Topics from Past Papers Flashcards
What is Coeliac disease?
T-cell mediated inflammatory autoimmune disease affecting the small bowel in which sensitivity to prolamin (gluten) results in villous atrophy and malabsorption
Presentation is bimodal (in infancy and at age 50-60) - more common in irish populations
Associations include:
- Positive family history
- HLA-DQ2 allele
- Other autoimmune disease i.e T1 DM, Graves disease, Hashimotos thyroiditis
What are the symptoms of Coeliac disease?
- Gastrointestinal symptoms
- Abdominal pain
- Distension
- Nausea and vomiting
- Diarrhoea
- Steatorrhoea (fatty stools)
- Systemic symptoms
- Fatigue
- Weight loss or failure to thrive in children
- General appearance: Check for pallor (secondary to anaemia), short stature and wasted buttocks (secondary to malnutrition), features of vitamin deficiency secondary to malabsorption (e.g bruising due to Vitamin K deficiency)
- Dermatological manifestation: Dermatitis herpetiformis (pruritic papulovesicular lesions over the buttocks and extensor surfaces of the arms, legs and trunk)
- There may be abdominal distension
What are the complications of Coeliac disease?
- Unexplained iron deficiency
- B12 or folate deficiency
- Hypersplenism (→ suspectibility to encapsulated organisms)
- Osteoperosis (DEXA scan may be required)
- Enteropathy associated T-cell lymphoma ( rare type of non-hodgkin lymphoma - likelihood is directly proportional to the strength of overall adherence to gluten free diet)
What is the diagnostic test for Coeliac disease?
First line is Anti-TTG IgA antibody ( IgA level should be measured in conjuction as Coeliac disease patients with IgA dieficient patients will have false negative anti-TTG IgA)
Anti-endomyseal antibody can be measured if IgA TTG is weakly positive
Anti-gliadin is not reccommended and HLA-DQ2 should not be done in non-specialist setting
Stool culture is necessary to exclude infection
GOLD STANDARD IS OGD and DUEODENAL/JEJUNAL Biopsy - should be referred after positive serological test (or negative test but high clinical suspicion) - should be carried out before gluten is withdrawan from diet and repeated after gluten is withdrawn
Histology from biopsy should reveal Sub-total villous atrophy (as entrocytes forming the tip of villi are destroyed), crypt hyperplasia (basal cells rapidly divide to try to compensate for distal villi cell destruction) and intra-epithelial lymphocytes
For blood test: FBC (which may show microcytic anaemia due to iron deficiency, a normocytic anaemia due to chronic inflammation or a macrocytic anaemia due to folate deficiency) - U+E and bone profile( vitamin D absorption may be impaired, LFT(albumin may be low secondary to malabsorption), Iron, B12, Folate
What is the management of Coeliac disease?
- Only management is life-long gluten free diet (patients often require education regarding what foods contain gluten)
- Patients require regular monitoring to check adherence to gluten free diet and to screen for complications
What is Crohn’s Disease?
Crohn’s disease is a chronic relapsing IBD.
Characterised by a transmural granulomatous inflammation which can affect any part of the gastrointestinal tract, commonly the ileum, colon or both
More likely in northern climates and developed countries - more common in caucasian people than in asian or black - Ashkenazi jews have 2-4x higher risk of crohns
Bimodal age of onset, most common age being between 15-40 and a smaller secondary peak between 60-80
Family history is a risk factor (10-25% of patients have a first degree relative who also suffers from Crohn’s)
What are the signs and symptoms of Crohn’s Disease?
- Gastrointestinal symptoms (crampy abdominal pain and diarrhoea)
- General appearance: Cacechtic (muscle weakness) and pale, may be digital clubbing
- Abdo: check for aphthous ulcers in mouth, may be abdo/right lower quadrant tenderness and right iliac fossa mass
- PR examination should be carried out to check for perianal skin tags, fistulae or perianal abscess
- Weight loss and fever
- Dermatological manifestations: Erthyema nodosum (painful erythematous nodules/plaques on the shins) - Pyoderma gangrenosum ( a well defined ulcer with a purple overhanging edge)
- Ocular manifestations: Anterior uveitis (painful red eye with blurred vision and photophobia) - Episcleritis (painless red eye)
- Hepatobilliary manifestations: gallstones ( more common in Crohns than in ulcerative colitis)
- Haematological and renal manifestations: AA amyloidosis (2ndary to chronic inflammation) and renal stones (more common in crohns vs ulcerative colitis)
What are the investigations in Crohn’s disease?
- Blood tests: Raised white cell count - Raised ESR/CRP - Thrombocytosis - Anaemia (2nd to chronic inflammation) - low albumin (2nd to chronic inflamm) - Iron, B12, Folate
- Stool culture necessary to exclude infection
- Faecal Calprotectin (antigen produced by neutrophils) will be raised (distinguishes IBD from IBS)
- Endoscopy with imaging required for diagnosis
- MRI is required for suspected small bowel disease
- Upper GI series may show string sing of Kantour ( string-like appereance of contrast-filled narrowed terminal ileum, suggestive of Crohn’s disease
What are the colonoscopy findings in Crohn’s disease?
- Intermittent inflammation (skip lesions)
- Cobblestone mucosa (due to ulceration and mural oedema
- Rose thorn ulcers (due to transmural inflammation) +/- fistulae or abscesses
- Non-caseating granulomas
What is the medical management to induce remission of Crohn’s Disease?
- Patients should be offered monotherapy with glucocorticoids (prednisolone or IV hydrocortisone)
- Enteral nutrition may be considered as an alternative in children (as steroids suppress growth)
- Azathioprine or mercaptopurine may be added to induce remission if there are 2 or more exacerbations in a 12-month period or the glucocorticoids cannot be tapered ( check for TPMT activity, if deficent cannot offer Aza or merca - offer methotrexate as add on therapy if aza or merca cant be tolerated)
What is medical management to maintain remission in Crohn’s disease?
- Azathioprine or mercaptopurine should be offered first line
- Methotrexate may be considered for patients who are intoleront or do not respond
What is the surgical management of Crohn’s disease?
Surgical management is rarely curative in Crohn’s unlike in Ulcerative colitis so maximally conservative
Dependent on the part of the GI tract that is affected
What is the management of peri-anal fistulae?
Drainage Seton is the management of choice for high (trans-sphincteric) fistulae
Fistulotomy is the management of choice for low (submucosal) fistulae
Sphincter saving methods include fibrin glue and fistula plug (not yet mainstream)
What is the management of peri-anal abscess?
- Should be started on intravenous antibiotics e.g ceftriaxone + metronidazole
- Require examination under anaesthetic and incision and drainage
What is hypoalbuminaemia?
Albumin is a protein synthesised by the liver which provides the blood with oncotic pressure - Deficiency in this protein leads to Oedema
Causes can be either due to impaired synthesis, increased loss, Dilution:
- Impaired synthesis
- Malabsorption i.e in Crohns
- Malnutrition
- Liver disease
- Malignancy
- Acute phase reaction e.g sepsis
- Increased loss
- Nephrotic syndrome
- Protein wasting enteropathies
- Burns
- Dilution
- Pregnancy
What is a chronic subdural haemotoma?
Chronic phase is >3 weeks after bleed - the haematoma becomes hypodesne relative to adjacent cortex
Can cause symptoms like increasing confusion, increased falls - occurs more in older people bleeding occurs slowly and symptoms might not appear for weeks
What is a Branchial cyst?
A branchial cyst is an embryological remnant from the development of the branchial arches
Manifests as a painless cystic mass anterior to the sternocleidomastoid muscle just below the ear - typically becomes apparently in early adulthood/late childhood after infection
Management is normally surgical or conservative
What is Hodgkin’s Lymphoma?
Hodkin’s lymphoma are malignant lymphomas characterised by the presence of Reed-Sternberg cells
Risk factors are: EBV, HIV, Immunosuppresion, Cigarette smoking
What are the clinical features of Hodgkin’s lymphoma?
Typically presents in young adults with cervical or supraclavicular (i.e in the anterior triangle of the neck) as a non-tender lemphadenopathy, though location of diseased nodes can vary
Alcohol induced pain is a suggestive symptom
May be symptoms caused by compression of surrounding structures e.g shortness of breath or abdominal pain
B symptoms (fever, night sweats and weight loss) occur in 30% of patients - important to examine the patient for lymphadenopathy and to check for hepatomegaly or splengamoly
How is a diagnosis of non-hodgkin’s lymphoma made?
Normally through lymph node biopsy (i.e excision biopsy) with evidence of Reed Sternberg cells being diagnostic
Blood results can predict poor prognosis via low haemoglobin and raised LDH, as they indicate high red cell turnover
Staging scans are needed to elucidate the extent of the disease
5 year surival varibale <40% to >95% depending on the type of disease
What is the management of Non-hodgkin’s lymphoma?
Treatment is usually with chemoradiotherapy
What is Rheumatoid arthritis?
Rheumatoid arthritis is a common chronic inflammatory autoimmune disease
The acute phase response of Rheumatoid arthritis is driven by the cytokine IL-6
Peak onset is in 40-60 year old - gradual onset over weeks and is consideribly more common in females (3:1) and smokers
How does Rheumatoid arthritis present in joints?
- Symmetical, polyarticular inflammatory arthiritis involving the small joints of the hand (metacarpophalangeal and proximal interphalangeal joints), wrists and feet
- Other joints become involved later as the disease progresses
- The distal interphalangeal joints usually spared in RA however which can help differentiate it from psoriatic arthritis (presents in a similiar fashion)
- The pain is inflammatory and as such is usally better with movement and associated with prolonged early morning stiffness (>30min)
- Joints are swollen, red, warn and tender on exmaination
Join pattern involvement in RA is very variable however and can take almost any form, including acute monoarthritis and palindromic rheumatism which causes recurrent, short lived(hours to days) episodes of arthritis in different joints before settling into a more permanent form
What are the specific joint deformities in Rheumatoid arthritis?
In hands:
Subluxation = partial dislocation within body
- Wrist subluxation
- Metocarpophalageal subluxation
- Swan-neck finger deformitiy (MCP felxion, PIP hyperextension, DIP hyperflexion)
- Boutonniere finger deformity (PIP flexion, DIP hyperextension)
- Ulnar deviation of proximal phalages
- Z shaped thumb
In feet:
- Hallux valgus
- Hammer Toes
- MTP subluxation
Occasionally extensor tendons of the hands and feet may rupture and require prompt surgical repair to maintain their function
Unlike seronegative spondylarthropathies, where lower back pain can be a prominent feature, RA spares the lumbar and thoracic spine - can involve the cervical spine, in particular the atlanto-axial joint C1-C2 - (as the stabilising ligaments of the joints are damaged, instability and subluxation of the A-A joint can occur → results in neck pain radiating to occiput but can also cause a myelopathy with weakness and altered sensation in upper limbs)
In RA, minor neck trauma in these patients can worsen subluxation and even cause upwards migration of the odontoid peg through the foramen magnum - C-spine imaging should be performed in any RA patient thought to be at risk
What are the peri-articular features in RA?
Carpal tunnel syndrome ( causing pain, weakness and paraesthesia in the median nerve distrubtion
Tenosynovitis ( typically of the flexor tendons in the hands, causing pain and swelling)
Bursitis (typically of the olecranon (elbow) and sub-acromial (shoulder) bursae causing pain and swelling
What are the general features of RA?
- General: Low grade fever, weight loss, fatigue
- Haem:
- Anaemia of chronic disease (most DMARDs can cause cytopenias as a side effect)
- Splenomegaly including Felty’s syndrome (triad of RA, splenomegaly and neutropenia)
- Amyloidosis - classically affects the kidneys causing nephrotic syndrome
- Generalised lymphadenopathy
- Derm:
- Rheumatoid nodules - firm dark skin nodules, usually around site of inflammation
- Small vessel vasculitis causing nailbed infarcts and arterial leg ulcers
- Raynauds syndrome
- Eyes:
- Keratoconjunctivitis sicca (dry eyes) - occur on its own or with sjogren’s syndrome with oral, genital and gastric ulcers
- Episcleritis and scleritis
- Resp:
- Pleural effusions containing rheumatoid factor
- Rhemautoid nodules may be seen on chest x-ray but are asymptomatic
- Pneumonitis leading to pulmonary fibrosis ( can also be a side effect of methotrexate)
- Osteoperosis
- Peripheral neuropathy
What are the blood test findings in RA?
- FBC - Anaemia of chronic disease is common
- Inflammatory markers - Erythrocyte sedimentation rate and CRP is raised
- Rheumatoid factor - specific for rheumatoid artheritis - Rf patients with RA+ have more systemic involvement and worse prognosis
- Anti-CCP - a positive anti-CCP is more specific than RF for rheumatoid arthritis and can support the diagnosis though does not confirm it
What are the radiological features of RA?
- Joint x-rays often initially normal but then later have:
- Soft tissue swlling
- Periarticular osteoporosis
- Juxta-articular erosions
- Narrowing of joint space
What is the symptomatic relief treatment in RA?
- Regular paracetamol and NSAIDs
- During flares, intra-articular or a course of oral steroids can be given
- Physiotherapy - exercise prescription to help maintain muscle strength around the joint and range of movement
- Occupational therapy - provide advice and physical aids to avoid putting stress on joints - during acute flares, splints can be appleid to joints
- Surgery is reserved for severly damaged joints and may include joint arthroplasty, fusion or synovectomy
What are the disease modifying anti-rheumatic drugs used in rhaematoid arthritis?
DMARDs include immunosuppresants such as methotrexate, sulfasalazine, hydroxycholoroquine and leflunomide
Give DMARDs as monotherpay first line with addition of second DMARD if remission not achieved
commence DMARDs as early as posisble after symptoms occur, ideally within 3 months
DMARDs can take seceral weeks to produce response
Can use biological agents for RA - most common are anti-TNF such as infliximab - only used when disease is severe (DAS28 >5.1) despite long term combination DMARD and taken in addition to DMARD - usually discontinue biologics if no significant improvement seen
RA patients should receive annual infleunza vaccine and pneumococcal vaccine every 5 years as per schedule - in patients on higher dose corticos or potent biologics, zoster vaccine is not reccommended
What are the consideration in RA patients trying to get pregnant?
Washout period of at least three months pre-conception for methotrexate - methotrexate should be avoided during pregnancy due to the risk of tetratogenicity
if patient becomes pregnant on methotrexate, refer to foetal medicine expert - in planned pregnancy, washout procedure should also be completed for patients on leflunomide and it should be avoided in pregnancy
Common for patients to have flares during postpartum - if mild, just paracetamol with weak opiod can be suffiecint - low dose prednisolone can be added to control flares
Hydroxychloroquuine and.or sulfasalzine with concomitant folic acid can be contiuned during pregnancy but should be initated by the rheum team
What is Nephrotic syndrome?
Nephrotic syndrome is a clinical syndrome that arises secondary to increased permeability of serum proteins through a damaged basement membrane in the renal glomerulus
Cytokines damage podocytes causing them to fuse together and destroy charge of the glomerular basement membrane → increased permeability to plasma proteins → massive protein loss in urine therefore serum albumin levels are reduced beyond the synthetic ability of the liver → patients with marked oedema as less albumin = less oncotic pressure - this leads to fluid leaking out into the interstitium - the liver attempts to maintain oncotic pressure by increasing synthesis of lipoproteins which causes hyperlipdaemia
What are the clinical features of Nephrotic syndrome?
- Proteinuria (>3-3.5g/day)
- Oedema
- Hypoalbuminaemia
- Hyperlipidaemia
- Lipiduria
- frothy appearence of urine
What are the causes of Nephrotic syndrome?
Most common cause is membraneous glomerulonephritis in adults. In children, the most common cause is minimal change disease
- Systemic disease
- Diabetes mellitus (glomerulosclerosis)
- SLE (membranous)
- Amyloidosis
- Minimal change glomerulonephritis
- Associated with upper resp tract infection
- Biopsy will show fusion of podocytes on electron microscope, normal under light microscopy
- Treat with steroids
- 1% go on to have end-stage renal failure
- Membranous nephropathy
- Associated with cancers (lung, colon, breast), inflammatory conditions (SLE, thyroid disease), infections (Hep B) and drugs (penicillamine and gold)
- Biopsy will show subepithelial immune complex deposits
- 40% have spontaneous remissions
- Focal segmental glomerulosclerosis
- More common in afro-carribbean populations
- associated with berger’s disease, sickle cell, HIV
- On biopsy will show focal scarring, IgM deposition
- Treat with steroids or cylophosphamide/ciclosporin
- 30-50% progress to end stage renal failure
- Membranoproliferative/mesangiocapillary
- Less common - presents with both nephritic and nephrotic
- associated with hep b hep c endocarditis
- 50% progress to end-stage renal failure
What are the clinical investigations and presentation of nephrotic syndrome?
- Periorbital and peripheral oedema
- Urine dipstick will show proteinuria and urinalysis will show raised albumin-creatanine ratio
- Renal biposy is indicated in all adults but should only be done in children with atypical presentation (steroid unresponsive, haematuria, under 1 years old and over 12 years old)
What are the complications of nephrotic syndrome?
- Infection (due to urinary loss of immunoglobulins)
- Venous Thromboembolism (due to urinary loss of thrombin III)
- Hyperlipidemia (increased hepatic production of lipids)
What is the management of nephrotic syndrome?
High dose steroids which should be tapered according to clinical response
What is Nephritic syndrome?
Nephritic syndrome is a condition causing haematuria, non-nephrotic range proteinuria (mild/moderate vs severe in nephrotic) and Hypertension. It also causes Oliguria (less than 300ml per day urine) and red cell casts in urine
How does nephritic syndrome present?
Can be viewed as a spectrum from nephrotic to nephritic:
- Pure nephrotic syndrome - minimal change disease
- Nephrotic syndrome with some haematuria - mambraneous glomerulonephritis, focal segmental glomerulosclerosis
- Nephritic syndrome with nephrotic-range proteinuria: membrano-proliferative ( aka mesangio-capillary) glomerulonephritis
- Pure nephritic syndrome: post streptocloccal glomerulonephritis, IgA nephropathy/Henoch-schonlein purpura, infective endocarditis, goodpasture’s disease, vasculitis
Can distinguish between post-streptocloccal glomerulonephritis and IgA nephropathy by the fact that post-strep glom typically presents 3-4 weeks after sore throat/skin infection where IgA nephropathy typically presents 3-4 days after mild URTI
What are the differntials of nephritic syndrome?
Remember SHARP AIM
- S - SLE
- H - Henoch-schonlein purpura
- A - Anti-glomerular basement membrane disease (aka goodpasture’s disease)
- R - Rapidly progressive glomerulonephritis
- P - Post streptococcal GN
- A - Alport’s syndrome
- I - IgA nephropathy (aka berger’s disease)
- M - Membranoproliferative GN
What is Molar pregnancy?
Molar pregnancy (aka hydatidiform mole) is when from conception there is an imbalance in the number of chromosomes from the mother and father
Highest risk is at each end of fertility (under 16, over 45)
Can be a complete mole or patial mole
What are the features of a complete mole?
- Complete mole is formed from 1 sperm and an empty egg with no genetic material
- Sperm then replicates to give a normal number of chromosomes → diploid and all chromosomes are of paternal origin
- There is no foetal tissue present - just proliferation of swollen chorionic villi
What are the features of a partial mole?
- Partial mole is formed from 2 sperms and a normal egg
- Both paternal and maternal genetic material is present
- Variable evidence of foetal parts
What is the presentation of Molar Pregnancy?
- Vaginal Bleeding
- Nausea
- Hyperemesis gravidarum
- Thyrotoxicosis (because hCG is closely related to TSH and can therefore activate it’s receptors)
- Uterus is larger than expected for gestational age. This enlargement is due to excessive growth of trophoblasts and retained blood
What are the investigations of Molar pregnancy?
- B-hCG levels are often much higher than would be expected in a normal pregnancy
- Trans-vaginal ultrasound is also used and in complete molar pregnancy shows a “snowstorm” appearance, low resistance of blood vessel flow and absence of a foetus
What is the management of Molar pregnancy?
- Requires urgent referral to a specialist centre for treatment as to reduce the time-frame for potential complications such as choriocarcinoma or invasion from developing
- Molar pregnancies cannot survive so managed with suction curettage to remove them from uterus - when fertility does not need to be preserved, then hysterectomy can be preformed
- Surveillance is reccommended - two weekly serum and urine hCG until back to normal - if partial mole, then repeat hCG done 4 weeks later, if normal patient is dicharged from surveillance - in complete mole have to send monthly repeat hCG samples for at least 6 months
What is Hyperemesis Gravidarum?
Hyperemesis gravidarum is severe vomiting with onset before 20 weeks of gestation
It is severe enough to require admission to hospital and is a diagnosis of exclusion
What are the differentials for Hyperemesis gravidarum?
- Infections: Gastroenteritis, UTI, hepatitis and meningitis
- Gastrointestinal problems: Appendicitis, cholecystitis, bowel obstructions
- Metabolic conditons: Diabetic ketoacidosis, thyrotoxicosis
- Drug Toxicity
- Molar pregnancy (abnormally high level of beta-hCG due to gestational trophoblastic disease can cause severe nausea and vomiting)
What is the management of Hyperemesis Gravidarum?
Generally supportive and includes the following:
- Fluid replacement therapy with normal saline
- Potassium chloride as excessive vomiting usually causes hypokalaemia
- Anti-emetic medications such as cyclizine (first line), promethazine, metoclopramide or prochlorperazine - Ondansetron or Domperidone may be used in severe cases
- Thiamine and folic acid to prevent development of Wernicke’s encephalopathy
- Antacids to relieve epigastric pain
- Thromboembolic stockings and LWMH as there is increase risk of VTE - due to combination of pregnancy, immobility and dehydration
What are the complications of Hyperemesis Gravidarum?
- Gastrointestinal problems: Mallory-weiss tears, malnutrition and anorexia
- Dehydration related to ketosis and VTE
- Metabolic disturbance such as hyponatreamia, Wernicke’s encephalopathy, kidney failure, hypoglycaemia
- Psychological sequelae such as depression, PTSD and resentment towards the pregnancy
- If condition is severe, foetus may be affected due to maternal metabolic disturbance - complications include low birth weight, intrauterine growth restriction and premature labour
What type of white blood cell type is elavated in strongyloides infection?
Eosinophils
What is Pancytopenia?
It is when full blood count shows:
- Anaemia (low RBC)
- Thrombocytopenia (low platelets)
- Leukopenia (low WBC)
What are the causes of Pancytopenia?
- Causes of decreased marrow haematopoetic function
- Chemo and radiotherapy (can be transient)
- Vitamin B12 and folate deficiency
- Marrow infiltration by haem malignancies (leukaemias or lymphomas)
- Myelofibrosis, in which there is progressive marrow fibrosis
- Multiple myeloma (a plasma cell dyscrasia)
- Parvovirus infection in haemolytic disease (such as sickle cell anaemia)
- Inherited causes of marrow failure
- Fanconi’s anaemia (autosomal recessive condition) and dyskeratosis congenita (x-linked)
- Increased desturction/sequestration of blood cells peripherally
- seen in conditions affecting the liver (hep b/c, autoimmune hepatitis and cirrhosis)
- Immune destruction of blood cells - occurs in drug induced pancytopenia (secondary to e.g sulphonamide or rifampicin
What are the causes of Neutrophilia?
- Severe stress
- Trauma
- Surgery
- Necrosis
- Burns
- Haemorrhage
- Seizures
- Active inflammation
- Polyarteritis nodosa
- Myocardial infarction
- Disseminated malignancy
- Corticosteroid use (less common)
- CML(less common)
What are the causes of neutropenia?
- Severe Sepsis
- Viral Infection
- Drugs
- Marrow failure (due to malignancy or infiltration)
- Hypersplenism (less common)
- Fely’s syndrome (less common)
- SLE (less common)
What are the causes of agranulocytosis?
- Drug causes:
- Carbamazepine
- Carbimazole
- Clozapine
Associated with depleted levels of basophils and eosinophils
What are the causes of lymphocytosis?
- Acute viral infection (especially EBV and CMV)
- Chronic atypical infection (tuberculosis, brucella, toxoplasmosis)
- Lymphoproliferative disorders (chronic lymphocytic leukaemia and lymphoma)
What are the causes of eosinophilia?
- Infections e.g parasitic worms
- Allergy including drug reactions
- Inflammatory diseases e.g eosinophilic granulomatosis and polyangitis
What are the causes of thrombocytopaenia?
Low platelet count can either be caused by decreased production (marrow disease or myelosuppresiv drugs) or increased destruction (immune-regulated, hypersplenism, consumption)
It is distinguished by functional thrombocytopenia in which platelet count is normal but platelet pattern bleeding occurs (such as Von willebrand disease and inherited platelet abnormalities)
What is adrenal insuffiency?
Adrenal insufficiency occurs where the destruction of the adrenal cortex leading to a reduction of glucocorticoid production
Can be primary (addison’s disease) or secondary (due to insufficient pituitary or hypothalamic action on adrenal glands)
