Endocrinology Flashcards
What are the three types of hormone?
Amine : catecholamine, setotonin, thyroxine
Steroid : cortisol, aldosterone, androgens, oestrogens, progesterones, vitamin D
Peptide: everything else
Thyroxine is chemically an amine but acts like a steroid
Amines/peptides - short half life, act on cell surface receptor, often act via a second messegnger
Steroid - longer biological half life, at on intracellular recepto, act on DNA to alter gene expression
What type of hormones act at the cell surface?
Peptide and amine hormones act at the cell surface via specific membrane receptors
The signal is transmitted intracellulary by one of three mechanisms
- via cAMP
- via a rise in intracellular calcium
- via receptor tyrosine kinases
Assume the action of peptide or amine hormone is via cAMP unless it is isulin or has the word growth in its name in which it is likely to act via a receptor tyrosine kinase
How do hormone receptors linked to cAMP generate cAMP?
hormone receptors linked to cAMP (e.g. TSH) typically have 7 transmembrane domains. The receptor does not directly generate cAMP but acts via G proteins (Gs) on the cell surface which in turn interact with cAMP generating enzyme, adenlyly cyclase on the cell surface/
Hormones that raise the level of cAMP intracellularly act via a stimulatory G-protein
Hormones that lowet the level of cAMP act via inhibitory of G protein
what conditions are associated with mutations in G proteins?
Acromegaly (40% of patients with acromegaly have an activating somatic mutaiton of G proteins in their pituitary tumour. As a result, the cells are always switched on and continuously make GH)
McCune Albright syndrome
Pseudohypoparathroidism -
What hormones release intracellular calcium as a second messenger?
GnRH
TRH (thyrotrophin releasing hormone)
Adrenaline
The receptors for these hormones activate different G proteins (Gq) which in turn activate the cytoplasmic enzyme phospholipase C (PLC).
This releases IP3 from membrane phospholipids. IP3 binds to the IP3-sensitive receptor on the endoplasmic recticuluim within the cell which causes calcium to be released from stores on the endoplasmic reticulum into the cytoplasm.
The calcium subsequently affects cell metabolism by binding to the prtoein calmodulin.
How to hormones act via receptor tyrosine kinase?
Insulin, GH, prolactin and growth factor receptors do not use second messengers. the receptors themselves can act as enzymes that phospphorylate other proteins when hormone is bound at the cell surface
What hormones act intracellulalry
steroid, vitamin D and thyroxine are sufficiently lipid soluble that they do not need cell surface receptors but can diffuse directy through the cell membrane
they then bind to receptors in the cytoplasm that protect the empty receptor.
The hormone receptor complex migrates into the nucleus where is alters the transcription of a large number of genes.
What conditions are due to hormone resistance?
Receptor defect
Laron’s dwarfism (GH)
Leprachaunism (Insulin)
Nephrogenic diabetes insipidus (ADH)
Androgen resistance (testicular feminisation syndrome)
Second messenger defect - pseudohypoparathyroidism
What hormones may fall and rise during illness?
Hormones that fall - TSH, T4/T3, LH, FSH, testosterone, oestrogen , insulin
May rise - GH (though IGF-1 falls), ACTH, glucocorticoids, adrenaline, glucagon, prolactin
What happens to hormone during starvation?
In starvation alone, without illness, all hormones fall except glucagon.
In anorexia there is also stess - all hormone fall except glucagon, GH and glucocorticoids.
What hormone changes are seen in obesity?
Hyperinsulinaemia
Increased cortisol turn over but not hypercortisolism
increased androgen levels in woman
reduced GH
conversion of androgens to oestrogens
What is leptin?
where is it release from and what does it act on?
a polypeptide hormobe
released from fat cells
acts on specific cells in the hypothalamus to reduce appetite
circulating leptin levels are directly proportional to fat mass so they tell the brain how fat an individual is.
Leptin appears to have stimulatory effects on metabolic rate and lebels will fall in starvation
Adequate leptin levels are needed for the onset of pubity
Obese individuals appear to be relatively resistant to leptin
What is Ghrelin?
First identified as GH releasing hormone
released from the stomach when subjects are fasting or in conditions of negative energy balance and triggers hunger
It stimulates gastric contraction and hence gastric empting
What is peptide YY where is it released from ?
Peptide YY is a member of the neuropeptide family - it is the main regulator of day to day appetite
it is released frol L cells in the small and large bowel
Levels rise after meals and reduce appetite
What is GLP-1, where is it released from ?
Glucagon like peptide 1 - also released from L cells of the intestines after meals and powerfully promotes insulin secretion in response to raised glucose (incretin effect) as well as possiblt reducing appetite.
It is inactivated by the enzpye DDP-4
What is oxyntomodulin and where is it released from?
Released from L cella and dervied from proglucagon - appears to act on the same receptor as GLP-1 but with less incretin and has more of an appetite supressing effect
What is neuropeptide Y and where is it released from?
Neuropeptide Y is released from the hypothalamus and increases appetite.
what leads to increases/decreased prolactin levels?
Prolactin is released from the pituitary
It is under negative control by dopamine from the hypothalamus
Prolactin is raised by
Phenothiazines, haloperidol
Antiemetics - e.g. metoclopramide
Damage to the hypothalamus e.g. radiation
pregnancy
nipple stimulation
damage to the pituitary stalk (e.g. pressure from pituitary tumour)
oestrogens
PCOS
Prolactin is surpressed by
Dopamine agonist drugs - e.g. bromocriptine, cabergoline
Causes of gynaecomastia ?
Pubertal
obesity - not true gynaecomastia
hypogonasism (e.g. Klinefelter’s syndrome, testicular failure
Cirrhosis, alcohol
Hyperthyroidism
Drugs - spironolactone, digoxin, oestrogens, cimetidine, anabolic steroids, marijuana
Tumours - adrenal or testicular making oestrogen, Lung pancreatic gastic making hCG, hepatomas converting androgens to oestrogens
What are thyroid hormones bound to in the plasma?
TBG abd thyroid binding prealbumin (TBPA)
How could you administer thyroxine to a confused patient?
You could administer the total weekly dose once a week. This is becuase T4 has a half life of 7 days.
Where is T4 converted to T3
patially in the circulation and partially in the thyroid.
What are the enzymes that act on thyroid hormones?
There are 3 deiodinase enzypes that act on thyroid hormones (D1-D3). D1 and D2 promote the generation of active hormone (T3) by converting T4 to T3.
D3 opposes this by promoting conversion of T4 to reverse T3 and destroying T3 by conversion to T2 (inactive)
D1 and D2 are inhibited by illness, propranolol and pylthiouracil, amioderone and ipodate - this will reduce the level of the active hormone but little change to T4.
what is renin?
Renin is released form the JGA of the kidney in response to low sodium delivery or reduced renal perfusion.
It is an enzyme that converts angiotensinogen to angiotensin I.
ACE in the lung coverts angiotensin I to angiotensin II
What is the end product of the RAAS system and what does it do?
the end product is angiotensin II
it has three action
Releasing aldosterone from the adrenal gland - retains sodium, excretes K in the distal tubule.
Vasoconstriction
Induction of thirst
contraindications for insulin stress test?
epilepsy
ischaemic heart disease
adrenal insufficiency
What advice should you give to patients who have hypercalcaemia secondary to malignancy?
Advice about maintaining good hydration (drinking 3-4 L of fluid per day), provided there are no contraindications (such as severe renal impairment or heart failure).
Reassure that a low calcium diet is not necessary, as intestinal absorption of calcium is usually reduced.
Advise the person to avoid any drugs or vitamin supplements that could exacerbate the hypercalcaemia.
Encourage mobilization where possible to avoid exacerbating the hypercalcaemia.
Advise the person to report any symptoms of hypercalcaemia.
what should be used to guide treatment in patients who have been started on a statin for primary prevention of CVD?
In the primary prevention of CVD using statins aim for a reduction in non-HDL cholesterol of > 40%
