid Gland Flashcards
What is the histiological structure of the thyroid gland?
Follicular cells + cuboidal/columnar epithelia surrounding colloid (which contains thyroglobulin - NOT cytoplasm)
C-cells (darker-staining) produce calcitonin
What is the anatomical location of the thyroid gland?
Anterior to the upper trachea (cricoid cartilage) and wrapped around the lower larynx anteriorly
What is the precursor for thyroid hormone synthesis? Outline how T4 & T3 are related.
Tyrosine residues on thyroglobulin proteins (therefore fat-soluble)
deiodination (peripheral tissues) Tetra-iodothyronine (T4 = thyroxine) ----------> Tri-iodothyronine (T3)
Note: T4 is the inactive prohormone
What is the hypothalamic-pituitary axis for thyroid hormone synthesis?
HYPOTHALAMUS: secretes thyrotrophin-releasing hormone (TRH)
PITUITARY: secretes thyroid-stimulating hormone (TSH)
THYROID: acute effects: synthesis, storage, and secretion of T3/T4
chronic effects: growth and division of follicular cells
What are the functional differences between T3 & T4?
T3 more potent/active than T4
T3 has shorter half-life than T4
T3 produced in fewer quantities than T4
T3 has lower binding affinity for TBG than T4
How are T3 & T4 transported in the blood?
99% bound to thyronine binding globulin (TBG) (rich in tyrosine)
Some bound to albumin & pre-albumin (TBPA)
1% free (unbound)
What other factors apart from thyroid hormones can affect TBG synthesis and clearance of T3 & T4?
Oestrogens, stress, cold, & exercise = stimulates TBG synthesis and clearance of T3 & T4
What is unique about the receptors binding to T3 & T4?
On cell membrane AND nuclear membrane
same as with cortisol
Outline the synthesis and release of T3 & T4 in follicular cells.
Active transport of iodine into follicular cells (Na+/I- symporter)
Synthesis of tyrosine-rich TBG
H2O2 lyses vesicle containing TBG precursor
Exocytosis of TBG into colloid, and iodination of side chains and coupling to MIT & DIT to form T4 and T3 (STORAGE)
(RELEASE) Endocytosis of TBG-T4 and lysing of vesicle by lysosome
Breakdown produces MIT & DIT which can be deiodinated to form I-
Release of T3 & T4 into bloodstream
How are thyroid hormones inactivated, and where?
T3 & T4 degraded by deiodination to T2 in liver and kidney (iodine recycled)
What are the general effects of thyroid hormones?
- increase BMR (e.g. no. & size of mitochondria, increase in oxygen consumption & heat production, increase in nutrient utilisation)
- stimulates catabolic pathways (lipolysis, glycoloysis, proteolysis, etc.)
- promotes normal growth & development of tissues (synthesis of specific proteins)
- increases responsiveness of tissues to sympathetic nervous system (noradrenaline)
What are the specific effects of thyroid hormones?
NERVOUS: increased myelination, speed of reflexes, mental activity (alertness, emotional tone, memory)
CARDIOVASCULAR: increased cardiac output, heart rate (directly and by noradrenaline synthesis)
SKIN: increased turnover of proteins & glycoproteins
BONE: increased bone turnover and resorption
GI: increased gut motility
What are the causes, signs, and symptoms of hypothyroidism in the new born? What is the diagnosis and treatment?
Cretinism (congenital lack of TSH due to pituitary tumour/iodine deficiency)
- failure in CNS development —> severe mental retardation
- decreased muscle & bone development —> diminished linear growth
- delayed sexual development
Diagnosis:
Measure [T3] & [T4] (newborns screened)
Treatment:
T4
What are the signs and symptoms of hypothyroidism in adults?
S&S:
- cold intolerance
- decreased perspiration
- cold, dry hands
- weight gain
- bradycardia (low heart rate)
- decreased cardiac output
- constipation
- mood swings/anxiety/depression
- myxoedema (dry, waxy swelling of skin & subcutaneous tissue)
- poor concentration & memory
- dry skin, brittle nails, and hair loss
- GOITRE
What are some of the causes of hypothyroidism? What is the treatment?
Hashimoto’s thyroiditis = autoimmune destruction of thyroid follicles due to production of antibody that blocks the TSH receptor on follicular cells
(Post-partum thyroiditis transient due to modifications to immune system)
Iodine deficiency
Post-sugery/radioactive treatment/anti-thyroid drugs
Congenital
Pituitary tumours (causing lack of TSH)
Treatment: oral T4 (note: dosage adjustment will be necessary until TSH secretion becomes normal)
What can cause a goitre in hypothyroidism?
High TSH overcompensating for low T3 & T4 (primary gland failure) causing hypertrophy of follicular cells
OR: iodine deficiency leading to hyperplasia of follicular cells
OR: lymphocyte infiltration (infection/autoimmune)
What are the effects of hyperthyroidism in children?
Earlier maturation
What are the signs and symptoms of hyperthyroidism in adults?
S&S:
- heat intolerance
- increased perspiration
- warm, moist hands
- weight loss
- increased appetite
- diarrhoea
- tachycardia (increased heart rate)
- increased cardiac output
- nervousness, irritability, emotional lability
- hyper-reflexive (tremor in outstretched hands)
- exophthalmos (proptosis = bulging eyeballs)
- GOITRE
What are the causes of hyperthyroidism?
- Grave’s disease = autoimmune production of antibody that stimulates TSH receptors on follicular cells
- Toxic multinodular goitre = overproduction of T3 & T4 independent of TSH
- Solitary toxic adenoma
- Excessive T3 & T4 therapy/iodine therapy/anti-arrhythmics e.g. anioderone
- Ectopic thyroid tissue
- TSH secreting tumours
What causes a goitre in hyperthyroidism?
Increased production of T3 & T4 despite low TSH (due to negative feedback)
Or lymphocyte infiltration (autoimmune/infection)
Or: tumour
What are the treatments for hyperthyroidism?
- Carbimazole (inhibits incorporation of iodine into TBG)
- Radioactive iodine (trapped in thyroid gland —> destroys) —> hypothyroidism
- Surgical removal (careful not to remove parathyroid glands)
How can the function of the thyroid be screened?
Technetium 99m shows areas of high activity in the thyroid when viewed with a gamma camera
What is compensated euthyroidism?
Borderline hypothyroidism (asymptomatic)
May progress to mild hypothyroidism
What is sick euthyroid syndrome?
Sick patients often have abnormal thyroid hormone levels due to stress & trauma
