Nephrology Flashcards
What genetic pattern of inheritance does Polycystic Kidney Disease have? What are the main genetic mutations?
Autosomal Dominant
PKD1/PKD2 - polycystic (ciliopathies)
Which mutations convey a poorer prognosis in PCKD
Truncating mutations
PKD1
Early manifestation of PCKD
Hypertension (with normal eGFR)
Extra-renal manifestation of PCKD
CNS: Cerebral aneurysm CVS: Valvular disease, cardiomyopathy, AF, aortic dissection and aneurysm Hepatic Cysts Pancreatic Cysts (IPMN) Seminal vesicle cysts
Main risk factor for progression/poor prognostic factors for PKCD
Male Early onset of symptoms Kidney size PKD1/Truncating mutations Proteinuria
Diagnostic Criteria for PKCD (with and without family history)?
\+ Family history >/= 3 cysts ( 15-39) >/= 2 cysts in both kidneys (40-59) - Family history >/= 10 cysts each kidney \+ bilateral kidney enlargement
Can use CT/MRI if needed
Can use genetic testing if necessary
Pharmacological management in PCKD
> CVS
> Targeted
RAAS Blocker (Ace inhibitor/ARB)
Tolvaptan (V2 vasopressin antagonist)
> Earlier treatment associated with more benefit
> eGFR <90, + eGFR progressively worsening by 2.5-5ml/min/yr over 5 years.
Main adverse effects of tolvaptan include: Polydipsia, polyuria/nocturia and LFT derangement
Thiazide induce hyponatraemia time frame
Most commonly occurs within 2 weeks of commencing or with intercurrent illness.
Treatment for PCKD
BP control <110/75
Reduce NA
Increase fluid intake
Tolvaptan
IGA nephropathy secondary causes
ETOH
Coeliac Disease
Treatment for IGA nephropathy
ACE to decrease proteinuria - BP target <130/80
Transplant
No benefit to immunosuppression
Acute allograft dysfunction
First 7 days: Ureteric obstruction/HLA mismatch
1-12 weeks: Acute rejection
AIN findings
Raised Cr Eosinophilia Urine sediment: WCC/RCC/WC casts Evidence of tubulointerstital damage Raised fractional sodium
Resistant Hypertension
Not complete
A C D > Not within limits despite triple therapy Add in
Note refractory, not response to 5 drugs.
RTA
Not complete
1: Hypokalaemia. Impaired hydrogen secretion (distal)
2: Hypokalaemia (Proximal). Impaired Bicarb reabsorption. Raised urinary PH.
4: Hypoaldosteronism
Histological finding of Amyloidosis affecting the kidney
Proteinuria only
Nodular Glomerulosclerosis
Congo red staining
Note often stem with cardiac involvement
Rapidly progressive glomerulonephritis causes
Anti-GBM
Small vessel vasculitis (ANCA)
Cryoglobulinaemia
Lupus Nephritis
RPGN is a clinical syndrome characterised by evidence of GN (haematuria/proteinuria/leukocytes in urine) and progression to kidney failure in a short period of time.
Most common causes of Nephrotic Syndrome in adults?
Secondary causes
Diabetes (Also most common overall)
Infection
Autoimmune disease
Primary causes
Minimal change disease
Focal segmental glomerulosclerosis (most common)
Membranous nephropathy (most common)
Membranoproliferative glomerulonephritis:
Nephrotic Syndrome
Nephrotic range proteinuria: 3500mg/24 hr or P:Cr 3000mg/g
Hypoalbuminaemia: <35
Oedema
Hyperlidipidaemia
Treatment for neprhotic syndrome
Treat cause
Statins (Hyperlipidaemia +/- treatment for triglycerides)
Anticoagulant in patients with additional risk factors or low risk with albumin <28 (prothrombotic tendency)
Low salt diet and diuretics (oedema)
Note patients with nephrotic syndrome are also more likely to develop infections ? due to loss of immunoglobulins through the glomerulus.
Nephritic Syndrome
Haematuria (+/- dysmorphic eryhtrocyte casts)
Proteinuria
+/- leukocytes
Clinically
Hypertension
Oedema
Kidney Failure
Reflects proliferation in the glomeruli.
Investigation for nephrotic syndrome?
Usually requires a kidney biopsy to diagnose
●Glycated hemoglobin (HbA1C, to diagnose diabetes)
●Antinuclear antibody and anti-double stranded DNA (dsDNA) antibody
●Anti-PLA2R autoantibody
●In patients older than 50 years – Serum free light chains and serum protein immunofixation
●Tests for hepatitis B and C viruses and HIV
●Serum C3 and C4 complement levels
Which cause of nephrotic syndrome is most likely to cause renal vein thrombosis>?
Membranous nephropathy
Seek secondary causes particularly occult malignancy
Treatment options for Membranous Nephropathy
1/3 spontaneous remission Persistent disease after 6-12 months or thromboembolic event RAS blockade Immunsuppression Rituximab (esp if PLAR2 +)
Secondary causes of minimal change disease
Malignancy - Hodgkins lymphoma - Thymoma Medications - NSAID's - Lithium - Pamidronate - Interferons
Treatment of minimal change disease
Initially: Glucocorticoids
Relapsing: Cyclophosphamide, calcinuerin inhibitors, mycophenolate or rituximab
Risk factors for progression of renal impairment
1) Renal impairment i.e GFR <90
2) Proteinuria (predicts ESRF and reducing it delays ESRF)
3) Diabetes
4) Hypertension
Mainstay of treatment for proteinuria in non-diabetic patients
Ace Inhibitor and salt restriction
Which anti-hypertensives reduce proteinuria and thus progression to renal failure
ACE inhibitor or ARB
- Reduce progression to ESRF
- Reduced cardiovascular death
Target BP in diabetic patients (no-nephropathy and nephropathy?)
No nephropathy: <130/85
Nephropathy: <125/75
Note blood pressure control has the greatest effect on delaying progression to ESRF in diabetics. Microvascular endpoints tight BP control is better than glycemic control.
Target BP in proteinuria?
<125/75
What is the most likely cause of death in a patient commencing dialysis?
Cardiovascular event
Need to monitor and control cardiovascular risk factors
Kidney biopsy findings in RPGN
Crescent formation
Specific diagnosis of cause is made with IF
Treatment of patient’s with non-infectious cause of RPGN
High dose pulse IV steroids then transition to oral steroids
- Pauci-immune GN: Cyclophosphamide/Rituximab
- ANti-GBM: Plasmapharesis in the context of pulmonary haemorrhage or rapid kidney failure to remove circulating antibodies
RPGN + Pulmonary Haemorrhage
Anti-GBM disease (Goodpastures)
Antibody against type IV collagen –> bind –> inflammatory response.
RPGN + Pulmonary Haemorrhage
Anti-GBM disease (Goodpastures). Cause of RPGN in young patients.
Antibody against type IV collagen –> bind –> inflammatory response.
Positive antibody for Anti-GBM 1
Kidney biopsy: crescents with linear deposition of immunoglobulin
Complement level = normal
Treatment: Plasmapharesis (to remove circulating antibodies), steroids and cyclophosphamide.
Pauci-immune glomerulonephritis causes and associations
Caused by microscopic vessel vasculitis affecting the kidney –> necrotising lesions but no immune deposits.
+/- systemic vasculitis
Complement levels normal.
Associated with
Granulomatosis Polyangitis (URT - C-ANCA (Pr3ANCA) +
Granulomatosis Polyangitis with eosinophils (Asthma/eosinophils)
Microscopic Polyangitis (Haematuria - PANCA (MPO ANCA) +
Treatment
Induction: Steroids + Cyclophosphamide +/- plasmapheresis
Rituximab for mild disease
Maintenance with azathioprine/mycophenolate/methotrexate
Pathophysiology of IGA Nephropathy
Abnormal IGA (Galactose deficient) –> Body forming antibodies against same –> immune complex formation –> inflammatory lesions in the glomerulus (or extra-renal sites in the context of HSP).
Classical presentations of IGA Nephropathy (two)
1) Asymptomatic microscopic haematuria
2) Haematuria post URTI (synpharyngitic nephritis)
Finding on microscopy of IGA Nephropthy
Mesangial proliferation and deposition of IGA
Crecent formation may be occasionally seen –> RPGN
Treatment for IgA Nephropathy
If proteinuria then commence on ACE
Can use steroids for six months
Which classes of lupus nephritis do you commence steroids for?
Most of III: Focal, proliferative <50% gloms involved
All IV: Diffuse, proliferagtive >50% gloms involved
V: Membranous LN If neprhotic range proteinuria
Induction: glucocorticoids + cyclophosphamide/mycophenolate
Infection related glomerulonephritis causative organisms
Streptococcus (onset 1-6 weeks post)
Staphylococcus (onset at time of infection)
Rarely gram negative organisms
Infection related glomerulonephritis diagnosis
Strep related: Anti-streptolysin-O antibodies or Anti-DNAase antibodies
Other
- Cultures to identify potential inciting organism
- Depressed complement levels, esp C3
- Kidney biopsy: diffuse endocapillary proliferation and exudative glomerulonephritis and C3 dominant IF staining (forming humps in a subepithelial location)
Membranoproliferative glomerulonephritis causes
Immune complex deposition - Monoclonal gammopathy - Autoimmune disease (SLE) - Hepatitis C Activation of the alternative pathway - Dense deposit disease - C3 glomerulonephritis
Membranoproliferative glomerulonephritis findings on biopsy
Immunoglobulin deposition +/- complement deposition
Mesangial and endocapillary proliferation with thickening of the basement membrane.
Glomerulonephritis with reduced complement levels
Infection related glomerulonephritis
Lupus nephritis
Membrano proliferative nephritis
Glomerulonephritis with normal complement levels
IgA Nephropathy Membranous nephropathy Anti-GBM1 Pauci-immune glomerulonephritis Minimal change disease FSGS
Hallmark of FSGS
Segmental scars in some glomeruli. Podocyte effacement but no immune deposits.
What type of collagen is affected in all port syndrome?
Type IV (similar as that affected in Anti-GBM disease or good pastures syndrome).
Elevation of which parameter carries this highest risk of mortality in dialysis patients?
Phosphate
How to reduce phosphate in dialysis patients?
1) Phosphate binder with food
2) Prevent hyperparathyroidism
- giving vitamin D
- Consider calcimimetics or PTH
Main reason to treat elevated phosphate in dialysis patients?
Reduce the risk of cardiovascular disease
Blood pressure targets
<140/90
<130/80 (diabetics)
Treatment for hypertension
1) ACE/ARB
2) Calcium channel blocker
3) Diuretic
*can individualised based on patient profile i.e for patient with BPH consider using prazosin.
Note: Three drugs at half standard dose will be more effective than one drug at maximal dose
Which anti-hypertensive to consider adding in context of resistant hypertension (hypertensive despite 3 agents)
Spironolactone (Rehot study) best add in if already on 2/3 agents.
Most common presentation of Conn’s
Hypertension and normokalaemia
Note severe = hypertension and hypokalaemia
HB target for patients on dialysis
110-130
When to given iron replacement therapy in CKD patients
HB <110
TSAT <30%
Ferritin <500
Given IV iron rather than oral iron as GIT absorption of iron insufficient to keep up with demand
In dialysis patients aim;
Ferritin >200
TSAT > 20%
What effect does vitamin D have on calcium and phosphate?
Gut absorption:
- Increase absorption of calcium and phosphate
Urinary losses:
- Reduces urinary losses of calcium and phosphate
Vitamin D = interested in building bone
What effect does Parathyroid hormone have on calcium and phosphate?
Urinary losses:
- Reduced urinary losses of calcium
- Increased urinary loss of phosphate
PTH is concerned with maintaining serum calcium homeostasis.
Initial investigation for primary hyperaldosteronism (conn’s syndrome)
Morning blood sample in seated patient
- Plasma aldosterone concentration
- Plasma renin activity
- ensure patient off eplenerone/aldosterone blockade/ amiloride
PAC/PRA >555 pmol/ng/ml = further investigation for primary hyperaldosteronism
Confirmatory test for primary hyperaldosteronism (conn’s syndrome) on finding of elevated PAC/PRA
1) Saline suppression test
(Normally bolus of salty water would decrease renin and thus aldosterone production)
2) Adrenal CT scan
3) Adrenal venous sampling to determine if unilateral or bilateral
Treatment for primary hyperaldosteronism
1) Unilteral: Surgical resection
2) Bilateral: Mineralocorticoid receptor antagonist.
Indications that increase in Cr is due to AKI rather than CKD
Time frame <3 months Absence of 1) anaemia 2) elevated phosphate 3) elevated parathyroid hormone 4) small kidneys
KDIGO staging of AKI
Stage 1) 1.5-1.9 reference value
Stage 2) 2.0-2.9 reference value
Stage 3) >3.0 times reference value
Causes of ATN
1) Ischaemia
2) Nephrotoxins
3) Pigment nephropahty
- Hb
- Myoglobin
- Bili
Treatment for AKI
1) Balanced crystalloid (Hartmanns)
- Less dialysis
- Lower K
- Less acidosis
2) Treat the cause
Tumor Lysis Syndrome
1) Elevated phosphate
2) Elevated potassium
3) Low Calcium
4) High urate
5) High LDH
Prevention of TLS
1) Hydration
2) Allopurinol (xanthine oxidase inhibitor)
3) Urinary alkalisation
4) Rasburicase
Hepato-renal syndrome
1) Urinary sodium <10
2) Falling GFR
3) No blood or protein in urine
4) Normal RUS
Treatment for hepatorenal syndrome
1) Trial of volume (cease diuretics, give fluid)
2) Terlipressin
3) Dialysis then liver transplantation
When does serum creatinine in radio-contrast nephropathy peak?
Peaks 5-7 days post bolus
Resolves within 14 days
Main cause of nephrotic syndrome in childhood?
Minimal Change Disease
Flattening of podocytes on EM
Responds well to oral steroids (not so in adults)
Treatment for Minimal Change Disease in adults?
Steroids
If no response then consider cyclophosphamide or cyclosporine
Poor prognostic factors in FSGS
1) Nephrotic range proteinuria
2) Hypertension
3) Decreased GFR
4) Interstitial fibrosis on biopsy
Which GN has the highest recurrent rate in transplant
FSGS
Treatment for FSGS
1) Prednisolone 3 months
2) Cyclophosphamide or cyclosporin for steroid non-responsive
Primary Membranous Nephropthy finding on histology
Thickened GBM
Intra-membranous Ig deposits and spikes
Utility of PLA2R antibody in Membranous Nephropathy
1) Diagnostically: does not remove
2) Recurrence: In treated or transplanted.
Most common cause of nephritic syndrome?
IgA Nephropathy
Most common cause of RPGN
Anca associated vasculitis
Investigations in RPGN
1) Renal biopsy
2) SLE serology
3) ANCA
4) Anti-GBM antibodies
A-HUS diagnosis
1) Thrombocytopenia \+ 2) Haemolysis \+ 3) End organ damage: kidney/neurological/GIT/cardiac
A-HUS treatment
1) Ecluzilmab MAB to C5a
Scleroderma renal crisis
1) Acute onset Hypertension
- Hypertensive encephalopathy
- Hypertensive retinopathy
2) Acute onset Renal failure
Scleroderma renal crisis risk factors
Risk factors
- More common in diffuse cutaneous SSc
- within 5 years of diagnosis (early manifestation of disease)
- anti-RNA polymerase III
- Glucocorticoid use
- Cyclosporin use
Scleroderma renal crisis treatment
1) Captopril
- low dose 6.25 if normotensive
- high dose 12.5 if hypertensive
Which immunosuppressant used in kidney transplants has the highest risk of diabetes?
Tacrolimus (Beta cell toxin - impairs pancreatic production)
Which GN do you use steroids post transplant?
IgA nephropathy
Induction therapy for kidney transplant
Basiliximab (Anti-CD25, bind to IL2 receptor)
Found to reduce acute rejection
Main use of ATG in kidney transplant
Steroid resistant rejection
Note increased risk of post transplant lymphoproliferative disorders with ATG if EBV donor positive but recipient negative
Mechanism of action of Tacrolimus/Cyclosporin
Calcinuerin Inhibitor
Note significant nephrotoxicity
Which immunosuppressant can you use in kidney transplant patient with neutropenia
Calcineurin Inhibitors (do not suppress bone marrow) Cytopenias common with Mycophenolate (approx 2-6 months)
Combination of immunosuppressives used in pregnancy
Calcineurin inhibitor (Tac or Cyclo), Azathrioprine (Switch Mycophenolate for Aza) and Prednisolone
Mechanism of action of Sirolimus/Everolimus
mTOR inhibitors
Note benefits include
- Reduced risk of cancers particularly reduced skin cancer risk
Causes of death in patient with kidney transplant (1st year then after the 1st year)?
Nb: Death with kidney graft loss is the main cause of graft loss overall
1) 1st year
- Cardiovascular
- Infection
- Cancer
2) After 1st year
- Cancer
- Cardiovascular
- Infection
Causes of death censored kidney graft loss (1st year then after the 1st year)?
1st Year 1) Graft thrombosis/technical graft loss 2) Rejection 3) GN After 1st T=Year 1) Chronic allograft nephropathy 2) GN
Risk factors for ATN post transplant
1) Deceased donor (very uncommon with live donor)
2) AKI in donor
3) Increasing age of donor
4) Length of cold ischaemia time
Investigation for suspected graft thrombosis
- Doppler ultrasound
- MAG-3 scan (nuclear medicine investigation)
Causes of worsening kidney graft function in 1st year
1) Acute rejection
2) CNI toxicity
3) BK virus
4) Renal artery stenosis
5) Obstruction/leak
6) Recurrence of disease
Which nephropathies are most likely to recur early post transplant
1) MPGN
2) aHUS
3) FSGS
4) IGA Nephropahty
5) ANCA associated
Investigation for suspected acute rejection
1) Biopsy
Risk factor for acute kidney graft rejection
1) Prior sensitisation
- transfusion
- pregnancy
- previous transplant
2) Young recipient older donor
3) Ischaemia time
4) Higher HLA mismatch
Treatment of acute kidney graft rejection
1) T-Cell Mediated
- Pulse methylprednisone
- Optimise immunosuppression
- ATG if steroid resistant
2) Antibody mediated
- Exchange transfusions
- IVIG
Treatment for BK associated nephropathy
1) Reduce immunosuppression
2) Consider IVIG/Steroids if element of acute rejection from biopsy
Prophylaxis for CMV in kidney transplant based on Donor and Recipient CMV status
1) D+R-: 6 months prophylaxis
2) D-R+ or D+R+: 3 months
3) D-R-: None required unless giving ATG
Malignancies with the highest incidence post transplant
1) NHL
2) Melanoma
Pathophysiology underlying ATN
ATP depletion which leads to hypoxia/oxidative stress which leads to necrosis/apoptosis.
Drugs that most commonly cause AIN
NSAIDs penicillins and cephalosporins, antimicrobial sulfonamides, ciprofloxacin and other quinolones, rifampicin diuretics cimetidine allopurinol proton pump inhibitors (PPIs) indinavir, and 5-aminosalicylates
Treatment for calcium oxalate stones
1) Hypercacliuria
Thiazide diuretics (induce hyponatraemia –> increased reabsorption of calcium)
2) Hyperoxaluria
Reduce oxalate consumption (rhubarb, chocolate and spinach)
Commence on calcium citrate or colestyramine
Treatment for low urinary citrate
Reduce animal protein
Alkalise serum with potassium citrate or sodibic
Treatment for struvite stones
Treat UTI (UTI predisposes to stone formation) Surgical removal if stone formed
Uric acid stones treatment
Maitain urine output 2L/day
Alaklise urine
Treatment for cysteine stone
Urinary alkalisation
Indication for kidney biopsy in diabetes with pre-existing diabetic nephropathy.
Dependent on the stem
- Persistent haematuria (looking for alternative causes of nephritic syndrome)
- ANCA with active urinary sediment and or features of vasculitis.
Note: Main prognostic element of diabetic nephropathy is progression of proteinuria while on RAS blockade.
Biopsy in acute rejection of allo-graft in kidney transplant
T-cell
Criteria for Acute renal allograft rejections
1) Deterioration in allograft function
+
2) Specific pathological changes in the graft
Two principal histological forms of acute rejection
1) Acute T cell-mediated cellular rejection
- Can develop at any time
- Lymphocytic infiltration of the tubules and interstitium (CD4/CD8)
2) Antibody mediated rejection (3-10% all transplants)
- Morpholgic evidence of acute tissue injury
- Circulating donor-specific antibodies
- Immunological evidence of antibody-mediated rejections including C4d deposition in the allograft
Main cause of EPO resistance in ESRD
Inflammation
Indication for Iron Infusion in patients with ESRD
1) Hb <100 TSAT <30 and Ferritin <300
2) Hb >100 TSAT <20 Ferritin <200
* Generally TSTA >30 Ferritin >300 = iron replete. If anaemia then use ESA.
Note: high circulating PTH may cause inhibition of early erythroid precursors/RBC survival
At what Hb threshold should you not give EPO?
Hb >120 (increased risk of stroke)
The main benefit for using EPO analogues in the management of CKD
Decrease in left ventricular hypertrophy.
Not clearly shown to improve QOL.
Most common cause of secondary FSGS
Malignancy
Treatment for IgA nephropathy
Aggressive RAS blockade and hypertensive treatment
Unless Crescentic disease then immunosuppression.
AD PKD more common in younger individuals
PKD 1 Age <50
AD PKD more common in older individuals
PKD 2 Age >50
PD membrane survival
1) Preservation of residual renal function - RAAS blockade
2) Preventing infection
3) Protecting peritoneal membrane integrity with low glucose concentrations
Which SGLT2 inhibitor is best to use in a patient with impaired renal function?
Canagliflozin (Can use eGFR<30) - Credence trial
Types of renal tubular acidosis, location of deficiency and key diagnostic clues
Type 2: Proximal tubule defect of reabsorption of HCO3. Mild metabolic acidosis with low urine PH
Type 4: Aldosterone deficiency or resistance
Type 1: Cortical collecting duct defect of H+ excretion, metabolic acidosis with high urinary PH, hypercalciuria and propensity to develop renal calculi.
Does dialysis improve Restless legs syndrome associated with end stage renal failure?
No
Definition of Acute Kidney Injury
KDIGO Guidelines
- Increase in serum creatinine by > or = 0.3mg/dl within 48 hours
- Increase in serum creatinine to > or = to 1.5 times baseline within 7 days
- Urine volume <0.5ml/kg/h for 6 hours
Nb: You cannot use EGFR in to context of AKI.
Staging of AKI by KDIGO guidelines based on serum creatinine
1: 1.5-1.9 times the baseline
2: 2.0-2.9 times the baseline
3: 3.0 times the baseline or initiation of renal replacement therapy
Drugs that can cause AIN
Beta Lactams
PPI
NSAIDs
Immunotherapy
How to use the urinary sodium in AKI
Low urinary sodium <40 = Renal Hypo-perfusion
High urinary sodium >40 = ATN
Note fractional excretion of sodium is better than urinary sodium.
Features of autoimmune polyglandular syndrome
Hypoadrenal (autoantibodies to 21-OH)
Hypothyroid (autoantibodies to Anti-TPO)
Hypoovarian (ovarian autoantibodies)
Pathogenesis involves the failure of AIRE leading to auto reactive T-Cells escaping to the periphery
ACTH levels for adrenal cause or pituitary/ectopic cause of Cushing’s syndrome
<1.1 = Undetectable = Adrenal
>3.3 - Pituitary/Ectopic cause
Test to differentiate between pituitary and ectopic causes of cushings syndrome
High dose dexamethasone suppression test ACTH surpasses (>50%) = likely pituitary (as the pituitary tumours retain some features of normal regulation of ACTH secretion) ACTH not surpassed (<50%) = likely ectopic
Next test if a pituitary source (cushings disease) is thought likely
i.e high cortisol –> ACTH high –> suppression with high dose dexamethasone –> MRI brain
Bilateral inferior petrosal sinus sampling with measurement of ACTH (unless MRI shows tutor >6mm)
Next test if a pituitary source (cushings disease) is thought likely
i.e high cortisol –> ACTH high –> suppression with high dose dexamethasone –> MRI brain
Bilateral inferior petrosal sinus sampling with measurement of ACTH (unless MRI shows tutor >6mm)
What hormones do each of the zones of the adrenal cortex produce
Reticularis: Androgens
Fasiculata: Cortisol
Glomerulosa: Mineralcorticoids
Features of Conn’s Syndrome (Aldosterone producing adenoma)
Hypertension
Hypokalaemia
Low renin
Metabolic alkalosis (due to loss of H+ ions by the intercalated cells)
Investigations for suspected hyperaldosteronism
Note: need to stop beta-blockers and diuretics for at least 4 weeks
1) Aldosterone Renin Ratio
2) Suppression test such as the saline infusion test or stimulation test with captopril
3) Adrenal CT
4) Adrenal Vein Sampling
Initial treatment for phaeochromocytoma hypertension and tachycardi
1) Alpha Blocker: Phenoxybenamine preferred (non competitive alpha antagonist)
2) Beta blocker: Only to be commenced once alpha blocker started due to risk of precipitating unopposed alpha vasoconstriction
Genetic conditions linked with phaecochromocytoma
1) VHL
2) MEN 2/Men 3
3) NF1
Features consistent with an adrenal incidentaloma
Size: <4cm
Shape: Round with regular margins
Attenuation: Houndsfield units <10
Rapid washout of contrast: >50% at 10 minutes
Which cells produce LH and FSH in males
LH “libido” –> Leydig cells –> Testosterone
FHS “sperm” –> Sertoli cells –> Spermatogensis
Main benefit of testosterone treatment on young hypogonadal men?
Improved libido and erectile function (although erectile function not different from phosphodiesterase inhibitors).
Congenital adrenal hyperplasia most common pathogenesis
AR inherited deficiency of 21-hydroxylasewhich results in impaired synthesis of cortisol and aldosterone and accumulation of 17-OH progesterone –> androgens
Clinical features of 21-hydroxylase deficiency
Excess androgens: ambiguous genetalia in women, amenorrhea or hirsutism
Deficiency of mineralcorticoids: Salt wasting crisis and hypotension
Deficiency of glucocorticoids: Adrenal crisis
Investigations and treatment for 21-Hydroxylase deficiency
Elevated 17-OH-progesterone levels (including after administration of ACTH)
Elevated renin levels
Treatment: Corticosteroid treatment and anti-androgens
Features of Graves Disease on investigation
Clinical exam - Diffuse goitre with bruit - Opthalmopathy - Pretibial myxodema TSH receptor antibodies: elevated Technetium 99 scan: Diffuse uptake
Treatment options for Graves Disease
1) Symptom Control: Propanolol
2) Control Hyperthyroidism
- Thionamides: PTU or Carbimazole: Caution in those with LFT derrangements
- Radioactive Iodine: Caution in young women or those with eye disease
- Surgical resection:L Can lead to parathyroid injury and graves can recur if there is any remnant of disease
Proposed pathogenesis of Graves orbitopathy
TSH receptors expressed on the surface of orbital fibroblasts –> Adipogenesis + Hyaluronic acid synthesis –> Expanded orbital muscles and adipose tissue
Main adverse effects of the thionamides (PTU and carbimazole)
PTU: Fulminant inflammatory hepatitis (rare), Safe in first trimester of pregnancy
Carbimazole: Non threatening cholestasis. Not safe in the first trimester of pregnancy but can be used in the trimesters thereafter. Increased risk of alopecia cutis, Ompahloecele and other birth defects
Graves orbitopathy risk factors for progression and treatment
Risk factors for progression - Smoking - Hypothyroidism from overtreatment with thionamides - Radioactive iodine treatments Treatment - Ophthalmologist review: pulse steroids - Radiotherapy int he acute phase - Debulking in the chronic phase \+/- Selenium treatment
What is thyrotoxic periodic paralysis?
Usually occurs in Asian individuals with thyrotoxicosis post high carbohydrate meal
