Growth, Endocrine and Metabolism Flashcards
What are the most common chronic diseases in childhood?
1) Asthma
2) Cerebral Palsy
3) Type 1 DM
List some types of diabetes found in children
1) T1DM (95%)
2) T2DM (1-2%)
3) MODY
4) Steroid induced DM
5) CF related DM
What is MODY?
Maturity-onset diabetes of the young
Monogenic = single gene defects of pancreatic SUR1 and Kir6.2 sub units of K+ channels in beta cells leading to impaired insulin secretion
What is the inheritance pattern of MODY?
Autosomal dominant
Which 2 groups of children tend to suffer steroid induced DM?
Post-transplant
Oncology
What is aetiology of T1DM?
Some evidence of genetic predisposition but often no FHx (FHx much more common in T2DM)
Autoimmune (T-cell mediated) damage of beta cells in islets of Langerhans
Children often develop T1DM after unknown trigger such as viral infection or diet
What gene is implicated in T1DM?
HLA DR3 and DR4
human leukocyte antigen
What is the pathophysiology of type 1 diabetes?
T-cell mediated autoimmune destruction of beta cells in pancreatic islets of Langerhans
Results in inability to secrete insulin therefore inability of cells to uptake blood glucose leading to hyperglycaemia
This results in a catabolic state with increased glycogenolysis, gluconeogenesis and lipolysis
Hyperglycaemia exceeds renal threshold leading to dehydration and electrolyte loss by osmotic diuresis
What is the % chance if one identical twin has T1DM that the other twin will also?
30%
In T1DM there is beta-cell destruction. At what % mass destruction does presentation usually occur?
50% (early) - 90% (late)
What is the peak age of onset of T1DM?
Age 5-7yrs (but increasing in toddlers) and just before the onset of puberty
What are the four T’s aimed to improve early recognition of T1DM?
Thirst
Toilet
Tired
Thin
How does T1DM present?
Several weeks of polyuria Lethargy Polydipsia Weight loss \+/- infection / poor growth / ketosis
What are the effects of insulin on:
1) Skeletal muscle
2) Liver
3) Adipose tissue?
1) Skeletal muscle
- Increased glycogenesis
- Increased protein synthesis
2) Liver
- Increased glycogenesis
- Decreased gluconeogenesis
3) Adipose tissue
- Increased adipogenesis
- Decreased lipolysis
How is T1DM confirmed?
WHO diagnostic criteria:
Signs of hyperglycaemia AND:
Random blood glucose at or above 11mmol/L
or fasting blood glucose at or above 7mmol/L
OR
No symptoms but raised blood glucose on 2 occasions
Oral glucose tolerance tests (OGTT) rarely required in children
What is the most common regime of managing T1DM?
Mixture of rapid acting and long acting insulin injected subcutaneously depending on daily insulin requirement
- 5-1 units/kg/24hr = prepubertal
- 5/units/kg/24hr = pubertal
How is insulin injected and why are different sites used?
Subcutaneously into arms, thighs and abdomen
Different sites used to avoid lipohypertrophy
Which hormones increase / decrease glucose levels?
Decrease blood glucose:
- Insulin
- Somatostatin (growth hormone inhibiting hormone)
Increase blood glucose = counter-regulatory hormones:
- Glucagon
- Cortisol
- Oestrogen
- Testosterone
- GH
- Adrenaline / noradrenaline
Why do continuous SC insulin pumps have diurnal variations in their basal dose (as well as bolus during mealtimes)?
Due to the diurnal variation of counter-regulatory hormones GH and cortisol
List three other methods of managing T1DM
1) Short-acting basal bolus with meals and long-acting (lasts 24 hours) at night
2) Multidose regime using insulin pen
3) Continuous subcutaneous pump with basal bolus (pump)
Below what mmol/L is considered hypoglycaemic in a diabetic pt?
Why is this not the same in an individual who does not suffer from DM?
<4mmol/L (4 = floor)
Those without DM may have blood glucose lower than this, however this is not as concerning as the body will identify this and their pancreatic insulin secretion will be adjusted accordingly
Those with DM are receiving exogenous insulin and thus will hypo further = more concerning
How can exogenous and endogenous insulin be differentiated ie if someone has had a hypo, what could you measure to identify if this was from injected insulin or from what the body has produced?
Insulin is produced in the body as a pre-insulin attached to C-peptide which is cleaved
High levels of C-peptide indicate high endogenous insulin
What OGTT is diagnostic of T1DM?
At or above 11mmol/l
What HbA1c is diagnostic of T1DM?
At or above 6.5% or 48mmol
What is given in hypoglycaemia?
If conscious:
- Lucozade, fruit juice, jelly babies, glucose tablets eg lift
General rules:
5g of glucose for 10kg child
10g of glucose for 30kg child
15g of glucose for 50kg child
If unconscious:
- Glucagon (good as works fast) - comes as powder that needs to be made up with water for injection
Give an example of a rapid and long acting insulin
Rapid acting
- Humalog
- Actrapid
- Aspart
- Novorapid
Long acting
- Lantus
- Levemir
What is the ‘honeymoon period’?
A period post diagnosis where insulin requirement is low
This is because there is still some pancreatic beta cells functioning
Period can vary from months to sometimes years - aim is to prolong this period for as long as possible
Greater pancreatic function at presentation = longer honeymoon period
List some pros of continuous insulin pumps
Great for compliance Fewer injections Increased lifestyle flexibility Accurate delivery Fewer hypos
List some cons of continuous insulin pumps
Cost
Risk of superficial infections
Pump failure can lead to DKA
Inconvenience of wearing an external pump / cosmetic
What should blood glucose be first thing in the morning?
4-7mmol/L
What often tends to happen with insulin requirements after initial use?
They increase after ‘honeymoon’ period
What is DKA?
Leading cause of mortality in childhood DM
Either absolute or relative insulin deficiency
What causes an absolute insulin deficiency in a child with DKA?
Previously undiagnosed T1DM or pt noncompliant with their insulin
What causes an relative insulin deficiency in a child with DKA?
Stress causes a rise in counter-regulatory hormones with relative insulin deficiency
eg catecholamines, glucagon, cortisol, growth hormone (eg in sepsis)
What is the pathophysiology of DKA?
Insulin deficiency means that when there is an increase in plasma glucose the glucose cannot enter the cells
The body think its in starvation so lipolysis occurs which produces fatty acids which are converted in the liver into ketones
High plasma glucose causes an osmotic diuresis (increase urination)
Dehydration + LOTS of LOSS of electrolytes (esp sodium and potassium):
- Untreated DKA leads to metabolic acidosis which causes potassium to go out of cells and hydrogen in
- Also the insulin deficiency leads to potassium to go out of cells
- When treated with insulin, potassium moves from EXTRAcellular space to INTRAceullular space which can cause profound hypokalaemia
SO basically in DKA blood potassium is deceptively high, it has all moved extracellularly so true value is lower
What vicious cycle occurs in DKA? How can it be broken?
Vomiting often occurs, compounding the stress and dehydration
= Can only be broken by providing insulin and fluids
In which age group is DKA most common in children with diabetes?
Children <5yr
What is the DKA triad?
1) Hyperglycaemia (>11)
2) Acidaemia (pH <7.3)
3) Ketonaemia (>3)
(bicarb <15)
How does DKA present?
1) Dehydration
2) Lethargy, confusion
3) Polyuria +/- polydipsia
4) Glucosuria
5) Weight loss
6) Abdo pain +/- vomiting (may mimic surgical abdo)
7) Kussmaul’s respirations
9) Ketotic breath (pear drops)
9) Shock / coma
10) Cerebral oedema
What investigations are performed for DKA?
Immediate: 1) Capillary blood glucose 2) Capillary blood ketones (or urinary ketones) 3) Capillary or venous pH and bicarbonate (do more VBG than ABG in kids as so painful)
Also:
4) Renal function (U&Es, eGFR, creatinine)
5) Urine dipstick (++ ketones)
6) FBC
7) ECG (hyperkalaemia)
8) Check for infection eg blood an urine cultures, CXR etc
What is Kussmaul’s respirations?
Deep, fast breathing associated with metabolic acidosis
Body is trying to blow off as much carbon dioxide as possible
Is fever normal for DKA?
No - seek source of sepsis
What are other causes of metabolic acidosis?
1) Overdose eg salicylates
2) Lactic acidosis
3) AKI
4) Septicaemia
5) Adrenal crisis/CAH
What are the most common causes of death in DKA?
1) Cerebral oedema - mortality of 25% and is more common in younger children
2) Hypokalaemia - monitor ECG
3) Aspiration pneumonia - NG tube if reduced GCS
How is insulin given in DKA?
IV infusion 0.1 units/kg/hour
Initial bolus not recommended
Continuous SC insulin pumps should be stopped while IV infusion is given, but long acting insulin treatment may be continued
What is the fluid management in DKA?
0.9% NaCl + KCl
If shocked (systolic <90): 20ml / kg fluid bolus over 15 mins This bolus is NOT deducted from % deficit when calculating maintenance rate
THEN (or just this if not shocked)
10 ml / kg fluid bolus over 60 minutes
This IS deducted from % deficit
What are the maintenance fluids in the management of DKA?
Risk of cerebral oedema so reduced volume:
If under 10kg: 2ml/kg/hr
If 10-40kg: 1ml/kg/hr
If over 40kg: fixed volume 40ml/hr
How are deficit fluids calculated in DKA?
Deficit fluids = % dehydration x weight x 10
Subtract any bolus given (but not the initial 20 ml / kg that would have been given in shock)
Given over 48hrs (so divide by 48)
Deficit rate + maintenance rate added together
(card at end about calculating % dehydration)
What is mannitol?
An osmotic diuretic
It elevates blood plasma osmolality, resulting in enhanced flow of water from tissues (eg brain and CSF) into interstitial fluid and plasma
What is failure to thrive (FTT)?
Less than expected growth over time during first 3 years of life when tracked on a growth chart
What is the most common general cause of failure to thrive? What factors can cause this?
Inadequate intake
- Environmental factors - poor access to healthy food
- Social/family factors - lack of knowledge regarding appropriate food, poor care, child abuse/neglect
- Poor appetite - chronic fever, chronic infections, anaemia
- Feeding problems - cerebral palsy, cleft lip, GORD
When should a premature baby have reached ‘normality’ for:
Head circumference
Weight
Height
Head circumference: 18 months
Weight: 24 months
Height: 40 months
= thus some premature babies with very low birth weight may not catch up until 5/6yrs
Is it normal for a baby to lose weight early in life?
Yes - normal for a baby to lose up to 10% body weight in first few days of life which is rapidly regained (but more slowly in breastfed babies)
Birth weight should be regained by 7-10 days
Birth weight should double by 5 months, triple by 1 year and quadruple by 2 years
What is ‘corrected age’?
Used for premature babies
Baby’s chronological age minus the number of weeks they were premature
Eg a baby born 12 weeks ago at 32 weeks gestation is treated as a 4 week old baby
What maternal factors during pregnancy may cause a baby to be small for date? (5)
1) Smoking
2) Alcohol
3) Use of medications
4) Recreational drugs esp amphetamines and cocaine
5) Any illness during pregnancy
6) Infections eg TORCH
+ Any cause of placenta insufficiency
What conditions have specific reference charts for growth?
Down’s syndrome
Turner’s syndrome
What is plotted on a growth chart?
Height
Weight
Head circumference
What may lead to poor absorption or metabolism of nutrients in children? (5)
1) GI disorders eg CF, coeliac and chronic diarrhoea
2) CKD or renal tubular acidosis
3) Endocrine eg hypothyroidism, DM, hypopituitarism
4) Inborn errors of metabolism
5) Chronic infection eg congenital HIV, TB, parasites
What may cause an increased metabolic demand in a child?
1) Hyperthyroidism
2) Chronic cardiac or respiratory disease eg HF, asthma, bronchopulmonary dysplasia
3) CKD
4) Malignancy
What investigations are done for FTT?
FBC Urinalysis U+Es LTFs inc total protein and albumin Coeliac screen Prealbumin = nutritional marker
+ specific tests if concerned eg HIV, sweat test, stools for parasite, TB testing
What is ambiguous genitalia?
A birth defect in which the outer genitals do not have the typical appearance on either a boy or a girl
Ambiguous genitalia = a form disorder of sexual development (DSD)
What 3 categories can sex differentiation be divided into?
1) Chromosomal sex or karyotype
- 46, XX
- 46, XY
- Variants
2) Gonadal sex
- Presence of testis or ovary
3) Phenotypic sex
- External genitalia
- Internal structures
What is virilisation?
Development of masculine traits in a female karyotype or precociously in a boy
Eg male pattern hair growth
What causes virilsation of 46, XX?
1) Congenital adrenal hyperplasia (CAH)
2) Prenatal exposure to male hormones e.g. medication
3) Tumours
What causes under-virilisation of 46, XY?
1) Androgen insensitivity syndrome (most common)
2) Defective testosterone production = Leydig cell hypoplasia
3) Defective testosterone metabolism = 5-alpha-reductase deficiency
What is CAH?
Enzyme defects mean there is decreased cortisol and aldosterone, and increased androgens
Main cause is 21-hydroxylase enzyme deficiency
What is the inheritance pattern of CAH?
Autosomal recessive
How may ambiguous genitalia present in females?
Clitoral hypertrophy
Variable fusion of labia
How may ambiguous genitalia present in males?
Severe hypospadias
Bifid scrotum
Bilateral undescended testes
What is hypospadias?
A congenital defect in which the opening of the urethra is on the underside of the penis instead of the tip
What investigations may be done for ambiguous genitialia?
Pelvis USS
Karyotyping
Until what point do male and female embryos develop in a similar manner?
7 weeks gestation
What is Rokitansky syndrome?
= Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome
Under-developed womb, or no womb, cervix or upper vagina
Ovaries and external gent normal
What are the most common disorders of sexual development?
1) Klinefelter syndrome
2) Turner syndrome
3) Mixed gonadal dysgenesis
4) Congenital adrenal hyperplasia (CAH)
5) Androgen insensitivity syndrome
6) Cryptochordism
What is Klinefelter syndrome?
47,XXY
How may Klinefelter syndrome present?
Tall stature Gynecomastia Small testes Azoospermia Learning difficulties
What is Turner syndrome?
45,XO
How may Turner syndrome present?
Webbed neck Low hairline Short stature Streak ovaries Coarcatation of the aorta Learning difficulties
How may CAH present?
- Hypoglycaemia
- Salt-losing adrenal crisis - vomiting and diarrhoea - dehydration
- Failure to thrive
- Hyperpigmentation
Low aldosterone = unable to retain enough sodium (salt)
This means too much sodium is lost in urine = ‘salt-wasting’
When is CAH normally detected? If not detected, what blood levels would be found?
Newborn screen
Hyponatraemia
Hyperkalaemia
Metabolic acidosis
Hypoglycaemia
High levels of 17-alpha-hydroxyprogesterone
What is the medical management of CAH?
Lifelong glucocorticoids to suppress ACTH levels to allow normal growth and maturation
- Hydrocortisone in neonates and children
- Prednisolone/dexamethasone in adolescents/adults
Mineralocorticoids (fludrocortisone), saline and glucose if there is salt loss
What is the inheritance and mutation of androgen insensitivity syndrome?
X-linked recessive
Androgen receptor gene mutation
How may androgen insensitivity syndrome present?
Wide phenotypic spectrum
1) Complete androgen receptor resistance:
- Female phenotype with bilingual inguinal hernias OR
- Primary amenorrhoea and scanty pubic hair
2) Partial androgen receptor resistance
- Ambiguous genitalia with labial masses OR
- Male with infertility, decreased pubic hair or beard growth and gynecomastia
What are the LH and FSH levels like in androgen insensitivity syndrome?
Elevated LH and FSH
What is the treatment for androgen insensitivity syndrome?
Hormone replacement therapy
+/- gonadectomy
What is cryptochordism?
The testes is not in the scrotum and is not descended by 4 months old
How common is cryptochordism?
Most common congenital abnormality in boys
2-4% of term male infants
What are some complications of cryptochordism?
Inguinal hernia
Testicular torsion / trauma
Subftertility
Malignant transformation
What may hormone levels be in Klinefelter syndrome?
High FSH and LH
Low AMH and inhibin B
Low testosterone
What is the management of cryptochordism?
Orchidopexy = surgically moving testes into the scrotum
Or removal of dysgenic testes
Hormonal therapy (hCG / GnRH) may help testicular descent
What are maintenance fluids in children
1st 10kg = 100 ml / kg / day
2nd 10kg = 500 ml / kg / day
Remainder = 20 ml / kg / day
(RATE ml / hr is total daily requirement divided by 24hr)
How is % dehydration calculated in DKA?
5% fluid deficit in mild DKA
- pH 7.20-7.29
and / or bicarb <15
7% fluid deficit in moderate DKA
- pH 7.1-7.19
and / or bicarb <10
10% fluid deficit in severe DKA
- pH <7.1
and / or bicarb <5
