Endocrinopathies II - adrenals Flashcards
Overview of Canine hypoadrenocorticism
(Addison’s disease).
Spectrum on conditions resulting in deficiencies of adrenal hormones.
Loss of the vital functions of cortisol (metabolism, immunity, gastrointestinal) and aldosterone (sodium and volume status) → variable clinical signs.
Categorization of Canine hypoadrenocorticism. (2+2)
Primary: autoimmune disease - direct adrenocortical injury.
&
Secondary: rapid withdrawal of adrenal suppressive medications (steroids), pituitary surgery, cancer.
Typical: cortisol + aldosterone deficiency
&
Atypical: cortisol deficiency (normal electrolytes), 25-30%
Typical Canine hypoadrenocorticism involves what type of deficiency?
Typical: cortisol + aldosterone deficiency
ATypical Canine hypoadrenocorticism involves what type of deficiency?
Atypical: cortisol deficiency (normal electrolytes), 25-30%
Typical signalment for Canine hypoadrenocorticism.
Any age, but mostly diagnosed in young to middle age.
- Mean age of 3-4 y
Female predisposition
Any breed possible but commonly affected breeds: standard poodle, portuguese water dog, great dane.
Clinical signs of Cortisol deficiency
→ ineffective GI mucosal barrier: anorexia, vomiting, diarrhea, weight loss
→ inadequate glucose synthesis: lethargy, weakness, shaking, collapse
Clinical signs of Aldosterone deficiency
→ Na loss via urine, osmotic diuresis: polyuria + compensatory polydipsia
What to note about clinical signs of Canine hypoadrenocorticism?
Can be very vague
Wax and wane, episodic
Especially after periods of stress
Typical: often sudden signs of volume depletion (shock)
Atypical: more often chronic, only cortisol deficiency signs (no PU/PD)
Physical exam of a Canine hypoadrenocorticism dog may reveal: (10)
Mild to severe abnormalities
Weak pulses
Dehydration
Hypotension
Bradycardia
Muscle weakness
Thin body condition
Abdominal pain
Hypovolemic/hypotensive shock
Seizures
Diseases with similar clinical presentations to hypoadrenocorticism.
Typical HA:
- acute kidney injury
- severe GI disease
Atypical HA:
- severe GI disease
- hepatic dysfunction
CBC findings in HypoA.
Absent stress leukogram (so eosinophilia, lymphocytosis).
Lymphopenia = cortisol deficiency extremely unlikely.
Biochemical findings in HypoA.
Electrolyte abnormalities: hypoNa, hyperK, Na:K <27, hypoCl, hyperCa
Hypoalbuminemia, hypocholesterolemia
Prerenal azotemia
Acidemia
Hypoglycemia
Liver enzyme increases
Urinanalytical findings in HypoA.
Isostenuria (urine with a specific gravity similar to plasma, around 1.008–1.012)
aldosterone deficiency leads to hyponatremia and water loss, contributing to hypovolemia. This results in decreased renal perfusion and impaired ability of the kidneys to concentrate urine.
The kidney’s ability to concentrate urine relies on the concentration gradient in the renal medulla, which depends on sodium and urea reabsorption.
chronic sodium loss reduces the medullary sodium concentration, leading to medullary washout. This impairs the kidney’s ability to create a high osmotic gradient needed for water reabsorption.
Without this gradient, water reabsorption is impaired, resulting in isosthenuria.
Describe Diagnostic testing for HypoA.
If suspicion is high do ACTH directly - the diagnosis relies on confirming cortisol deficiency by ACTH stim.
- Post-ACTH stimulation cortisol value <2 mcg/dL confirms it.
If suspicion is low, just do baseline cortisol testing.
- If >2 mcg/dL then HA is ruled out, if <2 proceed to ACTH-stim to confirm.
+ Na:K ratio of <27 is suggestive though note that 1/4 of HA cases have normal electrolytes and many other things can cause a low ratio too.
Descibre how to do the ACTH stim.
1st: Collect baseline serum cortisol sample.
Then: Inject exogenous ACTH, cosyntropin (5 mcg/kg IV up to 250 mcg per dog) and collect a second serum sample 1 h later.
NB Dog must not receive oral prednisone for at least 48 h before an ACTHstim because it will cross react and give falsely elevated cortisol values.
Treatment of HypoA.
Typical HA: glucocorticoid + mineralocorticoid supplementation life long
Treatment of cortisol deficiency using exogenous glucocorticoids.
Small daily dose: <0.1-0.25 mg/kg/day of prednisone/prednisolone.
Need to Double-triple before known stressful events.
If Clinical signs of Addison’s disease → increase the dose.
If Side effects of glucocorticoids → decrease the dose.
e.g. PU/PD, PP, panting, muscle wasting, elevated ALP, hair loss
How do endogenous glucocorticoids benefit mucosal integrity?
Glucocorticoids suppress the production of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6) and inhibit the activation of inflammatory cells such as macrophages, neutrophils, and T-cells.
GCs modulate the turnover of mucosal epithelial cells.
GCs enhance the expression of tight junction proteins such as occludin and claudins, which help maintain the tightness of the epithelial barrier.
reducing the production of prostaglandins and leukotrienes that promote vascular permeability.
GCs regulate goblet cells, which are responsible for mucus production, ensuring an adequate secretion of mucin.
etc.
Treatment of mineralocorticoid deficiency using what? (2)
Patients with hyperkalemia and/or hyponatremia need Mineralocorticoid supplementation:
- Desoxycorticosterone pivalate
- if DOCP cannot be used then, Fludrocortisone Oral, tablets
Both of the above are aldosterone analogs.
Describe the use of aldosterone analog
Desoxycorticosterone pivalate
Is an injectable.
Starting dose 2.2 (1.1-1.5) mg/kg IM/SC approximately (every) q25d.
Dose and dosing interval are determined by electrolyte monitoring 10-14 and 25 days after injection.
Electrolytes initially q10-14d, then once stabilized q3-4m.
Glucocorticoid supplementation alongside this one.
Describe the use of aldosterone analog
Fludrocortisone
Use if desoxycorticosterone cannot be used.
Are oral tabl.
0.01 – 0.02 mg/kg PO single dose/divided and given twice daily.
Dosage adjusted in 0.05-0.1 mg increments by assessing Na and K (every) q5d, increased until Na:K ratio >28.
Once dose is stabilized, some dogs can be transitioned to once daily.
Once dose is stabilized, recheck electrolytes q1m for 3-6 months, then q3-6m.
Only 50% of dogs require supplemental prednisolone by mouth in addition to the fludrocortisone by mouth.
Describe Addisonian crisis. (4)
Most serious and life-threatening manifestation of hypoadrenocorticism
Presents as Hypovolemic shock with Severe hyperkalemia and hyponatremia.
+/- historic episodic signs consistent with hypoadrenocorticism
Treatment of Addisonian crisis.
Immediate stabilization and IV fluids being the cornerstone of therapy. Correct hypovolemia and hypotension.
0.9% NaCl is recommended because it contains more Na and Cl and less K than other crystalloid fluids.
+Glucose if hypoglycemic/hyperK persists following 6-8 h of fluid therapy/bradycardia is profound.
Insulin if glucose fails to decrease K
Gastrointestinal support, early enteral nutrition.
Frequent monitoring of electrolytes, PCV
Single dose of steroid before testing may be required for stabilization.
- Dexamethasone 0.1 mg/kg IV - rapid onset of action, does not interfere with the cortisol assays (but pred does!).
Once stable, baseline cortisol/ACTH-stim
Mineralocorticoids only once the patient is stable, diagnosis is confirmed and Na >130 mEq/dL.
While dexamethasone does not cross-react with cortisol assays, it does suppress
pituitary secretion of ACTH and CRH from the hypothalamus. This could impact ACTHst results.
How can Canine hypercortisolism
(Cushing’s syndrome) be categorized? (2+2)
Endogenous oversecretion of cortisol
vs
Exogenous administration of glucocorticoids - iatrogenic
OR
Endogenous divided into:
pituitary dependent hypercortisolism - PDH
- 85% of cases are ACTH dependent due to pituitary tumor
adrenal dependent hypercortisolism - ADH
- 15% of cases are ACTH independent so due to adrenal tumor
The most common cause of Cushing’s syndrome in dogs is
iatrogenic, as use of glucocorticoids is common in managing a variety of neoplastic, inflammatory or immune-mediated conditions.
The most common type of endogenous Cushing’s disease in dogs is
pituitary-dependent hyperadrenocorticism (PDH). This form accounts for approximately 80-85% of cases.
Signalment of typical cushings dog.
Middle-aged to older, Mean 11 y.
Relatively common dz
No significant breed predisposition
- PDH: smaller dogs: poodles, dachshunds, terrier breeds
60-65% are female
Why is asking about Current/recent medications during anamnesis so important for HAC?
clinical signs of iatrogenic and naturally occurring Cushing’s syndrome are identical.
+
Several medications (e.g., anticonvulsants, diuretics, etc.) have side effects that mimic HAC.
Common clinical signs of HAC. (6)
Chronic cortisol excess is Gluconeogenic, immune-suppressive, anti-inflammatory, protein catabolic, lipolytic.
HAC dogs may have 1 or several clinical signs, vary in intensity.
PU/PD
Polyphagia
Apparent weight gain (pot belly)
Muscle weakness (secondary to the catabolic effects of glucocorticoids)
Panting
Hair loss
CNS signs that can be caused by HAC
Pituitary macrotumor syndrome: in PDH, a tumor invading and compressing tissues dorsal to the sella turcica.
Lethargy, (inappetance/anorexia, stupor, circling, aimless wandering, ataxia, behavioral changes, seizures)
Less common signs of HAC. (8)
Ligament laxity (e.g. plantigrade stance)
Facial nerve paralysis
Anestrus
Testicular atrophy
Thromboembolism (hypercoagulability)
Abdominal/retroperitoneal hemorrhage (invading FAT)
Pelvic limb edema
Cushing’s pseudomyotonia (looks like all 4 legs hop together)
Typical dermatologic findings on physical exam of dog with HAC. (10)
Endocrine bilateral truncal alopecia
Dull and dry hair
Thin skin
Failure to regrow shaved hair
Comedones
Bruising
Hyperpigmentation
Seborrhea (scaly/crusty patches)
Pyoderma
Calcinosis cutis (uncommon but characteristic)
Acute illness during HAC (2)
Is Rare as usually the disease is chronic, progressive but not typically acute.
Adrenal tumor rupture → acute hemorrhage
- Acute severe lethargy, weakness, pale mucous membranes, pain
Pulmonary thromboembolism is a recognized complication in dogs with HAC, perhaps due to an underlying hypercoagulable state.
CBC in a Cushings dog might reveal: (3)
Stress leukogram
Thrombocytosis
Mild erythrocytosis (steroid excess may stimulate erythropoiesis)
Serum biochemistry in a Cushings dog might reveal: (7)
Marked ALP increase (most consistent laboratory abnormality, observed in 85-95% of dogs), mild to moderate ALT increase
Hyperlipidemia (chol, trig) (observed in >50% of HAC dogs)
Mild hyperglycemia
Low BUN, azotemia is uncommon (30 to 50% of dogs with HAC)
Hypo OR hyperPhosphatemia (>40%)
Bile acids mildly increased (30%)
increased cPL
Urinalysis in a Cushings dog might reveal: (3)
USG <1.020 (polyuria)
Proteinuria (UPC)
UTI (culture)
Approximately 40% to 50% of dogs with Cushing’s syndrome have a UTI at the time of initial examination!
due to the anti-inflammatory effects of chronic hypercortisolism, many of these dogs do not have clinical signs .
About Thoracic Radiographs
Dogs suspected or known to have HAC should be evaluated with thoracic radiographs to search for
metastatic lesions and to evaluate the patient for any unsuspected concern.
Common nonspecific findings in dogs with HAC are an interstitial lung pattern and mineralized bronchi or tracheal rings .
Pulmonary thromboembolism is rare despite their “hypercoagulable state,” may have hypovascular lung fields (areas of increased radiolucency due to decreased perfusion distal to a thrombus) or alveolar pulmonary infiltrates.
Alveolar infiltrates correspond to areas of atelectasis, hemorrhage, or infarction.
Enlargement of the main pulmonary artery, right-sided cardiomegaly, and pleural effusion have been reported in dogs with PTE.
Abdominal radiographs in dogs suspected to have HAC. (5+)
Common: abdominal distention, excellent contrast (abdominal fat), hepatomegaly, bladder distention
Uroliths
Adrenal mass calcification
Dystrophic calcification in skin, renal pelvis, liver, gastric mucosa, branches of abdominal aorta.
Mild osteopenia (loss of bone density)
Why might you perform abdominal U/S on a suspected cushings case? (3)
Check the Adrenal glands
- PDH: bilaterally symmetrical adrenomegaly
- ADH: adrenal mass, contralateral adrenocortical atrophy
Sequelae to HAC (urolithiasis, gallbladder mucocele)
Rule out Nonadrenal conditions
How to endocrine test for HAC?
Only test when high clinical suspicion and Two or more clinical or biochemical abnormalities suggest HAC.
Stabilize or resolve any known comorbidities (e.g. DM) before CS testing.
- False positive results when performed in patients with concurrent nonadrenal illness/stress
The low-dose dexamethasone suppression test (LDDST) is the preferred diagnostic test and it may also differentiate between PDH and ADH.
How to perform the LDDST. (5)
low-dose dexamethasone suppression test
Prep: Fasting generally not required but
Excessive lipemia may affect results.
Glucocorticoids withdrawal before testing,
2 weeks for short acting & 4 weeks for longer acting.
- draw serum for baseline cortisol
- Administer 0.01 mg/kg dexamethasone IV
- Collect subsequent serum samples for cortisol values at 4 and 8 hours post injection.
How to interpret the results of LDDST?
Assess the 8 hr result first. Cortisol of >1.4 mcg/dL is consistent with a diagnosis of CS; continue with differentiation.
If the 8 hr result shows CS, then assess for evidence of partial suppression; if any criteria are present, the result is consistent with PDH-type.
- So, 4 hr cortisol concentration is <1.4 mcg/dL.
- 4 or 8 hr cortisol concentration is <50% of the baseline concentration.
- Up to 35% of dogs with PDH do not fulfill at least one of these criteria; therefore, failure to observe suppression does NOT confirm ADH.
If differentiation is still desired, abdominal ultrasound and/or an endogenous ACTH concentration can be pursued in order to diagnose ADH.-type
If the 8 hr cortisol concentration is between 1.0 and 1.39 mcg/dL but clinical suspicion for CS is high, consider performing an ACTH stimulation test or repeating the LDDST in 2–3 mo.
When might you use the ACTH stim test for cushings? (3)
The ACTHST should also be considered if the LDDST does not support a diagnosis of hypercortisolism but clinical suspicion remains high, to confirm iatrogenic CS, and to monitor CS therapy (!).
False positive results can occur with
- Chronic/moderate stress
- Nonadrenal illness (but less common than with LDDST)
BUT lacks sensitivity in dogs with adrenal tumors, leading to false-negative results in up to 41% of dogs with ADH.
If the stimulated cortisol concentration is below the diagnostic cutoff and clinical suspicion of CS remains high, an LDDST should be performed.
Describe how to perform the ACTH stim.
- Collect baseline serum cortisol sample.
- Inject cosyntropin (synthetic ACTH analog) (5 mcg/kg IV up to 250 mcg per dog) and collect a second serum sample 1 h later.
How to interpret ACTH stim.
A 1h post-ACTH cortisol value of >22 mcg/dL = CS. Indicates that the adrenal glands are overproducing cortisol and are excessively responsive to ACTH (PDH?).
If both pre and stimulated cortisol values are in ranges that mimic hypoadrenocorticism, this = iatrogenic CS or ADH.
→ continue to do LDDST if iatrogenic HAC is excluded.
Explain the UCCR test in cushings cases.
Urine cortisol-to-creatinine ratio
Use to exclude CS in patients with low clinical suspicion. Example: asymptomatic dog with an ALP elevation.
UCCR has High sensitivity, poor specificity for HAC.
- Many false positives (dogs with PU)
- Urine samples collected in a non-stressed home environment to minimize false positive results.
- A Low value almost always rules out CS.
Why bother differentiating between PDH and FAT?
PDH = pituitary dependent HAC
FAT = functional adrenal tumor
Differentiation between PDH and ADH is helpful because it helps direct therapeutic options and provides the owner with prognostic information.
However, if the owner has no intention of pursuing adrenalectomy if an adrenal tumor is identified, patients can be treated with trilostane without knowing whether the dog has PDH or ADH.
Diagnostics that help differentiate PDH from ADH include LDDST, abdominal ultrasound, and endogenous ACTH concentration.
Diagnostics that help differentiate PDH from ADH include (3)
LDDST, abdominal ultrasound, and endogenous ACTH concentration.
When should you pursue CT for CS dogs?
PDH: head CT if the dog clinical signs compatible with macroadenoma/owner would pursue radiation therapy or hypophysectomy
ADH: abdominal CT before adrenalectomy
Treatment of ADH.
Adrenalectomy is the preferred therapy for ADH. However, clients may decline this option because of cost, potential complications, and comorbidities.
when clients opt not to pursue surgery, medical management is the alternative approach.
Mitotane is an adrenocorticolytic drug that selectively destroys the adrenal cortex. Goal: Reduce cortisol production to a more manageable level by killing part of the adrenal tumor cells.
Trilostane can also be used.
Treatment of PDH.
Trilostane 1 mg/kg q12h - inhibits synthesis of adrenocortical hormones.
Previously, Mitotane - old fashioned adrenocorticolytic drug, prevously the primary treatment option for PDH.
How to monitor after initiating treatment for HAC?
Monitor Clinical signs + do cortisol testing.
Initial response is assessed after 2 weeks, then after 1 month, then q3-6m.
Cortisol testing to check is the current dose appropriate/dose adjustment is needed?
- pre-pill cortisol: obtain a sample for cortisol measurement before the morning pill.
- Do ACTH-stim 3-5 h after trilostane administration (consistent timing with every visit), use a lower dose of synthetic ACTH (1 mcg/kg IV).
What blood test do you do for monitoring of medicated HAC dogs?
ACTH-stim
the primary role for its use in monitoring treatment of naturally occurring CS is to rule out oversuppression of cortisol production - you dont want too low cortisol levels.
- pre-pill cortisol: obtain a sample for cortisol measurement before the morning pill.
- Do ACTH-stim 3-5 h after trilostane pill administration (consistent timing with every visit), use a lower dose of synthetic ACTH (1 mcg/kg IV).
Aldosterone function?
Aldosterone origin?
Na and K homeostasis
the outermost layer of the adrenal gland, the zona glomerulosa.
What is feline hyperaldosteronism?
Common clinical signs are hypokalemia and systemic hypertension. Weakness and lethargy are the most common clinical signs reported.
Severe systemic hypertension can result in ocular changes such as retinal detachment or hemorrhage.
Unilateral adrenocortical adenoma (benign)
Malignant adenocarcinoma less common
Middle-aged to older cats
Clinical signs of feline hyperaldosteronism
hypokalemia leading to,
Progressive muscle weakness: reluctance to jump, abnormal gait (plantigrade stance), cervical ventroflexion, lethargy
Sodium retention leading to,
hypertension,
Sudden blindness (retinal detachment)
Changes in behavior (lethargy, hiding, irritability).
Minimum diagnostics for hyperaldosteronism suspicion.
Minimum biochemical database would be
CKD changes.
Doppler BP
Abdominal US (look for Unilat adrenal mass, or Adrenal glands may appear normal)
Analyze Plasma aldosterone
- A Single very high value confirmatory
Treatment of feline hyperaldosteronism.
Depedning on if uni/bilateral disease.
Surgical
- Removal of the affected gland
- must be Stabilized medically before surgery
Medical/pharmacologic
- Hypokalemia: potassium gluconate (higher than standard doses) and spironolactone 1–2 mg/kg q12h
- for Hypertension: amlodipine 0.625–1.25 mg per cat per day
spironolactone mechanism of action
antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule.
causes increased amounts of sodium and water to be excreted, while potassium is retained.
Feline hypothyroidism overview
very Rare
A Single low T4 - interpret in the light of the entire clinical picture tho!
(Euthyroid sick syndrome can cause illusion)
clinical signs of feline hypothyroidism
congenital may present with:
slow growth, dumpy proportions
retained milk teeth and gingival overgrowth
iatrogenic or adult-onset:
bradycardia, seborrhea
Diagnosis of feline hypothyroidism
Low TT4 + elevated TSH
Low fT4
Azotemia
treatment of feline hypothyroidism
Levothyroxine sodium
- Initial dose 0.05-0.1 mg/kg daily
- Dose adjusted to target T4 levels between 1 and 3 mcg/dL
Clinical signs may persist for 2-3 months before finally resolving.
explain Iatrogenic hypothyroidism
Overdosing with methimazole, surgical removal of the thyroid glands, or Iodine treatment.
Methimazole: monitoring q6m.
When treating with iodine consider T4+TSH, and aim for appropriate Iodine dose so as not to cause hypo-.
Can contribute to decreased renal function
Treatment is needed when T4 <1 mcg/dL + elevated TSH
Feline hyperadrenocorticism is..
cat-Hypercortisolism, Cushing’s syndrome
Is infrequent
usually Pituitary dependent HAC
Middle-aged to older cats
Concurrent DM common and can be Difficult to regulate
Clinical signs of Feline hyperadrenocorticism
Weakness
Abdominal distension
Dermatological: fragile skin, failure to regrow hair (skin fragility sometimes associated with chronic exposure to excess cortisol)
Concurrent DM: PU/PD/PP
Weight loss, lethargy, GI signs uncommon
diagnosing Feline hyperadrenocorticism
At Minimum analyze for:
- Hyperglycemia + glucosuria
- ALP is usually WRI
- Hypercholesterolemia
- Stress leukogram in 50% of cases
Do LDDST
- Dexamethasone dose greater than in dogs
- Lack of suppression at 4 or 8 hr after administration confirms diagnosis
UCCR - Urinary Cortisol:Creatinine Ratio
- Initial screening
- At least two morning samples
- Negative likely rules it out, but from a positive test → do LDDST
ACTHST not recommended because of its poor sensitivity to detect feline HAC compared with the other available testing.
treatment of Feline hyperadrenocorticism
if adrenal tumor:
- Adrenalectomy with unilateral adrenal tumor
Radiation therapy with PDH
Or Trilostane 1 mg/kg q8-12h with food
