Paediatrics Endocrinology Flashcards
What is Type 1 diabetes mellitus (T1DM)?
Pancreas stops being able to produce insulin (cause is unclear - maybe genetic / triggered by viruses e.g. coxsackie B virus and enterovirus
What is the problem with a lack of insulin?
Body cannot take glucose from the blood and use it for fuel - causing hyperglycaemia
What is the aim for blood glucose?
4.4 and 6.1 mmol/L
What is insulin produced by?
Beta cells in the islets of langerhans in the pancreas
What type of hormone is insulin?
Anabolic hormone (building hormone)
How does insulin reduce blood sugar levels?
Increases cell uptake of glucose for fuel
Causes liver and muscle cells to store as glycogen
What is glucagon?
Hormone which increases blood sugar levels
Where is glucagon made?
Alpha cells in the Islets of Langerhans (catabolic hormone)
When is glucagon is released? What does it stimulate?
Response to low blood sugar levels to stimulate glycogenolysis (breaking down glycogen into glucose) and gluconeogenesis (converting proteins and fats into glucose)
What is ketogenesis?
Conversion of fatty acids to ketones by the liver when there is insufficient supply of glucose and glycogen stores are exhausted such as in prolonged fasting
What are ketones?
Water soluble fatty acids which can be used as fuel - can cross blood brain barrier and be used by the brain
What is characteristic for people in ketosis?
Acetone smell to breath
How do patients with T1DM present?
Diabetic ketoacidosis or hyperglycaemia
What is the classic triad of symptoms of hyperglycaemia?
Polyuria (excessive urine)
Polydipsia (excessive thirst)
Weight loss (mostly through dehydration)
What are some less typical presentations of T1DM?
Secondary enuresis (bedwetting in a previously dry child)
Recurrent infections
Symptoms are usually present for 1-6 weeks prior to developing DKA - varies significantly
What bloods should be taken with a new diagnosis of T1DM?
- Bloods: FBC, U&Es, formal laboratory glucose
- Blood cultures for suspected infection (i.e. fever)
- HbA1c for blood sugar over last 3 months
- TFTs and thyroid peroxidase antibodies to test for associated autoimmune thyroid disease
- Tissue transglutaminase (anti-TTG) antibodies for associated coeliac disease
- Insulin antibodies, anti-GAD antibodies and islet cell antivodies for antibodies associated with destruction of the pancreas and development of type 1 diabetes
What are the management principles for T1DM?
- Subcut insulin regimes
- Monitoring dietary carbohydrate intake
- Monitoring blood sugar levels on waking, at each meal and before bed
- Monitorign for and managing complications both short term and long term
What is the insulin regime for T1DM?
- Background, long acting insulin once a day
- Short acting inulin injected 30 mins before meals (alternatively can be given by an insulin pump)
Initiated by a diabetic specialist
What can injecting into the same spot cause?
Lipodystrophy (subcutaneous fat hardens and prevents normal absorption of insulin)
Check for this if patient is not responding to insulin as expected
What is a ‘basal bolus regime’ for insulin?
Basal = injection of long acting insulin e.g. “lantus” typically in evening
Bolus = injection of short acting insulin e.g. actrapid usually 3 times a day (also injected according to number of carbs consumed before every snack)
What is an insulin pump?
Small device which continuously infuses insulin at different rates to control blood sugar levels - alternative to basal bolus regime
Insulin is given through a cannula which is inserted under the skin (replaced every 2-3 days and insertion sites rotated
How can a patient qualify for an insulin pump?
Child over 12 and have difficulty controlling HbA1c
What are the advantages of an insulin pump?
Better sugar control
More flexibility with eating
Less injections
What are the disadvantages of an insulin pump?
Difficulties with learning to use pump
Having pump attached at all times
Blockages
Infection
What are the two types of insulin pumps?
Tethered pump
Patch pump
What is a tethered pump?
Pump + replaceable infusion set
Pump is attached around the waist - controls are usually on the pump itself
What is a patch pump?
Sits directly on the skin without any visible tubes
When out of insulin the entire patch pump is disposed of (usually controlled by a separate remote)
What are the short term complications of T1DM?
Hypoglycaemia
Hyperglycaemia (DKA)
What is hypoglycaemia?
Low blood sugar level caused by too much insulin or not processing carbs correctly e.g. malabsorption, diarrhoea, vomiting and sepsis
What are the typical symptoms of hypoglycaemia?
Hunger
Tremor
Swearing
Irritability
Dizziness
Pallor
If severe:
Reduced consciousness
Coma
Death
How is mild hypoglycaemia treated?
Rapid acting glucose e.g. lucozade
Slower acting glucose e.g. biscuits / toast to maintain blood sugar when rapid acting glucose is used
How is severe hypoglycaemia treated?
IV dextrose (10%) and IM glucagon
What are some other causes of hypoglycaemia?
Hypothyroidism
Glycogen storage disease
Growth hormone deficiency
Liver cirrhosis
Alcohol
Fatty acid oxidation deficits (e.g. MCADD)
What is nocturnal hypoglycaemia?
Complication of T1DM where the child is sweaty overnight, morning blood glucose levels may be raised - diagnosis can be made by continuous glucose monitoring
Treated by altering the bolus insulin regimes and snacks at bedtime
What is hyperglycaemia different from?
DKA
What are the macrovascular complications of T1DM?
Coronary artery disease (major cause of death)
Peripheral ischaemia (leading to poor healing, ulcers and diabetic foot)
Stroke
Hypertension
What are some microvascular complications of T1DM?
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
What causes the vascular changes in T1DM?
Chronic hyperglycaemia causes damage to the endothelial cells of blood vessels causing malfunctioning vessels which are unable to regenerate
What does suppression of the immune system in T1DM cause?
UTIs
Pneumonia
Skin and soft tissue infections (especially in feet)
Fungal infections, particularly oral and vaginal candidiasis
What is HbA1c measuring?
Glycated haemoglobin - how much glucose is attached to the haemoglobin molecules inside RBCs - reflects average blood glucose over last 3 months
Used to determine how effective interventions are
Blood sample in red top EDTA bottle
What is capillary blood glucose measured with?
Glucose meter - used to self-monitor sugar levels
What is flash glucose monitoring (e.g. FreeStyle Libre)
Uses a sensor on skin to measure the glucose level of the interstitial fluid in subcutaneous skin
5 minute lag behind blood glucose (so capillary blood glucose needed to check for hypoglycaemia)
User needs a reader to swipe over the sensor
Sensors need replacing every 2 weeks for the FreeStyle Libre system (quite expensive, funding not everywhere)
What is ketogenesis and when does it occur?
Liver takes fatty acids and converts to ketones happens when there is an insufficient supply of glucose and glycogen stores
How can ketone levels be measured?
Using a urine dipstick and in blood using a ketone meter
What is diabetic ketoacidosis?
Metabolic acidosis as a result of extreme hyperglycaemic ketosis (normally ketones are buffered in normal patients so blood doesnt become acidotic)
Why does DKA occur in T1DM?
Person isn’t producing enough insulin and not injecting adequate insulin to compensate for this
What are the main problems with DKA?
Ketoacidosis, dehydration and potassium imbalance
Why does dehydration occur in DKA?
As glucose is filtered into the urine this draws water out (osmotic diuresis) causes patient to urinate a lot (polyuria) resulting in severe dehydration which stimulated the thirst centre to drink lots of water (polydipsia)
What causes the potassium imbalance in DKA?
Insulin normally drives potassium into cells
In DKA serum potassium may be normal but total body potassium is low - thus when treatment with insulin starts patients can develop hypoglycaemia which can lead to fatal arrhythmias
What is a risk when rapidly correcting dehydration and hyperglycaemia?
Cerebral oedema - during DKA dehydration and high blood sugar concentration causes water to move from the intracellular space in the brain to the extracellular space - rapidly correcting this causes brain to swell and become oedematous
What should be monitored when correcting DKA?
Neurological observations (i.e. GCS) to look for signs of cerebral oedema
Signs of headaches, altered behaviour, bradycardia or changes to conciousness
What are the management options of cerebral oedema?
Slowing of IV fluids
IV mannitol
IV hypertonic saline
How does DKA present?
Polyuria
Polydipsia
N&V
Weight loss
Acetone smell to breath
Dehydration and subsequent hypotension
Altered consciousness
Symptoms of underlying trigger (i.e. sepsis)
How to diagnose DKA?
Hyperglycaemia ( > 11 mmol/l)
Ketosis (blood ketones > 3mmol/l)
Acidosis (pH <7.3)
What are the two aspects of correcting DKA?
Correct dehydration evenly over 48 hours (corrects the dehydration and dilutes the hyperglycaemia and ketones - too quick = cerebral oedema)
Give fixed rate insulin infusion
What are some other important principles of DKA management?
Avoid food boluses to minimise risk of cerebral oedema (unless required for resus)
Treat underlying triggers e.g. abx for septic patients
Prevent hypoglycaemia with IV dextrose once blood glucose falls below 14mmol/L
Add potassium to IV fluids and monitor
Monitor for signs of cerebral oedema
Monitor glucose, ketones and pH to assess their progress and determine when to switch to subcut insulin
What is adrenal insufficiency?
Adrenal glands dont produce enough steroid hormones, particularly cortisol and aldosterone (life threatening unless hormones are replaced)
What is addison’s disease?
Adrenal glands are damaged causing reduced secretion of cortisol and aldosterone aka primary adrenal insufficiency most commonly caused by autoimmune
What is secondary adrenal insufficiency?
Inadequate ACTH stimulating the adrenal glands causing low levels of cortisol to be released (result of damage to the pituitary gland)
What can cause secondary adrenal insufficiency?
Congenital underdevelopment (hypoplasia)
Surgery
Infection
Loss of blood flow
Radiotherapy
What is tertiary adrenal insufficiency?
Result of inadequate CRH release from the hypothalamus usually the result of being on long term steroids (exogenous steroids - longer than 3 weeks) causing suppression of the hypothalamus (long term steroids need to be slowly tapered)
What are the features of adrenal insufficiency in babies?
Lethargy
Vomiting
Poor feeding
Hypoglycaemia
Jaundice
Failure to thrive
What are some features in older children of adrenal insufficiency?
N&V
Poor weight gain / weight loss
Anorexia
Abdo pain
Muscle weakness / cramps
Developmental delay or poor academic performance
Bronze hyperpigmentation to skin caused by ACTH (this stimulates melanocytes)
What are the investigations for Addison’s Disease?
Cortisol / ACTH / aldosterone / renin
U&Es (hyponatraemia / hyperkalaemia)
Blood glucose (hypoglycaemia)
What is are the results in Addison’s disease (primary adrenal failure)?
Low cortisol
Low aldosterone
High ACTH
High renin
What are the results in secondary adrenal insufficiency?
Low cortisol
Normal aldosterone
Low ACTH
Normal renin
What is the short synacthen test (ACTH stimulation test)?
Confirms adrenal insufficiency
Performed in the morning - adrenal glands are most fresh
Giving synacthen - synthetic ACTH
Blood cortisol is measured at baseline, 30, 60 minutes (level should at least double)
If no rise then primary adrenal insufficiency (Addison’s disease)
What is the treatment of adrenal insufficiency?
Replacement steroids:
Hydrocortisone (glucocorticoid) replaces cortisol
Fludrocortisone (mineralcorticoid) replaces aldosterone
What is the ‘steroid advice’ for addisons insufficiency?
Steroid card and emergency ID tag to inform emergency services
Doses are increased during an acute illness to match the normal steroid response
What are paediatric patients with adrenal insufficiency monitored for?
Growth and development
Blood pressure
U&Es
Glucose
Bone profile
Vitamin D
What are the sick day rules in adrenal insufficiency? (if really unwell with temp over 38 degrees or vomiting and diarrhoea)
Increase dose of steroid and given more regularly
Blood sugar needs monitoring closely and eating carby foods
With diarrhoea / vomiting need IM injection of steroid at home and likely required admission for IV steroids
What is an Addisonian crisis?
Acute presentation of severe Addisons where the absence of steroid homones causes a life threatening presentation
How do patients with addisonian crisis present?
- Reduced consciousness
- Hypotension
- Hypoglycaemia, hyponatraemia, hyperkalaemia
What can trigger an Adrenal crisis?
Infection
Trauma
Stopping steroids abruptly
What is the management of an Addisonian crisis?
Intensive monitoring if they are acutely unwell
Parenteral steroids (i.e. IV hydrocortisone)
IV fluid resus
Correct hypoglycaemia
Careful monitoring of electrolytes and fluid balance
What is congenital adrenal hyperplasia?
Underproduction of cortisol and aldosterone
Overproduction of androgens
Caused by a congenital deficiency of the 21-hydroxylase enzyme / 11-beta-hydroxylase
Autosomal recessive
What is testosterone?
Androgen hormone - high levels in men and low levels in women
Promotes male sexual characteristics
What do glucocorticoid hormones do?
Help body deal with stress, raise blood glucose, reduce inflammation and suppress immune system
What is the main glucocorticoid hormone?
Cortisol which fluctuates during the day with higher levels in the morning and times of stress
When is cortisol released?
In response to adrenocorticotropic hormone (ACTH) from anterior pituitary
What do mineralcorticoid hormones do?
Act on kidneys to control balance of salt and water in blood
What is the main mineralcorticoid hormone?
Aldosterone
Where and when is aldosterone released?
Adrenal glandin reponse torenin
What does aldosterone do?
Increases sodium reabsorption into the blood and potassium secretion into the urine
What is the pathophysiology of congenital adrenal hyperplasia?
21-hydroxylase enzyme converts progesterone into aldosterone and cortisol - as there is a deficiency then it is instead converted into testosterone
How do female patients with CAH present?
At birth with ambiguous genitalia (virilised) and enlarged clitoris due to high testosterone levels
What are the signs and symptoms of severe CAH?
Poor feeding
Vomiting
Dehydration
Arrythmias
What are the electrolyte imbalances in severe CAH?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
What are the later symptoms of CAH (due to high androgen levels) in men and women respectively?
Female
- Tall
- Facial hair
- Absent periods
- Deep voice
- Early puberty
Male
- Tall
- Deep voice
- Large penis
- Small testicles
- Early puberty
What is the ‘textbook clue’ for congenital adrenal hyperplasia?
Skin hyperpigmentation because low levels of corticol causes an increase in ACTH (a byproduct of production is melanocyte simulating hormone)
What is the management of congenital adrenal hyperplasia?
Cortisol replacement with hydrocortisone
Aldosterone replacement with fludrocortisone
Female patients with “virilised” genitals may require corrective surgery
Where is growth hormone produced?
Anterior pituitary gland
What does growth hormone do?
Stimulates cell production
Growth of organs, muscles, bones and height
Stimulates release of insulin-like growth factor 1 (IGF-1) by the liver
What promotes and supresses the release of GH
Promotes = GHRH and Ghrelin
Supresses = Somatostatin
What can congenital growth hormone deficiency be caused by?
Disruption to the growth hormone axis at the hypothalamus or pituitary gland can be due to a known genetic mutation e.g. GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes OR sue to empty sella syndromewhere th pituitary gland isunder-developed or damaged
What can cause acquired growth hormone deficiency?
Secondary to infection, trauma or surgery
What is it called when the pituitary does not produce a number of pituitary hormones?
Hypothyroidism or multiple pituitary hormone deficiency
How does growth hormone deficiency present at birth?
Micropenis (in males)
Hypoglycaemia
Severe jaundice
How does growth hormone deficiency present in infants and children?
Poor growth (stopping / severely slowing from 2-3)
Short stature
Slow development of movement and strength
Delayed puberty
What is the growth hormone stimulation test?
Giving glucagon, insulin, arginine and clonidine (medications which usually stimulate release of growth hormone) and monitoring the response (every 2-4 hours after)
What are the other investigations for growth hormone deficiency?
Test for thyroid and adrenal deficiency
MRI brain for structural pituitary / hypothalamus abnormalities
Genetic testing for associated genetic conditions e.g. Turner syndrome and Prader-Willi syndrome
X-ray (usually of the wrist) or a DEXA scan to determine bone age and predict final height
What is the treatment of growth hormone deficiency?
Daily subcut injections of growth hormone (somatropin)
Treatment of other hormone deficiencies
Close monitoring of height and development
What can cause hypothyroidism in children?
Congenital / acquired
Why is thyroid hormone important in children?
Essential for development of brain and body - hypothroidism can cause intellectual disability
What can cause congenital hypothyroidism?
Underdeveloped thyroid gland (dysgenesis)
Fully developed gland which doesn’t produce enough hormone (dyshormonogenesis)
Cause isn’t clear
When is congenital hypothyroidism screened for ?
Newborn blood spot screening test
How does congenital hypothyroidism present?
Prolonged neonatal jaundice
Poor feeding
Constipation
Increased sleeping
Reduced activity
Slow growth and development
What is the most common cause of acquired hypothyroidism?
Autoimmune thyroiditis aka Hashimoto’s thyroiditis causing autoimmune inflammation of the thyroid gland and subsequent underactivity
What is Hashimoto’s disease associated with?
Antithyroid peroxidase (anti TPO) antibodies
Antithyroglobulin antibodies
What conditions is Hashimoto’s disease associated with?
Type 1 diabetes and coeliacs disease
What are the symptoms of acquired hypothyroidism?
Fatigue and low energy
Poor growth
Weight gain
Poor school performance
Constipation
Dry skin and hair loss
What are the investigations for hypothyroisism?
TFTs
Thyroid ultrasound
Thyroid antibodies
What is the management of hypothyroidism?
Levothyroxine orally once a day to replace normal thyroid hormones (titrated based on TFTs and symptoms)
