Endocrinology Flashcards
Diagnosis of CAH
High risk (previously affected child):
- Genetic counselling and testing of proband and parents to confirm both carry mutation.
- Pre-implantation genetic diagnosis.
Low risk (genital ambiguity on USS):
- Foetal karyotype and USS for Mullerain structures.
- If 46XX and normal karyotype classic CAH is a consideration - optimise medical management when born.
Neonatal diagnosis:
- Guthrie card measures 17-OHP levels and those above cut off have diagnostic testing performed.
- False positives in premature, SGA, very unwell and when taken too early.
Neonatal presentation (between 1-4 weeks):
- Ambiguous genitalia (girls), adrenal crisis (boys).
- Serum 17-OHP level elevated.
Non-classic forms:
- Late onset androgen excess.
- If basal 17-OHP unconvincing perform ACTH stimulation test.
- 17-OHP should rise significantly by 60min.
- Cortisol should also be measured and 17-OHP:cortisol ration will be elevated.
- Urine steroid profile shold be taken prior to steroid administration to differentiate types of CAH.
Medical management of CAH
All, regardless of type require glucocorticoids (hydrocortisone).
- Provide negative feedback and suppress ACTH secretion.
- This prevents adrenal stimulation and inhibits excess androgen production.
- Due to concerns re: long acting agents on growth these are only used once linear growth completed (dexamethasone/prednisilone).
Those with salt-wasting (all with raised plasma renin) require mineralocorticoid replacement to normalise sodium balance.
- Dose adjusted according to BP and plasma renin.
- Additional salt substitution may be required (necessary in almost all cases in the first 3 months).
Girls with moderate to severe clitoral enlargement or fused labia are offered corrective surgery.
- Timing and place in mild clitoral enlargement controversial.
Non-salt losing esp. in boys may lead to >5y advanced bone age when first diagnosed.
- Starting glucocorticoid therapy can slow growth and bone maturation.
- High risk that treatment of these children with hydrocortisone will lead to onset of precocious puberty.
- Androgens exert maturing influence on hypothalamus but suppress gonadotrophin, sudden suppression of androgens leads to gonatrophin release from pituitary.
- Manage with long acting leuteinising hormone.
Combination of antiandrogen and aromatase inhibitor may require lower dose of hydrocortisone.
Prevention of acute complications of CAH
Adrenal crises may be averted with anticipatory strategies:
- Stress steroids.
- Provide family with a plan.
- Medic alert bracelet.
- Have a file plan on hospital system.
- Ensure GP aware of importance of treatment in hospital for gastroenteritis, fever etc.
- Ensure family inform both surgeon and anaesthetist if child requires surgery.
Optimising growth in CAH
Timely diagnosis may lead to prevention of precocious puberty leading to short stature.
Education of patient and parents to ensure management compliance.
- Optimised medication dosing allow normal growth, response to stress and pubertal development.
- Too little hydrocortisone leads to ongoing overproduction of androgens, too much to poor growth.
- Too little fludrocortisone leads to salt craving and low blood sodium, too much to hypertension.
Psychological support in CAH
Females with ambiguous genitalia or surgery for ambiguous genitalia may need to discuss issues with sexuality.
Girls should not have repeated genital examinations performed.
Clinical photography is only warrented with consent as a record of anatomy pre-surgery.
Minimise days off school.
Involve child in the management of their CAH as appropriate for age.
Support and encourage during times of rebellion - do not threaten.
Identify and treat negative family responses to CAH - overindulgence, over-anxiousness, neglect and disinterest, resentment and over-controlling parents.
At initial diagnosis be aware of depression in patient, siblings and parents and counsel accordingly.
Often non-compliance in adolescence - the least receptive time of the patients life.
Most teens with CAH require additional emotional support - attendance at groups or one on one with a therapist.
Encourage parents to emphasis the positive aspects of adequate control and explain need for increased dosage in illness and to be supportive and avoid chastisement in rebelious periods.
By 18 most are more responsible in caring for their CAH.
Social supports in CAH
All families should have access to an experienced social worker.
- Disease represents a significant financial burden for many families.
- Help with awareness of benefits available to them.
- Psychological support and screening for social risk factors.
CAH groups help with access to helpful ideas and people.
Routine follow-up in CAH
See every 3-4 months.
Growth, Tanner stage, blood pressure and evidence of complications should be noted at each visit.
Investigations: 17-OHP, plasma renin activity and electrolytes.
Adjustment of medication based on review and investigations.
Yearly bone age.
Steroid medications and their equivalents
Prenatal intervention in CAH
Female foetus with previous CAH in sibling - administration of dexamethasone to mother.
- Very controversial
- Informed consent must be obtained.
- Maternal side effects (Cushings, marked weight gain, irritability, mood swings, diabetes, hypertension and striae with permanent scarring), variable genital outcome, long-term outcome on children is unknown.
- CVS at 9 weeks therefore treatment has to be commenced prior to knowledge of sex.
Diagnosis of T1DM
Patient with classic symptoms (polydypsia, polyuria and weight loss) + random BSL >11.8mmol/L
Asymptomatic require 2 criteria:
Fasting BSL >7 + 2 hour post-prandial >11.
Cases requiring formal OGTT are rare.
DKA:
- Comprises 30-40% of presentations.
- Significant risk of death particularly from cerebral oedema.
- Significant PTSD associated with admission.
Age specific aspects of blood sugar control in T1DM
Infants to preschoolers:
- Avoid hypoglycaemia and preserve cognitive function.
- Aim BSL 6-15mmol/L.
School-age to puberty:
- Avoid hypoglycaemia.
- Aim BSL 4-10mmol/L.
Adolescence:
- Aim to maintain as low a HbA1c as possible.
- Aim BSL 4-8mmol/L.
Insulin therapy in T1DM
Average doses:
- Honeymoon - 0.5IU/kg/d
- Preadolescent - 1IU/kg/d
- Adolescent - 1-2IU/kg/d
Insulin regimes:
- Daily (long acting/mix long and short only).
- Twice daily (2/3 given before breakfast and 1/3 before dinner. Each dose 2/3 intermediate and <span>1</span>/3 short acting).
- Twice daily with additional short or ultra short.
- Basal bolus (long acting evening and 3 pre-meal short acting - only for motivated adolescents).
- Premixed (biphasic - used only in non-compliance/inability to mix).
- Insulin pumps (rapid acting at basal rate).
Types of insulin used in T1DM
Ultra-fast/short acting:
- Onset 5 - 15 minutes.
- Peak 30-120 minutes.
- Lasts 4 hours.
- Humalog, Novorapid, Apidra.
Fast/short acting:
- Onset 30-60 minutes.
- Peaks 2-4 hours.
- Lasts 6-8 hours.
- Humulin R, Actrapid.
Long acting:
- Onset 1-2 hours.
- Peaks 4-12 hours.
- Lasts 8-24 hours.
- Humulin N, Protophane.
Long acting insulin analogues:
- No peak, lasts 24 hours after given.
- Once or twice a day.
- Need fast acting for meals.
- Lantus (insulin glargine - requires SA).
Biphasic insulins:
- Start to work immediately.
- Peak 4-12 hours.
- Last 8-24 hours.
Intercurrent illness in T1DM
Insulin must be given despite illness.
Adequate carbohydrate intake must be kept up.
BSL’s should be checked 2 hourly.
BSL >15 - check for ketones, avoid carbohydrate, maintain low-calorie fluids and give stat dose of 20% usual daily insulin (SA).
Alternatively give extra 10-20% daily insulin requirement as short acting every 2-4 hours.
If vomiting or high ketones, check BSL hourly with admission to hospital if required.
Patients should have a sick day plan.
Management of hypoglycaemic episodes
Best treatment is prevention - anticipate likely provoking circumstances.
Symptoms or BSL <3.5 should be treated immediately with fast acting sugar (glucagon if LOC).
All family members should be instructed in administration of glucagon.
Generally takes 10 min to feel better, resist giving further sugar in this time.
If meal due within 30 min, give it early. If not give extra as complex carbohydrate.
If having early morning high BSL, perform nocturnal sugars to ensure not having overnight hypoglycaemia.
All should have a medic alert bracelet.
Family should have an emergency plan for hypoglycaemia.
Insulin pumps in T1DM
Funded by Pharmac based on meeting criteria.
Often required to check BSL more frequently than when using insulin pens.
Need to be able to accurately carbohydrate count.
When used optimally leads to better BSL control, lower HbA1c and improved BMI and reduction in risk of long term complications.
Disadvantages: always connected, more frequent BSL testing, skin infection, site problems and weight gain.
Increased risk of DKA - use ultra SA insulin if pump fails DKA within hours.
Always have pens available if needed.
Can be removed up to 2 hours at a time.
Most units have well organised pathways for obtaining confidence in management.
Should be diabetes CNS or Paediatric availability 24 hours a day to trouble shoot.
