Endocrine Flashcards
Describe three hormonal responses to exercise
- Glucagon releases sugar from stored glycogen and stimulated gluconeogenesis
- Cortisol enhances the metabolic utility of glucose
- Adrenaline helps to pump leaked K back into the cell via the Na/K pump as there is a tendency for K concentration to increase in the blood during exercise
How do steroid hormones leave the cell?
Simple diffusion
Describe the steps in insulin secretion
- Beta cell imports glucose by facilitated diffusion by GLUT2
- Glucose is transformed to glucose-6-phosphate by glucokinase
- This yields ATP, which binds to the Kir6.2 subunit of the KATP channel
- This causes the channel to close, which depolarises the membrane
- This causes voltage gated Ca channels to open and so insulin is released
How are ATP, ADP and Mg related to the KATP?
ATP binds to the Kir6.2 subunit to close the channel
ADP+Mg binds to the SUR1 subunit to open the channel
Give at least one example of each of the following insulins:
- Rapid acting analogue
- Short acting
- Intermediate acting
- Long acting analogue
- Rapid acting analogue-intermediate mixture
- Short acting-intermediate mixture
- Rapid acting analogue: Humalog, NovoRapid
- Short acting: Humulin S, ActRapid
- Intermediate acting: Humilin I, insulatard
- Long acting analogue: Lantus, Levemir
- Rapid acting analogue-intermediate mixture: Humalog Mix25
- Short acting-intermediate mixture: Humulin M3
What are target blood sugars pre meal and 1-2 hours after beginning a meal?
Pre meal: 4-7
1-2h after beginning: <10
How many units of insulin should you start a patient on?
0.3 units per kg body weight for the whole day
How many units of insulin should you add per CHO?
1 unit per 10g CHO
What should a diabetic patient’s blood sugar be before going to bed?
8
When should you not use Metformin?
Renal impairment with eGFR <40 or creatinine >150
When should you stop Metformin?
Pre-operatively or in severe illness - risk of lactic acidosis
Aside from effects in insulin + glucose, what else does Metformin do?
Decreases triclycerides
Decreases BP
TZDs
- Side effect
- Contraindication
- Prevent micro or macrovascular complications?
- 3-4 kg weight gain due to increased fat mass and fluid retention
- heart failure - because of fluid retention
- prevent macrovascular complications
Do SUs prevent micro or macrovascular complications?
Microvascular
Main side effect of Acarbose?
Diarrhoea and flatulence
What should an annual review of diabetes include?
Weight Blood pressure Bloods: HbA1c, renal function, lipids Retinal screening Foot risk assessment Record severe hypoglycaemia episodes of admission with DKA
Give some examples of autonomic neuropathy
Resting tachycardia Urinary infrequency Erectile dysfunction Hypoglycaemic unawareness Delayed gastric emptying Dry foot
What is proximal neuropathy in diabetes?
Dermatomal distribution of a single neuron e.g. pain in the thighs, buttocks or legs, leading to profound muscle wasting
What is focal neuropathy in diabetes?
Sudden weakness in one nerve or a group of nerves causing muscle weakness or pain e.g. carpal tunnel, ulnar neuropathy, foot drop
What are normal urinary creatinine albumin ratios in men and women?
Men <2.5 mg/mmol creatinine
Female <3.5 mg/mmol creatinine
Treatment of Charcot’s foot?
Cast
What are the following in DKA:
- Creatinine
- Sodium
- Amylase
- WCC
- BP
Creatinine if often raised
Sodium is often reduced
Amylase is frequently raised - doesn’t necessarily mean pancreatitis
WCC is often raised - doesn’t necessarily mean infection
BP is reduced
What is the insulin regimen for DKA?
Fixed rate intravenous insulin infusion
Also give IV 0.9% NaCl
If hypotensive give bolus of 500 mls normal saline
Even if hypotension is resolved, patient still needs large volumes of fluid
What is potassium like in DKA and how should you treat it?
Likely will need to replace it - add KCl to bags of fluid
Initially patient is hyperkalaemic - because insulin is required to drive K into the cells
Titrate potassium to hourly VBG
K >5.5 - don’t replace
K 3.5-5.5 - replace by using 40 mmol infused solution
K <3.5 - seek senior help
What other investigations should you do in DKA?
Often infection with no fever, so do MSU, blood cultures, CXR
Start broad spec antibiotics early if infection is suspected
Give two causes of hyperkalaemia in DKA
The patient is in acidosis, so there is increased H+ - this is then driven into the cell at the expensive of K+
Insulin is required for uptake of K into cells
What is the classic triad in HHS?
Hypovolaemia
Hyperglycaemia
Hyperosmolar
Name two precipitants of HHS
Glucocorticoids
Thiazide diuretics
Also MI, bowel infarct
Give two precipitants of LA
Metformin
Septicaemia
What is lactate?
End product of anaerobic metabolism of glucose
What are the two types of LA?
Type A - associated with hypoxia
Type B - associated with liver disease
Lab findings of LA?
Raised anion gap
Decreased bicarbonate
Age of onset of MODY
Before 25
Also strong FHx
What are the clinical differences between the two types of MODY?
Glucokinase type - onset at birth, stable hyperglycaemia
Transcription factors type - onset in teenage years, progressive hyperglycaemia
What is LADA also called?
What does the presentation mimic?
Aka slowly progressive type I
“Typical” type II diabetes, but tend to not be overweight
Also autoantibody positive
Name an enzyme that insulin inhibits
Glycogen phosphorylase - i.e. inhibits degradation of glycogen to glucose
Describe the synthesis of insulin
Formed from preproinsulin - cleaved to proinsulin in the ER
Proinsulin contains A and B subunits, linked by C
C peptide is cleaved off of proinsulin at the Golgi apparatus
A and B are now bound by disulphide bonds
This structure is insulin
The insulin receptor is what type of receptor?
Tyrosine kinase receptor
What does the insulin receptor consist of?
Two alpha subunits
Two beta subunits
Two tyrosine kinase - enzyme which is active when phosphorylated
Describe activation of the insulin receptor
Two insulins bind to the alpha subunits
This causes tyrosine kinase to phosphorylate the target protein (called IRS-1)
IRS-1 then exerts the intracellular effects of insulin
Give seven functions of thyroid hormone
- Increases basal metabolic rate
- Increases thermogenesis
- Increases insulin-independent glucose uptake into cells
- Increases fatty acid oxidation in tissues
- Increases protein synthesis
- GHrH production + secretion requires thyroid hormones
- Permissive sympathomimetric action - increases responsiveness to adrenaline and sympathetic NS
What are the types of deiondinase enzymes and what are their uses?
Important in de/activation of thyroid hormone
D1 - commonly found in liver and kidney
D2 - found in the tissues - main one concerned in interplay between T3 and T4
D3 - found in foetal tissue + placenta + brain
How do carbimazole and propylthiouracil work?
Inhibit attachment of iodine to thyroglobulin
Treatment of hypothyroidism?
Must gradually restore metabolic rate, or patient will get arrhytmias
Younger - thyroxine 50-100 ug daily
Older - thyroxine 25-50 ug daily
What is DeQuervains thyroiditis?
Aka subacute thyroiditis
Vital trigger, usually self limiting after a few months
Initially have hyperthyroidism, then hypothyroidism, then back to normal
What does differentiated thyroid cancer refer to?
Why is the word “differentiated” important?
Papillary and follicular
Differentiated - two reasons
- Looks like normal thyroid cells
- Vast majority take up iodine and secrete thyroglobulin
What is Medullary thyroid cancer associated with?
MEN2
What is seen on histology of medullary thyroid cancer?
Amyloid deposition
What is the most serious type of thyroid cancer?
Anaplastic - causes rapid growth, involvement of neck structures and death
How is cytology of thyroid cancer graded?
What are follicular lesions graded at?
Thy 1 - insufficient/uninterpretable Thy 2 - benign Th 3 - atypia, probably benign/equivocal Thy 4 - atypia suspicious of malignancy Thy 5 - malignant Follicular lesions are Thy 3
What does AMES stand for?
Age
Metastases
Extent of primary tumour
Size of primary tumour
What is Tayside lymph node removal policy in papillary thyroid cancer?
Central compartment clearance and lateral node sampling
When and how is whole body iodine scanning done?
After surgery Monday - rhTSH IM injection Tuesday - rhTSH IM injection TSH should be greater than 20 for best results Wednesday - give the capsule Friday - scan
How should you treat a patient after thyroid remnant ablation?
Suppress TSH with thyroxine - improved prognosis if suppressed TSH in the long term
What can be used as a tumour marker post thyroid ablation?
What can throw this reading of?
Thyroglobulin
Antibodies to thyroglobulin can throw it off - scan these patients every 6 months
Important risk of thyroid remnant ablation?
Small but significant increased risk of leukaemia
What does a primary follicle contain and what is the purpose of the contents?
Contains an oocyte surrounded by granulosa cells and theca cells
Theca cells produce androgens, which are converted to estrogens by the granulosa cells via the enzyme aromatase
What happens to the corpus luteum after ovulation?
It is left behind in the ovary and starts to secrete progesterone
Give to functions of progesterone
Causes the endometrium to thicken
Inhibits FSH and LH
What is the role of androgens and diabetes in PCOS?
Hyperinsulinaemia causes an increase in androgens in the body
The rise in insulin drives thecal cells of the follicle to produce more androgens
The granulosa cells convert this to excess estrogen
High levels of estrogen and androgens cause a disordered release of LH and FSH
What is the role of estradiol in the negative feedback loop?
Low concentrations of estradiol inhibit the release of FSH
High estradiol has a positive feedback on the pituitary to stimulate LH release
Where are Leydig cells found?
Where are Sertori cells found?
What else is found here?
Leydig - interstitium of the seminiferous tubules
Sertori - seminiferous tubules
Also in the seminiferous tubules are spermtogonia - male germ cells with the ability to become sperm
What is the role of Leydig cells?
LH targets Leydig cells and causes them to secrete testosterone
What is the role of Sertoli cells?
Tertosterone produced by Leydig cells stimulates Sertoli cells to maintain libido, maintain muscle + bone growth, maintain male secondary sexual characteristic
FSH stimulates Sertoli cells to release androgen binding protein
What all do Sertoli cells need for stimulation?
Presence of testosterone
Stimulation from FSH
What is the role of ABP in the male reproductive system?
ABP binds to androgen in the seminiferous tubule to promote sperm growth aka spermatogenesis and spermiogenesis
Which two things are required for sperm production?
ABP and testosterone
What role do Sertoli cells have in the negative feedback loop?
Release inhibin - inhibits the secretion of FSH in order to regulate sperm production
What is the difference between the size of the gametes in spermatogenesis compared to oogenesis?
Sperm are smaller than spermatocytes
Ova are larger than oocytes
What is the difference in onset between spermatogenesis and oogenesis?
Spermatogenesis begins at puberty
Oogenesis begins in the foetus (pre-natal)
How long does spermatogenesis take?
65-75 days in the human male
In spermatogenesis, where do meiosis and mitosis occur?
Meiosis inside the cell
Mitosis outside
At birth, what does each follicle contain?
A dormant primary oocyte - a diploid cell that is resting in prophase of meiosis I
What happens to the follicles after puberty?
Every 28 days, FSH from the pituitary stimulates one of the dormant follicles to develop
The primary oocyte then completes meiosis I and starts meiosis II
What is the role of LH in oogenesis?
It halts the egg at metaphase II, to allow cytoplasmic maturation
When fertilized, completion of meiosis occurs
Which hormones are responsible for the fertile and infertile cervical mucus?
Estrogen - fertile cervical mucus
Progesterone - infertile (thick) cervical mucus
Describe the clinical features of Rubella syndrome
Rash at birth Low birth weight Small head size Heart abnormalities Visual problems Bulging fontanelle
How can you confirm ovulation?
Midluteal (D21) serum progesterone - >30 nmol/l in two samples
What are hormone profiles like in WHO ovulatory disorder II?
Normal gonadotrophs/excess LH
Normal estradiol
Low progesterone
Raised testosterone (in PCOS)
When in the cycle is clomid given?
Day 2-6 (i.e. for 5 days)
NB - cumulative conception rate plateus at 12 months on this drug
Treatment of hyperprolactinaemia?
Dopamine agonist - Cabergoline, Bromocriptine
In which ovulatory disorders in estradiol low?
WHO type I
WHO type III
Treatment of premature ovarian failure?
Hormone replacement with estrogen
Egg or embryo donation
Dysmenorrhoea (before menstruation) + dyspareunia + menorrhagia + painful defaecation + chronic pelvic pain = ?
Endometriosis
How would you investigate tubal disease in women?
If no known risk factors - hysterosalpingogram
Laparoscopy if known or suspected tubular pathology from suspicious history
List some causes of functional hypothalamic amenorrhoea
Weight change Stress Exercise Anabolic steroids Iatrogenic - surgery, radiotherapy Recreational drugs Head trauma Infiltrative disorders e.g. sarcoidosis
What is the gold standard test for pituitary function?
Insulin stress test
You give someone insulin to make them go hypo - stimulated the hypothalamus
Normal response is for cortisol and GH to rise significantly
What happens in the water depravation test?
Give patient no water for 8 hours to try and stimulate ADH production
Can’t measure ADH directly, so measure the concentration of the urine
What is the most common cause of Cushing’s syndrome?
Exogenous steroid use
What is Cushing’s disease?
Bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma
What are some clinical features of ACTH-dependent Cushing’s?
Skin pigmentation Hypokalaemic metabolic acidosis Weight loss Hyperglycaemia Classic features of Cushings are often absent
When is an overnight dexamethasone suppression test positive?
if > 50
Describe the meaning of the results in a high dose dexamethasone suppression test
If ACTH still high then problem is adrenal of SCLC
If ACTH is suppressed by 50% or more then pituitary adenoma
What other physiology should you consider in Cushings, aside from cortisol?
Zona reticularis is also controlled by ACTH - if Cushing’s is caused by high ACTH, then ZR will be affected
This produces large amounts of testosterone in the body
Give two common causes of hypokalaemia
Hyperaldosteronism
Bartter’s syndrome
What is barter’s syndrome?
Defect in Loop of Henle
Bloods show hypokalaemia
