Managing Addison s Disease
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1 Managing Addison s Disease Dr Charles R Buchanan Consultant Paediatric Endocrinologist Kings College Hospital, London Thomas Addison Guy s Hospial Described Symptoms 1855
2 My experience 25 years as a Paediatric Endocrine Consultant - approx 3.5 million population serving Kent / Sussex / Surrey 3 families each with 2 boys ALD 2 adolescent presentation (mild) 4 prepubertal -severe 1 successful BMT 15 Primary Addison s (1 T1 diabetes; 2 APECED) ~ 75 patients with Congenital Adrenal Hyperplasia = primary adrenal insufficiency- best basic practice experience A few really rare congenital adrenal insufficiency disorders
3 The Pituitary-Adrenal-Renal Axis Arterial blood pressure tone and blood glucose Kidney salt retention to support water retain and BP Primary adrenal disorders in general do not affect the medulla (adrenergic responses to stress)
4 ALD progressively destroys the Adrenal cortex through accumulation of VLCFAs with loss of glucococorticoid and mineralocoticoid function in no particular order.
5 Presentation of Addison s: Symptoms: Excess skin pigmentation, postural hypotension, non-specific fatigue, abdo pains, nausea, vomiting, low grade fever Crisis / collapse: Dehydration / HypoNa / Hyper K / Hypoglycaemia coma Death! Screening if diagnosed ALD first repeated until abnormal: - morning (9.00h) ACTH /cortisol may miss evolving adrenal insufficiency - Short Synacthen test (cortisol response) - Plasma Renin Activity? Raised may indicate mineralocorticoid deficit independent of glucocorticoid status
6 Addison s disease: Confirmation of diagnosis Elevated serum ACTH Low 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 Aetiology determined by P450 steroid antibodies (auto-immune) +/- associated AI syndromes VLCFA raised (males) Genetic testing (e.g. NROB1in congenital adrenal hypoplasia) Assorted metabolic disorders may be multisystem
7 :
8 Management aims from outset: 1) Family to understand the underlying condition and lifelong importance of adequate treatment 2) Replace Glucocorticoid: Hydrocortisone (10-12 mg/m2/day) (potency = 1.0) x2 or 3 doses (Cortisone acetate) x 0.8 Prednisolone x 4 3) Replace mineralocorticoid (salt retention) Fludrocortisone (synthetic equivalent to aldosterone) No restriction of dietary Salt
9 Treatment: Mineralocorticoid replacement: Fludrocortisone microg oral once daily am. Adjust according to: Plasma Renin activity (PRA) (Blood pressure)
10 Treatment : Glucocorticoid Delayed release Hydrocortisone Conventional Hydrocortisone x3 doses / day Once daily before bed Mah, PM et al Clin Endo : New Innovations: Plenadren / Chronocort Twice daily split dose
11 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 / cortisone (2-4 hrly day profile)
12 Drug Interactions:
13 Treatment problems 1) Some children don t like hydrocortisone taste: try Corlan tablets - GPs like as cheap! But for buccal ulcer treatment not GI absorption. 2) 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): 1) Delayed release hydrocortisone formulation under development see previous 2) Continuous subcut. Hydrocortisone infusion like insulin for diabetics expensive but feasible.
14 30 year experience - single centre: Primary Adrenal Insufficiency (Addison s) 5.2 AC episodes /100 patient years (111pts) 2ary Adrenal Insufficiency (hypopituitary) 3.6 AC episodes /100 patient years (319 pts) 3ary Adrenal Insuffiency (glucocorticoid-induced) 15.1 AC episodes /100 patient years (28 pts) - most precipitated by infection and in patients with comorbidities
15 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 ) Home / Subcut. Glucagon (to correct hypoglycaemia) ) School IM / (rectal) Hydrocortisone ) Pack Hospital (TWIMC letter with instructions) don t be shy! Ambulance service registration as steroid dependent patient
16 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 (TWIMC) Carry 2 separate sets of tablets and emergency pack when travelling on holiday (especially overseas) Extra Immunisations (for patients on steroid replacement: Pneumococcal pneumonia Hepatitis A / B (e.g. Twinrix ) Influenza
17 Patient support:
18 : January 2016
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