Endocrinology Flashcards
Where is GH produced?
Anterior pituitary gland
What is the action of GH?
Stimulates cell reproduction and growth of organs, muscles, bones and height
Stimulates release of insulin-like growth factor
Where is IGF-1 released from and what is its action?
Released by the liver and promotes growth
What is congenital GH deficiency a result of?
Disruption of the growth hormone axis at the hypothalamus or pituitary gland
What are some causes of congenital GH deficiency?
Genetic mutations (e.g. GH1, GHRGHR) Empty sella syndrome (underdeveloped pituitary gland) Hypopituitarism/ multiple pituitary hormone deficiency
What are some causes of acquired growth hormone deficiency?
Secondary to infection, trauma or surgery
How may GH deficiency present in neonates?
Micropenis
Hypoglycamia
Severe jaundice
How may older children present with GH deficiency?
Poor growth
Short stature
Slow development of movement/ strength
Delayed puberty
What test is done to look for GH deficiency?
Growth hormone stimulation test: measuring response to medications that normally stimulate the release of GH.
What other investigations are done when looking at GH deficiency?
Test for thyroid and adrenal deficiency
MRI brain (pituitary or hypothalamic abnormalities)
Genetic testing
Xray for bone age
How is GH deficiency managed?
Daily subcutaneous injections of GH
Treat other hormone deficiencies
Close monitoring of height and development
What is the pathophysiology of T1DM?
Pancreas stops being able to produce insulin (unknown why), meaning cells can’t use glucose, causing hyperglycaemia
What is the ideal blood glucose concentration?
4.4-6.1 mmol/ L
Where is insulin produced?
Beta cells in the Islets of Langerhans in the pancreas
What kind of hormone is insulin?
Anabolic (builiding)
What are the 2 ways insulin reduces blood sugar?
Causes cells to absorb glucose from the blood and use it as fuel.
Causes muscle and liver cells to absorb glucose and store it as glycogen.
What kind of hormone is glucagon and where is it produced?
Catabolic hormone produced by the alpha cells in the Islets of Langerhans in the pancreas
What occurs during ketogenesis?
When there is insufficient supply of glucose and glycogen stores are exhausted, the liver converts fatty acids to ketones to be used as fuel
What percentage of new T1 diabetics present in DKA?
25-50%
What is the triad of symptoms that T1 diabetes presents with?
Polyuria
Polydipsia
Weight loss
What are some less typical potential presentations of T1 diabetes?
Secondary enuresis (bedwetting in a previously dry child) Recurrent infections
What bloods should be taken on a new T1 diabetes diagnosis?
FBC U&E's Lab glucose Blood cultures HbA1c TFT's + TPO anti-TTG antibodies Insulin, anti-GAD and Islet cell antibodies
Why are TFT’s and TPO’s done in a newly diagnosed T1 diabetes?
To test for autoimmune thyroid disease
Why are anti-TTG antibodies looked for in new T1 diabetes diagnosis?
TO test for coeliac disease
Why are Insulin antibodies, anti-GAD antibodies and islet cell antibodies tested for on new T1 diabetes diagnosis?
To test for antibodies associated with the destruction of the pancreas and the development of T1 diabetes
What are the different components of T1 diabetes management?
Insulin regimes
Monitoring carbohydrate intake
Monitoring blood sugar
Monitoring/ managing complications
When should T1 diabetics check their blood sugar levels?
On waking
At each meal
Before bed
What are the different insulin regimes available?
Basal- bolus
Insulin pump
What can injecting insulin in the same spot cause?
Lipodystrophy- where the subcutaneous fat hardens and prevents normal absorption of insulin
Why should patients cycle their injection sites?
To prevent lipodystrophy and ensure effective absorption of insulin
What is the basal part of the basal-bolus regime?
Injection of long acting insulin once a day to give constant background insulin
What is the bolus part of the basal-bolus regime?
Injection of short acting insulin before meals, and according to the number of carbohydrates consumed with each snack
How do insulin pumps work?
Continuously infuse insulin at different rates through a cannula inserted under the skin
How often is the cannula repalced on an insulin pump?
Every 2-3 days
What is the criteria needed to qualify for an insulin pump on the NHS?
> 12
Have difficulty controlling HbA1c
What are the advantages of an insulin pump?
Better blood sugar control
More flexibility with eating
Fewer injections
What are the disadvantages of an insulin pump?
Difficulties learning to use it
Having it attached at all times
Blockages in the infusion set
Small risk of infection
What are the two types on insulin pump?
Tethered pump
Patch pump
What are tethered pumps?
Devices with replaceable infusion sets and insulin. Pump usually has all controls on it and can attach to belt/ pocket ect.
What is a patch pump?
Patch attached directly onto body and works via remote. Whole thing needs changing (not just infusion set and location)
What are the short term complications of T1 diabetes?
Hypoglycaemia
Hyperglycaemia (& DKA)
What causes hypoglycaemia in diabetes?
Too much insulin
Not enough carbohydrates
Not processing carbohydrates properly (malabsorption, diarrhoea, vomiting, sepsis)
What are the typical symptoms of hypoglycaemia?
Hunger Tremor Sweating Irritability Dizziness Pallor
How is hypoglycaemia treated?
Combination of rapid acting glucose (e.g. lucozade) and slower acting carbohydrates
What are the signs of severe hypoglycaemia?
Reduced consciousness
Coma
Death
How is severe hypoglycaemia treated?
IV dextrose
IM glucagon
What are other causes of hypoglycaemia?
Hypothyroidism Glycogen storage disorder GH deficiency Liver cirrhosis Alcohol Fatty acid oxidation defects
When does hypoglycaemia commonly occur in T1 diabetics and how is this managed?
Nocturnal hypoglycaemia
Treat by altering basal-bolus regime and have snacks at bedtime
How is hyperglycaemia managed?
Increase insulin dose
What are the different types of long term complications that can occur with T1 diabetes?
Macrovascular
Microvascular
Infections
What does chronic exposure to hyperglycaemia do to blood vessels?
Damages endothelium, leading to leaky malfunctioning vessels that are unable to regenerate
What does chronic hyperglycaemia to to the immune system?
Suppresses it, and creates optimal environment for infectious organisms to thrive
What are the macrovascular complications of T1 diabetes?
Coronary artery disease
Peripheral ischaemia (poor healing, ulcers, diabetic foot)
Stroke
Hypertension
What are the microvascular complications of T1 diabetes?
Peripheral neuropathy
Retinopathy
Nephropathy
How is T1 diabetes monitored?
HbA1c
Capillary blood glucose
Flash glucose monitoring
What is measured on HbA1c?
Glycated haemoglobin- reflects average blood glucose over last 3 mnths
How often is HbA1c measured in T1 diabetics?
Every 3-6 months to track average blood sugar and assess effectiveness of interventions
What is Flash glucose monitoring?
Using a sensor on the skin to measure the glucose level of the interstitial fluid in the subcutaneous tissue
What is the FreeStyle Libre system?
Device that sits on upper arm and continuously monitors blood glucose
What is the time lag when using flash glucose monitoring?
5 minutes
What are ketones?
Water soluble fatty acids that can be used as fuel
How can ketone levels be measured?
Urine dipstick
Blood using ketone meter
What does hyperglycaemic ketosis do to the blood?
Causes metabolic acidosis
When does DKA occur?
When the patient is not producing adequate and not injecting adequate insulin to compensate
What are the key problems in DKA?
Ketoacidosis
Dehydration
Potassium imbalance
Why do you get dehydrated in DKA?
Hyperglycaemia overwhelms the kidneys and causes glucose to be filtered into the urine. This draws water out (osmotic diuresis), resulting in severe dehydration
Why do you get potassium imbalance in DKA?
Insulin usually drives potassium into cells. Therefore without it potassium stays in the blood
What happens to serum potassium in DKA and why?
It is either high (due to no insulin driving it into cells) or normal due to kidneys balancing the levels with the amount excreted in the urine
What happens to total body potassium in DKA?
It is low as none of it is being stored in the cells
What can happen when insulin treatment starts in patients with DKA/
They can develop severe hypokalaemia, which can lead to fatal arrhythmias
What are children with DKA at high risk of developing?
Cerebral oedema
Why does DKA increase the risk of cerebral oedema?
Dehydration + hyperglycaemia cause water to move from the intracellular space in the brain to the extracellular space, causing brain cells to shrink and become dehydrated. Then, the correction with fluids and insulin causes a rapid shift back to the intracellular space, causing the brain to become oedematous
What should be monitored closely to look for signs of cerebral oedema when treating DKA?
GCS
Headaches, altered behaviour, bradycardia
How is cerebral oedema managed?
Slowing IV fluids, IV mannitol and IV hypertonic saline
How dose DKA present?
Polyuria Polydipsia N&V Weight loss Acetone breath Dehydration + hypotension Altered consciousness Symptoms of underlying trigger (e.g. sepsis)
What is the criteria for diagnosing DKA?
Hyperglycaemia (>11mol/l)
Ketosis (>3mmol/l)
Acidosis (ph<7.3)
What are the 2 principles of DKA management?
- Correct dehydration over 48 hours
2. Give fixed rate insulin infusion
What other factors should be considered when managing DKA?
- Avoid fluid boluses
- Treat underlying triggers (Abx for sepsis)
- Prevent hypoglycaemia with IV dextrose
- Monitor potassium and add to fluids if needed
- Monitor for signs of cerebral oedema
- Monitor glucose, ketones and pH to assess progress
What is adrenal insufficiency?
Where the adrenal glands don’t produce enough steroid hormones
What are the main steroid hormones produces by the adrenal glands?
Cortisol and aldosterone
What is Addison’s disease?
Primary adrenal insufficiency- condition where the adrenal glans have been damaged causing reduction in cortisol and aldosterone secretion
What is the most common cause of primary adrenal insufficiency?
Autoimmune
What is secondary adrenal insufficiency?
When there inadequate ACTH stimulating the adrenal glands, resulting in low levels of cortisol being released
What is the causes of secondary adrenal insufficiency?
Loss or damage to pituitary gland: Congenital underdevelopment Surgery Infectino Radiotherapy Loss of blood flow
What is tertiary adrenal insufficiency?
The result of inadequate CRH release by the hypothalamus
What is the most common cause of tertiary adrenal insufficiency?
Long term oral steroids causing suppression of the hypothalamus
Why should long term steroids be tapered slowly?
If they are withdrawn suddenly, the hypothalamus does not wake up fast enough to produce adequate endogenous steroids.
What are the features of adrenal insufficiency in babies?
Lethargy Vomiting Poor feeding Hypoglycaemia Jaundice Failure to thrice
What are the features of adrenal insufficiency in older children?
Nausea and vomiting Weight loss/ poor weight gain Anorexia Abdominal pain Muscle weakness/ cramps Developmental delay Bronze hyperpigmentation in Addison's
Why do you get bronze hyperpigmentation in Addison’s?
High ACTH levels stimulate melanocytes
What investigations should be done with suspected adrenal insufficiency?
U&E’s
Blood glucose
Cortisol, ACTH, aldosterone and renin levels
Short synacthen test
What will be the results of tests in Addisons disease?
Low cortisol
High ACTH
Low aldosterone
High renin
What will be the results of tests in secondary adrenal insufficiency?
Low cortisol
Low ACTH
Normal aldosterone
Normal renin
What is the short synacthen test?
Synacthen (synthetic ACTH) given in the morning. Blood cortisol taken at baseline, 30 and 60 minutes after administration.
What is a normal result of the short synacthen test?
Cortisol level should at least double
What does a failure of cortisol to rise indicate in a short synacthen test?
Primary adrenal insufficiency
How is adrenal insufficiency managed?
Replacement steroids
What steroid hormones are given to manage adrenal insufficiency?
Hydrocortisone to replace cortisol
Fludrocrotisone to replace aldosterone
What should patients on steroid hormone be given?
Steroid card and emergency ID tag to inform emergency services they are dependent on steroids for life
What should be monitored in patients with adrenal insufficiency?
Growth & development BP U&E's Glucose Bone profile Vitamin D
What should patients on steroids do during acute illness? (Sick day rules)
Increase dose of steroids until illness has resolved
Blood sugar monitoring
IM steroid if have diarrhoea or vomiting
What is an adrenal crisis?
An acute presentation of severe Addisons
How does an adrenal crisis present?
Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia and hyperkalamia
When might adrenal crisis occur?
First presentation of Addison’s disease,
Triggered by infection, trauma or other acute illness
Abrupt stopping of long term steroids
How do you manage Addisonian crisis?
Intensive monitoring
Parenteral steroids
IV fluids
Hypoglycaemia
What is congenital adrenal hyperplasia?
Underproduction of cortisol and aldosterone, and overproduction of androgens
What causes CAH?
Autosomal recessive condition causing deficiency of 21-hydroxylase enzyme
What type of hormone is testosterone?
Androgen
What is the action of glucocorticoid hormones?
Help body deal with stress, raise blood glucose, reduce inflammation and suppress immune system
What is the main glucocorticoid hormone?
Cortisol
When are cortisol levels higher?
In the morning
During times of stress
What is cortisol released in response to?
ACTH from the anterior pituitary
What is the action of mineralocorticoid hormones?
Act on the kidneys to control the salt and water balance in the blood
What is the main mineralocorticoid hormone?
Aldosterone
What is aldosterone released in response to?
Renin
What is the action of aldosterne?
Acts on the kidneys to increase sodium reabsorption in the blood and increase potassium secretion into the urine
What is the action of 21-hydroxylase?
Enzyme responsible for converting progesterone into aldosterone and cortisol (NOT testosterone)
What is progesterone converted into?
Aldosterone
Cortisol
Testosterone
What is the pathophysiology of congenital adrenal hyperplasia?
Defect in 21-hydroxylase enzyme means that there is extra progesterone that cannot be converted to aldosterone or cortisol, so is instead converted to testosterone
What are the aldosterone, cocrtisol and testosterone levels in CAH?
Low aldosterone & cortisol
High testosterone
How does severe CAH present at birth in females?
Virilised genitalia
What is virilised genitalia?
Ambiguous genitalia- enlarged clitoris
How do patients with more severe CAH present shortly after birth?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
What are the signs and symptoms of severe CAH?
Poor feeding Vomiting Dehydration Arrhythmias Virilisation
When do patients with severe CAH usually present?
At birth
When do patients with mild cases of CAH usually present?
During childhood or after puberty
What do the symptoms of mild CAH tend to be related to?
High androgen (testosterone) levels
How do females with mild CAH usually present?
Tall for age Facial hair Absent periods Deep voice Early puberty Hyperpigmentation
How do male patients with mild CAH usually present?
Tall Deep voice Large penis Small testicles Early puberty Hyperpigmentation
Why do you get hyperpigmentation in CAH?
Pituitary gland responds to low levels of cortisol by producing more ACTH/ A byproduct of ACTH is melanocyte simulating hormone.
How is CAH managed?
Cortisol replacement with hydrocortisone
Aldosterone replacement with fludrocortisone
Corrective surgery for virilisation
What is congenital hypothyroidism?
Where the child is born with an underactive thyroid gland or gland that does not produce enough hormone
What is dysgenesis?
Underdeveloped thyroid gland
What is dyshormonogenesis?
Fully developed gland that does not produce enough hormone
Where is congenital hypothyroidism screened for?
Newborn blood spot screening test
How may patients with congenital hypothyroidism present if not picked up at screening test?
Prolonged neonatal jaundice Poor feeding Constipation Increased sleeping Reduced activity Slow growth and development
What is acquired hypothyroidism?
Where a child develops an underactive thyroid gland that was previously functioning normally
What is the most common cause of acquired hypothyroidism?
Autoimmune thyroiditis (Hashimoto’s)
What antibodies is Hashimoto’s associated with?
anti-TPO and antithyroglobulin
What symptoms do you get with Hashimoto’s?
Fatigue Poor growth Weight gain Poor school performance Constipation Dry skin/ hair loss
How is hypothyroidism investigated?
Thyroid function tests
Thyroid USS
Thyroid antibodies
How is hypothyroidism managed?
Levothyroxine once daily
