Thyroid hormone physiology

Question 1

outline the negative feedback loop of TH

Answer 1

hypothalamus secretes TRH. this stimulates anterior pituitary gland to release TSH, which stimulates thyroid to release T3 and T4. T4 is converted to T3 by deiodinase enzymes for it to have a biological effect, which then communicates with the anterior pituitary for negative feedback. somatostatin also reduces basal TSH release.

Question 2

how does somatostatin affect TH and growth hormone?

Answer 2

inhibits release of TH and growth hormone.

Question 3

which structure secretes somatostatin and how does it affect insulin and glucagon?

Answer 3

D cells in islets of Langerhans of the pancreas.

inhibits release of insulin and glucagon.

Question 4

what are the 3 main hormones secreted by the thyroid glands?

Answer 4

T3, thyroxine (T4) and calcitonin.

Question 5

How does TH affect growth?

Answer 5

TH has a direct action on cells, and indirectly influences GH production and potentiates its effect on its target tissue.
TH is important fora normal response to parathyroid hormone and calcitonin, as well as skeletal development.

Question 6

what is the functional unit of the thyroid gland and what is it composed of?

Answer 6

thyroid follicle composed of follicular cells and intrafollicular colloid

Question 7

what are the effects of iodine deficiency?

Answer 7

reduces TH production because it prevents conversion of T4 to T3 as iodothyronine will be insufficient, increase in TSH secretion, goitre.

Question 8

what are the functions of TH?

Answer 8

increases basal metabolic rate by increasing:
carbohydrate metabolism; synthesis, mobilisation and degradation of lipids; protein synthesis.
essential for normal development of CNS, esp. myelination of nerve fibres.

Question 9

how does TH increase the measured basal metabolic rate?

Answer 9

by increasing oxygen consumptionand heat production

Question 10

what can increased TH administration result in?

Answer 10

augmented cardiac rate and output. increased tendency for arrhythmia e.g. atrial fibrillation.

Question 11

what is the primary mechanism of TH action and how does it increase carbohydrate metabolism?

Answer 11

increase in number and size of mitochondria and increased activity of metabolically important enzymes.
glycogenesis and glucose uptake by muscle and adipose cells, potentiates the effects of insulin and catecholamines, increase in glucose absorption by GI tract.

Question 12

TH does not increase the basal metabolic rate; therefore the oxygen consumption in which organs and glands?

Answer 12

brain, uterus, testes, spleen.

anterior pituitary gland, thyroid gland.

Question 13

how is TH transported in the blood and what does T4 bind to?

Answer 13

TH is insoluble so 99% are protein-bound. only unbound hormone is biologically active.
majority of T4 binds to thyronine-binding globulin (TBG) and a minority binds to thyroxine-binding pre-albumin (TBPA) or albumin.

Question 14

what is hyperthyroidism, what are its symptoms and its two common forms?

Answer 14

Excessive secretion and activity of TH.
High metabolic rate, increased skin temperature, sweating andheat intolerance, nervousness, tremor, tachycardia, increased appetite associated with weight loss.
Graves’ disease and toxic nodular goitre.

Question 15

what is Graves’ disease caused by and what is its pathogenesis?

Answer 15

organ-specific autoimmune disease caused by autoantibodies stimulating TSH receptors which increases T4 when activated.
suspected increase of TSH receptor-like proteins in orbital tissue. enhanced sensitivity to catecholamines.

Question 16

what are the causes of simple, non-toxic goitre?

Answer 16

dietary deficiency of iodine causes rise in plasma TRH if prolonged, increasing the size of the gland.
ingestion of goitrogens e.g. from cassava root.

Question 17

what is Hashimoto’s thyroiditis?

Answer 17

autoimmune destruction of thyroid gland. there’s an immune reaction against thyroglobulin, which can lead to both hypothyroidism and myxoedema.

Question 18

hypo- and hyperthyroidism is associated with which condition?

Answer 18

atrial fibrillation

Question 19

which drug is used to treat thyroid deficiency, what is its action, its route of administration and its side effects?

Answer 19

levothyroxine.
suppresses TSH secretion in treating some thyroid tumours.
by mouth or by injection.
at excessive doses: palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss.

Question 20

what is the treatment for hypothyroidism?

Answer 20

replacement therapy with thyroxine. monitor by measuring TSH: insufficient T4 suppresses TSH secretion.
calcium + vit D therapy.

Question 21

what is an alternative treatment to surgery and what are the indications?

Answer 21

radioactive iodine. it’s selectively concentrated in the thyroid gland causing tissue damage, reducing TH secretion.
hyperthyroidism and thyroid cancer.

Question 22

which condition does carbimazole treat and what is its action and its side effects?

Answer 22

hyperthyroidism.
pro-drug. converted to active form methimazole after absorption which reduces production of T3 + T4.
common: rashes + pruritus (treated with antihistamines). serious rare side effect: neutropenia + agranulocytosis. Teratogenic.

Question 23

which condition does propylthiouracil treat and what is its action and its side effects?

Answer 23

hyperthyroidism (including Graves’).
inhibits TH synthesis and conversion of T4 to T3.
common: rashes and pruritus (treated with antihistamines).
risk of agranulocytosis and serious liver injury, including liver failure and death.

Question 24

which drugs can induce goitre?

Answer 24

lithium (treats bipolar depression), iodides in vitamin preparations and some cough remedies.

Question 25

How are thyroid hormones synthesised, stored and secreted?

Answer 25

uptake of plasma iodine follicle cells.
oxidation of iodine and iodinationof tyrosine residues of thyroglobulin.
secretion of thyroid hormone.

Question 26

How is MIT and DIT degraded?

Answer 26

rapidly degraded by halogenases to free the iodide, which is then re-utilised by combining with thyroglobulin

Question 27

What are the signs and symptoms of hypothyroidism?

Answer 27

low metabolic rate, slow speech, deep hoarse voice, lethargy, bradycardia, sensitivity to cold and mental impairment, characteristic thickening of the skin, can lead to myxoedema.

Question 28

When is hypothyroidism and subclinical hypothyroidism diagnosed?

Answer 28

Hypothyroidism: when low levels of TH result in elevated levels of TSH.
Subclinical hypothyroidism: when TSH levels are elevated above the upper limit of the assay reference range, with normal TH levels.