Scenario 16 Flashcards
Defeciency of TRH is a …. Deficiency of thyroid axis?
3
A deficiency in TSH is a …. Deficiency of the thyroid axis
2
A deficiency in t3/4 is a …. Deficiency of the thyroid axis
1
A person with low T4 and high or low TSH is…
Hypothyroid
A person with high T4 and low/ normal TSH is
Hyperthyroid
A person with thyrotoxicosis has …
High T4 and low TSH
Hashimotos affects …% of the population?
3
Hashimoto’s thyroiditis is a disease resulting from….
Autoimmune Ig against thyroglobulin or thyroid peroxidase
What level of iodine leads to non-toxic goitre?
Less than 50 micrograms per day
2 drugs to treat hypothyroidism
Thyroxine and liothyronine
What is a goitrogen?
A substance that suppresses the function of the thyroid by interfering with iodine uptake
How long does it take for a person taking anti thyroid drugs to become euthyroid?
4-8 weeks
How long is treatment for graves with anti thyroid drugs maintained?
12-18 months
2 anti thyroid drugs
Carbimazole and propylthiouracil (prevent conversion from T4–>T3)
Side effects- neutropenia and agranulocytosis
What is used to treat hyperthyroidism by radiation and what is its half life?
Radio iodine and 8 days
When do you use radio iodine to treat hyperthyroidism?
Failed drug treatment, need for urgent treatment, toxic nodules
What sequence of events leads from iodine deficiency to hyperthyroidism?
Iron deficiency leads to decreased T4,thyroid cell hyperplasia, mutation of TSH receptor to constitutively active form
What cytokine induces bystander activation in autoimmune thyroid disease?
TNF alpha
What causes Graves?
Autoimmune Ig acting as TSH receptor agonist
What are the effects of cortisol?
Increase blood glucose levels, increase gluconeogenesis, increase the use of fatty acids for energy and decrease the use of glucose for energy
What does the zone glomerulosa secrete?
Aldosterone
What does the zone fasciculata secrete?
Cortisol
What does the zone reticularis secrete?
Weak androgens
What input does the adrenal medulla receive?
Cholinergic pre ganglionic sympathetic input
What does cortisol down regulate?
Release of ACTH from ant pit and CRH from hypothalamus
Which 2 factors up regulate CRH release from the hypothalamus and therefore cortisol?
Circadian rhythm and stress
In the adrenal gland which second messenger is activated by ACTH to stimulate the production of cortisol?
cAMP
What hormones are produced in the adrenal cortex?
Cortisol and aldosterone
What are the role of glucocorticoids?
Increase gluconeogenesis, protein breakdoen, increase osteoclasts activity and decrease glucose uptake into the cell, protein synthesis, osteoblasts activity, COX2 expression, cytokine production, nitric oxide production, histamine release, IgG production
Does cortisol or aldosterone have greater affinity for a mineralocorticoid receptor?
Equal
Which enzyme coverts cortisol into cortisone?
11betaHSD
When steroids enter the cell and bing to receptor what dissociated from the receptor?
Hsp90
Which element and amino acid are used to make T3 and T4?
Iodine and tyrosine
Thyroid epithelial cells secrete
Thyroglobulin
The thyroglobulin that accumulates is called
Colloid
When the thyroid is stimulated what do the follicular calls do to the iodinated thyroglobulin?
Endocrine them and break them down in lysosomes
Where in the thyroid is the iodinated thyroglobulin stored?
Lumen of the follicles
Which enzyme oxidises iodide to iodine in the thyroid?
Thyroid peroxidase
What effect to high iodine levels have on thyroid hormone synthesis?
Inhibition by inhibition of the iodide pump
What chemical class to the posterior pit hormones belong to?
Peptide
Release of GH is controlled by which hormones?
GHRH and somatostatin
What four physiological stimuli stimulate GH secretion?
Stress, exercise, sleep, post prandial glucose decline
When are GH levels at the peak?
Sleep stages 3-4
When are PRL levels at their peak
2 hours after sleep begins
When do ACTH levels reach their peak?
Before waking up
Which second messenger does the V1a and b (3) ADH receptor activate?
IP3 and DAG
Which second messenger does the V2 receptor activate?
cAMP
Where in the body are V1a
Blood vessels (vasoconstriction)
Where are V1b (3)?
Corticotrophs in the ant pit (increase ADH release)
Where are V2 receptors?
DCT and collecting tubule and duct of the nephron (increase h2O permeability)
Through which 2 mechanisms does ADH increase blood pressure?
Vasoconstriction and reabsorption of h2O in the nephron
What general effect do T3/4 have on the body?
Increase BMR
Is t3 or 4 more active
T3
Which arteries supply the thyroid?
Superior and inferior thyroid
What effects do thyroid hormone have?
Increase transcription, protein synthesis, na/k atpase, atp turnover, oxygen consumption, heat production, cardiac muscle contractility, gut motility, erythropoiesis, bone turnover, protein turnover
What is the dietary iodine requirement?
150 micrograms/day
What is the thyroid derived from?
Endoderm
What is the half life of T3 and T4
1 day, 6 days
Aldosterone is a…
Mineralocorticoid
What tissue does aldosterone target?
DCT of the nephron
What is the action of aldosterone?
Increases Na and Cl reabsorption in the kidneys and increased K and H secretion. also increases bp
What effect do pregnancy, progesterone and prostaglandins have on aldosterone secretion?
Increase it
What are 2 main causes of primary hyperaldosteronism?
Aldosterone producing adrenal adenoma, bilateral adrenal hyperplasia
What does primary hyperaldosteronism present with classically?
Hypertension, hypernatraemia, hypokalaemia, alkalosis
Which drugs are used to treat primary hyperaldosteronism?
Aldosterone receptor antagonist- spironolactone or eplerenone and K sparing diuretic (Amiloride)
Primary aldosteronism is also called?
Conns syndrome (>30 aldosterone:plasma renin activity ratio)
What chemical class does PTH belong to?
Peptide
How are chief cells organised
Irregular cords around blood vessels
…. Levels of calcium in the plasma up regulate PTH secretion
Low
What GH producing tumour causes what?
Acromegaly
Abnormally high levels of plasma PRL is caused by
Hyperprolactinaemia
3 symptoms of hyperprolactinaemis in males and females?
Gynaecomastia, erectile dysfunction, infertility and for females galactorrhoea and infertility
2 drugs to treat hyperprolactinaemia
Cabergoline, bromocriptine (D2 receptor agonists)
4 pharmacological stimuli stimulate GH secretion?
Drug induced hypoglycaemia, amino acid infusion, small peptide hormones, monoamines
Hypersecretion of GH before the fusion of long bone epiphyses results in
Gigantism
Hypersecretion of GH after the fusion of long bone epiphyses results in
Acromegaly
Hyposecretion of GH before the fusion of long bone epiphyses results in
Short stature
Hyposecretion of GH after the fusion of long bone epiphyses results in
adult GH deficiency
3 drugs to treat acromegaly
D2 receptor agonist- bromocriptine, cabergoline or somatostatin analogue (octreotride)
2 drugs to treat small stature
recomninant human GH- somatotropin, recombinant human IGF-1- mecasermin
Procedure for a GH stimulation test
Fast for 12 hours then give insulin/ arginine- should cause an increase in GH
Procedure for a GH suppression test and normal result
Fast for 12 hours then give insulin/ arginine- should cause increase in GH
2 other treatments to treat acromegaly
Surgery and radiotherapy
Hypersecretion of ADH results in
SIADH
Hyposecretion of ADH results in
Diabetes Insipidus
What condition is SIADH related to?
Small cell carcinoma of the lung
What does SIADH present with (3)
Fluid retention, hyponatraemia, urine osmolarity>serum osmolarity
3 drugs to treat SIADH
Impairment of ADH signalling- demeclocycline, ADH receptor antagonists- Conivaptan (V1a/V2), Tolvaptan (V2)
What is diabetes insipidus?
Polydipsia and poly uria with severely dilute urine and reduction in fluid intake having no effect on urine concentation. No glucose in the urine
Drugs to treat central DI?
Desmopressin
What does GH act on to stimulate bone growth?
Chondrocytes
How is DI diagnosed?
Water deprivation test- no increase in urine osmolality
What is the serum and urine osmolality in DI?
Serum >290m specific gravity
What is nephrogenic ADH?
Lack of renal response to ADH
Characteristics of peptide hormone secreting cell
Lots of rER, golgi and secretory vesicles
Characteristics of steroid secreting cells
Lots of sER, mitochondria, lipid droplets
Anatomy of the pituitary
Round 1cm diameter, connected to the floor of III ventricle by infundibulum just post to optic chiasma, lies in depression of the body of the sphenoid and is covered by dura
What are the parts of the ant pit (adenohypophysis)
Pars distalis, pars tuberalis and pars intermedia
What are the parts of the posterior pit (neurohypophysis)
Pars nervosa and infundibulum
What class of hormones are ADH and oxytocin
Peptides
How are ADH and oxytocin released?
Made in cell bodies of neurons in hypothalamus (supraoptic and paraventricular nuclei) and transported down axons to terminals where they are released into fenestrated capillaries on stimulation of the cell bodies. Accumulations of hormones within the axons are called Herring bodies
Which ant pit pars distalis cells are acidophils?
Somatotrophs and Mammatrophs
Which ant pit pars distalis cells are basophils?
Thryrotrophs, corticotrophs and gonadotrophs
Which cells are in pars tuberalis of ant pit?
Gonadotrophs
What does the pars intermedia secrete?
Melanocyte stim hormone
How is the secretion of the ant pituitary regulated?
Neuroendocrine cells of hypothalamus whose axons project to the median eminence discharging into capillaries of pit portal vessels which bathe the cells of the ant pit
What are the advantages of a portal system?
Need less releasing hormone, more immediate response, can use same hormones again somewhere else
Which hormones are tyrosine derivatives?
Dopamine, adrenaline and thyroxine
Which hormones are peptide hormones?
TRH, ACTH, PRL, insulin
Glycoprotein hormones- LH, FSH, TSH, hCG (alpha chain species specific, beta hormone specific)
Which hormones are steroid hormones?
Mineralocorticoid- Aldosterone
Glucocorticoid- Cortisol
Sex- oestrogen, progesterone, testosterone
What is bioassay
Good for determining biologically active hormone (intact animal, isolated tissues BUT problems
What is radioimmunoassay
Antibody radioactively labelled hormone but too much RA waste
What is ELISA
Antibody with associated enzyme- colour change
What is ultradian release
period less than 24 hours
What is circadian release
24 hours (eg cortisol)
Infradian
Longer than 24 hours
Seasonal
Prolactin
What are adverse effects of glucocorticoids?
Suppression of response to infection, suppression of endogenous glucocorticoid production, metabolic effects, osteoporosis, iatrogenic Cushing’s syndrome
What is Cushing’s?
Disease due to pit tumour, syndrome due to other reasons but both high cortisol
What are the symptoms of Cushing’s
Easy bruiding, poor wound healing, muscle wasting, thinning of skin, increased abdominal fat, buffalo hump, moon face, osteoporosis, obesity, increased appetite, increased susceptibility to infection, infertility in women
What are the treatments for Cushing’s disease?
Metyrapone- 11 beta hydroxylase inhbitor, Ketoclonazone, pasireotide, mifeprestone
What is Addison’s disease?
Chronic adrenal insufficiency
What are the symptoms of Addisons disease?
Muscular weakness (low BP, depression), anorexia, hypoglycaemia
What is thryotoxicosis?
State of increased circulating thyroid hormone without knowing the source
What are the signs and symptoms of thyrotoxicosis/ hyperthyroidism?
Hyperactivity, heat intolerance, sweating, palpitations, fatigue, weight loss, increased appetite, diarrhoea, polyuria, tachycardia, goiter, fine hair
What are the s and s of hypothryroidism
cold intolerance, weight gain, constipation, dry skin, coarse hair, slow reflexes
What is phaeochrocytoma?
tumour of adr medulla secreting NA,Adr- headaches, palpitations, chest pain, weight loss, hypertension
What are the s and s of Graves disease?
weight loss, sweating, tremor, tachycarida, diarrhoea, goitre, exophthalmos and upper lid retraction
What is goitre?
Abnormal swelling of the thryoid gland
How do you define a disease as autoimmune?
Evidence of loss of immunological tolerance to self, clinical responsiveness to immune suppression and passive transfer of disease by immune effectors
