Endocrinology/Growth Flashcards
What plasma glucose is considered hypoglycaemia?
<2.6
Clinical features of hypoglycaemia? (3)
- Sweating
- Pallor
- CNS signs of irritability, headache, seizures and coma
- Neurological sequelae may be permanent if persists
- → Inc epilepsy, severe learning difficulties and microcephaly
- Risk greatest in early childhood during period of most rapid brain growth
Causes of hypoglycaemia?
- Common in neonates as high energy requirements
After neonatal period:
Fasting
- Insulin XS
• XS exogenous insulin
• βcell tumours/disorders
• Drug induced (sulphonylurea)
• Autoimmune (insulin receptor antibodies)
• Beckwith syndrome
- W/O hyperinsulinaemia
• Liver disease
• Ketotic hypoglycaemia of childhood
• Inborn errors of metabolism, e.g. glycogen storage disorders
• Hormonal deficiency: GH↓, ACTH↓, Addison disease, congenital adrenal hyperplasia
Reactive/non-fasting
- Galactosaemia
- Leucine sensitivity
- Fructose intolerance
- Maternal diabetes
- Hormonal deficiency
- Aspirin/alcohol poisoning
What is ketotic hypoglycaemia?
- Poorly defined entity in which young children readily become hypoglycaemic after short period of starvation
- → Due to limited reserves for gluconeogenesis
- Child often short & thin and insulin levels are low
- Regular snacks and extra glucose drinks when ill will usually prevent hypoglycaemia
- Condition resolves spontaneously in later life
Treatment of hypoglycaemia?
- IV infusion of glucose
- → 2 ml/kg of 10% dextrose followed by 10% dextrose infusion
- Care to avoid giving XS vol as solution is hypertonic and could cause cerebral oedema
- If delay in establishing infusion or failure to respond, glucagon given IM (0.5–1 mg)
- If higher conc than 10% required in neonate → low sugar highly likely to be secondary to hyperinsulinism
- Corticosteroids used if possibility of hypopituitarism or hypoadrenalism
Triggers of T1DM? (4)
enteroviral infections
diet
pos cow’s milk proteins
overnutrition
Common sx of T1DM? (3)
- Polyuria
- Polydipsia
- Wt loss
Less common presenting sx of T1DM? (4)
Secondary nocturnal enuresis
Skin sepsis
Candida/other infections
DKA
3 investigation findings that confirm T1DM?
- Markedly raised random blood glucose (>11.1 mmol/L)
- Glycosuria
- Ketonuria
- If doubt → fasting blood glucose (>7 mmol/L) or raised HbA1c helpful
What insulin regime are most children started on?
- |nsulin pump or 3-4 times/day injection regimen (basal bolus)
- → Short acting before snacks (bolus) and long acting in evening (basal)
What is the normal insulin requirement in children?
- 0.5-1 U/kg/day
- >2 U/kg/day in puberty
What glucose level to aim for in DM?
4-6mmol/L
In practice 4-10 in children, 4-8 in adults
HbA1c aim in DM?
<7.5% or 58mmol/mol
Why do you need increased insulin in puberty in DM?
Antagonised by GH, oestrogen and testosterone
What factors increase glucose levels? (8)
- Insulin omission
- Food
- Illness
- Menstruation
- GH
- Corticosteroids
- Sex hormones at puberty
- Stress of an operation
What factors decrease glucose levels? (5)
Insulin Exercise Alcohol Some drugs Marked anxiety/excitement
Short term complications of DM? (2)
- Hypoglycaemia
- DKA
What needs to be regularly reviewed in children with DM? (6)
- Growth/ pubertal development
- BP (1x/y)
- Renal disease
- Eyes
- Feet
- Other associated illnesses - coeliac + thyroid disease more common
Presenting features of DKA? (8)
- Smell of acetone on breath
- Vomiting
- Dehydration
- Abdo pain
- Hyperventilation due to acidosis (Kussmaul breathing)
- Hypovolaemic shock
- Drowsiness
- Coma and death
Ix for DKA? (8)
- Blood glucose (>11.1 mmol/L)
- Blood ketones (>3.0 mmol/L)
- U&Es, creatinine (dehydration)
- Blood gas analysis (severe metabolic acidosis)
- Urinary glucose and ketones (both are present)
- Evidence of a precipitating cause, e.g. infection (blood and urine cultures performed)
- Cardiac monitor for Twave changes of hypokalaemia
- Weight
Management priorities in DKA? (6)
- Fluids - correct dehydration over 48-72h
- Insulin - infusion
- Potassium (initially high yet need replacement once passed urine)
- Acidosis (should correct with fluids)
- Re-establish oral fluids, diet and subcutaneous insulin
- Identification and treatment of an underlying cause
How is insulin given in DKA?
- Infusion of 0.05-0.1 U/kg/h after 1h, titrating according to blood glucose
- Do not give bolus and monitor regularly
- Aim for reduction of 2 mmol/h of blood glucose as rapid reduction dangerous
- Change to 0.18% saline or 4% dextrose after 24h when blood glucose fallen to 14 mmol/L to avoid hypoglycaemia
- Do not stop infusion until 1h after subcut
How do you calculate genetic target height for child?
Mean of father’s + mother’s height with +7cm for boy, -7 cm for girl
Range given by +/- 10 in boy, +/-8.5 in girl
What are the causes of short stature? (7)
- Familial
- IUGR/extreme prem
- Constitutional delay of growth/puberty
- Endocrine - hypothyroid, GH deficiency, IGF-1 deficiency, steroid XS
- Nutritional/ chronic illness
- Psychosocial deprivation
- Chromosomal disorder/syndrome
What is constitutional delay of growth and puberty?
- Delayed puberty, often familial, usually having occurred in parent of same sex
- Commoner in males
- Variation of normal timing of puberty rather than abnormal condition
- May be induced by dieting or XS physical training
- Affected child will have delayed sexual changes compared with peers, and bone age would show moderate delay
- Legs long in comparison to back
- Eventually target height will be reached
- Condition may cause psychological upset
- Onset of puberty can be induced with androgens or oestrogens
What proportion of children with IUGR/ extreme prematurity remain short?
1/3
If weight is on higher centile than height and child is short, what cause may this suggest?
Endocrine
What is Laron syndrome?
Defective GH receptors
- -> GH insensitivity
- High GH levels, low IGF-1
- -> Extreme short stature
What is Cushing syndrome?
Corticosteroid XS
Name 3 chronic illnesses that may present with short stature?
- Coeliac
- Crohn’s
- Chronic renal failure
Name 4 syndromes that may result in short stature?
Down’s
Noonan’s
Turner’s
Russel-Silver
Sx of Russell-Silver syndrome? (8)
Sx include:
- Arms and legs length differences
- Cafe-au-lait spots
- FTT
- Delayed bone age
- Short height
- Swelling of fingers/toes
- GI reflux
- Kidney problems
Important aspects to ask in history of child presenting with short stature? (7)
- Birth wt, length, head circumference & gestation
- Pregnancy hx - IUGR, infection, drug/smoking/alcohol
- Feeding hx
- Developmental milestones
- FH of constitutional delay or other diseases?
- Features of chronic illness- hypothyroid, pituitary tumour, cushing’s, coeliac, Crohn’s, psychosocial deprivation
- Medications?
3 features of puberty in females and usual age?
- Breast development - 8.5-12.5y (1st sign)
- Pubic hair growth & rapid height spurt - almost immediately after breast
- Menarche - on av 2.5y after start of puberty (only 5cm growth left)
3 features of puberty in males?
- Testicular enlargement (1st sign)
- Pubic hair growth - 10-14y
- Height spurt - when testicular vol 12-18ml, usually 18m delay from onset
Other features of puberty that occur in both sexes? (4)
- Acne
- Axillary hair
- Body odour
- Mood changes
Average blood loss during menarche?
<80ml
Age cut offs for definition of delayed puberty?
Absence of pubertal development by 14 for F and 15 for M
Causes of delayed puberty? (3)
- Constitutional delay of growth/puberty (most common)
- Hypogonadotropic hypogonadism (systemic disease, hypothalamic-pituitary disorders, acquired hypothyroidism)
- Hypergonadotropic hypogonadism (chromosomal abnormalities, steroid hormone enzyme deficiencies, acquired gonadal damage)
Basic Ix for delayed puberty?
In boys:
- Pubertal staging, esp testicular volume
- Identification of chronic systemic disorders
In girls:
- Karyotype performed to ID Turner syndrome
- Thyroid and sex steroid hormones should be measured
Drugs used in delayed puberty?
Males:
- Oral oxandrolone in young males
- Low dose IM testosterone in older males
Females
- Oestradiol
NB treatment not usually required
Define precocious puberty
Development of secondary sexual characteristics <8yo in F and 9yo in M
When accompanied by growth spurt
What is
a) thelarche
b) pubarche?
a) Onset of breast development
b) Onset of pubic hair development
2 types of precocious puberty?
- Gonadotropin-dependent (central, ‘true’ PP) - Premature activation of hypothalamic– pituitary–gonadal axis → raised LH>FSH
- Gonadotropin-independent (pseudo, ‘false’ PP) from XS sex steroids → raised FSH & LH
Most common cause of precocious puberty in girls and boys?
Girls - idiopathic/familial
Boys - Organic esp intracranial tumours
Indications of organic cause of precocious puberty in girls? (3)
- Dissonance (sequence of pubertal changes abnormal), e.g. isolated pubic hair with virilisation of genitalia, suggesting XS androgens from either congenital adrenal hyperplasia or an androgensecreting tumour
- Rapid onset
- Neurological S+S, e.g. neurofibromatosis
Ix for precocious puberty in girls?
USS of ovaries and uterus
- In premature onset of normal puberty, multicystic ovaries and enlarging uterus identified
FSH & LH
What examination is done in precocious puberty in boys?
Examination of testes:
• Bilateral enlargement suggests gonadotropin release, usually from intracranial lesion
- Small testes suggest adrenal cause (e.g. tumour or adrenal hyperplasia)
- Unilateral enlarged testis suggests gonadal tumour
MRI for tumours in hypothalamic region
FSH & LH
Overweight & obese BMI in children?
Very severe obese?
Extreme obesity?
Overweight - >91st centile
Obese >98th centile
V severe >3.5SD
Extreme >4SD
If >12y - BMI >25, 30, 35 & 40 respectively
RFs for obesity? (4)
- Low socio-economic background
- Time spent in front of small screens
- High fat intake
- Low fruit/veg intake
Endogenous causes for obesity? (4)
Hypothyroidism
Cushing’s
- Short
Prader-Willi
- LD/dysmorphism
Gene defects eg leptin deficiency
- V obese and <3y
Complications of obesity? (10)
- Orthopaedic – SUFE, tibia vara (bow legs), abnormal foot structure and function
- Idiopathic intracranial HTN (headaches, blurred optic disc margins)
- Hypoventilation syndrome (daytime somnolence; sleep apnoea; snoring; hypercapnia; heart failure)
- Gallbladder disease
- PCOS
- T2DM
- HTN
- Abnormal blood lipids
- Other medical sequelae, e.g. asthma, changes in LV mass, higher risk of malignancies (endometrial, breast and colonic carcinoma)
- Psychological sequelae – low selfesteem, teasing, depression
Syndromes associated with obesity? (6)
- Prader-Willi syndrome
- Psuedohypoparathyroidism
- Laurence-Moon-Biedl syndrome
- Cohen syndrome
- Down syndrome
- Turner syndrome
Presenting features of T2DM in children? (4)
- Acanthosis nigricans
- Obesity
- HTN
- Strong FH
- No thirst or increased urination
Treatment for T2DM?
- Activity
- Diet
- Metformin
- Potential insulin therapy where required
Features of Prader Willi syndrome? (4)
- Hypotonia
- Developmental delay
- Hyperphagia (XS desire to eat)
- Obesity
Causes of congenital hypothyroidism? (4)
Maldescent of thyroid & athyrosis
- Commonest cause of sporadic congenital hypothyroidism
Dyshormonogenesis
- Inborn error of thyroid hormone synthesis
- 5-10% cases
Iodine deficiency
- Commonest cause worldwide, rare in UK
Hypothyroidism due to TSH deficiency
- Isolated TSH deficiency rare (<1% cases)
- Usually associated with pan-hypopituitarism (→ hypoglycaemia, micropenis)
Clinical features of hypothyroidism?
Usually asymptomatic - picked up on screening
Otherwise: • FTT • Feeding problems • Prolonged jaundice • Constipation • Pale, cold, mottled dry skin • Coarse facies • Large tongue • Hoarse cry • Goitre (occasionally) • Umbilical hernia • Delayed development
What is measured to detect hypothyroidism on Guthrie test?
TSH
- Will be high
- Thyroid dysfunction due to pituitary abnormalities may not be picked up (low TSH)
Treatment of congenital hypothyroidism?
- Thyroxine started at 2-3w of age
- Early treatment essential to prevent LD
- With treatment, intelligence should be in normal range for majority
- Thyroxine dose titrated to maintain normal growth, TSH & T4 levels
What is juvenile hypothyroidism usually caused by?
Autoimmune thyroiditis
Clinical features of juvenile hypothyroidism?
LOTS
- Short stature/growth failure → accompanied by delayed bone age
- Cold intolerance
- Dry skin
- Cold peripheries
- Bradycardia
- Thin, dry hair
- Pale, puffy eyes with loss of eyebrows
- Goitre
- Slow-relaxing reflexes
- Constipation
- Delayed puberty
- Obesity
- Slipped upper femoral epiphysis
- Deterioration in school work
- Learning difficulties
What usually causes hyperthyroidism in children?
Graves disease (autoimmune thyroiditis)
Treatment of hyperthyroidism?
- 1st line → carbimazole or propylthiouracil (interfere with thyroid hormone synthesis)
- → Risk of neutropenia – urge to seek help + blood count if sore throat and fever on starting med
- Treatment given for 2y → should control thyrotoxicosis, but eye signs may not resolve
- When stopped 40-75% relapse
- → 2nd course drugs or subtotal thyroidectomy
- Radioiodine treatment simple and no longer thought to cause neoplasia
- Follow up needed → often hypothyroid
- Beta-blockers can be added initially for symptomatic relief of anxiety, tremor, tachycardia
Causes of Cushing syndrome in children?
NB very rare
ACTH driven
• Pituitary adenoma (older children)
• Ectopic ACTH-producting tumours (v rare in children)
ACTH-independent
• Corticosteroid therapy – MOST COMMON
• Adrenocortical tumours – may also be virilisation (young children)
What is diabetes insipidus and sx (3)?
Low ADH (posterior pituitary) or kidney has reduced response to ADH
- -> - Polyuria
- Nocturia
- Polydipsia
Causes of GH deficiency? (6)
- Idiopathic (most common)
- Congenital mid-facial defects
- CNS tumour – craniopharyngioma, hypothalamic tumour
- CNS radiation
- Trauma eg head injury
- Meningitis
