Endocrinology Flashcards
1
Q
From what structure does the anterior lobe of the pituitary develop?
A
Adenohypophysis (which develops from Rathke’s pouch)
2
Q
From what structure does the posterior pituitary develop?
A
Neurohypophysis
3
Q
The neurohypophysis is an extension of what?
A
The hypothalamus
4
Q
T/F: The anterior pituitary is a collection of nerve endings that stores and releases hormones produced by the hypothalamus.
A
False: it’s the POSTERIOR pituitary that does this
5
Q
What are the five cell types of the anterior pituitary?
A
- Corticotrophs
- Thyrotrophs
- Gonadotrophs
- Somatotropin’s
- Lactotrophs
6
Q
What hormone from the hypothalamus stimulates corticotrophs and what does it cause them to release?
A
Corticotropin-releasing hormone (CRH) stimulates them to release adrenocorticotropic hormone (ACTH)
7
Q
What hormone from the hypothalamus stimulates thyrorophs and what does it cause them to release?
A
Thyrotropin-releasing hormone (TRH) stimulates them to release thyroid-stimulating hormone (TSH)
8
Q
What hormone from the hypothalamus stimulates gonadotrophs and what does it cause them to release?
A
Gonadotropin-releasing hormone (GnRH) stimulates them to release leuteinizing hormone (LH) and follicle stimulating hormone (FSH)
9
Q
What hormone from the hypothalamus stimulates somatotrophs and what does it cause them to release?
A
Growth hormone-releasing hormone (GHRH) stimulates them to release growth hormone (GH)
10
Q
What hormone from the hypothalamus stimulates lactotrophs and what does it cause them to release?
A
It’s unknown what acts on lactotrophs to stimulate release, but they secrete prolactin
11
Q
What is the inhibitory hormone of somatotrophs?
A
Somatostatin (aka growth hormone inhibitory hormone). It is the same somatostatin that is found in the GIT, just located in the brain
12
Q
What is the inhibitory hormone that acts on lactotrophs?
A
Prolactin inhibitory hormone (PIH)
13
Q
Does the posterior pituitary produce hormones?
A
NO - it stores and releases hormones produced in the supraoptic and paraventricular nuclei of the hypothalamus
14
Q
What hormone is produced by the supraoptic nuclei and what is its function?
A
Vasopressin/antidiuretic hormone (ADH) —> acts on V2 receptors in the collecting ducts of the nephron which results in insertion of aquaporin-2 channels for reabsorption of water
15
Q
What hormone is produced by the paraventricular nuclei and what is its function?
A
Oxytocin —> causes uterine contraction, lactation, and promotes maternal nurturing behavior
16
Q
Growth hormone is also known as what?
A
Somatotropin
17
Q
What are the functions of growth hormone?
A
- Increase protein synthesis
- Increase mobilization of fatty acids from adipose tissue —> lipolysis and fatty acid oxidation (protein-sparing effect) during fasting
- Decreased utilization of glucose throughout the body
18
Q
What molecule mediates most actions of growth hormone?
A
Insulin-like growth factors (IGFs) aka somatomedins
19
Q
Where is IGF-1 predominantly made?
A
Liver —> will be produced in response to GH
20
Q
Development of IGF-1 within the liver from the action of growth hormone is dependent on what?
A
Insulin
If you have a diabetic that has not been treated with insulin yet they could have falsely low IGF-1 levels just because there isn’t enough insulin in the portal vein
21
Q
IGF-1 has inhibitory effects on GH production through what effects?
A
- Direct inhibition of GH
- Upregulation of somatostatin which will result in decreased GH production by the hypothalamus
22
Q
What hormone will influence release of GH from the pituitary?
A
Ghrelin
23
Q
GH predominates in the __ state
A
Fasting
24
Q
GH has insulin __
A
Antagonism
25
Insulin-like activity INCREASES/DECREASES in response to IGF-1
Increases
26
What non-hormone factors stimulate growth hormone secretion?
1. Decrease BG
2. Decreased FFA
3. Increased amino acids
4. Starvation, fasting, protein deficiency
5. Trauma, stress, excitement
6. Exercise
7. Testosterone, estrogen
8. Deep sleep (stages II, IV)
Remember hormones are GHRH and ghrelin
27
What non-hormone factors inhibit GH secretion?
1. Increased BG
2. Increased FFA
3. Aging
4. Obesity
Remember hormones are GHIH (somatostatin) and Somatomedins (IGFs)
28
Pituitary dwarfism is also known as
Congenital hyposomatotropism
29
What dog breeds are typically associated with pituitary dwarfism?
GSDs, Karelian bear dogs, saaroloos wolfhound, Czechoslovakian wolf dog
**Rare in cats
30
What mutation is associated with pituitary dwarfism and how is it inherited?
LHX3 mutation, autosomal recessive
31
What is the pathophysiology of pituitary dwarfism?
Pituitary cysts or pituitary hypoplasia —> unclear if the cysts cause the hypoplasia or are a consequence of it
32
In GSDs with pituitary dwarfism, what hormone abnormalities might you find on screening tests?
Combined GH, TSH, and prolactin deficiency
33
What age do pituitary dwarfism patients typically present?
3-5 months of age
34
What are common musculoskeletal clinical signs associated with pituitary dwarfism?
Musculoskeletal:
- Proportionate growth failure (unlike congenital hypothyroidism where short legs and big head)
- Pointed nose/fox like facial features
- Delayed closure of growth plates
- Delayed dental eruption
35
What are common dermatologic clinical signs associated with pituitary dwarfism?
Dermatological:
- Soft woolly hair coat
- Lack of guard hairs
- Hair loss (areas of wear - collar, sitting)
- Hyperpigmented, scaly, thin wrinkled skin
- Papules, pyoderma, comedones
36
What are common reproductive clinical signs associated with pituitary dwarfism?
- Cryptorchidism
- Testicular atrophy
- Persistent anestrus
37
What CBC and chem findings might you find with pituitary dwarfism?
**Often normal, but may see
CBC: mild anemia due to hypothyroidism
Chem: hypophosphatemia (b/c of changes happening at bone), hypoalbuminemia, azotemia (develops over time)
38
How is pituitary dwarfism diagnosed?
Genetic testing for LHX2 —> if positive, no further testing needed
Growth hormone stimulation test —> GH measurement after stimulation with GHRH, colonizing, xylazine, ghrelin **DIFFICULT TO PERFORM**
39
How is pituitary dwarfism treated in dogs?
1. Human-recombinant, porcine, ovine, or bovine GH supplementation (usually porcine b/c it’s the most genetically similar)
2. Progesterone —> induces GH synthesis in the mammary gland
No protocols described in cats
Response: Often see regrowth of secondary hair, some dogs may develop a full hair coat. May see linear growth determined by status of growth plates at time of therapy (although typically very little improvement).
Risk of treatment leading to DM b/c of progesterone
Prognosis: guarded even with treatment; dogs usually euthanized by 3-5y of age if not treated
40
Hypersomatotropism is also known as
Acromegaly
41
What is the typical signalment of an acromegalic patient?
Feline
~10y
Male (88%) >>> female
DSH > DLH
42
What is the pathophysiology of acromegaly in CATS?
GH-producing acidophil pituitary adenoma —> produces too much GH —> increased IGF-1 levels resulting in proliferation of bone, cartilage, soft tissues, and and increased size of organs
43
Despite increased IGF-1 levels, acromegalic cats are typically still insulin resistant. Why?
The increased IGF-1 levels are unable to counteract insulin-resistance induced by excessive GH concentrations —> the GH is too excessive they can’t convert enough GH to IGF-1
44
What are common clinical signs of acromegaly in cats
Think DM signs: PU/PD, plantigrade stance, polyphagia (from DM and the excessive production of GH)
Also broadening of head, prognathia inferior, widening of interdental spaces, respiratory stridor +/- distress (due to increased/thickening of oropharyngeal tissue), CNS signs
WEIGHT PATTERNS ARE HUGE CLUE
Typically these cats will lose weight due to the secondary DM but stabilize with super high doses of insulin and then actually gain weight which doesn’t usually happen in uncontrolled diabetics
45
At what dose of insulin should you start questioning if a cat has acromegaly?
When you get above 2 units/kg q12h
46
What organs typically become enlarged in acromegalic cats?
Heart
Kidneys
Spleen
Pancreas
Adrenals
Thyroid
47
What percentage of cats with acromegaly can have neurologic signs?
10-15%
48
What abnormalities might you see on CBC in an acromegalic cat?
Relative erythrocytosis due to dehydration
49
What abnormalities may you see on chemistry panel in an acromegalic cat?
- Hyperglycemia
- Hyperproteinemia (due to dehydration)
- Mild increases in ALT and ALP activity (due to mobilization of fats and sugars that cause hepatocytes to swell —> vacuolar change)
- Hyponatremia b/c glucose pulls more water into vascular space to dilute out sodium
- Hyperphosphatemia without azotemia (GH/IGF-1 mediates increased renal tubular absorption of phosphorus; will look like decreased GFR without azotemia)
- Azotemia (50% of acromegalic cats develop CKD within 8-36m of diagnosis; mechanism not fully understood but may be due to glucosuria causing glomerulopathy)
50
What abnormalities might you see on a UA with an acromegalic cat?
- Glucosuria
- Proteinuria (when azotemia present)
51
When should you consider testing for acromegaly?
Cats with difficult to regulate DM in which other common concurrent problems (stomatitis/gingivitis/UTIs, corticosteroid administration) have been eliminated
Remember >2U/kg of insulin q12h
52
What is the diagnostic test of choice for acromegaly?
IGF-1 measurement
53
Why is IGF-1 measurement preferred for diagnosis of acromegaly in cats?
- Reflects 24h GH secretion
- Is not secreted in pulses (unlike GH) so single random sampling is sufficient
- Structure is conserved across species, so more assay availability (unlike GH)
- Stable, so serum sample can be sent by regular mail (GH cannot)
54
What concurrent disease can decrease IGF-1 making interpretation of the assay difficult if acromegaly is of concern?
- Malnutrition
- Liver failure
- Renal failure
- Hypothyroidism
- Poorly controlled DM
- Oral estrogen intake
55
Why might IGF-1 be normal when assessed prior to starting insulin therapy in acromegalic diabetic cats?
Remember IGF-1 is produced because of insulin in the portal vein —> in cats with diabetes, it may be low because there is not enough insulin available to stimulate IGF-1 production
56
If IGF-1 is normal in a cat you suspect has acromegaly and you have not yet started insulin, when should you recheck?
6-8 weeks after insulin therapy is initiated
57
What is the “gray zone” for IGF-1 testing?
800-1000ng/mL - if in this range and suspicion for acromegaly is high, consider pituitary imaging
58
What are goals of treatment of acromegaly?
Two goals:
1. Treat acromegaly (sx, SRT)
2. Treat concurrent DM
59
T/F: Pituitary surgery is the gold standard for treatment of acromegaly
TRUE - but technically demanding, one study showed remission of DM in a cat 3 weeks after surgery
60
What medications are used to decrease GH secretion?
Somatostatin analogs (octreotide, lanreotide, pasireotide)
Also dopamine agonist L-deprenyl
All showed very little effect EXCEPT pasireotide
61
A 2017 study (Gostelow et al, JVIM) showed which somatostatin analong to be most effective in treatment of acromegaly?
Pasireotide
A 2017 study (Gostelow et al, JVIM) showed long-acting pasireotide induced diabetic remission in 3/8 cats
62
SRT shows improvement in symptoms and improved control of DM in what percentage of cats?
Improvement of symptoms in 2/3 of cats
Improved control of DM in 50-92% of cats
63
What is prognosis for acromegaly with and without treatment?
Guarded to poor if not treated (months)
If they have pituitary surgery or SRT - favorable outcomes, MST 25m
64
What is the etiology of acromegaly in DOGS?
Almost always induced by endogenous or exogenous progestogens giving rise to GH hypersecretion from the mammary gland
AKA they’re either getting progesterone or have a progesterone-secreting tumor in the mammary glands
65
What breeds of dogs are predisposed to acromegaly?
Swedish and Norwegian Elkhounds
Border collies
Beagles
66
T/F: GH-producing tumors in the pituitary gland of dogs resulting in acromegaly are very common
FALSE - very rare, opposite of cats
Somatotrophic adenoma only described in 2 dogs
67
What is the treatment for acromegaly in dogs?
If diestrus-associated acromegaly in intact females: OHE
If due to exogenous progesterone - stop giving them
If a mass producing progesterone - remove the mass
68
What are the three zones of the adrenal cortex and what do they produce?
1. Zona glomerulosa - mineralocorticoids (aldosterone)
2. Zona fasciculata - glucocortocoids (cortisol)
3. Zona reticularis - sex hormones (progesterone, estrogens, androgens)
“The deeper you go the better it gets”
Salt —> sugar —> sex
69
All hormones produced by the adrenal cortex are derived from what molecule?
Cholesterol
70
Conversion of cholesterol to aldosterone is regulated by what enzyme?
Aldosterone synthase
Zona glomerulosa is rich in aldosterone synthase
71
Conversion of cholesterol to glucocorticoids (cortisol) and sex hormones is regulated by what enzyme?
17a hydroxylase Aka cholesterol desmolase
Zona faciculata and reticularis are both rich in this enzyme (inhibitors of this enzyme exist in people)
72
T/F: Trilostane is a 17a hydroxylase inhibitor
FALSE - it’s a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase
73
What is the half life of corticotropin-releasing hormone (CRH) in plasma?
~60 minutes
74
CRH produced in the __ is released by the __ and acts on __ in the __. This stimulates release of __ which stimulates secretion of __ from the adrenal gland.
CRH produced in the PARAVENTRICULAR NUCLEI is released by the HYPOTHALAMUS and acts on CORTICOTROPHS in the ANTERIOR PITUITARY. This stimulates release of ACTH which stimulates secretion of GLUCOCORTICOIDS from the adrenal gland.
75
Adrenocorticotropic hormone (ACTH) is derived from what?
POMC - proopiomelanocortin
76
What is the half life of ACTH in plasma?
~10min
77
T/F: ACTH causes some secretion of mineralocorticoids and sex hormones, but to a lesser extent than glucocorticoids
True
78
What hormone provides negative feedback on the hypothalamic-pituitary-adrenal axis?
Cortisol
79
Why does elevated cortisol result in elevated blood glucose?
Causes increase in gluconeogenesis and decrease in insulin responsiveness and production, and decreases glucose utilization b/c there’s less insulin in circulation
80
What are the five effects of cortisol?
1. Increased blood glucose
2. Decreased insulin sensitivity
3. Increased protein mobilization
4. Increased mobilization of fat
5. Decreased inflammation and immune system function
81
How does cortisol cause increased protein mobilization?
Decrease in cellular proteins while increasing production of proteins from liver and in plasma
82
How does increased cortisol decrease inflammation and immune system function?
1. Decreases expression of adherence molecules on sides of blood vessels —> less migration of WBCs into interstitium
2. Decreases permeability of capillaries —> less diapedesis
3. Decreases lymphocyte production —> lymphopenia on stress leukogram
4. Increases lysosome stabilization w/in phagocytes —> less able to fight off pathogens
83
What does the SMILED acronym for a stress leukogram mean?
Segs, monos increased
Lymphs, eos decreased
84
Do the majority of dogs have adrenal or pituitary dependent hyperadrenocorticism?
Pituitary-dependent (PDH) —> 85% have pituitary tumors
85
What percentage of dogs with hyperadrenocorticism have adrenal tumors?
15%
86
Iatrogenic hyperadrenocorticism result from?
Exogenous steroid administration
87
Bilaterally adrenomegaly is associated with ADH or PDH?
PDH - increased ACTH stimulation from pituitary acts on both adrenals
Negative feedback loop from cortisol doesn’t work
88
Unilateral adrenomegaly with atrophy of the contralateral adrenal gland is consistent with ADH/PDH?
ADH
Negative feedback loop from cortisol still works and you get decreased ACTH production to act on the unaffected adrenal gland
89
Canine Pituitary tumors are commonly adenoma or carcinomas?
Adenomas (carcinomas are rare)
90
Are most pituitary adenomas more commonly micro or macro and what is the size cutoff?
Most commonly microadenomas (<10mm)
Macroadenoma = >10mm
91
What percentage of dogs at diagnosis of a pituitary adenoma have a tumor <3mm?
21-48%
92
Adrenal tumors are commonly UNILATERAL/BILATERAL
Unilateral
93
Adrenal tumors > ___cm are more likely to be carcinomas
>2cm
Also those that are invading regional vasculature
94
What is the common signalment of patients with hyperadrenocorticism?
Dogs
Middle aged to older (>= 89% older than 6y)
Poodles, Dachshunds, terriers, Beagles, GSDs, Labs
95
ADH/PDH tends to occur more in smaller dogs, and ADH/PDH tends to occur more in larger dogs
PDH in smaller dogs
ADH in larger dogs
96
What breeds are more commonly associated with PDH?
Poodles
Dachshunds
Terriers
Beagles
97
What breeds are more commonly associated with ADH?
Poodles
GSDs
Dachshunds
Labradors
98
How does hyperadrenocorticism result in polyuria?
Increased cortisol inhibits ADH’s action on V2 receptors leading to secondary nephrogenic diabetes insipidus, so you get polyuria
USG is <1.015, often less than 1.008
99
Why do dogs with hyperadrenocorticism get muscle wasting?
Cortisol causes protein catabolism
100
Why does calcinosis cutis develop with hyperadrenocorticism?
Cortisol causes secondary hyperparathyroidism (90% of dogs with HAC have high PTH) —> leads to Ca & Phos deposition
101
Why do dogs with HAC get hepatomegaly?
Cortisol causes increased protein, fat, and glucose mobilization —> vacuolar hepatopathy —> hepatomegaly
102
Why do dogs with HAC get a “pot bellied” appearance
Hepatomegaly, weakened abdominal muscles, abdominal fat accumulation, enlarged bladder from polyuria all contribute
103
Why do dogs with HAC have increased panting?
Weakened respiratory muscles, hepatomegaly, and decreased lung compliance (from pulmonary/bronchial mineralization) all contribute
104
What CBC changes may you see in dogs with HAC?
1. “Stress Leukogram” - SMILED
- Neutrophilia and monocytosis from steroid-enhanced demargination
- Lymphopenia from steroid-induced lymphocytes
- Eosinopenia from bone marrow sequestration of eosinophils
2. Mild polycythemia - cortisol tells BM to make more RBCs
3. Thrombocytosis (75-80% of dogs) - cortisol tells BM to make more platelets
105
What chemistry changes can be seen with HAC?
1. Liver enzyme changes
- ALP >>> ALT (80-90%) due to corticosteroid induced ALP (cALP) coming from bile canilicular membranes of hepatocytes
- Mild ALT increase (<500U/L) b/c of swelling of hepatocytes from the vacuolar hepatopathy
2. Hypercholesterolemia and hypertriglyceridemia b/c cortisol results in lipolysis
- Results in lipemia
106
What UA changes might you see in a dog with HAC?
1. Hyposthenuria to isosthenuria - USG <1.020 but often <1.008
2. Proteinuria - occurs in >50% of dogs with HAC
- Usually UPC <5, and they never get secondary hypoalbuminemia
- Glomerulosclerosis, glucocorticoid-induced glomerular hypertension
3. UTIs - found in 50% of dogs with hyperadrenocorticism, but <5% have clinical signs of infection (relates to decreased diapedesis of WBCs)
107
What changes to pre- and post-bile acids may you see with HAC?
May be mildly increased, occurs in about 30% of dogs with HAC
108
T/F: 55% of HAC dogs without pancreatitis can have positive SNAP cPLs
True
109
cPLI has been shown to be HIGHER/LOWER In dogs with HAC who do not have pancreatitis
HIGHER
Basically don’t assume they have active panc if you’re suspicious of HAC
110
Why do dogs with HAC often have a secondary hypothyroidism?
Cortisol alters thyroid hormone binding to plasma proteins, metabolizes thyroid hormone and decreases peripheral deionization of T4 and T3
111
What percentage of dogs with HAC have hypertension, and what is the proposed mechanism?
31-86%
Etiology is unclear but thought to result from increased sensitivity to norepinephrine
112
What potential complication of HAC is the primary driver for treatment?
Development to PTEs
113
T/F: A urine cortisol:creat ratio can diagnose Cushings
NO - used to think it would help rule it out, but even that is not as sensitive
Sensitivity used to be 99%, new study showed 75%
Low specificity
114
What test is the only way to diagnose iatrogenic Cushings?
ACTH stim test (dog will have PU/PD and ALP, but ACTH stim looks like Addisonian)
115
What is Cortrosyn?
ACTH
116
What is the cutoff for an “exaggerated” response on a post sample of the ACTH stim test that would indicate Cushings disease?
<22ug/dL
Post-ACTH values:
Normal: <18ug/dL
Grey zone: 18-22ug/dL **if the patient has clinical signs and falls in this value, either do a LDDST or new guidelines say ok to assume they’re Cushinoid
Exaggerated: >22ug/dL
117
Steps for interpreting LDDST
1. Look at 8h mark to determine who is Cushinoid - if cortisol is >1.4ug/dL, they’re Cushinoid
2. Look at 4h mark - if they suppress <1.4ug/dL, it’s definitely pituitary dependent OR if 4 or 8h is <50% of baseline, it’s PDH
Remember adrenal dependent is overproduction of ACTH and negative feedback is not intact, so they don’t care if you give more cortisol
118
T/F: You can use a high dose dex suppression test to determine if a dog has HAC or not
NO - it is a differentiating test - it will NOT tell you if a dog has Cushing’s or not, must do a LDDST prior for this
119
How much more dexamethasone are you giving with a HDDST vs. LDDST?
10x
120
How to interpret HDDST?
1. If 8h sample is <1.4mg/dL (or lab cutoff) = PDH
2. If 4h sample <1.4mg/dL (or lab cutoff) = PDH
3. If 4h or 8h sample is <50% of baseline = PDH
If none of the above are met = PDH or ADH —> imaging or eACTH
121
Treatment of ADH?
Adrenalectomy, especially if tumor >2cm
122
Treatment for PDH?
Surgery - hypophysectomy especially for pituitary macroadenomas
RT can be considered
Medical management - trilostane, mitotane, ketoconazole
123
How long after starting a dog on trilostane or after changing a dose should you check an ACTH stim test?
10-14 days
**test 4-6h post pill**
124
What is the difference between mitotane and trilostane
Trilostane effects are reversible, mitotane is not
125
What is the MOA of mitotane?
It’s adrenocorticolytic - causes selective necrosis of the zona fasciculata and reticularis (it’s thought the zona glomerulosa is resistant)
126
Why is mitotane not preferred for ADH treatment over trilostane?
MST not statistically different between drugs, and more side effects with mitotane
127
What is the prognosis for untreated HAC based on a 2017 study?
MST 506 if untreated vs. MST not reached with treated group
New consensus is to treat b/c it does increase lifespan
128
T/F: HAC is rare in cats and most are adrenal dependent.
False - it is rare, but most are pituitary dependent (80% PDH, 20% ADH)
129
What percentage of feline adrenal tumors are adenomas vs. carcinomas?
50% adenomas, 50% carcinomas
130
What are clinical signs of HAC in cats?
80% of cats are diabetic at time of diagnosis
PU/PD - not present until development of DM
**SKIN FRAGILITY
Weight loss (not weight gain)
131
How do chemistry findings in cats with HAC differ from dogs?
- High ALP activity is NOT a consistent finding (10-20%) - cats don’t have the corticosteroid induced isoenzyme like dogs
- Hyperglycemia, glucosuria in 90% of cats
- Hypercholesterolemia in 50% of cats
- Elevated ALT in 33% of cats
132
T/F: The ACTH stim test is just as sensitive in cats as dogs.
FALSE - has poor sensitivity in cats (30-50%), best used to look for Addisons
133
What is the test of choice to diagnose HAC In cats and how does it vary from dogs?
LDDST - use the HDDST dog dose of dexamethasone (0.1mg/kg)
134
Are mitotane or ketoconazole recommended for treatment of HAC in cats?
NO b/c of side effects
135
What is the prognosis for HAC in cats?
<50% survive beyond one year b/c o the skin stuff and DM
136
Why does the body need cortisol (aka what does it mediate in the body)?
- Hepatic gluconeogenesis and glycogenesis
- Protein and fat metabolism
- Maintain vascular reactivity to catecholamines
- Maintain endothelial integrity
- Maintain GI mucosa (via influence of digestion and intestinal absorption, and increasing brush border enzymes)
137
What are consequences of hypocortisolemia?
- Hypoglycemia
- Muscular weakness, increased susceptibility to stress
- Hypotension
- Increased vascular permeability leading to hypoalbuminemia and hypovolemia
- Vomiting/diarrhea, weight loss
- Hypoalbuminemia, hypoglobulinemia, hypocholesterolemia
138
What regulates aldosterone secretion (4 pathways)?
1. Renin-angiotensin axis
2. Increased plasma potassium concentration
3. Increased plasma sodium concentration (minor)
4. Increased plasma ACTH concentration (minor)
139
What is the most prominent promoter of aldosterone release?
Angiotensin II
Also K+
140
If you remove the pituitary, will you have a mineralocorticoid deficiency?
NO - b/c ACTH is a minor player in mineralocorticoid secretion
141
What cells within the collecting duct does aldosterone act on?
Principle cells - activates NaKATPase pump to increase potassium into cell and moving it into urine, pulls sodium into cell and puts that out into plasma —> conserve body salt
Intercalated cells - results in H+ ions being excreted into urine
142
What electrolyte changes are seen with hypoaldosteronism?
Hyponatremia - b/c not able to absorb it from urine
Hypochloremia - b/c chloride follows sodium
Hyperkalemia - b/c there’s no exchange for sodium at principal cells
143
What is the mechanism through which hypotension develops with hypoaldosteronism?
Hyponatremia leads to concurrent loss of water —> decreased ECF —> hypovolemia —> hypotension
144
Most hypoadrenocorticism is PRIMARY or SECONDARY
PRIMARY (95%) - affecting adrenal glands, not pituitary
145
How much of the adrenal glands must be lost before hypoadrenocorticism develops?
>= 90%
146
What is atypical Addison’s?
Deficiency of glucocorticoids but not mineralocorticoids
(Typical Addison’s lacks both)
147
What is secondary hypoadrenocorticism?
Reduced secretion of ACTH from the pituitary gland. Leads to glucocorticoid deficiency ONLY
148
If you took a biopsy of the adrenal glands in a dog with Addison’s, what would you expect to see?
Severe lymphoplasmacytic inflammation and adrenocortical atrophy involving all layers of the adrenal cortex
This is suspected to be immune-mediated adrenal it is in majority of cases.
149
When you abruptly withdraw exogenous corticosteroids, do you cause primary or secondary hypoadrenocorticism?
SECONDARY
150
What is the typical signalment of a patient with Addison’s?
- Canine
- Breeds are typically Standard poodles, Portuguese water dogs, Nova Scotia Duck Tolling Retrievers, Bearded Collies, Great Danes
- Typically female (~70%) but this is not true for predisposed breeds
- Median age of onset 4y (younger in DTR (3y) and Great Danes
151
What breeds typically get Addison’s and what is the pattern of inheritance?
Standard poodle, Portuguese water dog, Nova Scotia Duck Tolling retriever - autosomal recessive
Bearded Collie - pattern of inheritance is unknown
152
What clinical signs of addison’s are attributed to glucocorticoid deficiency only?
Anorexia, vomiting, diarrhea, weight loss, lethargy/depression, weakness/shaking/shivering, rarely seizures
153
What clinical signs are attributed to mineralocorticoid deficiency?
PU/PD, hypovolemia shock, collapse, dehydration
154
What CBC findings might you see in an Addisonian patient?
Non-regenerative anemia (27% of cases)
**LACK OF STRESS LEUKOGRAM**
- Lymphocytosis (10%)
- Eosinophilia (20%)
- Neutrophilia (32%)
155
What abnormalities might you see on the chemistry panel of an Addisonian patient?
***HYPERKALEMIA (more common than Hyponatremia)
Hyponatremia
Hypercalcemia (30%)
Azotemia (88%)
Hyperphosphatemia (68%)
Hypoglycemia (17%)
Hypoalbuminemia (39%)
Hypocholesterolemia (7%)
Increased liver enzymes (40%)
156
What parasites can cause pseudo-Addison’s?
Whipworms
157
What changes might you expect on the urinalysis of an Addisonian dog?
Isosthenuria to minimally concentrated urine
This is due to hyponatremia which causes medullary washout (1.008-1.020)
158
How is Addison’s diagnosed?
Baseline cortisol: if >2ug/dL it rules out Addison’s
If <= 2ug/dL you need further testing with ACTH stim
159
How is Addison’s treated in the acute setting?
- Fluids
- Glucocorticoid supplementation (dexamethasone)
- Deoxycorticosterone pivalate (DOCP)
160
Why is it okay to use dexamethasone in and acute Addisonian crisis?
It does not cross react with the cortisol assay acutely (<24h), but can after several doses
161
How is Addions’s treated chronically/long term?
- Glucocorticoid supplementation (prednisone 0.05-0.2mg/kg/d) - double during times of stress
- Deoxycorticosterone pivalate (DOCP; 2.2mg/kg q28d)
Alternative is fludrocortisone (0.02mg/kg/d) which has both cortisol and mineralocorticoids, but has to be given daily and usually you need more glucocorticoids vs. mineralocorticoids so dose adjustment is challenging
162
How do you treat atypical Addions’s?
Mineralocorticoids only but most convert and need glucocorticoids too
163
What is prognosis for Addison’s?
Excellent!!
DOCP can be expensive in large dogs and might lead to euthanasia
Pred side effects may also lead to euthanasia
EDUCATE
164
T/F: Addison’s in cats is common
FALSE - very rare
165
What is the typical signalment of a cat with Addison’s?
1.5-14y
All DLH or DSH
Male = female
166
Is it common or uncommon to see bloodwork changes in cats with Addison’s?
UNCOMMON
167
Hyperaldosteronism is more common in CATS/DOGS
Cats
168
In feline hyperaldosteronism, is renin elevated or decreased?
Decreased - excess circulating aldosterone leads to renin suppression
169
What are the consequences of too much aldosterone?
- Hypernatremia
- Hypokalemia
- Hypertension
- Weakness
170
Is feline hyperaldosteronism typically unilateral or bilateral?
Unilateral
Usually unilateral adrenocortical adenoma (39%) or carcinoma (48%)
171
What is the typical age at which feline hyperaldosteronism is diagnosed?
Middle aged to older, mean age 12-13y
172
What are clinical manifestations of hypokalemia in feline hyperaldosteronism?
Hypokalemic polymyopathy - persistent and progressive weakness; ventroflexion of neck b/c they lack a nuchal ligament
173
At what degree of hypokalemia do you typically see hypokalemic polymyopathy
<3mg/dL
174
What clinical signs are typically associated with hypertension in feline hyperaldosteronism?
- Acute blindness and/or sudden change in eye color (can be due to intraocular hemorrhage or retinal detachment)
- Cardiac changes (murmur, cardiomegaly, ventricular hypertrophy)
175
What changes might you see on a chemistry panel with hyperaldosteronism?
- Hypokalemia (although absence does not rule it out)
- Serum sodium typically normal
- Elevated CK (especially with hypokalemic myopathy)
- +/- mild azotemia
176
When should you consider evaluation for feline hyperaldosteronism?
Any cat with
- An adrenal nodule and unexplained hypokalemia or hypertension
- Hypertension or hypokalemia refractor to therapy
177
How is feline hyperaldosteronism diagnosed?
1. Aldosterone:Renin ratio - will distinguish primary from secondary
- Primary: high ratio
- Secondary: low ratio
Problem is renin is not widely commercially available and is effected by meds like ACEis and beta-blockers, as well as dietary salt; additionally, aging and neutering cats may decrease plasma renin concentration in healthy ranges
2. Urine Aldosterone: Creatinine Ratio
3. Plasma Aldosterone concentration - markedly elevated in most cats with hyperaldosteronism; may be within upper end of RI in mild cases, so consider in light of serum potassium concentration (low potassium concentration is a potent suppressor of aldosterone secretion)
178
How is feline hyperaldosteronism treated?
Surgery for solitary adrenal masses —> typically curative
If unresectable, or if there is evidence of metastasis or bilateral hyperfunction:
- Address the hypokalemia w/mineralocorticoid receptor blockers (spironolactone) and potassium supplementation
- Address hypertension with calcium channel blockers (amlodipine) +/- ACEis
179
Per the ACVIM consensus statement on hypertension, are ACEis first line therapy for cats?
NO - they are in dogs, but cats don’t respond as robustly so typically they’re used for Proteinuria
180
The enzyme that is responsible for conversion of norepinephrine to epinephrine is under the influence of what despite being located in the adrenal medulla?
Cortisol
181
Typically NOREPINEPHRINE/EPINEPHRINE is more predominant in the adrenal medulla?
Epinephrine (70% vs. norepinephrine 30%)
182
Where are alpha 1 receptors located and what effect do they have?
Vascular smooth muscle —> vasoconstriction
183
Where are beta1 receptors found and what is their effect?
Myocardium —> increased HR and contractility
184
Where are beta2 receptors found and what is their effect?
Vascular smooth muscle —> vasodilation in skeletal muscle, arterioles, coronary arteries, and veins
Bronchioles smooth muscle —> relaxation/bronchial dilation
Intestinal smooth muscle —> decreases intestinal motility
185
In the urinary bladder, what type of receptors (alpha or beta) are responsible for increased sphincter tone and which are responsible for relaxing the detrusor
Alpha - increased sphincter tone
Beta - relax detrusor
186
In adipose tissue, what receptor type is responsible for increasing lipolysis?
Beta
187
What cells and where in the adrenal gland do pheochromocytomas arise?
Arise from catecholamine-producing chromaffin cells in the adrenal medulla
188
Are pheochromocytomas typically unilateral or bilateral?
Unilateral
189
What is the typical signalment of a pheochromocytoma patient?
Canine
Mean age 12y
No breed or sex predilection
190
When you have metastasis with a pheochromocytoma, do you typically see more norepinephrine or epinephrine?
Norepinephrine because there’s no cortisol in the blood to convert it to epinephrine
191
What are epinephrine and norepinephrine metabolized to and by what enzyme?
Epinephrine —> metanephrine
Norepinephrine —> Normetanephrine
COMT enzyme (catechol-O-methyltransferase)
192
Why do we measure normetanephrine and metanephrine rather than epi/norepinephrine?
Epi/norepinephrine are short lived
193
What are clinical signs associated with pheochromocytomas?
A LOT - they’re typically episodic and random, and can be many things. Severity is typically associated with tumor size
194
How are pheochromocytomas diagnosed?
- Hypertension (BP >300mmHg only identified in dogs with pheos)
- Urine metanephrines - specifically normetanephrines are more helpful than metanephrine
195
What is the treatment of choice for pheochromocytomas?
Adrenalectomy
196
What is the MOA of phenoxybenzamine?
Oral, non-competitive, non-selective alpha-adrenoreceptor blocker
197
What are negative prognostic factors for pheochromocytoma
Tumors >5cm
Evidence of metastasis or thrombosis
198
TRH released from the hypothalamus acts on ___ in the anterior pituitary to stimulate release of __, which travels to the thyroid gland and stimulates secretion of __ and __.
TRH released from the hypothalamus acts on THYROTROPHS in the anterior pituitary to stimulate release of TSH, which travels to the thyroid gland and stimulates secretion of T3 and T4.
199
The thyroid gland is composed of __ that are filled with __.
Composed of follicles
Filled with colloid
200
What is colloid in thyroid follicles?
A glycoprotein that is the base of what thyroid hormones are made of; also traps iodide
201
How many molecules of iodine are attached to T3 and T4?
T3 has 3
T4 has 4
202
How are T3 and T4 moved from colloid to blood stream?
T3 and T4 are bound to thyroglobulin in the colloid of thyroid follicles. When TSH binds the TSH receptor, a conformation change happens in the cuboidal cells lining the follicles and they take Thg-T3 and Thg-T4 into the cell, where they combine with lysozymes which cleave the thyroglobulin. T3 and T4 are released into blood stream, thyroglobulin is recycled.
203
What enzyme plays and important role in development of thyroid hormones within the colloid (basically getting iodine to connect to thyroglobulin-tyrosine complexes to form T3 and T4)?
Thyroid peroxidase (TPO)
204
What are the three roles of thyroid peroxidase?
1. Oxidates iodide to iodine
2. Organification - Attaching iodine to tyrosine residues of thyroglobulin to form monoiodotyrosine (MIT) and diiodotyroxine (DIT)
3. Coupling - combining MIT and DIT to form T3, or two DITs to form T4
205
What is the active form of thyroid hormone?
T2 - triiodothyronine
206
Which form of thyroid hormone increases with stress in people?
Reverse T3 - helps differentiate euthyroid sick syndrome in people, but not available in dogs
207
Thyroid hormone is secreted in primarily what form?
T4
208
What protein primarily transports thyroid hormone in the blood?
Thyroxine-binding globulin
209
Thyroid hormone has a HIGH/LOW affinity for plasma-binding proteins?
HIGH - released slowly to tissue cells (T3 faster than T4)
210
What enzyme converts T4 to T3 at the level of the tissues?
Deiodinases
211
What are genomic functions of thyroid hormones?
1. Activate nuclear receptors
2. Thyroid hormone receptor forms heterodimer with retinoid X receptor (RXR) at specific thyroid hormone response elements —> these are important for development of CNS, growth, cardiovascular effects
212
What are non-genomic functions of thyroid hormone?
1. Regulation of ion channels - has been show to increase activity of NaKATPases
2. Oxidative phosphorylation
213
What are the effects of thyroid hormone on growth and development?
1. Thyroid hormone acts synergistically with GH and IGF-1
2. Promotes Chandra genesis
214
What are the effects of thyroid hormone on metabolism?
1. Increased lipid metabolism —> fat mobilization
- Increases concentrations of FFAs in plasma
- Enhances oxidation of fatty acids
- Increases cholesterol synthesis BUT increases cholesterol reabsorption because it increases cholesterol conversion to bile acids, which lowers plasma cholesterol
2. Carbohydrate metabolism
- Enhances insulin-dependent entry of glucose into cells
- Increases gluconeogenesis and glycogenolysis
3. Protein metabolism
- Anabolic and catabolic —> when increased, catabolic predominates
215
What are the effects of thyroid hormone on vitamin consumption?
Thyroid hormone increases quantities of enzymes. Vitamins are essential parts of enzymes and coenzymes, so you get relative vitamin deficiency
216
What are the effects of thyroid hormone on the cardiovascular system?
1. Vascular
- Promotes vasodilation —> decreases SVR —> enhances blood flow
- Direct stimulation of erythropoietin synthesis —> erythrocytosis —> increases circulating blood volume which causes an increase in preload
- Decreased SVR will lead to RAAS activation, causing renal sodium retention by aldosterone, resulting in increased circulating blood volume —> increased preload
2. Heart
- Positive chronotropic effect: increases HR
- Positive iontropic effect: increases cardiac contractility
- Increased HR and contractility leads to increased cardiac output (b/c remember CO = HR x SV, and thyroid hormone is increasing both)
217
What are the effects of thyroid hormone on the GIT?
1. Increases appetite and food intake
2. Increases rate of digestive secretions
3. Increases motility of GIT such that we can see
- Hyperthyroidism —> diarrhea
- Hypothyroidism —> constipation (more in people than dogs)
218
What are the effects of thyroid hormone on the CNS?
Thyroid hormone is important for brain and neuronal development, specifically differentiation of oligodendrocytes making myelin
Excitatory effects on CNS
- Too much = anxiety, nervousness
- Too little = sluggish/dull
219
What are the three forms of hypothyroidism and some Ddx for each?
1. Primary = thyroid dysfunction
2. Secondary = TSH deficiency; issue is in the pituitary (ddx pituitary malformation, pituitary destruction from a mass/surgery/RT, Thyrotroph suppression from concurrent illness)
3. Tertiary = problem in hypothalamus; RARE; (Ddx hypothalamic mass)
220
What form of hypothyroidism is most common in dogs?
Primary - 95% of cases
221
What is the most common etiology primary hypothyroidism in dogs?
Lymphocytic thryroiditis - thyroid gland is invaded by lymphocytes, plasma cells, macrophages. Thought to be immune-mediated (thyroglobulin and TPO = main antigens)
222
What percentage of thyroid tumors cause neoplasticism destruction leading to hypothyroidism?
10%
223
How much of the thyroid gland needs to be destroyed before clinical signs will appear?
80%
224
Are thyroid tumors in dogs typically functional or nonfunctional?
Nonfunctional
225
What is the typical age of a hypothyroid dog?
Middle aged to older
226
What dog breeds are predisposed to hypothyroidism?
Golden retrievers
Doberman pinschers
227
What clinical manifestations of hypothyroidism do we see?
1. Metabolic - lethargy/inactivity, weight gain, mental dullness, cold intolerance
2. Dermatological - endocrine alopecia, hyperpigmentation, pyoderma, myxedema
3. Neuromuscular - Polyneuropathy/myopathy, vestibular signs (central or vestibular), facial/trigeminal nerve paralysis, seizures, disorientation, myxedema coma, laryngeal paralysis
4. Cardiovascular - bradycardia, cardiac arrhythmias
5. GI - esophageal hypomotility (megaE maybe but usually doesn’t get better when hypoT is treated so unclear the cause and effect); consolation (more common in people)
6. Repro - infertility, prolonged parturition
228
What is myxedema coma?
Accursed due to accumulation of mucopolysaccharides and hyaluronic acid in the dermis that binds water. Leads to profound weakness, hypothermia, bradycardia, non-pitting edema, hypo ventilation, and stupor leading to coma.
**THIS IS RARE**
229
What changes might you see on the CBC of a dog with hypothyroidism?
1. Normocytic, normochromic, non-regenerative anemia (30% of cases)
2. Target cells - due to cholesterol loading
230
What changes might you see on the chemistry panel of a dog with hypothyroidism?
1. Lipemia!!
2. Fasting Hypercholesterolemia in 75% of cases
3. Fasting hypertriglyceridemia
4. Mild increases in ALT, AST, and ALP activities
231
What is the gold standard diagnostic test for canine hypothyroidism?
TSH stimulation test - not done frequently b/c of expense of recombinant TSH
232
If a TSH stimulation test cannot be performed, what values are recommended to assess for hypothyroidism in a dog?
T4
fT4
TSH
233
Total T4 is lower in what breeds?
Sighthouds
234
A __ total T4 with a __ fT4 provides diagnosis of hypothyroidism when clinical signs and lab work are consistent.
Low normal total T4
Low fT4
235
Circulating cTSH is usually __ in primary hypothyroidism.
increased
**do not measure this alone, must be used in conjunction with T4 and fT4
236
What medications can affect thyroid testing?
Sulfonamides (↓ TT4, ↓ fT4, ↑ TSH)
- Block iodination of thyroglobulin
- Effect on thyroid function depends on dose & duration
- Only one that actually results in clinical signs of hypothyroidism!
Phenobarbital (↓ TT4, ↓ fT4, may ↑ TSH)
- NO clinical disease!
Glucocorticoids (↓ TT4, ↓ fT4, ↓ TSH)
- Influence peripheral metabolism of thyroid hormones
- Inhibit TSH release
Clomipramine (↓ TT4, ↓ fT4, does not affect TSH) - tricyclic antidepressant
237
What is levothyroxine?
Synthetic L-T4 sodium
238
Why do we treat hypothyroidism with T4 and not T3 if T3 is the active form?
So the body can determine how much T3 it needs
239
How long after starting treatment would you reassess thyroid levels in a hypothyroid dog?
6-8 weeks
240
What is the most common cause of primary hyperthyroidism in cats?
Adenomatous hyperplasia
- Usually bilateral (70%)
241
What are the environmental risk factors for hyperthyroidism?
1. Excess or deficient iodine in diets
2. Canned cat food with pop top lids
3. Soy isoflavones - genistein and daidzein inhibit TPO; diets with soy cause increased T4 and fT3
4. Selenium
5. Goitrogens - bisphenol (epoxy resins, polycarbonate plastics), polybrominated diphenyl ether flame retardants (PBDEs)
242
What is the typical age of a cat with hyperthyroidism?
13 years
243
What cat breeds are associated with a decreased risk of hyperthyroidism?
Tonkinese
British shorthairs
Burmese
Siamese
Himalayan
Abyssinian
244
What are the clinical manifestations of feline hyperthyroidism?
1. Metabolic - polyphagia, weight loss, hyperactivity, heat intolerance/cool seeking
2. Dermatologic - unkempt hair coat, alopecia, matted fur
3. Neuromuscular - tremors, weakness
4. Cardiovascular - tachycardia, heart murmur, gallop rhythm, hypertension
5. GI - vomiting (direct action of T4 on CTZ; also b/c they are overeating and have increased GI motility); diarrhea (due to increased GI motility)
6. Renal - PU/PD
245
What CBC changes might you see in a cat with hyperthyroidism?
1. Erythrocytosis - T4 stimulates BM precursors and EPO production
2. Increased MCV (in 22% of cases) - due to decreased RBC maturation time
3. Heinz bodies - cause more oxidative damage
4. Lymphopenia
5. Leukocytosis
246
What chemistry changes might you see in a cat with hyperthyroidism?
1. Increased liver enzymes (90% have increase in >= 1 LEZ)
- ALT can be mild to moderate (up to 4x)
- ALP - bone isoenzyme
- Hyperbilirubinemia
2. Azotemia
- Increased BUN
- Increased creatinine due to muscle catabolism and/or concurrent CKD
- Hyperphosphatemia - due to bone metabolism and/or concurrent CKD
3. Hyperglycemia (d/t stress or b/c thyroid hormone stimulates release of glucose in the bloodstream)
4. Hypokalemia - not as common as with hyperaldosteronism or CKD
247
What abnormalities might you see on the UA of a cat with hyperthyroidism?
1. Variable USG - most will have USG >1.035, 4% of cases have USG <1.015; SHOULD NOT BE <1.008 b/c the PU/PD is secondary to medullary washout
2. Proteinuria - resolves with treatment of hyperthyroidism
3. Bacteriuria infrequently, usually not clinical for it
4. Ketonuria due to high metabolic state
248
How is feline hyperthyroidism diagnosed?
Baseline total T4
249
T/F: If you have a cat with clinical signs of hyperthyroidism but get a normal tT4 on your first screening, you have ruled out hyperthyroidism.
NO - if they have clinical signs you should recheck a T4 in 1 month if signs are mild to moderate. If signs are severe, check an fT4, thyroid scintigraphy, or T3 suppression test
250
T/F: A tT4 in the upper half of the RI with a high fT4 is diagnostic for hyperthyroidism in a cat with appropriate clinical signs.
True
251
What is the MOA of methimazole?
Inhibition of thyroid peroxidase
252
What are side effects of methimazole?
1. GI - usually related to tablet and not transdermal form
2. Facial excoriation - can happen with either oral or transdermal form
3. Blood dyscrasias (bone marrow suppression) - Thrombocytopenia, neutropenia
5. Hepatotoxicity
6. Acquired myasthenia gravis - rare
253
What is the MOA of I131 treatment?
I131 emits gamma rays and beta particles. The beta particles (1-2mm) cause follicular cell death
254
What is the mechanism of the Y/D diet?
Deficient in iodine, and thyroid needs iodine to make thyroid hormone
255
What produces parathyroid hormone?
Chief cells of the parathyroid gland
256
Where does parathyroid hormone act? 3 sites
Renal tubules
Bone
Duodenum
257
Parathyroid hormone __ calcium and __ phosphorus.
Increases calcium
Decreases phosphorus
258
What is the main source of vitamin D in dogs?
Diet
This is why dogs with chronic enteropathy can have hypovitaminiosis D
259
What two organs are important for activation of vitamin D?
Kidneys
Liver
260
Where does vitamin D act? 2 sites
GI tract
Bone
261
Vitamin D __ calcium and __ phosphorus.
Increases calcium
Increases phosphorus
262
Where is calcitonin produced?
C cells of the thyroid
263
Where does calcitonin act?
Bone
264
Calcitonin __ calcium and __ phosphorus.
Decreases calcium
No action on phosphorus
265
What two main types of neoplasia have hypercalcemia mediated by PTHrp?
Lymphoma
AGASACA
266
What are ddx for hypercalcemia?
HOGS IN YARD (DRAGON SHIT)
Hyperparathyroidism
Osteolytic
Granulomatous (fungal)
Spurious (hyperlipemia)
Idiopathic (#1 in cats)
Neoplasia (MM, LSA, AGASACA)
Young
Addison’s
Renal
D - vitamin D toxicity
267
What are ddx for hypocalcemia?
Hypoparathyroidism
Vit D deficiency (PLE, EPI)
Pancreatitis
Eclampsia
Hypoalbuminemia (total)
Phosphate enema toxicity
268
Are parathyroid nodules usual singular or multiple, and are they benign or malignant?
Singular in 80-90% of cases
Typically adenomas (87% of cases)
269
What breed is the poster child for primary hyperparathyroidism?
Keeshonds
270
What chemistry panel abnormalities might you see with primary hyperparathyroidism?
1. Total hypercalcemia
2. Low normal to hypophosphatemia
3. Most NOT azotemic (PTH renal protective) - about 4% have azotemia
4. Increased ALP activity (40%) - bone isoenzyme (ALT typically normal)
271
What UA abnormalities might you see in a dog with hyperparathyroidism?
1. Mean USG 1.012
2. Hematuria
3. Pyuria
4. Bacteria
5. Calcium oxalate and calcium phosphate stones possible
272
T/F: Primary hypoparathyroidism is common.
False - rare
273
What are the five cell types of the endocrine pancreas and what do they secrete?
Alpha cells - produce glucagon
Beta cells - produce insulin
Gamma cells (aka PP cells or F cells) - produce pancreatic polypeptide
Delta cells - produce somatostatin
Epsilon cells - produce grehlin
274
What is the chemical structure of insulin?
Protein composed of A & B chains connected by two disulfide bridges
275
Canine insulin is most similar to what other species?
Porcine
276
Feline insulin is most similar to what other species?
Bovine
277
What are the net affects of insulin?
Lower blood concentrations of glucose, FAs & amino acids
Promote intracellular conversion to their storage forms of glycogen, triglycerides & protein
278
Presence of insulin required to move glucose into cells EXCEPT in what organs/cell types?
brain, liver, WBC, RBC
279
What stimulates insulin secretion?
Hyperglycemia
Increased free fatty acids in blood
Increased amino acids in blood
GI hormones (gastrin, CCK, secretin, GIP)
280
What is the rate limiting step for steroid hormone synthesis?
Cholesterol desmolase
281
How does insulin decrease gluconeogenesis?
Promoting protein synthesis in peripheral tissues
Decreasing activities of hepatic enzymes involved in conversion of amino acids to glucose
282
Hyperglycemia stimulates __ of insulin from __
Synthesis and release of insulin from pancreatic islet cells
283
Oral intake of glucose provides release of what GI hormones that also stimulate insulin?
Gastric
CCK
Gastric inhibitory polypeptide (GIP)
284
Glucagon stimulates beta cells in the pancreas to secrete what 4 compounds?
Insulin
Somatostatin
Epinephrine
Norepinephrine
285
In what three locations is glucagon produced?
Alpha cells of pancreas
Stomach (gut glucagon)
Small intestine (glicentin)
286
Where does glucagon exhibit it’s main effects and what does it do there?
Liver: increases cAMP which leads to decreased glycogen synthesis, increased glycogenolysis, and increased gluconeogenesis to increase blood glucose concentrations
Also promotes lipolysis and increases in FAs which negatively feed back on glucagon production
287
What factors stimulate glucagon secretion?
Hypoglycemia = MAIN FACTOR
Intestinal hormones (except secretin)
Increased blood amino acids
288
What factors inhibit glucagon secretion?
Increased somatostatin levels
Hyperglycemia
289
Glucagon levels will be ____ in syndromes of insulin insufficiency
Paradoxically elevated
290
Where is somatostatin synthesized and stored?
Pancreatic delta cells
291
What stimulates somatostatin release?
Hyperglycemia
Increased amino acids
Increased fatty acids
GI hormones released from upper GIT
292
Where does somatostatin act?
LOCALLY (paracrine fashion) - acts on islets of langerhans to decrease insulin and glucagon secretion
293
What are the primary actions of somatostatin?
Inhibits digestive processes by decreasing nutritive absorption and digestion
Decreases motility and secretory activity of the GIT and gallbladder
Inhibits secretion of all endocrine cell types of the islets of langerhans (effects are greater on alpha cells compared to beta cells) —> inhibits glucagon secretion
294
Of the pancreatic hormones, only __ stimulates somatostatin production.
Glucagon
295
What factors decrease insulin secretion?
Hypoglycemia
Fasting
Increased somatostatin
Alpha-adrenergic activity/leptin
Glucagon, growth hormone, and cortisol
