ENDOCRINOLOGY WK 5 Flashcards
1
Q
common causes of hypoglycaemia
A
- Treatment
o Insulin
o Sulphonylureas
- Patient error o Too much insulin o Too little carbs o Missed/late meal o Exercise
- Alcohol
- (same for sulphonylureas) – eg gliclazide, glipizide
2
Q
other less common causes of hypoglycaemia
A
- Decreased insulin requirement eg weight loss
- Liver disease, alcohol
- Conditions assoc. with T1DM
o Coeliac disease
o Addison’s disease (cortisol important counterregulation)
o Hypothyroidism
o Hypopituitarism - Complications of diabetes
o Autonomic neuropathy
o Injection sites/ lipohypertrophy
o Renal failure
o Counterregulatory failure
3
Q
counter-regulation of hypoglycaemia
A
Glucagon – produced by alpha cells in pancreas
- Insulin and glucagon in balance in health
- Glucagon brings blood sugar up
Epinephrine
Cortisol (pro-longed)
Growth hormone (pro-longed)
4
Q
why do hypoglycaemia symptoms change as diabetes progresses
A
- Changes in counterregulatory hormones over time
- Table below shows the % of deficiencies of counterregulatory hormones
- Lose glucagon response 100% by 5-10 yrs
- If you have diabetes for long have more neurological symtpoms because of this eg muddled instead of shaky
5
Q
what symptoms do elderly diabetics get with hypoglycaemia and why
A
- When you’re older (had diabetes longer) epinephrine levels released at lower blood glucose levels
- Means you get a smaller peak of epinephrine
- Start to develop brain dysnfunction before hypoglycaemia
- Confused during hypo and so don’t know what to do = severe
6
Q
what is the effect of having a hypo on risk in future
A
More hypos you have the less hormonal release you get
- Happening all the time so body doesn’t react as strongly
- Less warning you get = greater risk
7
Q
diagnosis of hypoglycaemia
A
Whipple’s triad – 2 out of 3 - Typical symptoms - Biochemical confirmation (no agreed cut-off but 4mmol/l in general – this isn’t actually that low but is a good safety margin) - Symptoms resolve with carbohydrate Remember ‘atypical’ presentation esp in elderly - Hemiparesis In theory, confuirm w/ lab blood glucose - But don’t delay treatment
8
Q
management of hypoglycaemia
A
- If alert – sweet drink or dextrose tablet
- If not alert – 20% dextrose iv
- If can’t access, give 1mg iv glucagon plus sweet drinl (not effective if alcoholic hypo)
- Follow up rapid acting carbs with slow release carbs
- 10% glucose infusion if long-acting insulin or SU
- If not recovering, consider other cause
- Full cognitive recovery can lag by 45 mins (driving)
- Glucagon injection
o Inject sterile water into powder, soak it back up and inject it
9
Q
aftercare of hypoglycaemia
A
- Follow-up glucagon/ dextrose with a starchy snack
- Patients presenting to hospital with hypo are-
o Older
o Live alone
o Co-morbidity
o Sulfonylurea therapy - Discharge if make full recovery and responsible adult at home – not if sulfonyurea-induced
- Infrom the diabetes team
- Close monitoring of blood glucose for next 72 hours
- Was there an obvious remedial cause
- If not, cut right back on insulin
10
Q
pathogenesis of Diabetic ketoacidosis
A
- Stop taking insulin
- glucose circulating but cells can’t take this up without insulin
- so most turn to other sources of energy…
o mobilise free fatty acids to make ketone bodies
o used as an alternative source of fuel when no glucose uptake - ketone bodies are acidic – cause metabolic acidosis
- as get rid of ketones in urine they cause an osmotic diuresis
o pee out lots of ketones which pulls out lots of water with it also
o makes you hypovolaemic
Other sources of fuel - break down muscles to make amino acids eg lactate and arginine
- plugged into gluconeogenesis cycle to make more glucose that we still can’t use
- extra glucose is peed out – water is taken with it – dehydration and decreased GFR
11
Q
If you don’t have enough insulin but still some (aka Type 2 diabetes)
A
- switches off the fatty acid pathway so only breakdown of muscle instead
- so don’t become acidotic
- but have persistent cycle of high glucose > pee it out > dehyration
- but no acidosis
12
Q
management of diabetic ketoacidosis
A
- Fluids > intitially fast then slower, to rehydrate
- Iv insulin > switch off ketone body production
- Monitor potassium – metabolic acidosis shifts K+ to extracellular space, as you give insulin, K+ moves into the cells and K+ falls
- Protocol driven
- Seek precipitant, commonly infection (inc. stress response inc. cortisol and GH) and errors/omissions
- Often no cause found
- In 10% of cases, DKA is first presentation of T1DM
13
Q
diagnosis of diabetic ketoacidosis
A
- Polyuria, polydipsia
- Hypovolaemia
o JVP dec, BP dec, HR inc
o ~5L fluid deficit
o Sifnificant electrolyte deficit Na+, K+ and Cl- - Abdo pain, N&V
- Kussmaul resps, ketotic breath
- Muscle cramps
14
Q
aftercare of DKA
A
- Swap to s/r isulin once patient eating and drinking
- Ensure basal insulin give > 1hr before iv insulin stops
- Try to identify precipitant
- Don’t miss oppprtunity for pt education
o Sick day rules
o Adjusting insulin - Involve DSN/ dietician, ensure F/U
- Look out for any complications
15
Q
hyperosmolar hyperglycaemic syndrome (HONK)
A
- Usual finding is MARKED hyperglycaemia, raised osmolality and mild/no ketoacidsosis
- Mortality up to 33%
- 2/3 cases in previously undiagnosed DM
- Affects middle-aged or elderly type 2 DM
16
Q
diagnosis of HONK
A
- Hyperglycaemia (>30mmol/l, but often 60-90 mmol/l)
- Serum osmolality >320mmol/Kg
- No/mild ketoacidosis
- Severe dehydration and pre-renal failure common
Calculated osmolarity = 2x (Na + K) + glc + urea - If above 320 = hyposmolar hyperglycaemic
17
Q
presentation of DKA
A
- Insidious onset
- Profound dehydration (9-10L) deficit
- Hypercoagulability (exclude CVA, DVT, PE)
- Confusion, coma, fits
- Gastroparesis, N&V, haematemesis
18
Q
management of DKA
A
- Slower, prolonged rehydration (older, underlying heart disease etc)
- Gradual reduction in Na+
- Gentler glucose reduction
- Anticoagulation vital – prophylactiv sc Heparin
- Seek the precipitant (infection, MI etc)
19
Q
lactic acidosis and metformin use
A
- Evidence that MF causes lactic acidosis is poor
- It does not increase lactate levles in T2DM
- Short t1/2 so rarely accumulates in absence of advanced RF
- Usually, tissue hypoxia is ‘trigger’
- Review of cases of MF-associated lactic acidosis 1995-2000 showed no cases were caused solely by MF
- Cochrane review 2002 concluded that treatment with MF not assoc. with inc. risk of LA
20
Q
when to stop metformin to prevent lactic acidosis
A
- Stop MF if eGFR <30 (or worsening fast)
- Withdraw during tissue hypoxia but can reinstate later
o Shock
o MI, significant CCF
o Sepsis
o Dehydration
o Acute renal failure - Withdraw for 3 days after iodine-containing contrast medium given
o Check U/E before reinstating 48h later - Withdraw 2 days before general anaesthetic and reinstate once renal function stable
21
Q
making a diagnosis of diabetes in childhood
A
MAKING AN EARLY DIAGNOSIS - THINK – symptoms (4 x Ts) o Toilet – using more o Thirsty o Thinner o Tired - TEST – immediately o Finger prick capillary glucose test o If result >11mmol/l - TELEPHONE urgently o Contact your local specialist team for a same day review
22
Q
presentation of diabetes in children
A
- Glucose is a powerful osmotic agent
- Subsequent polyuria and secondary polydipsia
Nocturnal enuresis Dehydration Weight loss - Insulin is an anabolic hormone so in absense of insulin body is catabolic state breaking down its muscle mass contributing to weight loss Lethargy and behavioural changes Blurred vision Vaginal candidiasis
23
Q
insulin treatment in children with diabetes
A
- Must be started as soon as possible after diagnosis (usually within 6 hours if ketonaemia is present)
- Children can develop dehydration + acidosis within 24 hours of first presentation
o Children < 2 yrs old are more at risk - This is to prevemt metabolic decompensation and diabetic ketoacidosis
24
Q
ketone metre - uses and interpretation
A
- Put blood on a strip
- Normal ketone reading – 0.1-0.2
- Can be higher if haven’t eaten in a while (0.3)
- Ketone reader reads up to 8mmol/l over this registers as HI
- Reading of 3 is likely to develop ketoacidosis
- But DKA can’t be diagnosed solely from this reading
25
common causes of DKA in children
DKA is the result of an absolute or relative deficiency of insulin
- Newly diagnosed diabetes
o In children with established TIDM – the risk is 1-10% per patient per year
o Infections
o Non compliance with treatment (75%). Children whose insulin is administered by a responsible adult rarely get DKA
o Insulin pump therapy – no background insulin circulating
Begin to develop ketones in 6 hours
Because no inhibition by insulin of hormone sensitive lipase
26
pathophysiology of DKA - how it affects/ presents in children
- An accelerated catabolic state, impaired peripheral glucose utilization, increased lipolysis + ketogenesis
- Hyperglycaemia + hyperketonaemia cause osmotic diuresis + dehydration
- Dehydration becomes a major feature
o Vomiting in children with diabetes is a sign of insulin deficiency until proven otherwise
o Hyperglycaemia and hyperetonaemia causes a degree of gastric stasis and gut iylias
o So indiv. Cont. to want to drink whilst in DKA
o Fluid unable to process fluid load in stomach and so instead vomit due to lack of movement through the gut
- Lactic acidosis from hypoperfusion
27
clinical presentation of DKA - symptoms and biochemistry in children
- Dehydration
- Nasusea, vomiting and abodminal pain, mimicking an acute abdomen
- Acidotic respiration (kussmaul) deep + sighing
- Altered conscious level
Biochemical data
- pH <7.3 +/or bucarbonate <15mmol/L
- base excess – strongly negative
- high anion gap
- hyperglycaemia
- hyperketonaemia
28
key aims of paediatric DKA
- meticulous monitoring of clinical condition of the patient and the biochemical data
- correct dehyrdation slowly (over 48 hours in those < 18 yrs)
- correct acidosis slowly + reverse ketosis – iv insulin infusion and NOT bicarbonate therapy
- restore BE to near normal
- avoid complication of therapy – paediatric cerebral oedema
29
education plan for newly diagnosed child
ward based – basic education
o admit all young people with new diabetes diagnosis to the ward
o commence basal bolus insulin regimen
- home based – social issues
- school/ nursery visits
o on insulin regimens – require diabetes care throughout skl/ nursery day
Clinic based – on-going package of care
- new patient clinic
- review pateint (at review patient see patient 3-4 months)
- young person’s clinic (aged 16-18 yrs)
30
aims of sick day management
- Do not omit insulin > always check blood ketone value
- Switch off ketogenesis (requires additional insulin)
- Ensure sufficient carbohydrate substrate is available
- Achieve normoglycaemia
o Febrile patients generally have an increased insulin requirement (25-50%)
o Patient with D+V within no ketonaemia may have a reduced insulin requirement (20% in each dose)
- Altered insulin doses may be required for up to one week after intercurrent illness
- Treat current illness
31
HbA1c targets for children and young people
- Explain to children and young people with type 1 diabetes that their families or carers
o That an HbA1c level of 48mmol/mol or lower will minimise their risk of long term complications
o Who have an HbA1c level above 48mmol/mol that any reduction in levels reduces that risk
32
how does blood glucose effect HbA1c values in 3/4 months
- Day 1-6 > very low contribution
- Day 7-30 > 50%
- Day 31-60 > 25%
- Day 61-90 > 15%
- Day 90-120 > 10%
33
Time in range to measure glycaemic control
Precentage of time % that a person spends within their target glucose range, usually 3.9-10mmol/l
Time below range is the percentage of time spne tbelow 3.9mmol/l
Produced by libre data (continuous glucose monitoring)
34
time in range and how it relates to HbA1c - targets
- Direct relationship between HbA1c and time in range
o The higher the time in range the lower the HbA1c
- The clinic TIR (time in range) target is a70% as strongly correlates with an HbA1c of 53mmol/mol
- It is also important to look at time below range
o Recommeneded TBR below 4%
- Important to note that what may appear small success ie 5% increase in TIR is significantl imporving glycaemic control
35
barriers to achieving glycaemic contorl
- Day to day family life
- Fear of hypoglycaemia and seizures
- School day
- Activitie / exercise / holidays
- Insulin omission
- Fave injection sites – lipohypertrophy
- Diabulimia (deliberate insulin omission to lose weight)
36
insulin injection sites
stomach
thigh
bottom
- not in arms because not enough subcutaenous fat
37
insulin pumps - availability, why teenagers need them
- Scottis govt. funding
- Current patient on pumps 266 (59.5%)
Why should get an insulin pump as a teenager…
- Don’t want to avoid exercise
- Don’t want to feel different from friends
- Want to feel like a normal teenager again
38
diabetes burnout
- A state of emotional exhaustion caused by the cont. distress of diabetes
- Described by health prof. as ‘difficult’ ‘non-adherent’
- Signs of burnout are disengagement from self care tasks
- Rarely ‘open’ to any advie for change on offer
- Inc. fears – but feel unable to take control
39
when do we test for diabetes in pregnancy
- Do tests for women we think may have gestational diabetes at ~24-28 weeks
- As at this point hPl is highest
40
pre-existing type 1 diabetes in pregnancy effects
- hPL causes insulin resistance also
- amount of insulin required increases
- sometimes a drop in insulin requirements in first trimester
- then gradually requirement increases in second trimester
41
what happens after pregnancy affected by GDM
- Insulin resistance will go and so will the diabetes after pregnancy
- But if have GDM in one pregnancy signif. Inc. lifetime risk of devleoping T2DM
- Eg have GDM in 20s, develop T2DM by age of 30
42
risks of diabetes to the baby
```
- Big babies ie macrozomia
o If baby >4.5kg
o Due to hyperglycaemia in pregnancy
- Babies getting stuck during delivery
o Have to fracture the babies humerus/ clavicle to get baby out
- Amnecephaly
o A nerual tube defect
o 5mg of folic acid 3 months before pregancy to decrease risk
- Premature birth
```
43
risk of diabetes to the mother
- Miscarriage
- Pre-eclampsia
- Preterm labour
- Intrapartum complications
- Progression of microvascular complications
- Severe hypoglycaemia
- Ketoacidosis
- Death
44
preconception care in patients with pre-existing diabetes
Optimise glycaemic control
- Monthly HbA1c
- HbA1c as low as possible and <53mmol/mol as min.
- Blood glucose metere, ketone testing in T1DM, hypoglycaemia management and awareness
Review medications
- Stop statins, ACEi/ARB, oral hypoglycaemics
- Continue metformin, (glibenclamide sometimes), commence insulin if required
45
optimising glycaemic control for pregnancy
- Balance between reducing renal, retinal and pregnancy complications vs risk of hypoglycaemia
- Need to be careful when trying to lower HbA1c vv quickly
- If you bring blood glucose down really quickly can lead to eye disease
46
retinopathy in pregnancy
- 43%v of women with retiopathy show progression during pregnancy
- Sight-threatening retinopathy rare (2%)
- RF are poor glycaemic control and hypertension
- Screening each trimester in pre-existing diabetes
47
gestational diabetes - what is it and what are complications
Defined as ‘carbohydrate intolerance of variable severity with onset or first recognition during pregnancy’
- Includes women with undiagnosed type 1, type 2 or monogenic
- Usually develops 28 wks after gestation
Complications (all reduced by intensive management)
- Macrosomia/ shoulder dystocia
- Neonatal hypoglycaemia
- Neonatal death
- Late intra-uterine death
48
what is the affect of mothers high blood glucose on baby pre and post natal
If mum has high blood glucose, she will have a high insulin but only glucose crosses the placenta
- Baby makes own insulin from 11 weeks
- Insulin is anabolic > big baby
- After delivery babies insulin remains high but glucose drops
o RISK OF HYPOGLYCAEMIA
49
screening for GDM
- All women with RF or intermediate results in ealry preganacy should have a 75g OGTT at 24-28wks
Risk factors
- BMI >30kg/m2
- Prev. baby with birth weight >4.5kg
- Previous GDM
- Family history of diabetes in a 1st degree relative
- Ethinic minority high risk population
50
diagnosis of GDM and what happens if it's diagnosed initially
```
75g OGTT
- Fasting glucose >5.1mmol/l (>7.0)
- 2 hr >8.5mmol/l (>11.1)
IF diagnosed…
- Come to clinic
- Monitored
- See dietician
- 2/3rds chance receive medication during pregnancy
```
51
management of GDM
- HBGM
- Dietetic input
- Metformin / insulin
- GLUCOSE TARGETS
o Fasting <5.5mM (morning)
o Pre-prandial <6mM (before dinner and tea)
o 2 hr post-meal in evening value <7
- Weekly CTG and liquor volumes from 36 wks
- Induced at term
- Insulin stopped once delivered
o OGTT at 12 wks, 12 monthly screening for T2DM
52
typical antenatal experience of a woman with GDM
```
(assuming uncomplicated)
- Min. 30 visits to hospital
- Fortnightly visits until 30 wks
o US scans (fetal anomaly, cardiac, fetal growth, liquor vol.)
o Retinal scans (1st antenatal visit at 28 wks)
o Anaesthetic appointements
- Weekly visits until 36 wks
- 2x weekly until 39-40 wks
- Min. GP and community midwife contact
```
53
pre-existing diabetic glycaemic targets - and what drug is sometimes used to reduce risk of pre-eclampsia
```
SIGN Glycaemic targets
- Pre-prandial 4-6mM
- 1 hr post-prandial <8mM
- 2hr post-prandial <7mM
- Before bed <6mM
Aspirin 75mg from 12-36 wks (reduces pre-eclampsia risk)
```
54
hypoglycaemia in pregnancy
- Insulin requirements change during pregnancy due to gestational hormones
- Hypoglycaemia
o Common (14-45% of patients)
o Occurs most often suring 1st trimester
o RF > prev. severe hypo, diabetes duration, impaired awareness, erratic control
- Re-educate pregannt women on hypoglycaemia
55
how are babies delivered when women has pre-existing diabetes and GDM
Pre-existing diabetes…
- Usually IOL or elective C section at 37-38 wks
GDM > labour induced before 40 wks
- Bc of increased risk of IUD and other maternal/ fetal complications
- Inc. risk of instrumental delivery and C section (60%)
56
postnatal care of GDM
- Pre-pregnancy planning for next pregnancy!
- Encourage breastfeeding
- Adjust treatment regimen when necessary
- GDM – 50% 5 yr risk of T2DM
o Diet, weight, exercise advice
o 12 week OGTT
o Annual screening for T2DM
57
growth hormone release
- GH release controlled by stimulatory factor – GHRH (growth hormone releasing hormone)
- GHRH – peptide synthesised by neurones in the arcuate nucleus, and released from neurosecretory terminals at the median eminence
- Binds to specific G-protein coupled receptor on pituitary somatotrophs, stimulates GH synthesis and release from stored pools
58
Inhibition of growth hormone
GH secretion is also controlled by an inhibtory factor – somatostatin
- Somatostatin > a peptide synthesised by neurosecretory neurone of the periventricular nucleus
- Somatostatin inhibits secretion of GH from somatotrophs and inhibits the secretion of GHRH
59
other hormones that regulate GH
- GH regulated by other hormones
o Estrogen
o Thyroid hormone
Hypothyroidism – poor growth, blunting of GH to stimuli & reduced pituitary GH levels
o Glucocorticoids
Intial stimulatory effect but later suppressive effect
Also regulated by…
- Catecholamines > stimulatory
- Ghrelin > stimulatory
60
growth hormone secretion throughout the day
GROWTH HORMONE SECRETION IS PULSATILE AND HAS CIRCADIAN RHYTHM
- On average 10 pulses a day
- Peak in slow wave sleep (affected by ‘jet-lag’
- Not affected by continuous GHRH administration or by inactivating mutations GHRH receptor
- Probs determined by somatostatin pulsatility
61
effects of sex, age and exercise on GH
Sex
- Woman have higher mean GH levels during day
- Due to sex differences in somatostatin
Age
- Decline with age
- Is there a role of GH in senescence, part. Altered body composition
- GH levels are lower in obesity and are restored by massive weight loss
EXERCISE
- Exercise – stimulant for GH secretion
- Occur ~ 10-15 mins after start of exercise
- Anerobic may be a better stimulant than aerobic
- May be mediated by Ach, adrenaline, endogenous opiods
62
GH signalling
- GH receptors in many tissues
- 1 GH molecule binds to 2 GHR molecules leading to dimerisation
- Critical step is activation of receptor-associated Janus Kinase (JAK2)
- Phosphorylation of STAT
- Translocates to nucleus and acts as a transcription factor
- Insulin-like growth factor-1 (IGF-1) gene activation
63
physiological effects of GH - direct and indirect
Direct effects
- Eg adipocytes have GH receptors
- GH stimulates them to breakdown TG(triglycerides) and suppresses ability to take up circulating lipids
Indirect effects
- Mediated primarily by IGF-1 secreted from the liver etc. in response to GH
- Most growth promoting effects of GH are due to IGF-1
64
IGF-1
- Liver is principle source of circulating IGF-1
- Also produced by most other tissues
- Autocrine/ paracrine effect probably respo nsible for most linear growth
65
what are the 3 period of growth in early years
INFANCY PERIOD
- Rapid deceleraiton in growht velocity
- Largely nutritionally determined
CHILDHOOD PERIOD
- Largely determined by GH secretion
- Growth till 3 yrs is an additive combination of infnacy and childhood components
- So, good nutrition remains key first 2-3 yrs of life
PUBERTY PERIOD
- GH + sex steroids
- Sex steroids are anabolic and have an effect on GH secretion
- Girls before boys
66
causes of short stature and ppor growth in childhood
- Nutrition
- Chronic disease (eg CF, asthma, IBD, coeliac, renal, liver)
- Genetic conditions (turner syndrome, trisomy 21, noonan syndrome, skeletal dysplasias)
- Steroids (oral, topical, inhaled, endogenous)
- Hypothyroidism
- Psychosocial deprivation
67
central causes of short stature and poor growth in childhood
```
Pituitary abnormalities
- GH deficiency
- TSH deficiency
- Gonadotrophin deficiency
Causes
- Genetic
- Tumours eg craniopharyngioma (pressure effects on pituitary)
- Irradiation
- Trauma
```
68
childhood GH deficiency
```
1:4000 children
Treatment GH
Other rare conditions-
- IGF-1 receptor abnormalities
- IGF-1 gene mutations
```
69
adult GH deficiency
2-3 per 10,000
Symptoms
- Decreased enegry, social isolation, depressed mood, anxiety
Clinical features
- Inc. body fat
- Dec. muscle mass
- Dec. bone density, inc. risk of fracture
- Impaired cardiac function
- Dec. insulin sensitivity and impaired glucose tolerance
biggest cause is non-functioning pituitary adenomas
70
treatment of GH deficiency in children and adults
In childhood…
- Given GH and return to normal
- £30,000 a yr
```
In adults…
- Controversial as it’s so expensive
- may imporve
o QOL
o Cardiovascular risk
o Lipids
o Exercise tolerance
o Body compisition
o Bone health
```
71
GH excess
- Tumour of pituitary (99%)
o If you get this before epiphyses have fused = gigantism
o After growing ends of long bones have fused = acromegaly
Prevelance 50-60 per million
- Rare other causes inc. McCune-Albright
72
acromegaly symptoms
- Facial change
- Excessive sweting
- Carpal tunnel syndrome
- Tiredness and lethargy
- Headaches
- Infertility
73
untreated acromegaly
- Increases in morbidity, overall mortality at least 2x general population
- Early studies > 50% of patients dead by 60yrs (diabetes, cardiovascular, respiratory or cerebrovascular disease)
- Improved treatment of disease and complications meand patients are surviving longer – may be susceotible to other complications such as malignancy
74
treatment of acromegaly
- Aims > normalise GH levles, reduce tumour size, preserve anterior pituitary function
- Surgery – transphenoidal possible (may use radiotherapy first)
- Drugs – if surgery fails
o Somatostatin analogues
o Long-acting GH recpetor antagonists
o Dopamine agonists
- Radiotherapy – if surgery fails and control difficult
75
test for GH deficiency
- GH deficiency
o Insulin tolerance test ITT (gold standard)
Inject insulin, wait for child to go hypoglycaemic then take GH reading
Hypoglycaemia is a goof stimulant for GH
- Other things that stimulate GH…
o Arginine
o Clonidine
o Glucagon
- Overnight GH sampling
76
test for GH excess
- Give glucose
- Essentially oral glucose tolerance test
- Should see a growth hormone suppression
- If you have GH excess – you wont see suppression
77
what charts are used to assess growth
```
Growth charts
- Plot height and weight
Height velocity charts
- Assesss rate of growth – cm/yr
BMI charts
- Identify BMI out with normal range
```
78
how do we factor parents into growth charts
```
Need height of each parent
For a girl…
- Plot mums height on chart
- Plot dads height MINUS13cm
For a boy…
- Plot dads height
- Plot mum height PLUS 13 cm
Midpoint between the 2 = mid paretal centile – plus or minus 6 cm
```
79
'faltering growth' aka failure to thrive
A baby or toddler is not growing at the rate that you would normally expect
- 5% of children under the age of 2 at some point
- It is not a condition in itself – there are lots of different possible explanations, with feeding problems being the most common
Causes…
- Too little intake
- Failure to absorb
- Chronic disease
Poor weight gain CASUES poor growth
Almost never a hormone issue
80
abnormal growth age 2->puberty
- Underlying pathological examination
- Even if eat small amount you normally grow normally
- Inc. incidence of hormone problems
Key indicators
- Stature out with parental target height
- Slow growth or rapid growth (not being short or tall)
81
growth disorder - how to take a history
Elicit problem
- Duration, severity, emotional/psychological
Perinatal history
- Birth weight and length, gestation, drugs, delivery, infection, jaundice, oedema, hypoglycaemia, micropenis
Family history
- Short stature, timing of puberty, heritable disease, endocrine disease
Systemic symtpoms
- Chroic illness, eurological nutritional review
Developmental history, social circumstances and diet
82
growth disorder - examination
Measurement
- Height, weight, head circumference, body proportion
Body habitus
- Eg broad chest, truncal obesity, muscle bulk
Dysmorphism
- Facial, midline defects, ears, palate, others
Hands and feet
- Short metacarpals, clinodactyly, palmar creases, lymphoedema, clubbing
Neurological
- Visual fields, acuity, fundi, nystagmus
Puberty and genitalia
- Puberty staging, penis size
Signs of systemic illness
83
how to take a history of puberty
Measurement
- Height, weight, head circumference, body proportion
Body habitus
- Eg broad chest, truncal obesity, muscle bulk
Dysmorphism
- Facial, midline defects, ears, palate, others
Hands and feet
- Short metacarpals, clinodactyly, palmar creases, lymphoedema, clubbing
Neurological
- Visual fields, acuity, fundi, nystagmus
Puberty and genitalia
- Puberty staging, penis size
Signs of systemic illness
84
examination of puberty in children
```
Parents present, privacy, non-parent chaperone, appropriate simple explanation
Girls
- Breast staging
- Pubic hair
- Axillary hair
- Acne
- Body habitus
Boys
- Testiculaer volumes (or lengths)
- Genital stage
- Pubic hair
- Axillary hair
- Acne
- Facial hair
- Body habitus
Self staging using growth chart pictures if examination declined
```
85
normal testicular volume changes in boys and what is the length and height gain of puberty
```
Testicular volumes = testosterone production
- Onset puberty = 4mls – age 11yrs
- Onset growth spurt at 10mls – age 13 yrs
- Adult male vols of 25mls – age 16 yrs
Normal range start = 9-14yrs
- Onset puberty pre 9yrs = precocious
- Onset puberty after 14yrs = delayes
Takes 5 yrs? Pubertal height gain 25cm
```
86
normal ranges for girls - breast development and onset of puberty and whats the average length of puberty and height gain
```
Oestrogen producation (ovaries enlarging)
- Onset puberty = breats bud and onset of growth spurt = 10.5 yrs
- End puberty = onset menses = 13 yrs
Normal range to start = 8-13 yrs
Onset puberty before 8 yrs = precocious
Onset puberty after 13 yrs = delayed
Takes 2.5 yrs
- Growth after onset menses ~6cm
```
87
adrenarche definition
- Onset of production of adrenal androgens – 2 years or more – prior to onset of puberty
- Due to maturation of adrenal cortex – zona reticularis
- Begins by 6-8 yrs in normal indiv.
- Presence or absence does not influence onset of true puberty
88
clinical features of adrenarche- when to worry and pathological diagnosis
Clinical Features
- Axillary and/or pubic hair, greasy hair and skin, acne, body odour
- >95% variant of normal
When should you worry
- Signs of virilisation or rapid growth
Pathological diagnosis
- Androgen secreting tumour or lat onset CAH (enzyme insufficiency in adrenal glands)
- Parents worried that it’s onset of puberty – but only if testicular enlargement or breast development
- But usually normal
89
menstruation - normal age
- Occurs at end of sexual maturation – B4-5
- Mean age = 13 yrs
- Normal range – 11-15yrs
- Irregular cycles common
90
what combos of height/weight should raise alarm bells and why
- Slow growth and thin
o Chronic disease eg coeliac disease, IBD
- Slow growth and fat
o Endocrine problem eg hypothyroidism
- Rapid growth in childhood
o Sex steroid exposure eg precocious puberty
91
precocious puberty
- Central precocious puberty > gonadotrophin dependant
o Onset breast development before 8 yrs
o Testicular volumes >3mls before 9yrs
- Pseudopuberty – gonadotrophin independent
o Disharmonious pubertal events
o Eg vaginal bleeding without breast development
92
central vs pseudo precocious puberty causes
```
CENTRAL PRECOCIOUS PUBERTY
- Central activation of pubertal axis
- Gnadal enlargement
- Normal sequence of events
VS…
PRECOCIOUS PSEUDOPUBERTY
- Peripheral activation of sex steroids
- Not centrally activated
- Incomplete pubertal sequence
- No gonadal enlargement
- Eg congential adrenal hyperplasia
- Ovarian tumour
```
93
concerns raised by possible precocious sexual development
- Possible sinister underlying cause
- Psychologically unacceptable
o Embarrassment of inappropriately early sexual changes, excessive tall stature, earlu onset menstruation
o Long term sequelae – short stature (but only if age at onset is <7yrs in girls and <8 yrs in boys
94
concerns raised by delayed or incomplete sexual development
- Possibly a sinsitr underlying cause eg acquired hypothyroidism
- Emotional and psychologi al upset of immaturity, esp. when associated with short stature
- Long term sequelae
