Diagnosing Addison's - Addison's Disease Self Help Group

Diagnosing Addison’s: a guide for GPs Sheet 2 of 2DiagnosingAddison’s:a guidefor GPsFor further information about Addison’s,to join the group or make a donation, please visit ourwebsite at www.addisons.org.ukThe Addison’s Disease Self-Help Group works to supportpeople with adrenal failure and to promote better medicalunderstanding of this rare condition. Registered charity1106791, established 1984.The Addison’s Clinical Advisory Panel is a group ofendocrinologists with an interest in adrenal medicine.It advises the ADSHG on medical matters.This leaflet has been authored by:Prof John Wass Churchill Hospital, OxfordDr Trevor Howlett Leicester Royal InfirmaryProf Wiebke Arlt University Hospital, BirminghamProf Simon Pearce Royal Victoria Infirmary, NewcastleProf John Monson St Bartholomew’s Hospital, LondonPlease contact:ADSHG information, PO Box 1083, Guildford GU1 9HXEmail: info@addisons.org.ukWebsite: www.addisons.org.ukThis leaflet may be copied for personal use or by medicalpractitioners for the education of their patients. Otherwise,it should not be reproduced without written permissionfrom the ADSHG.n Symptoms of hypocortisolaemia or adrenal crisis, in whichnausea and vomiting are predominant features, are frequentlyattributed to gastric infection. One-third of Addison’s patientsreport receiving hospital treatment for adrenal crisis on one ormore occasions prior to their diagnosis, without their conditionbeing identified.n In pregnancy, Addison’s symptoms may be mistaken forhyperemesis and chloasma. Pregnancy, oral contraceptive orHRT usage make interpretation of serum cortisol difficult due toelevation of background CBG and delayed hepatic clearance.n Exogenous steroid usage for conditions such as mouth ulcerhas been documented to mask underlying adrenal insufficiency.Worst outcomes if missedUntreated Addison’s disease is universally fatal and thepatient may die quite rapidly from adrenal crisis.In adrenal crisis, hypovolaemic shock, cardiac arrest, strokeor other circulatory complications can occur even in young,fit patients; complications from hypoxia may leave thepatient permanently disabled. Children with adrenal crisis areparticularly susceptible to hypoglycaemia, which can causepermanent brain damage if not quickly reversed.Where the patient has severe hyponaetremia, correction canlead to cerebral oedema or central pontine myelinolysis.EpidemiologyAutoimmune Addison’s disease affects about one in 10,000individuals, with an upper estimate of around 8,400 diagnosedcases in the UK. In common with other autoimmune andinflammatory diseases (type 1 diabetes, asthma), there isevidence of increasing incidence in westernised societies.Diagnosis can occur at any age, from 5 to 80. Almost half of alldiagnoses occur outside the most common age of onset (30 -50 years).Key questions for the GP1. Does this patient have postural hypotension?2. Is this patient losing weight without trying?3. Does this patient have low/borderline blood sodium?4. Does this patient have salt, soy sauce or liquoricecravings, or increased thirst and urination?5. Does this patient have appropriate pigmentation;has there been a change in skin colour?GP follow-upThorough patient education and training is required to ensurethat:1. All patients know how to adjust their replacement steroidmedication for illness, injury or strenuous exercise2. The patient and a partner are competent to administer an IMinjection of 100mg hydrocortisone in emergencies and are fullysupplied with needles, syringes and injectable hydrocortisonesodium phosphate (Efcortesol)3. The patient understands the need to wear medicalemergency jewellery, preferably a MedicAlert bracelet.A = Always tired (94%)D = Dizzy when standing (79%)D = Drop in blood pressure on standing (77%)I = Inexplicable weight loss (86%)S = Skin colour changes (80%)O = Only eating sparingly/anorexia (76%)N = No strength in handgrip or limbs (91%)S = Sick or nauseous (73%)Further readingClinical Knowledge Summaries, Addison’s disease,http://www.cks.nhs.uk/addisons_diseaseVaidya B et al, Addison’s disease, easily missed,BMJ 2009;339:b2385 (published 2 July 2009)Baker, S & Wass, JAHW, Addison’s disease, a patient’s journey,BMJ 2009;339:b2384 (published 2 July 2009)Pulse Today, How not to miss: Addison’s disease, 1 CPD hour,http://www.pulsetoday.co.uk/how-not-to-miss-addisons-disease-1-cpd-hour/13577350.article#.UKtgJ6Vi8-gFurther information for GPs and their patients can be obtained fromthe Addison’s Disease Self-Help Group at www.addisons.org.ukDiagnosingAddison’s:a guidefor GPsThis leaflet outlinesthe role of the GPin the earlydetection ofadrenal failureAddison’s disease (hypoadrenalism) isa rare, potentially fatal condition where theadrenal glands cease to function. Life-longtreatment with replacement steroid hormonesis required.With the right balance of daily medication,people with Addison’s can expect to have anormal life span and to lead full and productivelives. It is not unknown for people with Addison’sto live into their 90s. The most famous Addison’spatient was US President John F Kennedy.www.addisons.org.uk© ADSHG/009/March 2013www.addisons.org.uk

Diagnosing Addison’s: a guide for GPs Sheet 1 of 2Symptoms and clinical signsAs well as overwhelming exhaustion, patientswith adrenal failure typically report weight loss, lossof appetite and dizziness on standing. Nausea, muscleweakness with cramps, abdominal, joint or back painsare often present. A preference for salty foods andincreased thirst are common.Key signs are deepening skin pigmentation, low bloodpressure and a drop in blood pressure on standing(postural hypotension). Symptoms reported by patientsare shown in the chart below. As this identifies, fewpatients report the full complement of symptoms.Psychosis is occasionally documented; minor depressionand tearfulness may be observed accompanying chronicexhaustion.GP role in urgent admissionsWhere the patient shows signs of adrenal crisis - typically,persistent vomiting with profound muscle weakness,hypotension, headache, extreme sleepiness or even coma - thepatient should be admitted to hospital as an emergency andif possible stabilised by a saline infusion (for volume repletion)prior to transfer.94% 91% 86% 80% 79% 77% 76% 73%SevereFatiquehyperpigmentationweaknessweightloss© ADSHG/009/March 2013dizzinessblackoutsreducedbloodpressureloss ofappetiteIf admission is delayed for any reason or if the patient is inextremis with strong clinical suspicion of hypoadrenalism,then consider a 100mg hydrocortisone injection beforetransportation to hospital.GP role in patient screeningWhere the patient is stable, the GP should assessfor clinical signs, especially:1. Measurement of blood pressure sitting and standing.Postural hypotension usually results in a 20 mmHg drop inblood pressure on standing.2. Questioning of the patient to establish if they struggle toclimb stairs, get up from a sitting/squatting position or carryweights such as the grocery shopping. (Proximal myopathy orglobal muscle weakness).3. Inspection for patchy hyperpigmentation or, in Caucasians,unusual pigmentation of the palmar creases (not present inall cases). Hyperpigmentation generally occurs in areas ofincreased friction and may be visible where clothes rub againstthe skin or on the oral mucosa, depending on the patient’snatural level of melanocytes.nauseavomitingAddison’s symptoms at diagnosis55% 54% 52% 51%difficultyconcentratingAutoimmune Addisons N = 614prompted recallmuscle/jointpainssaltcravings33% 33%headachestomachpainsPrimary care investigationsInitial laboratory investigations can be carried outin primary care. These are:1. Electrolytes (low Na, high K)n Electrolytes may be borderline/normal where the patient isnot in crisis.2. Blood glucosen Blood glucose may be borderline/low, especially in adrenalinsufficiency of pituitary origin.3. 9am cortisoln The diagnosis is highly likely if 9am cortisol is lessthan 100nmol/L - unless the patient is already on oral orinhaled steroids.n The diagnosis is unlikely if cortisol is greater than 400 nmol/L- but not excluded if the patient is acutely unwell at the time.n For values between 100 and 400 nmol/L the diagnosiscan only be excluded by a short Synacthen test (ACTHstimulation test). Patients in the early stages of disease mayhave 9am cortisol values towards the top of this range.Referral to a secondary specialistWhenever there is a real suspicion of adrenal insufficiency,the GP is encouraged to refer the patient to a specialistendocrinology unit for a Synacthen (ACTH stimulation) test.The urgency of this referral will depend on the clinical context.If the patient is hypotensive and vomiting, or where the 9amcortisol is less than 100 nmol/L, an immediate and urgentreferral is required.Associated investigations may include:n Plasma renin (must be drawn at the processing lab)n Plasma ACTHn Serum DHEA-Sn Thyroid function testsn Organ-specific antibodiesn Where pituitary involvement is suspected, furtherinvestigations of the hypothalamic-pituitary-adrenal axismay be necessary.The differential diagnosisSome of the early signs overlap with type 1 diabetes, althoughin adrenal failure the blood glucose should be normal oreven low. Excessive fatigue and sleepiness, increased thirstand urination, unexplained weight loss are common to bothconditions.In early stage autoimmune (primary) adrenal disease, thepredominant signs are usually those of mineralcorticoiddeficiency (postural dizziness, increasing thirst and urination, saltcravings). Increasing pigmentation is due to elevated pituitaryACTH, as a consequence of HPA feedback from decliningglucoocorticoid levels.In early stage pituitary disease, signs of glucocorticoiddeficiency will predominate, notably anorexia, weight loss andmuscle weakness. Hypoglycaemia may be present in children,but skin pigmentation usually remains unchanged or displays analabaster-like pallor.Adrenal destruction triggered by disseminated infections suchas tuberculosis, fungal infection or histoplasmosis is morecommon in regions such as the Indian subcontinent and LatinAmerica; mucocutaneous hyperpigmentation is more frequentlyobserved here. HIV is a growing cause of adrenal failure.Associated endocrine conditionsHypothyroidism occurs alongside autoimmune Addison’s inover 40% of patients, although one usually predates the other.Where they develop simultaneously, commencing thyroidreplacement without glucocorticoid therapy may precipitatehypoadrenal symptoms and adrenal crisis, as thyroid hormoneincreases the metabolic rate and breakdown of residual cortisol.Elevated TSH may be an indicator of hypoadrenalism in an illpatient with extreme fatigue but without the typical featuresof hypothyroidism. It may return to normal with steroidreplacement.Diabetes (type 1 or 2) occurs alongside autoimmune Addison’sin around 10% of cases. In established diabetes, a markedreduction in the insulin requirement can be a warning sign ofdeveloping hypoadrenalism.Potential pitfallsn Random (untimed) serum cortisol has a low sensitivity forAddison’s disease, especially where the patient is in the earlystages of adrenal failure. If you think of the diagnosis on clinicalgrounds then it is worth referring for a Synacthen test, unless a9am cortisol is over 400 nmol/L.n The slowly progressive nature of adrenal failure means manypatients are wrongly identified as depressive or anorexic untilintercurrent infection precipitates an adrenal crisis. Around onethirdof patients report being told that their symptoms were “allpsychological” prior to diagnosis. Some anti-depressants aresodium-depleting and may precipitate adrenal crisis in patientswith undiagnosed adrenal insufficiency.