week 11 Flashcards
What can hypothyroidism be treated with?
levothyroxine
30mins before breakfast and caffeine containing liquids.
liothyronine
carbimazole
Where are thyroid hormones produced?
thyroid gland by the thyroid follicles
Colloid
proteinaceous depot of thyroid hormone precursors
Synthesis of thyroid hormones
1) Iodine co-transported with Na+.
2)Diffusion into follicle cell.
3)Iodine transported to colloid, oxidized and attached to rings of tyrosine’s in TG. (thyroglobulin)
4)Iodinated ring is added to a DIT at another spot.
5)Endocytosis of TG
6)Lysosomal enzymes release T3 and T4 from TG.
7)T3 and T4 are released from cell
What is the most active thyroid hormone?
T3
How is T4 changed to T3
deiodination
How is thyroid hormone secretion controlled?
Hypothalmus———————————————————–
Thyrotophin-releasing hormone TRH secretion I
Anterior pituitary—————————————————–
Thyroid-stimulating hormone TSH secretion I Thyroid gland I
Thyroid hormone (secrettion) ———————————-
Targtet cell responce
Euthyroid state
Thyroid hormone secretion is normal
Hypothyroid state
Thyroid hormone secretion is subnormal
Hyperthyroid state
Thyroid hormone secretion is excessive
Actions of thyroid stimulating hormone
stimulate T3 and T4 production
increases protein synthesis
increases DNA replication and cell division
increases rough endoplasmic reticulum and cell machinery required for protein synthesis.
What causes a goitre?
hypothyroidism, hyperthyroidism and euthyroidism, excessive exposure to TSH.
Actions of T3 and T4 hormones
T4 secreted to T3
Increased basal metabolic rate, heat production, growth and development, maintenence of normal activity
What are the effects of an iodine deficiency?
Metal retardation, reduction in physical growth, deaf-mutism, cretinism (rare)
Iodine RDA
150 mcg/day
TSH and T4 levels in correspondance to;
Normal
Hyperthyroidism
Hypothyroidism primary
Hypothyroidism secondary
TSH normal T4 normal
TSH low T4 high
TSH high T4 low
TSH low T4 low
Signs and symptoms of hypothyroidism
cold intolerance, weight gain, tiredness, bradycardia, constipation, depression, pale dry skin, puffy face
Hashimoto’s thyroidism
autoimmune disorder and the main cause of hypothyroidism.
Self-reactive T lymphocytes recruit B cells and T cells into the thyroid.
B cells produce antibodies of thyroid epithelial cells. T cells become cytotoxic T lymphocytes leading to cells destruction and decreased production of the thyroid hormones.
T4 decreases and TSH increases
Is Hashimotos more common in men or women?
twice as prevalent in women
Treatment of Hashimoto’s/primary hypothyroidism. Side effects?
Levothyroxine - synthetic T4.
Hair loss, headaches, sleep problems, nervousness, fever, pounding heart, appetite changes
Liothyronine - synthetic T3.
Risks of osteoporosis and heart arrythmia.
shorter half-life
Secondary hypothyroidism
uncommon
pituitary doesn’t produce TSH or hypothalamus doesn’t produce sufficient TRH.
T3 T4 and TSH are below normal
What may happen as a result of untreated hypothyroidism?
Myxoedema coma
extreme hypothermia (24-32C), seizures, respiratory depression
Drugs effecting thyroid function
Corticosteroids - decreased production of TRH and TSH
Lithium - inhibits release of T3 and T4
Amiodarone - contains iodine and can cause hypo and hyperthyroidism
Cholestyramine - reduces absorption of thyroxine
Signs of hyperthyroidism
heat intolerance, palpitations, weight loss, restlessness, fatigue, sweating, frequent bowel movement, goitre
Cause of hyperthyroidism
thyroid produces excess of T4, reduction in TSH due to negative feedback loop.
T3 also elevated.
Graves disease
most common cause of hyperthyroidism
caused by TSI - thyroid stimulating immunoglobulin which increases secretion of thyroid hormones
autoimmune disease
Treatment of hyperthyroidism
Surgery, radioactive iodine - administered orally.
Antithyroid drugs
Thioamides (carbimazole, propylthiourcail)
inhibit thyroid peroxidase and prevent hormone synthesis.
Effect of onset is slow - increased risk of infection.
What is the difference in chemical structure of T3 and T4
T4 has an extra iodine
How are T4 and T3 transported around the body?
Bound to proteins in the blood.
Levothyroxine logP and pKa
logP 7.4 and pKa 10, 9 ,4
Liothyronine logP and pKa
LogP 6
pKa 10,9,4
How does carbimazole work?
a prodrug in which the active form inhibits thyroid peroxidases which convert tyrosine into MIT and DIT. = no T3 and T4. Log P of carbimazole 0.3, LogP of methimazole -0.3.
Hormones secreted by the adrenal glands.
Adrencorticoids, minerlacorticoids, glucocorticoids, sex hormones, adrenaline, noradrenaline
What are mineralocorticoids? Give example
Aldosterone
Made in Zona glomerulosa
Important for Na+ reabsorption and K+ excretion in kidneys.
What are glucocorticoids? Give example
Cortisol
Made in the Zona fasciculata
Regulate body’s response to stress, also help regulate glucose levels.
What are sex hormones? Give example
Androgens
Synthesized in Zona reticularis
Regulate reproductive function
What is cortisol secretion controlled by?
hypothalamic pituitary adrenal axis
Cortisol secretion
stress
hypothalamus ——————————————————–
corticotrophin-releasing hormone (CRH) secretion I
anterior pituitary —————————————————
adrenocorticotrophic hormone (ACTH) secretion I
adrenal cortex I
cortisol —————————————————————–
target cell response
Factors increasing cortisol production
sleep deprivation, trauma, extreme fasting
When does cortisol release peak values?
upon waking - diurnal variation
Cellular actions of cortisol
increases circulating glucose levels
maintains responsiveness of blood vessels to vasoconstrictive stimuli
can have anti-inflammatory action
What effect does an increased level of cortisol have of plasma levels of glucose, fatty acids and amino acids
increases them
What is Addison’s disease?
adrenocortical insufficiency
primary adrenal insufficiency
due to destruction or dysfunction of the adrenal cortex, effects both mineral and glucocorticoid function.
Symptoms of Addison’s disease.
darkening of the skin
extreme fatigue
weight loss and reduced appetite
low blood pressure
GI distrubance
salt craving
low blood glucose
Causes of Addison’s disease
Infections, invasion, haemorrhage
What impact does Addison’s disease have on the cortisol flow chart?
decreased secretion of cortisol due to negative feedback
increased secretion of corticotrophin releasing hormone and adrenocorticotrophic hormone.
What is it that causes hyperpigmentation in Addison’s disease?
increased levels in adrenocorticotrophic hormones that constantly stimualte melanocytes.
Treatment of Addison’s
Hydrocortisone (sometimes prednisolone or dexamethasone) 15-30mg
Fludrocortisone (mineralocorticoid)
Secondary adrenal insufficiency and treatment
Lack of ATCH secretion from pituitary
Don’t show hyperpigmentation or salt craving.
Can occur if glucocorticoid medication is stopped too abruptly
Treatment; glucocorticoid e.g. hydrocortisone, mineralocorticoid is unnecessary as the gland itself is not damaged.
Tertiary adrenal insufficiency
Lack of corticotrophin releasing hormone secretion from the hypothalamus
How do glucocorticoid drugs work?
Suppress hypothalamus and anterior pituitary.
Anti-inflammatory’s = predinsolone, dexamethasone, hydrocortisone, beclamethasone
Adrenal crisis symptoms
sudden severe pain in lower back, severe vomiting and diarrhoea, dehydration, low blood pressure, loss of consciousness
What is cushing’s syndrome? What are the symptoms
Hypersecretion of cortisol.
red cheeks, moon face, fat pads, thin skin, red striations, high blood pressure, thin arms and legs, pendulous abdomen, poor wound healing
Causes of Cushing’s disease
pituitary tumor
adrenocortical tumors
What are the two classes of Cushing’s syndrome?
Adrenocorticotrophic (ACTH) dependent; body making too much ACTH due to pituitary or ectopic tumor
Adrenocorticotrophic (ACTH) independent; ACTH level too low, Adrenal glands making too much cortisol due to adrenal tumor
What drug interactions may cause Cushing’s syndrome?
Drugs that inhihibt P450 enzymes as they prolong the action of glucocorticoids
e.g. many antidepressants, itraconazole, ritonavir
