Paeds - Endo (textbook + 0-finals) Flashcards
What is the difference between type 1 and type 2 diabetes mellitus?
Type 1 is the result of an autoimmune response that causes destruction of insulin producing B cells in the pancreas = absolute insulin deficiency.
Type 2 has a strong genetic component and association with obestity and sedentary lifestyle.
Characterised by progressing inslin resistance in peripheral cells and declining pancreatic B cell function (impaired insulin secretion) resulting in relative insulin deficiency.
What is the bodys ideal blood glucose conc?
4.4 - 6.1 mmol/L
Describe the role of insulin and glucagon
Insulin is produced by the beta cells in the Islets of Langerhans in the pancreas.
- Anabolic hormone
- reduces sugar by causing cells to absorb glucose from blood to use as fuel
- causes muscle and liver cells to absorb glucose from blood to store as glycogen
Glucagon is produced by alpha cells in the Islets of Langerhans
- catabolic hormone
- Released in response to low blood sugar levels and stress
- makes liver break down stored glycogen to glucose (Glycogenolysis)
- makes liver convert proteins and fats into glucose (Gluconeogenesis)
How would a child with T1DM present for the first time?
- typically present in diabetic ketoacidosis (DKA)
- Classic triad of polyuria, polydipsia, weight loss (mainly through dehydration)
- secondary enuresis (bedwetting in a prev dry child)
- Recurrent infections
How would you investigate a child presenting with T1DM for the first time?
- Baseline FBC, U&Es, Blood glucose
- Blood cultures if pyrexic
- HbA1c
- TFTs and Thyroid Peroxidase Antibodies for autoimmune thyroid disease
- Tissue Transglutaminase (anti-TTG) antibodies for coeliac disease
- Insulin antibodies, anti-GAD antibodies, islet cell antibodies
How would you manage a child with T1DM?
Insulin
-
Basal Bolus Insulin Regimes
- Basal = long acting insulin like “Lantus”
- Bolus = short acting insulin like “Actrapid” usually 3x a day before meals
- Injecting in the same spot can cause Lipodystrophy (subcut fat hardens and prevents normal absorption of further insulin injections, so tell patients to cycle their injection sites)
OR
-
Insulin Pumps
- continuous insulin infusion at different rates to control blood sugar levels
- replaced every 2-3 days and insertion sites are cycled
- Child must be >12 and have difficulty controlling their HbA1c
- Pros = better blood sugar control, more flexibility with eating, less injections
- Cons = education on use, always attached, blockages can occur, risk of infection
What are some symptoms of hypoglycaemia?
- Severe = reduced consciousness, coma, death
- dizziness
- pallor
- irritability
- hungor
- tremor
- sweating
How would you manage someone who is hypoglycaemic? (mild and severe)
Mild
- Combination of Rapid acting glucose eg. lucozade
- AND Slower acting glucose eg. biscuits or toast
Severe (impairment of consciousness, seizures, coma)
- IV Dextrose and IM Glucagon
What are some causes of hypoglycaemia?
- In a diabetic:
- too much insulin
- not enough carbs, or not processing the carbs (eg. V&D, malabsorption)
- Hypothyroidism
- Glycogen storage disorders
- growth hormone deficiency
- liver cirrhosis
- alcohol and fatty acid oxidation defects
Easy way to fix when someone is hyperglycaemic but not in DKA?
Increase their insulin dose.
Eventually patients will get to know their response to insulin and adminster the right dose to correct hyperglycaemia.
Be conscious that it can take a few hours to have an effect and repeated doses can lead to hypoglycaemia.
What is the pathophysiology of DKA?
(How do the most dangerous aspects - dehydration, K+ imbalance, and acidosis occur)
- In T1 Diabetics, DKA happens when they are not producing or injecting enough insulin to process glucose
- Ketogenesis happens when glucose and glycogen stores are depleted eg. in prolonged fasting or low carb diets
- Liver takes fatty acids and turns them into ketones
- Ketones cross the blood brain barrier and can be used as fuel by the brain
- Glucose and Ketone levels in the blood get higher and higher
- Kidneys produce bicarbonate to buffer ketone acids and maintain normal blood pH
- eventually ketone acids use up bicarbonate and blood becomes acidic = Ketoacidosis
- Hyperglycaemia overwhelms kidneys so glucose becomes filtered into the urine
- glucose in urine draws water out with it via osmotic diuresis = Polyuria = Severe Dehydration = Severe Thirst (Polydipsia)
- Insulin usually drives potassium into cells
- without sufficient insulin, total body K+ becomes low as no K+ is being stored in cells
- serum K+ is high or normal as kidneys are still balancing blood K+ and urinary excreted K+
- When treated with Insulin, patients can rapidly develop hypokalaemia = fatal arrhythmias
Why are children with DKA at high risk of developing cerebral oedema?
- Dehydration + High blood sugar conc cause water to move from intracellular space in the brain to extracellular space
- Brain cells shrink and become dehydrated
- Rapid correction of dehydration and hyperglycaemia (with fluids + insulin) can Rapidly shift water from EC space back into IC space in the brain cells
- This causes brain to swell and become oedematous
How would you manage and monitor for cerebral oedema?
- Neurological observations (eg. GCS) should be monitored hourly
- Look out for headaches, altered behaviour, bradycardia, changes in consciousness
Management
- slow the IV fluids
- IV Mannitol
- IV Hypertonic Saline
How would a patient with DKA typically present?
Triad of…
- Hyperglycaemia (>11mmol/L)
- Ketosis (>3mmol/L)
- Acidosis (HCO3 <15mmol/L, ph<7.3)
CKS
- finger prick blood glucose >11mmol/L
- Polydipsia
- Polyuria
- weight loss
- inability to tolerate fluids
- persistent vomiting/ diarrhoea
- abdo pain
- visual disturbance
- lethargy/ confusion
- fruity acetone smell on breath
- acidotic breathing = Deep sighing (Kussmaul) Respiration
- Dehydration
- dry skin and mucous membranes, reduced skin turgor
- Severe = sunken eyes and prolonged cap refill
- Shock = tachycardia, hypotension, decreased consicousness showing decreased cerebral perfusion, lethargy, reduced urine output showing decreased renal perfusion
*
How would you diagnose DKA?
- Hyperglycaemia (blood glucose >11mmol/L)
- Ketosis (blood ketones >3mmol/L)
- Acidosis (pH <7.3)
How would you manage DKA in chidlren?
- correct dehydration evenly over 48 hours
- avoid fluid boluses unless for resus
- too quickly = cerebral oedema
- fixed rate insulin infusion
- avoid hypoglycaemia with IV dextrose once blood glucose <14mmol/L
- K+ must be greater or equal to 3.3 before insulin therapy is initiated
- Add IV KCl to IV fluids if K+<5.3
- monitor serum K+ ever 2 hours
- Monitor for cerebral oedema
- Monitor glucose, ketones, pH
- Treat underlying triggers eg. antibiotics for sepsis
How is congenital hypothyroidism picked up?
Newborn Blood Spot Screening Test (Guthrie Test)
Otherwise presents with:
- prolonged neonatal jaundice
- poor feeding
- constipation
- increased sleeping
- reduced activity
- slow growth and development
- pale, cold, mottled dry skin
- coarse facies
- large tongue
- hoarse cry
- occasionally goitre
- umbilical hernia
What is the most common cause of acquired hypothyroidism?
Hashimotos Thyroiditis = Autoimmune thyroiditis
- antithyroid peroxidase antibodies
- antithyroglobulin antibodies
- associated with Type 1 DM and Coeliac Disease
Symptoms
- fatigue and low energy
- poor growth
- weight gain
- poor school performance
- Constipation
- Dry skin and hair loss
How would you investigate and manage hypothyroidism in children?
- refer to paediatric endocrinologist
- Thyroid Function Blood Tests (TSH, T3, T4)
- Thyroid US
- Thyroid antibodies
Management
- oral Levothyroxine once a day
What are some causes of congenital hypothyroidism?
- maldescent of thyroid and athyrosis
- Dyshormonogenesis = error of thyroid hormone synthesis
- Iodine deficiency
- Hypothyroidism due to TSH deficiency
- usually associated with pituitary dysfunction (presents as GH, Gonadotrophin, and ACTH deficiency = hypoglycaemia, micropenis, undescended testes)
What is the most common cause of hyperthyroidism?
- autoimmune thyroiditis (Graves Disease)
- secondary to the production of thyroid stimulating immunoglobulins
- T4 and T3 are elevated, TSH is suppressed to low levels
What are some symptoms of Hyperthyroidism?
- anxiety, restlessness, palpitations
- Tiredness and difficulty sleeping
- sweating, sensitivity to heat
- diarrhoea
- weightloss despite increased appetite
- patchy hair loss or thinning
- Goitre
- Eye signs less common in children
- exophthalmos
- opthalmoplegia
- lid retraction
- lid lag
How would you manage hyperthyroidism?
Medication
- Carbimazole or propylthiouracil
- Risk of neutropenia from antithyroid medication
- B Blockers for symptomatic relief (anxiety, tremor, tachy)
How does neonatal hyperthyroidism occur?
In mothers with thyrotoxicosis, there can be transplacental transfer of Thyroid Stimulating Immunoglobulins
What is congenital adrenal hyperplasia?
Autosomal Recessive congenital deficiency of 21-hydroxylase enzyme
(sometimes deficiency of 11-hydroxylase)
Results in really high Androgens (testosterone), and really low Glucocorticoids (cortisol) and Mineralocorticoids (aldosterone)
- because there is insufficient 21-hydroxylase to convert progesterone into aldosterone and cortisol.
- Therefore all the progesterone is being converted into testosterone instead.
How would mild CAH present?
Mild typically present in childhood or after puberty due to symptoms related to high androgens
- tall for their age
- deep voice
- early puberty
- female = facial hair, absent periods
- male = large penis, small testicles
- Skin hyperpigmentation
- Anterior Pituitary responds to low cortisol by increasing ACTH (a by product of ACTH is Melanocyte Stimulating Hormone)
How would severe CAH present?
- Females present at birth with virilised genetalia
- “ambiguous genitalia” and an enlarged clitoris due to high testosterone
- Shortly after birth:
- Hyponatraemia
- Hyperkalaemia
- Hypoglycaemia
- above leads to poor feeding, vomiting, dehydration, arrhythmias
How would you manage CAH?
- Cortisol replacement via hydrocortisone
- Aldosterone replacement via fludrocortisone
- Corrective surgery for females with virilised genitals
What is primary, secondary and tertiary adrenal insufficiency?
Primary
- aka Addisons disease
- destruction of adrenal cortex, resulting in reduced secretion of cortisol and adrenaline
- usually due to autoimmune disease
Secondary
- inadequate secretion of ACTH from pituitary, resulting in reduced stimulation of adrenal glands
- Causes = congenital underdevelopment (hypoplasia) of pituitary gland or damage to pituitary via surgery, infection, decreased blood flow, radiotherapy
Tertiary
- Inadequate CRH release by the hypothalamus
- usually the result of patients being on long term oral steroids (>3 weeks), resulting in suppression of hypothalamus
- should taper steroids slowly to allow time for adrenal axis to regain normal function and start producing endogenous steroids again.
How would adrenal insufficiency present in babies and children?
Babies
- lethargy
- vomiting
- poor feeding
- hypoglycaemia
- jaundice
- failure to thrive
Older kids
- nausea and vomiting
- poor appetitie
- poor weight gain or weight loss
- abdo pain
- muscle weakness or cramps
- developmental delay or poor academic performance
- Hyperpigmentation due to Addisons causing high ACTH stimulation
What investigations would you do in suspected adrenal insufficiency?
- U&Es (hyponatraemia, hyperkalaemia)
- Blood glucose (hypoglycaemia)
- Adrenal antibodies
- CXR may show TB and calcified adrenal glands
- Measure Random serum Cortisol, 0900 levels of ACTH, Serum Aldosterone, Renin levels before steroids
- Addisons = low cortisol, high acth, low aldosterone, high renin
- Secondary = low cortisol, low acth, normal aldosterone, normal renin
- Short Synacthen Test
- give synthetic ACTH (synacthen) in the morning
- measure baseline cortisol 30-60 mins after administration
- synacthen should stimulate cortisol levels to at least double
- Measurement of less than double baseline cortisol = primary adrenal insufficiency
How would you manage adrenal insufficiency?
- Hydrocortisone to replace cortisol
- Fludrocortisone to replace aldosterone
- Give patients a steroid card and emergency ID tag to inform emergency services they are dependent on steroids
- Monitored by paediatric endocrinologist (Group and development, BP, U&Es, Glucose, Bone profile, Vit D)
What are the sick day rules for adrenal insufficiency and steroid treatment?
Sick Day rules (temp over 38 or D&V)
- increase dose of steroid and given more regularly until illness has resolved
- eat more carb containing foods, measure blood sugar closely
- IM injection of steroid at home if D&V, may need admission for IV steroids
What is an addisonian crisis?
an acute presentation of severe addisons - the absence of steroid hormones has resulted in a life threatening presentation
- reduced consciousness
- hypotension, hypovolaemic shock
- due to the aldosterone deficiency
- fever, vomiting
- abdo pain
- hypoglycaemia
- hyponatraemia
- hyperkalaemia
Can be first presentation of Addisons, or established Addisons triggered by infection/ illness/ trauma/ abrupt steroid cessation in someone whose natural steroid production has been suppressed by exogenous steroids.
How would you manage an addisonian crisis?
- intensive monitoring and emergency admission
- Hydrocortisone IM or IV
- IV fluid resuscitation
- Correct hypoglycaemia
- Monitor Electrolytes and fluid balance
What is Cushings Syndrome?
A state of excess free circulating glucocorticoid (cortisol).
In kids it is usually a SE of Long term glucocorticoid treatment for conditions like nephrotic syndrome or asthma.
can also be due to:
- ACTH producing tumours (eg. in pituitary or small cell lung cancer etc)
- Cushings Disease = Cushings Syndrome due to pituitary adenoma
- Adrenal Tumours
- usually in young children (may also be virilisation)
What are some features of Cushings Syndrome
Symptoms
- slow growth
- red cheeks
- weight gain
- thin skin, easy bruising
- amenorrhoea/oligomenorrhoea
- polyuria
- dyspepsia
- acne
- reduced libido
- back pain
Signs
- round “Moon face”
- hirsutism
- pigmentation (In ACTH dependent causes like pituitary adenoma)
- HTN
- Osteoporosis/osteopenia
- dorsal fat pad = “buffalo hump”
- Kyphosis = hunch back
- Purple or red striae on abdo
- Supraclavicular fat pads
- oedema
- proximal myopathy
- Glycosuria
- Diabetes/ impaired glucose tolerance
*
How would you investigate suspected Cushings?
- Consider in children with obesity
- a child who was obese due to dietary excess woud be tall compared with their midparental height
- Cushings syndrome children would be short
- Midnight cortisol level is high
- normal diurnal variation of cortisol is high in morning, low at midnight
- 24 hour urine free cortisol is high
- 1mg overnight dexamethasone suppression test
- After administering dexamethasone at night, there is failure to suppress plasma 0900 cortisol levels the next morning
- OR 48 hour low dose dexamethasone test
- Cushings patients will fail to suppress cortisol level to <50nmol/L
- CT or MRI of abdo will show adrenal tumour
- MRI brain will show pituitary adenoma
- CXR to show carcinoma of bronchi
How would you manage Cushings?
Control cortisol hypersecretion medically first
- metyrapone
Cushings Disease
- Radiotherapy = External Pituitary Irradiation (preferred in children)
- Medicine = Bromocryptine (try to reduce ACTH secretion)
- Surgery = transphenoidal removal of tumour
- Bilateral adrenalectomy as last resort
- Can result in Nelsons syndrome (hyperpigmentation due to high ACTH)
- Bilateral adrenalectomy as last resort
Remove ectopic ACTH Tumours .
Radiotherapy and surgical removal of adrenal carcinoma.
