Paeds - Endocrinology

Question 1

Type 1 Diabetes in Children

Pathophysiology
Clinical Features
Investigations
Long Term Management

Answer 1

1. ) Pathophysiology - autoimmune destruction of β-cells in the pancreas stops insulin production, this prevents the absorption and storage of glucose into the cells
   - aetiology is unknown but may be triggered by certain viruses e.g. Coxsackie B virus and enterovirus
2. ) Clinical Features
   - 25-50% of new T1DM present as DKA, sx usually present from 1-6 weeks prior to the DKA
   - remaining present with sx of hyperglycaemia:
   - classical triad: polyuria, polydipsia, weight loss
   - other sx: polyphagia, enuresis, recurrent infections
3. ) Investigations
   - 1°: urine dip to check for ketones to exclude DKA
   - baseline bloods: FBC, U+Es, CBG, HbA1c
   - screen for associated diseases: anti-TTG (Coeliac), TFTs+TPO-abs (autoimmune thyroid disease)
   - antibodies associated with pancreatic destruction: insulin-abs, anti-GAD-abs and islet-cell-abs
4. ) Long Term Management - lifelong
   - SC insulin regimes, monitoring carbohydrate intake
   - monitoring sugar levels: flash glucose monitoring (e.g. Freestyle Libre), capillary BG, HbA1c
   - monitoring and managing complications including:
   - short term: hypoglycaemic episodes, DKA
   - long term: macrovascular, microvascular, infections

Question 2

Insulin Therapy

Basal-Bolus Dosing
Injection of Insulin
Insulin Pumps

Answer 2

1. ) Basal-Bolus Dosing
   - basal: long-acting insulin injected once a day (same time every day) to provide constant background insulin throughout the day e.g. Lantus (glargine)
   - bolus: rapid-acting insulin injected 15-30mins before a meal or snack, the dose is dependent on the no(g) of carbs in the meal e.g. Actrapid, Novorapid (aspart)
   - 1 unit of Novorapid decreases BG by 3-4mM
2. ) Injection of Insulin
   - site: children can use the abdomen, thighs, buttocks, avoid upper arms unless older/more fat present
   - must rotate locations to prevent lipodystrophy
   - must not inject into ‘lumpy’ sites as that can reduce insulin absorption, eventually, insulin can be randomly released all at once which can lead to a hypo
3. ) Insulin Pumps - alternative to basal-bolus regimes
   - continuously infuses insulin through a SC cannula at different rates to control blood sugar levels
   - cannula is replaced every 2-3 days at different sites to prevent lipodystrophy and absorption issues
   - must be >12yrs old and have difficulty controlling HbA1c to qualify for an insulin pump under the NHS

Question 3

Diabetic Ketoacidosis

Pathophysiology
Clinical Features
Investigations/Diagnosis

Answer 3

1. ) Pathophysiology - ketogenesis occurs when the body thinks it’s starving (no glucose or glycogen stores)
   - the liver converts FAs into ketones to use as fuel which causes metabolic acidosis in T1 diabetics as they run out of bicarbonate to buffer the ketones
   - often occurs during prolonged fasting or very low carbohydrate diets or during heavy alcohol sessions
2. ) Clinical Features
   - osmotic diuresis: hyperglycaemia causes polyuria which causes dehydration which triggers polydipsia
   - severe dehydration can lead to clinical shock
   - acetone (fruity) smell in the breath
   - other sx: abdominal pain, N+V, weight loss, lethargy, visual disturbance, altered consciousness
   - precipitating factors include: poor insulin adherence, stress/trauma, infection, pancreatitis, drug interactions (e.g. corticosteroids, diuretics, sympathomimetics)

3.) Investigations/Diagnosis
- diagnostic triad: hyperglycaemia (>11mM), acidosis
(pH <7.3) ketonaemia (>3mM) OR ketonuria (+++)
- CBG, ABG, ketone meter or urine dipstick

Question 4

Management of Diabetic Ketoacidosis

Correcting Dehydration
Correcting Hyperglycaemia
Preventing Hypokalaemia
Cerebral Oedema
Other

Answer 4

1. ) Correcting Dehydration - with IV fluids
   - this dilutes the hyperglycaemia and the ketones
   - correct evenly over 4hrs (avoid fluid boluses unless in resus) to prevent cerebral oedema
2. ) Correcting Hyperglycaemia - with FRIII +/- IV dextrose
   - fixed-rate insulin infusion to allow cells to use glucose again and switch off the production of ketones
   - slow correction to prevent cerebral oedema
   - prevent a hypo w/ IV dextrose once BG <14mM
3. ) Preventing Hypokalaemia - with K+
   - in DKA there is low intracellular K+ (no insulin) but serum K+ remains balanced as it can be excreted
   - treatment with insulin rapidly drives K+ into cells which can cause severe hypokalaemia very quickly
   - K+ is added to IV fluids to prevent hypokalaemia
   - hypokalaemia can lead to fatal arrhythmias
4. ) Cerebral Oedema - high risk, especially in children
   - rapid correction causes a rapid shift in water from extracellular –> intracellular space in brain cells
   - causes the brain swelling –> cell destruction, death
   - neuro obs should be monitored hourly to look for sx: headaches, ↓HR, altered behaviour/consciousness
   - Mx: slowing IV fluids, IV mannitol, IV hypertonic saline
5. ) Other
   - treat any underlying triggers e.g. Abx for sepsis
   - need regular monitoring: BG, ketones, pH
   - correct hypomagnesaemia (a complication of DKA)
   - return to SC insulin when DKA is biochemically resolved: pH >7.3, ketones <0.3mM, HCO3 >15mM

Question 5

Hypoglycaemic Episodes (‘Hypos’)

Causes
Clinical Features
Immediate Management
Implications on Driving Licence

Answer 5

1. ) Causes
   - insulin: incorrect injection techniques +/- the timing
   - ↓↓food intake, vigorous exercise, drinking alcohol
   - other drugs: e.g. gliclazide, ß-blockers, haloperidol
   - CKD, Addison’s disease, hypothyroidism
2. ) Clinical Features - BG < 4mM
   - mild: hunger, anxiety, irritability, palpitations
   - moderate: confusion, lethargy, impaired vision,
   - severe: seizures, ↓consciousness, coma
3. ) Immediate Management
   - fast-acting carbs (15-20g) or 200ml of orange juice - up to x3 every 15 mins e.g. dissolved sugar, glucogel, pure fruit juice,
   - IV dextrose and IM glucagon for severe hypos
   - long-acting carbs after BG >4mM to prevent relapse

Question 6

Adrenal Insufficiency

Pathophysiology
Clinical Features
Investigations

Answer 6

1. ) Pathophysiology - adrenals do not produce enough steroid hormones esp cortisol and aldosterone
   - 1°Addison’s disease: (autoimmune) destruction of adrenals leading to reduced secretion
   - 2°ACTH deficiency: adrenals are not stimulated, this can be due to congenital hypopituitarism, surgery, infection, loss of blood flow or radiotherapy
   - 3°CRH deficiency: often due to long term oral steroid use (>3wks) causing suppression of the hypothalamus

2.) Clinical Features
- babies: poor feeding, vomiting, hypoglycaemia, lethargy, jaundice, failure to thrive
- older children: N+V, abdo pain, muscle weakness, ↓appetite, weight loss/failure to thrive, development delay, bronze hyperpigmentation (↑ACTH in Addison’s)

3. ) Investigations - blood tests
   - initial test: U+Es (↓Na, ↑K+), BG (hypoglycaemia)
   - diagnostic tests: cortisol, ACTH, aldosterone and renin levels, prior to giving steroids (if possible)
   - 1° (Addison’s): ↓cortisol, ↓aldosterone, ↑ACTH, ↑renin
   - 2°: ↓ACTH, ↓cortisol, normal aldosterone and renin
   - short synacthen test: to confirm Addison’s disease, synthetic ACTH is administered but cortisol fails to rise appropriately (< 2x baseline after 60mins)

Question 7

Management of Adrenal Insufficiency

Treatment of Adrenal Insufficiency
Sick Day Rules
Addisonian Crisis (aka Adrenal Crisis)

Answer 7

1. ) Treatment of Adrenal Insufficiency
   - replacement steroids: hydrocortisone (replace cortisol), fludrocortisone (replace aldosterone)
   - steroids are important for life (should not be missed)
   - patients are given a steroid card to inform emergency services they are dependent on steroids for life
   - monitored for growth and development, BP, U+Es, glucose, bone profile, and vitamin D
2. ) Sick Day Rules - during acute illness
   - coughs/colds w/o fever require no adjustment
   - increased demand for steroids when more unwell (e.g. >38ºC or D+V), and increased risk of a hypo
   - steroid dose is doubled (hydrocortisone only)
   - eat more carbohydrates regularly until the illness is resolved
   - need IM or IV (admission) steroids if there is D+V
3. ) Addisonian Crisis (aka Adrenal Crisis) - an acute life-threatening presentation of severe Addison’s
   - can be triggered by acute illness/infection/trauma, or abrupt stoppage of external steroids (3° insufficiency)
   - sx: ↓BP, ↓BG, ↓Na+, ↑K+, ↓consciousness
   - don’t wait for investigations, immediate tx is required:
   - intensive monitoring of electrolytes and fluid balance
   - IV hydrocortisone, IV fluid resus, correct any hypos

Question 8

Puberty

Clinical Features
Puberty in Girls
Puberty in Boys

Answer 8

1. ) Clinical Features
   - onset: 9-13 yrs in girls, 10-14 in boys
   - Tanner stages of sexual development for staging
   - end of puberty is linked to the fusion of the epiphyseal growth plates of the long bones

2.) Puberty in Girls - 9-13
- thelarche (9-11): breast bud development (first stage)
- adrenarche: ↑production of androgens leads to:
hair growth (pubic first), acne, sweating, body odour
- growth: in vertical height (fastest around 12yrs)
- menarche: menstruation begins, avg is 13yrs

3. ) Puberty in Boys - 10-14
   - testicular development (first stage): testicular volume >4ml (using orchidometer) indicates onset of puberty
   - adrenarche: hair growth (pubic –> axillary –> facial), deepened voice, acne, odour, ability to ejaculate
   - growth: in vertical height and body size (14-17 peak)

Question 9

Precocious and Late-Onset Puberty

Precocious (Early) Puberty
Causes of Precocious Puberty
Late-Onset Puberty
Causes of Late-Onset Puberty

Answer 9

1. ) Precocious (Early) Puberty - <8 in girls, <9 in boys
   - common in girls and usually idiopathic and familial
   - more concerning in boys (underlying tumour/trauma)
   - true: early activation of the HPA
   - false: gonadotrophin independent, often presents w/ isolated development of one pubertal characteristic
   - can lead to short stature, psychological disturbance, early menarche (disruptive), safeguarding concerns

2.) Causes of Precocious Puberty
- true precocious puberty: brain tumours, post-sepsis, surgery, radiotherapy, trauma, birth anoxia
- false precocious puberty: CAH, hypothyroidism, exogenous sex steroids, gonadal tumours
- atypical patterns of puberty: CAH, Cushing’s, PCOS
adrenal tumours, isolated thelarche or menarche, ovarian cyst and secondary oestrogen

3. ) Late-Onset Puberty
   - boys: no testicular development before 14yrs of age
   - girls (more concerning): no breast development before 13yrs OR no menarche by the age of 16
4. ) Causes of Late-Onset Puberty
   - maturational delay (idiopathic, can run in families)
   - gonadal failure: Turner’s or Klinefelter’s syndrome
   - hypothalamic-pituitary axis dysfunction
   - chronic and severe disease, chemo/radiotherapy
   - glycogen storage disorders, galactosaemia
   - girls only: Turner’s, anorexia nervosa, low body weight/athletic lifestyle, autoimmune failure (POI)

Question 10

Congenital Adrenal Hyperplasia

Pathophysiology
Presentation in Severe Cases
Presentation in Mild Cases
Management

Answer 10

1. ) Pathophysiology - deficiency of the 21-hydroxylase enzyme causes underproduction of cortisol and aldosterone and overproduction of androgens
   - 21-hydroxylase converts progesterone into cortisol and aldosterone so absence means progesterone is converted into testosterone instead
   - genetic condition, autosomal recessive inheritance
2. ) Presentation in Severe Cases - at birth
   - ambiguous genitalia and enlarged clitoris in females due to the high testosterone levels
   - present shortly after birth w/ ↓BG, ↓Na+, ↑K+ leading to poor feeding, vomiting, dehydration, arrhythmias
3. ) Presentation in Mild Cases - childhood/puberty
   - both: tall for their age, deep voice, early puberty, skin hyperpigmentation (↑ACTH in response to ↓cortisol)
   - boys: large penis and small testicles
   - girls: facial hair and amenorrhea
4. ) Management - paediatric endocrinologist
   - F/U closely for their growth and development
   - hormone replacement: cortisol (hydrocortisone) aldosterone (fludrocortisone)
   - corrective surgery for genitalia in females

Question 11

Growth Hormone Deficiency

Pathophysiology
Clinical Features
Investigations
Treatment

Answer 11

1. ) Pathophysiology - disruption to the GH axis at the hypothalamus or can be due to pituitary gland
   - congenital: genetic mutations or empty sella syndrome where the pituitary gland is damaged
   - acquired: secondary to an infection, trauma, surgery
   - can occur in isolation or w/ other pituitary hormone deficiencies e.g. hypothyroidism, adrenal insufficiency and deficiencies of the gonadotrophins (LH and FSH)
2. ) Clinical Features
   - at birth: severe jaundice, hypoglycaemia, micropenis
   - older children: poor growth, short stature, slow development, delayed puberty
3. ) Investigations
   - GH stimulation test: measure the response to drugs that should stimulate GH release e.g. glucagon, insulin
   - test for other deficiencies: e.g. thyroid, adrenals
   - MRI-brain: structural pituitary or hypothalamus issues
   - genetic testing for associated genetic conditions such as Turner syndrome and Prader–Willi syndrome
   - X-ray (wrist) or a DEXA scan can determine bone age and help predict final height
4. ) Treatment - paediatric endocrinologist
   - daily SC injections of growth hormone (somatropin)
   - treatment of other associated hormone deficiencies
   - close monitoring of height and development