1. Managing Addison’s Disease
Dr Ved Bhushan Arya MD PhD
Consultant Paediatric Endocrinologist
Kings College Hospital, London
Thomas Addison Guy’s Hospial
Described Symptoms 1855

2. Hypothalamic Pituitary Adrenal Axis

4. Actions of Glucocorticoids (Cortisol)
Maintains normal blood glucose levels during starvation
Maintains normal blood pressure (role in heart contractility effectiveness and vascular tone)

5. Actions of Mineralocorticoids (Aldosterone)
Enhances the reabsorption of sodium from kidneys – maintains blood volume and blood pressure
Increases the excretion of potassium through effect on kidneys – If potassium in blood very high  cardiac arrhythmia

6. Adrenoleukodystrophy (ALD)
Progressive accumulation of VLCFAs in the
Adrenal Cortex
Adrenal Cortex progressively destroyed
Loss of glucocorticoid and mineralocorticoid function

7. Presenting signs and symptoms in patients with Primary Adrenal Insufficiency
Nerup J. Acta Endocrinol. 1974; 76:27-141

8. Primary Adrenal Insufficiency: Confirmation of diagnosis
Elevated serum ACTH
Low serum cortisol (in context of clinical condition)
Elevated plasma renin activity (an indicator of salt depletion and low blood volume) with inadequate aldosterone level
Possibly low plasma sodium/raised plasma potassium
RENIN
ALDOSTERONE

9. Screening if diagnosed ALD first – repeated until abnormal
Morning (09:00h) ACTH and cortisol may miss evolving primary adrenal insufficiency
Short Synacthen (ACTH stimulation) test
Plasma Renin Activity

10. Frequency of Primary Adrenal Insufficiency in X-ALD phenotypes
Estimated Relative Frequency
Adrenocortical Insufficiency
Childhood Cerebral
31-35%
79%
Adolescent
4-7%
62%
Adult Cerebral
2-3%
>50%
Adrenomyeloneuropathy
40-46%
50-70%
Addison only
Varies with age; Up to 50% in childhood
100%
Asymptomatic
Common before 4 years of age
> 50% (with testing)

13. J Clin Endocrinol Metab, February 2016, 101(2): 364-389

14. Management Aims
Family to understand the underlying condition and lifelong importance of adequate treatment.
Replace Glucocorticoid:
Hydrocortisone (10-12mg/m2/d) (potency = 1.0) 2-3 divided doses
Prednisolone (potency 4.0)
Replace Mineralocorticoid (salt retention)
Fludrocortisone (synthetic equivalent of aldosterone)
No restriction of dietary salt

15. Cortisol concentrations in healthy volunteers
Cortisol concentrations measured by immunoassay on thee times daily immediate-release hydrocortisone 20 – 40 mg in adrenal insufficiency patients

16. Monitoring and Adjusting Treatment
Growth
Height, Weight 3 – 6 monthly – aim to avoid excessive weight gain or growth suppression
Mineralocorticoid dose:
Blood Pressure
Plasma Renin Activity (PRA)
Glucocorticoid dose: various options
Primarily symptoms e.g. tiredness, headache – deficiency
Blood/Salivary profile: cortisol 2-4 hourly day profile

17. Drug Interactions:

18. Treatment problems
Some children don’t like hydrocortisone taste: try “Corlan” tablets - GPs like as cheap! But for buccal ulcer treatment – not GI absorption.
Hydrocortisone requires frequent doses to mimic natural cortisol diurnal rhythm ; prefer x3 /day in chidhood ? x2 /day from teenage
3) Prednisolone lasts longer (used more in teenagers & adults) but increased risks of:
Growth suppression
Weight gain / obesity
Osteoporosis
Possible Future Solution(s):
Delayed release hydrocortisone formulation – under development
Continuous subcut. Hydrocortisone infusion – like insulin for diabetics – expensive but feasible.

19. Sick day management
Treat the underlying illness if systemic with fever or vomiting (GP / hospital as necessary)
Hydrocortisone (oral) dose increase x 2 or 3
Fludrocortisone dose unchanged
Maintain adequate fluid and glucose / carbohydrate source (Dioralyte alone = insufficient glucose)
Provide :
“Hypostop” Dextrose gel
Subcut. Glucagon (to correct hypoglycaemia)
IM / (rectal) Hydrocortisone
Hospital (TWIMC letter with instructions) – don’t be shy!
Ambulance service registration as steroid dependent patient
Home/School Pack

20. Extra Precautions
Ensure routine immunisations in infancy not delayed (“because child on steroids……”)
MedicAlert or similar identification tag +/- steroid card
Steroid cover for elective surgery/anaesthetics
Carry 2 separate sets of tablets and emergency pack when travelling on holiday (especially overseas)
Extra Immunisations (for patients on steroid replacement)
Pneumococcal
Hepatitis A/B (e.g. “Twinrix”)
Influenza

21. 30 year experience – single centre
Primary Adrenal Insufficiency (Addison’s) – 5.2 AC episodes/100 patient years (111 pts)
Secondary Adrenal Insufficiency (Hypopituitary) – 3.6 AC episodes/100 patient years (319 pts)
Tertiary Adrenal Insufficiency (Glucocorticoid induced) – 15.1 AC episodes/100 patient years (28 pts)
Most precipitated by infection and in patients with co-morbidities

22. Cortisol concentrations in healthy volunteers
Newer Developments
Cortisol concentrations in healthy volunteers
Cortisol concentrations on once daily Plenadren mg in patients with adrenal insufficiency

23. Cortisol concentrations in healthy volunteers
Newer Developments
Cortisol concentrations in healthy volunteers
Cortisol concentrations on twice daily Chronocort 20mg at 23:00h and 10mg at 07:00h in patients with congenital adrenal hyperplasia

24. Capsules containing 0.5mg, 1mg, 2mg and 5mg doses of immediate release multipariculate granules

25. Thank You