Misc Endocrinopathies Flashcards
Hypersomatotropism
- Overproduction of growth hormone
Acromegaly
- Syndrome that results from excessive GH production
What causes hypersomatotropism and acromegaly?
- Functional adenoma in the pars distalis of the anterior pituitary
What organ responds to the excessive growth hormone in acromegaly?
- Liver, which produces somatomedins AKA insulin like growth factors (IGF)
What is the most important insulin like growth factor?
- Somatomedin C (IGF-1)
- This leads to clinical signs of acromegaly
What condition is seen concurrently with acromegaly?
- DM almost always
When should you consider hypersomatotropism in a patient?
- Diabetic cat that is not well controlled by 2-4 months, does not go into remission with appropriate insulin and diet change, or requires an insulin dose of 1.5-2 U/kg or higher
Who gets acromegaly?
- Typically older cats (8-14 years)
- Males
What is the first sign of acromegaly?
- uncontrolled diabetes mellitus
- Weight gain with uncontrolled diabetes mellitus, where it should usually cause weight loss
Clinical signs of acromegaly
- Classic enlargement of extremities, jaw, tongue, forehead
- Clubbing of paws
- Organ enlargement
- Stridor due to growth of soft tissue in mouth and pharyngeal region
- Degenerative joint disease
- Cardiomegaly, systolic murmurs, interventricular septal thickening, thickening of left ventricle (congestive heart failure)
- Potential hypertension
- Potential CNS signs (large pituitary masses or diabetic neuropathy)
- Thickening of skin and excessive skin folds around the head and neck
- Renomegaly, proteinuria (glomerulosclerosis), diabetic nephropathy - chronic renal failure
Diagnosis of acromegaly
- usually accomplished using a combination of history, clinical signs, and multiple diagnostic tests
- No definitive test exists
- Potential testing could be IGF-1 concentration, GH levels (not in US), or advanced imaging like CT or MRI of the brain
Treatment of acromegaly
- Surgery
- Radiation
- Medical therapy
- Palliative
Surgery to correct acromegaly
- Transsphenoidal hypophysectomy
- Remission of DM common within 4 weeks
Radiation for acromegaly
- response variable
- Can take longer than a year
Medical therapy for acromegaly
- Somatostatin analogs, but still being researched
Palliative care for acromegaly
- Give lots of insulin and diet change (LOTS of insulin)
- Poor long term prognosis (CHF, CRF, CNS signs)
What usually causes acromegaly in dogs?
- Adenoma
- Excessive progesterone
Excessive progesterone in female dogs and acromegaly
- Exogenous administration
- Endogenous production seen in cycling older intact female dogs
- Triggers production of GH from mammary tissue
- Correct by spaying
Feline Cushing’s cause
- Noniatrogenic or spontaneous hyperadrenocorticism is rare in cats
- Iatrogenic HAC is also rare
Prevalence of PDH vs ADH in feline Cushing’s
- PDH more prevalent (75-80%)
- ADH (20-25%)
Feline Cushing’s PDH
- usually due to adenoma of pars intermedia or pars distalis of pituitary gland
- rarely pituitary carcinomas have been seen
Feline Cushing’s ADH
- usually caused by a benign functional adenoma of one adrenal (65%)
Clinical signs of Cushing’s in cats
- Most present with signs of diabetes potentially poorly controlled
- Excess of either endogenous or exogenous glucocorticoid leads to marked insulin resistance
- PU/PD LESS common
- More often weight loss
- Abdominal distension or “pot belly appearance”
- Panting, muscle atrophy, unkempt hair coat, bilateral symmetric alopecia
- Predisposition for infections (urinary, skin, respiratory, abscesses, toxoplasmosis, etc.)
Do you see weight gain or weight loss more commonly in feline Cushing’s?
- Weight loss
What should you consider when handling cats with Cushing’s?
- Fragile skin syndrome
- Tearing of the skin under normal conditions - HANDLE GENTLY!
- Do not develop calcinosis cutis
What signs could be due to pituitary macroadenoma in feline Cushing’s?
- CNS signs
- Blindness, abnormal behavior
Virilization in feline Cushing’s
- Spines on castrated males
- Virilization with sex hormones secreting adrenal carcinomas
CBC changes in feline Cushing’s
- Stress leukogram inconsistent
Chemistry changes in Cushing’s
- No steroid inducible ALP in cats
Urinalysis changes in feline Cushing’s
- Dilute urine rare with HAC in cats
- Lack of an effect of cortisol on feline ADH secretion or sensitivity
- USG can be affected by glucosuria (if DM)
- Can see proteinuria
Screening test of choice for feline Cushing’s?
- LDDST
- higher dose of dex used vs dogs (10x)
Other screening tests for feline Cushing’s
- ACTH stim (2/3 of cats with HAC will have cortisol concentrations within normal limits)
- UCCR - poor specificity but good sensitivity
Differentiation between ADH and PDH in feline Cushing’s
- HDDS (50% of PDH cats show no suppression)
- Endogenous ACTH
- Imaging - AUS, CT, MRI***
Palliative treatment in feline Cushing’s
- Not really an option
- They are miserable if untreated
- Fragile skin and 2° infections
Medical treatment for feline Cushing’s
- Trilostane (preferred)
- Mitotane (less effective)
- Metyrapone (enzyme inhibitor that may be effective in some cats)
Radiation in feline Cushing’s
- unreliable response
Surgical treatment of feline Cushing’s
- Hypophysectomy
- Bilateral adrenalectomy
Hypophysectomy
- Limited availability
- Expensive
Bilateral adrenalectomy for tx of feline Cushing’s
- Increased risk
- Poor wound healing
- Lifelong supplementation
Etiology of hyperaldosteronism
- Adrenocortical carcinoma
- Adenoma (unilateral or bilateral)
- Bilateral nodular hyperplasia
Who gets primary hyperaldosteronism (species)?
- Most commonly seen in cats
- Dogs can rarely be affected
- May be the most common adrenocortical disorder in cats
- Often misdiagnosed as CKD due to effects on the kidney
Who gets primary hyperaldosteronism (age)?
- Middle-aged to older cats
- Median 13 years old (5-20 years)
What are the primary clinical signs due to in primary hyperaldosteronism?
- Hypertension (end organ damage)
- Hypokalemia (not usually hypernatremia)
Other clinical signs of primary hyperaldosteronism
- Pendulous abdomen/mass
- PU/PD
- Muscle atrophy
- Arrhythmia
- Non-specific: panting, restlessness, anorexia, weight loss
Hypokalemia (<2.5mmol/L) in primary hyperaldosteronism clinical signs
- Polymopathy
- Muscle weakness that is episodic or acute
- Plantigrade stance (cat isn’t jumping)
- Cervical ventroflexion
- Inability to jump
- Lateral recumbency, collapse
Clinical signs attributable to hypertension
- Mydriasis
- Hyphema
- Loss of vision (retinal detachment, intraocular hemorrhage)
Physical exam findings with primary hyperaldosteronism
- Hypertension
- Ocular changes: intraocular hemorrhage, increased tortuosity, retinal edema, detachment
- hypokalemic polymyopathy
- Palpable mass in abdomen
- Arrhythmia
Laboratory abnormalities with primary hyperaldosteronism
- Hypokalemia and metabolic alkalosis are most important changes seen**
- Others are azotemia, increased phosphorus, increased CK, hyperglycemia, and hypernatremia
Diagnosis of primary hyperaldosteronism
- Ultrasound, CT, MRI
- Look at adrenals for evidence of a mass
- Evaluate for metastasis
- Evaluate for local invasion
Surgical treatment for primary hyperaldosteronism
- Adrenalectomy for unilateral adenoma or carcinoma
- High rate of complications leading to death
- Survivors live >1 year
Medical treatment for primary hyperaldosteronism
- Potassium supplementation (K gluconate)
- Aldosterone blocker (Spironolactone)
- Antihypertensives (Amlodipine)
Differentials for hypoglycemia
- Malnutrition
- Parasites
- Artifact
- Hepatic insufficiency
- Cellular consumption (WBC, e.g. with hepatozoon which causes a very high WBC)
- Xylitol toxicity
- Endocrine: Insulinoma, IGF (many tumors), insulin overdose, hormone deficiency (cortisol, growth hormone)
Insulinoma overview
- Pancreatic beta-cell tumors
- Excess production of insulin by a functional tumor
- Most common canine islet cell neoplasia
Are insulinomas usually benign or malignant?
- most are carcinomas
Species that get insulinomas
- Dogs: uncommon
- Cats: RARE
- Ferrets: common!!
Age predisposition of insulinoma
- 9 years average
Breed predisposition of insulinoma
- medium ot large breed dogs
Sex predisposition of insulinoma
- No sex predilection
Clinical signs associated with insulinoma
- Associated with hypoglycemia, but otherwise healthy
Physical exam findings associated with insulinoma
- Usually no significant abnormalities
- Overweight; anabolic effects of insulin
CBC findings on insulinoma
- Normal
Chemistry panel findings on insulinoma
- Marked hypoglycemia
- +/- mild hypokalemia
- +/- elevated ALP or ALT (if metastasized to the liver)
Urinalysis findings on insulinoma
- Unremarkable usually
Diagnosis of insulinoma
- CBC/Chem/UA
- Paired insulin/BG levels
- Abdominal radiographs/ultrasound/CT
Paired insulin/BG levels - when to obtain the sample?
- Blood sample must be obtained when the animal is hypoglycemic
Hallmark of insulinoma with paired insulin/BG levels
- Increased blood insulin concentration despite a low blood glucose concentration
Abdominal radiographs for insulinoma
- Usually normal, as they are very small tumors
Abdominal ultrasound for insulinoma
- Pancreatic mass in 50%
- Metastatic lesions in 20% (liver, lymph nodes)
CT findings for insulinoma
- Pre-op for larger tumors
Surgery insulinoma treatment
- Treatment of choice…
- Has often metastasized
- High recurrence rate
- Difficult to find tumors
Chemotherapy insulinoma treatment
- Streptozotocin
- Destroys beta cells in pancreas and metastatic sites
- Remission in some dogs
- Nephrotoxic
Prognosis if insulinoma treated with chemotherapy vs surgery
- Prognosis similar to surgery
- surgery usually preferred because of the nephrotoxicity of the chemotherapeutic agents
Medical management of insulinoma
- Avoid sharp rises in BG
- Frequent, small meals every 4-6 hours
- High in protein, fat, and complex carbs
- Avoid simple sugars
Anti-insulin drugs for insulinoma
- Glucocorticoids
- Diazoxide
- Somatostatin (octeotide)
- Glucagon
Glucocorticoids for insulinoma
- Increase gluconeogenesis, decrease BG uptake, stimulate glucagon secretion
Diazoxide for insulinoma
- Inhibits insulin release
- Very expensvie
Somatostatin for insulinoma
- Extremely expensive
- Antagonizes insulin
Glucagon for insulinoma
- Increases gluconeogenesis
Prognosis of insulinoma
- 12-14 months survival time (including dogs that went to surgery)
Prognosis of insulinoma with young dogs
- worse
Insulinoma post-op hyperglycemia/normoglycemia vs hypoglycemia
- Better prognosis if hyper or normoglycemia
