ENDOCRINE DISEASES LECTURE OUTLINEcvpba.org/.../09/ArgentinaEndocrineDieseasesofFerrets.pdfENDOCRINE...

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ENDOCRINE DISEASES OF FERRETS

ISAZA, 2017


Ramiro Isaza, DVM, MPH, DACZM, DECZM

Professor, Zoological Medicine

College of Veterinary Medicine

University Florida

LECTURE OUTLINE

� FERRET ENDOCRINE DISEASES

� Hyperadrenocorticism

� Insulinoma

� Hyperestrogenism

� Ovarian Remnant

CLASS TEXTBOOK

� ADDITIONAL READING:

� Chapter 7 - ENDOCRINE, 86–102 (104-106)

LECTURE UPDATE

� Two new (2017) review articles:

HISTOLOGY OF THE ADRENAL� ZONA GLOMERULOSA (G) - OUTER LAYER

� Mineralcorticoids

� ZONA FASCICULATA (F)- MIDDLE LAYER� Glucocorticoids

� ZONA RETICULARIS (R)� Sex steroids

� MEDULLA (M)� Epinephrine

HYPERADRENOCORTICISM HYPERADRENOCORTICISM

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HYPERADRENOCORTICISM

HISTOLOGY OF THE ADRENAL� ZONA GLOMERULOSA (G) - OUTER LAYER

� Mineralcorticoids

� ZONA FASCICULATA (F)- MIDDLE LAYER� Glucocorticoids

� ZONA RETICULARIS (R)� Sex steroids

� MEDULLA (M)� Epinephrine



PATHOGENESIS

� NOT CUSHING'S

� DOGS

� Elevated plasma cortisol

� FERRETS

� Elevated Androstenedione

� 17-Hydroxyprogesterone

PATHOGENESIS

� DISEASE OF THE ADRENAL GLAND

� Adrenocortical hyperplasia (56%)

� Adrenocortical adenoma (16%)

� Adrenocortical carcinoma (26%)

� METASTASIS IS RARE ?

� Locally invasive and recurrence



PATHOGENESIS

� “3-4” YEARS AFTER GONADECTOMY

� stimulation of gonadal cells in adrenal

� adrenal and gonads evolve from the same urogential ridge tissue

� NO GENDER PREDILECTION

� NO PREDILECTION FOR EITHER SIDE

GONADECTOMY RESEARCH

� There is a time related linear correlation between surgical neutering and development of hyperadrenocorticism

� The median interval between neutering and diagnosis of hyperadrenocorticism is 3.5 yrs

� (Schoemaker et al. 2000).


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ISAZA, 2017


CLINICAL SIGNS

(J Am Vet Med Assoc 2008;232:1338–1343)

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ISAZA, 2017


CLINICAL SIGNS

� ALOPECIA

� PRURITUS


CLINICAL SIGNS

� FEMALES

� Swollen vulva


CLINICAL SIGNS

� MALES

� Urinary “blockage” caused by an enlarged prostate

� Squamous metaplasia

� Often the bladder can be expressed manually

LABORATORY DIAGNOSIS

� CBC AND CHEMISTRY – NORMAL

� Anemia is rare!


PCV 36-48 %

WBC 4.3-10.7NEUTROPHILES 18-47

LYMPHOCYTES 41-73

MONOCYTES 0-4 %

EOSINOPHILS 0-4 %

BASOPHILES 0-2 %


� SEVERAL SEX STEROID HORMONE PRECURSORS ELEVATED

� Estradiol

� Androstenedione

� 17-Hydroxyprogesterone

� Dehydroepiandrosterone

** (University of Tennessee, Clinical Endocrinology Lab.)



� OTHER TESTS� ACTH Stimulation and dexamethasone suppression tests are not diagnostic

� Urine cortisol: creatinine not specific enough


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ISAZA, 2017

DIAGNOSTICS

� RADIOGRAPHS

� Non-diagnostic

� ULTRASOUND

� L - 7.5 mm

� W - 3.7 mm

� D - 2.8 mm

HYPERADRENOCORTICISM HYPERADRENOCORTICISM

THERAPEUTICS

� SURGICAL REMOVAL

� CONFIRMS DIAGNOSIS

� SURGERY TECHNIQUES

� Surgical mortality (2-5%)

� CONSIDERATIONS

� Good survival

� Recurrence common

� 17% - 32% within a few years

GENERAL

� Thorough exploratory

� Evaluate adrenal glands

� 2-3mm wide and 7-8mm long

� Light pink, homogenous

ADRENAL SURGERY

LEFT ADRENAL

� Craniomedial to the left kidney in fatty tissue

� Dissect the gland free while ligating one or more small vessels

ADRENAL SURGERY

LEFT ADRENAL

ADRENAL SURGERY

LEFT ADRENAL

ADRENAL SURGERY

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ISAZA, 2017

RIGHT ADRENAL

� The right adrenal gland is beneath the caudate liver lobe, close to both the vena cava and the hepatorenal ligament

ADRENAL SURGERY

RIGHT ADRENAL

ADRENAL SURGERY

RIGHT ADRENAL

ADRENAL SURGERY

Quesenberry, K.E. and Carpenter J.W. (eds.). 2012.

ADRENAL SURGERY

REMOVAL OR DEBULK?� Remove with the capsule

� Hemoclips

� Cryosurgery

� Laser surgery

ADRENAL SURGERY

SUPPORTIVE POST SURGERY CARE

� Fluids

� Nutritional support

� Monitor for electrolyte imbalances

� Dexamethasone sodium phosphate if lethargic or if electrolytes are abnormal

ADRENAL SURGERY

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ISAZA, 2017

POTENTIAL COMPLICATIONS

� Life-threatening hemorrhage -vena cava

� Recurrence of adrenal disease� Contralateral gland becomes diseased

� Diseased gland is not entirely removed

ADRENAL SURGERY

RESOLUTION OF CLINICAL SIGNS

� Prostatomegaly reduces within 48 hours

� Vulvar swelling reduces within a week

� Regrowth of fur begins within two weeks and is usually complete within 2-3 months

ADRENAL SURGERY


THERAPEUTICS

� MEDICAL MANAGEMENT

� Deslorelin acetate implant (Suprelorin)

� Recurrence common (30%)

� Does not cure neoplasia or growth


THERAPEUTICS


� Deslorelin acetate implant (Suprelorin)

� Recurrence of most cases

� Does not cure neoplasia or limit growth


THERAPEUTICS


� One study (Lennox and Wagner, 2012) compared Deslorelin to surgery

� Recurrence with Deslorelin at 16.6 months

� Surgical recurrence at 13.6 months

� Non-randomized study…


THERAPEUTICS


� Leuprolide acetate (Depo lupron)� Synthetic gonadotropin-releasing hormone (GnRH)

� Mitotane, o,p’-DDD (Lysodren)� Kills the adrenals

� Bicalutamide (Casodex), Flutamide (Eulexin)� Androgen receptor blockers

� Anastrozole (Arimidex)� Blocks estrogen

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ISAZA, 2017


THERAPEUTICS


� Leuprolide acetate (Depo lupron)� Synthetic gonadotropin-releasing hormone (GnRH)

� Mitotane, o,p’-DDD (Lysodren)� Kills the adrenals

� Bicalutamide (Casodex), Flutamide (Eulexin)� Androgen receptor blockers

� Anastrozole (Arimidex)� Blocks estrogen


THERAPEUTICS

� OTHER MEDICAL MANAGEMENT

� Melatonin

� Abarelix ?

� GnRH antagonist

� Pig GnRH Vaccine ?

� GonaCon “wildlife” GnRH vaccine ?

THERAPEUTICS

� GnRH Vaccination (GonaCon)


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ISAZA, 2017

GnRH Vaccination


THERAPEUTICS

� MEDICAL VS SURGICAL

� Age

� Bilateral disease

� Recurrence

� Possibly both ?

MY CURRENT RECCOMENDATION

� Since all ferrets are castrated by law, we can expect this disease

� I use a combination of surgery, followed by deslorelin implants before recurrence

� Consider vaccination when proven

HYPERADRENOCORTICISM INSULINOMA

PANCREATIC BETA ISLET CELL TUMOR

� SIGNALMENT

� Very common

� > 3 years old

� 2-7 years (median 5 years)

� Slow onset

� No sex predilection

� Multifocal spread in 53%

INSULINOMA

PATHOGENESIS

� UNKNOWN CAUSE:

� High carbohydrate commercial diets ?

� Lack of 100% meat

� No strong evidence for this theory

� Genetics ?

INSULINOMA

CLINICAL DIAGNOSIS

� PRESUMPTIVE DIAGNOSIS BASED ON THE “WIPPLE TRIAD”

� Clinical signs (weakness, neurological signs)

� Concurrent low glucose (≤ 60-70 MG/DL)

� Immediate response to glucose treatment

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ISAZA, 2017

INSULINOMA


� PRESUMPTIVE DIAGNOSIS BASED ON CLINICAL SIGNS AND BLOOD GLUCOSE

� ≤ 60-70 MG/DL

INSULINOMA


� BLOOD INSULIN LEVELS ABOVE 250-300 PMOL/L WITH LOW GLUCOSE < 70MG/DL IS ABNORMAL

INSULINOMA


� CBC, CHEMISTRIES (OTHER THAN GLUCOSE), AND RADIOGRAPHS ARE USUALLY NORMAL

� ULTRASOUND IS INCONSISTENT

INSULINOMA

CLINICAL SIGNS:� LETHARGY (95%)

� WEAKNESS (82%)

� DIFFICULTY AROUSING FROM SLEEP (76%)

� PTYALISM (EXCESSIVE SALIVA) (61%)

� PAWING AT THE MOUTH (58%)

� WEIGHT LOSS (47%)

� HIND-LIMB “ATAXIA” (36%)

INSULINOMA

THERAPEUTICS

� SYMPTOMATIC

� Frequent small meals

� Kayro syrup and Nutrical for rescue TX

� MEDICAL

� Diazoxide

� Prednisone

� SURGERY

SURGICAL NOTES

� Nodules are single, multiple, or diffuse

� Take concurrent liver biopsy

� Maintain on 2.5% dextrose during surgery

� Postoperative pancreatitis is rare

� Clients warned that this is only palliative

� Expect 86-100% recurrence

PANCREATIC SURGERY

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PANCREATIC ANATOMY

� “V” Shaped

� Right Limb

� Left limb

� Body� Common pancreatic duct

PANCREATIC SURGERY

SURGICAL EXCISION� Inspect the liver and spleen for metastasis

� Visually inspect and palpate the pancreas� Nodules (1-2 mm)

� Lighter in color

� Firmer

PANCREATIC SURGERY

NODULECTOMY

� Blunt dissection may be used to shell out nodules

� Bleeding should be minimal and easily controlled

PANCREATIC SURGERY

PANCREATECTOMY� Indications

� Multiple nodules

� Ligate the pancreatic tissue

Quesenberry, K.E. and Carpenter J.W. (eds.). 2012.

PANCREATIC SURGERY

POST-OP

� IV dextrose

� Small frequent meals

� Pancreatitis is rare

� Blood glucose levels every 12 to 24 hours

FOLLOW-UP

� Fasting blood glucose every 1-3 months

PANCREATIC SURGERY

MY CURRENT RECCOMENDATION

� No strong recommendations!

� Surgery provides definitive identification and temporary relief of clinical signs

� Medical Management also temporary

� Prednisone

� Diazoxide

� Symptomatic management

PANCREATIC SURGERY

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ISAZA, 2017

HYPERESTROGENISM

FEMALE REPRODUCTIVE CYCLE� SEASONALLY POLYESTROUS

� INDUCED OVULATORS

� MATING CAUSES OVULATION WITHIN 30-40 HR

� ESTRUS CONTINUES IF NOT BRED

� CHRONICALLY HIGH ESTROGEN LEVEL

SUPPRESSES THE BONE MARROW

� CAN RESULT IN DEATH

HYPERESTROGENISM

CLINICAL SIGNS

� SWOLLEN VULVA

� WEAKNESS, ANOREXIA, WEIGHT LOSS

� BILATERALLY SYMMETRICAL ALOPECIA

� PALE MUCUS MEMBRANES

HYPERESTROGENISM


� CBC AND CHEMISTRY

� ANEMIA

� THROMBOCYTOPENIA


PCV 36-48 %

WBC 4.3-10.7NEUTROPHILES 18-47

LYMPHOCYTES 41-73

MONOCYTES 0-4 %EOSINOPHILS 0-4 %

BASOPHILES 0-2 %

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THERAPEUTICS

� DETERMINE SEVERITY OF DISEASE

� PCV > 20% has a fair to good prognosis

� PCV 14-19% has a guarded prognosis

� PCV < 14% has a poor prognosis

HYPERESTROGENISM

THERAPEUTICS

� SUPPORTIVE CARE

� BLOOD TRANSFUSION

� REDUCE SERUM ESTROGEN LEVELS

� OHE (stabilize prior to surgery)

� hCG or GnRH to induce ovulation

� Mate to a vasectomized male

HYPERESTROGENISM

CLINICAL SIGNS

� PRESENTS EXACTLY LIKE HYPERESTROGENISM IN A “SPAYED” FEMALE

� ALSO IDENTICAL TO HYPERADRENOCORTICISM

OVARIAN REMNANT

CLINICAL DIAGNOSIS

� Test dose of hCG or GnRH

THERAPEUTICS

� Exploratory surgery

OVARIAN REMNANT

� INSPECT OVARIAN STUMPS AT THE CAUDOLATERAL POLE OF EACH KIDNEY

OVARIAN REMNANT CONCLUSIONS

ENDOCRINE DISEASES LECTURE OUTLINEcvpba.org/.../09/ArgentinaEndocrineDieseasesofFerrets.pdfENDOCRINE...

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