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Canine/feline endocrinopathies (Diabetes mellitus (Diagnostic approach…

- - - - Caninsulin: 0.5 IU/kg SC BID (solution is 40 IU/mL, most insulin syringes are 100 IU/mL). Test BG at 3, 6 & 9 hrs after first dose (adjust if hypoglycaemia).
      - Diet/exercise: high protein, low carb. Aim for gradual weight loss with consistent exercise regime.
      - Treatment of co-morbidities: spey intact females, treat concurrent disease, avoid insulin-antagonising drugs (e.g. glucocorticoids).
    - - Glargine insulin: precipitates once injected and slowly released (given SC BID). BG < 20 mmol/L = 0.25 IU/kg ideal BW, BG > 20 mmol/L = 0.5 IU/kg ideal BW. Negligible BG increase in first 3 days.
      - Diet/exercise: as for dogs.
      - Treatment of co-morbidities: as for dogs.
    - - Clinical signs
      - Body weight
      - Water intake
      - Serum fructosamine
- - - - Typically no significant changes except for haemoconcentration, azotaemia (pre-renal) and hypernatraemia. Exclude other causes of PU/PD on basis of findings.
    - - Confirms PU (USG <1.025 dogs, < 1.030 cats) and may rule out renal insufficiency/ failure.
    - - DI patients will not be able to concentrate urine in the face of azotaemia.
    - - Performed immediately after water deprivation test. CDI will concentrate urine, NDI will not.
    - - Synthetic ADH administered BID for 3-4 days. Causes reduced water intake in CDI patients, no effect in NDI patients.
- - - - Stress leukon, thrombocytosis, nRBCs, mild erythrocytosis (females)
      - Marked ALP increase, mild ALT increase, mild fasting hyperglycaemia, normal to decreased BUN, hypercholesterolaemia/lipidaemia, mildly elevate bile acids, mildly elevated Na, mildly decreased K.
    - - USG < 1.015 (often < 1.008), +/- evidence of UTI (always do a urine culture via cysto! Immune response is suppressed with Cushing's so may be subclinical).
    - - Ultrasound
        
        PDH: bilateral adrenal enlargement (most common)
        
        ADH: unilateral adrenal enlargement/contralateral atrophy
      - eACTH
        
        PDH: ACTH levels normal to high (> 28 pg/mL)
        
        ADH: ACTH levels low to undetectable (< 5pg/mL)
      - LDDST*
        
        As above
    - - LDDST
        
        Dexamethasone inhibits ACTH release, decreasing cortisol production.
        
        Fasted (12 hrs), then given dex and serum [cortisol] measured at 0, 4 & 8 hrs.
        
        Cushing's = no cortisol suppression*
        
        *May differentiate PDH/ADH (some PDH cases have a characteristic "drop" and then "escape" at 4 & 8 hrs respectively)
        
        Affected by stress (stressed animals may not suppress)
      - Urine cortisol:creatinine
        
        Most sensitive screening test (many false +ves, so a +ve result is not diagnostic)
        
        Greater than 17 almost always seen with Cushing's
        
        Less than 17 strong indication that there is no Cushing's
        
        Confirm positive results with LDDST
        
        Cannot distinguish ADH/PDH
      - ACTH stimulation
        
        ACTH stimulates cortisol production
        
        Exaggerated cortisol production with Cushing's
        
        Quickest screening test, but more common for monitoring
        
        Affected by stress (stressed animals will have higher cortisol levels)
        
        Cannot distinguish ADH/PDH.
    - - Very good serosal detail (fat), hepatomegaly, distended bladder, dystrophic calcification of tissues (e.g. bronchioles), osteoporosis of vertebrae.
  - - - Mitotane
        
        Adrenocorticolytic (necrosis of ZF/ZR)
        
        Side-effects are transient GIT signs (vomiting, diarrhoea)
        
        Loading dose (takes approx. 7 days) of 50 mg/kg/day, then maintenance is same dose divided weekly.
        
        Side-effects difficult to differentiate from hypocortisolaemia (to do this do an ACTH stim test)
      - Trilostane
        
        Inhibits 3 beta-hydroxysteroid pathway (blocking adrenal steroid synthesis)
        
        1-3 mg/kg SID/BID
        
        DO NOT handle if pregnant or administer to patients with impaired renal/hepatic function
        
        Side-effects are lethargy, inappetence, vomiting, diarrhoea
      - Crisis prednisolone supply
        
        In case of Addisonian crisis* (lethargy, weakness, ataxia, anorexia, vomiting)
        
        *Haemoconcentration, hyperK, hypoNa, hypoglycaemia, azotaemia, metabolic acisosis
      - Monitoring
        
        Clinical signs (eating, drinking, appetite), intermittent ACTH stim testing
    - - Surgical adrenalectomy recommended
- - - - Glucocorticoid-related: anorexia, vomiting, diarrhoea (+/- haemorrhagic), weight loss, lethargy, weakness, shaking.
    - - Mineralocorticoid-related: PU with compensatory PD, dehydration.
  - - - NO stress leukon, mild anaemia, azotaemia (pre-renal), hypocholesterolaemia, hypoalbuminaemia, hypoglycaemia, hypercalcaemia.
      - Hyperkalaemia, hyponatraemia (Na:K < 25:1 suggestive, < 15:1 strongly suggestive). DDx for low Na:K are T. vulpis, acute renal injury, effusions (chylothorax), GIT inflammation.
    - - USG < 1.030 (medullary washout from persistent diuresis)
    - - No response in [cortisol]: pre- and post-ACTH cortisol measurements < 25 nmol/L.
    - - Hypovolaemic changes
    - - Peaked T waves, absent P waves, widened QRS
  - - - IV dexamethasone (if crisis), 0.9% NaCl (30-80 mL/kg/q24hrs or 20 mL/kg boluses), insulin/dextrose (intracellular K shift), Ca gluconate (protects myocardium). Correct half of fluid deficit over 6 hrs, then other half over 24 hrs. Monitor vitals, CRT, pulse pressure, and hydration every 4 hrs and electrolytes every 4-8 hrs. Also reassess PCV/TP, urine output and renal parameters.
    - - Fludrocortisone (mineralocorticoid + glucocorticoid).
      - Desoxycorticosterone pivatate (pure LA mineralocorticoid injection) + prednisone.
- - - - 20 mL/kg Hartmann's over first hour and then reasses. Do not use low-Na fluids (cerebral haemorrhage).
    - - Insulin therapy. Practically, intermittent insulin injections preferable to CRI.
    - - Potassium shift extracellularly with hyperglycaemia and acidosis, but is lost in urine. Can add KCl to fluids for 24 hrs.
    - - 5% dextrose/KCl IV, mannitol.