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ACVIM Specialty Exam > Endocrine > Flashcards

Endocrine Flashcards

1
Q

Apart from GHRH, what is another stimulus for GH secretion, and what is its origin & roles?

A

Ghrelin. More potent GH secretagogue than GHRH in young dogs. Produced & secreted from the stomach.
Potent regulator of energy homeostasis. Stimulates food intake, gastric & intestinal emptying.

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2
Q

Which conditions can suppress ghrelin in cats? Is this change reversible?

A

Suppressed in cats with HST & HST+DM.
Ghrelin levels increased in HST-DM cats post-RT –> reached similar levels to control cats, so a potential marker of treatment efficacy/monitoring (NB: IGF-1 remain unchanged). Negative feedback system with GH.

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3
Q

Metabolic effects of excessive growth hormone?

A

Direct effects: insulin resistance –> DM. Also lipolysis.

Increased insulin-like growth factor-1 (IGF-1) production –> increased tissue growth (note IGF-1 increases insulin sensitivity & decreases lipolysis - opp of GH).

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4
Q

Vitamin D metabolites?

A

Calcidiol = 25-hydroxycholecalciferol/hydroxyvitamin D3.
Calcitriol = 1,25-dihydroxycholecalciferol/dihydroxyvitamin D3.
Vitamin D binding protein
Vitamin D receptors – mostly in kidneys, duodenum (less in skin & ileum), dogs don’t really have active receptors in skin unlike humans
–> With steatorrhea & loss of fat-soluble vitamins, hypoCa can occur.

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5
Q

Vitamin D formation pathway?

A

Liver converts Vit D2 (eggs, fish) & D3 (fish, eggs + made in skin) into calcidiol + stores excess vit D.
Calcidiol is converted to calcitriol (biologically active form, 1000x potency for Vit D receptors) in the renal proximal tubules via 1-alpha hydrolase enzyme (produced in renal PTs > skin, immune cells, osteoblasts). Conversion of calcidiol to calcitriol requires PTH.
Excess calcidiol is converted to 24,25- dihydroxycholecalciferol (inactive form).

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6
Q

List 8 consequences of chronic hypercortisolism in dogs?

A

DM
Systemic hypertension
Proteinuria
Glomerulosclerosis
GB mucocele
Pancreatitis
Increased susceptibility to infections
PTE

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7
Q

How to differentiate histologically between phaeochromocytoma and cortical tumours?

A

Chromogranin stains medullary tumours.
Difficult to distinguish if benign or malignant histologically.

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8
Q

How to calculate urinary free water clearance? What changes are expected with SIADH?

A

Urinary free water clearance (%) = 1 - (Urine Na+ - Urine K+) / Serum Na
SIADH = low serum Na+ & negative free water clearance. I.e. low Na & water retention (effects of excessive ADH)

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9
Q

Abdominal organ changes seen in HST cats?

A

Increased kidney length, adrenal thickness & pancreas thickness

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10
Q

List types of autoimmune polyglandular syndromes (APS) reported in dogs.
Which is most common?

A

APS type 1: DM, ectodermal mucositis etc.
APS type 2: hypoA, hypoT.
- HypoA is the most common initial endocrinopathy observed in polyendocrine gland failure in dogs, usually followed by the development of hypoT.
APS type 3: liver cirrhosis + endocrinopathies

Tx considerations:
- Initiate tx for hypoA first, then tx for others (e.g. levothyroxine).
- Dogs with DM + hypoT - balance insulin dose & levothyroxine.

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11
Q

Are chemiluminescent assays reliable for fT4 measurement in dogs with hypoT?

A

No especially if they have thyroid globulin antibodies. 2015 study - 25-38% dogs with positive antibodies and hypothyroidism) had normal fT4 levels. Need to use equilibrium dialysis.

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12
Q

What % of cats have normalisation of T4 on an iodine-restricted diet, and at what time points does it typically occur? Are there any pre-treatment variables which affect outcome?

A

42% cats by 21-60days, 83% by 61-180 days (100% by this time in another study).
Cats with higher initial T4 had post-diet T4 that stayed above RI.

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13
Q

Gene mutation is reponsible for pituitary dwarfism in GSD? What other abnormality may this be associated with in GSD & Czech Wolfdogs?

A

LHX3 mutation
A-A instability

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14
Q

Consumption of what diets have been linked to thyrotoxicosis in dogs? Is this reversible?

A

Commercial meat-based foods/treats presumably contaminated by thyroid tissue
Reversible with diet discontinuation

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15
Q

Diagnostic utility of TSH for hyperT in cats?

A

High Sn (98% have undetectable levels) but poor Sp (69%). Increased Sp when combined with TT4/fT4.

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16
Q

What is the cortisol:ACTH ratio useful for?

A

Diagnosis of hypoA without use of synacthen.
HypoA dogs have LOW ratio. High Sn 100% & Sp 99%.
(Potential false positives due to overlap with dogs with HA-mimicking diseases)

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17
Q

What is the preferred test to diagnose phaeochromocytoma in dogs?

A

Urinary normetanephrine : creatinine ratio. No overlap with HAC or healthy dogs based on previous studies.

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18
Q

What findings from LDDST and/or UCCR following dexamethasone administration is consistent with PDH?

Plasma ACTH [ ] - PDH vs ADH?

A

50+% decrease in plasma cortisol or UCCR consistent with dex-suppressible hypercortisolism.
(Up to 30% PDH dogs don’t suppress)

PDH - plasma ACTH intermittently increased (unregulated/inappropriate secretion)
ADH - plasma ACTH low (suppressed due to neg feedback)

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19
Q

Pathophysiology of food-responsive HAC?
Diagnostic test findings?
Treatment?

A

GIP released at every meal abnormally triggers the release of cortisol by binding to aberrant receptors in the adrenal cortex.

Supportive
- Basal plasma ACTH concentration will be suppressed.
- CRH stimulation test –> ACTH slightly increased –> consistent with ACTH-independent HAC.
- Imaging - Bilateral adrenomegaly but pituitary gland WNL
Diagnostic
- Pre & 3hrs post meal: measure UCCR, plasma cortisol, plasma ACTH. Expect rise in UCCR & plasma cortisol, but plasma ACTH concentration will remains low-undetectable.

Treatments:
- Octreotide completely prevents meal-induced hypercortisolemia (people).
- Trilostane used in case report in a dog (given 2hr before meal).

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20
Q

What is an incretin? Name 2 examples and how it is degraded. What is its MOA?

A

GI hormones release from L or K cells in the GIT
Gucagon like peptide (GLP-1). E.g. exenatide.
- Cleaved by DPP-4 (another drug target = DPP-4 inhibitors)
- GLP-1 promotes insulin release in response to glucose, inhibit beta cell apoptosis, inhibits glucagon release & delays gastric emptying. Effects are glucose-dependent.
- In DM cats receiving insulin tx, concurrent exenatide ER formulation was associated with reduced insulin requirements & higher remission.

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21
Q

Which 2 transition metals may be beneficial in the treatment of DM cats? What are the mechanisms?

A

Chromium & vanadium. Co-factors for insulin function. Chromium improves glucose tolerance in healthy cats & vanadium improves CSx & fructosamine in DM cats.

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22
Q

What is the recommended CHO content of food for DM cats

A

JFMS consensus: <12-15% ME

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23
Q

What is acarbose? What is the effect in healthy cats and is this diet dependent?

A

Oral hypoglycemic agent affecting glucose absorption. Inhibits pancreatic amylase and alpha-glucosidase.

Reduced BG in cats fed a high CHO diet but not a low CHO diet. A low CHO diet was more effective than using this medication with a high CHO diet. Best used in cats that eat all their food at once.

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24
Q

What is the incidence of relapse in cats with diabetic remission? What factors can predict this?

A

30% relapse.
Fasting BG 7.5+ and impaired glucose tolerance predicted; taking 5 hours to normalise or BG increasing to 14+

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25
Q

What is the average dose required for Detemir insulin? Risks/considerations?

A

0.12IU/kg. Hypoglycemia in 22%, caution in small dogs.

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26
Q

Name an example of a sulfonylurea. MOA? Adverse effects?

A

Glipizide.
Stimulate insulin release by binding to ATP-sensitive K+ channels & blocking their activity within pancreatic beta cells. This closes K+ channels, depolarises cell membrane so leads to increased intracellular Ca2+&raquo_space; insulin release.
AE: GI signs, liver enzyme elevations, jaundice

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27
Q

Name an example of a meglitinide. MOA?

A

Nateglitinide.
Similar to sulfonylureas - closes ATP-sensitive K+ channels & stimulate insulin release. Short acting.

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28
Q

Name an example of a biguanide. MOA? Side effects?

A

Metformin.
Insulin sensitiser in target tissues; increases glucose uptake in muscle and reduces hepatic glucose production.
Lack of strong evidence for use, with only 1/5 cats exhibiting a response in one study and 1 cat died in a study testing it (unknown cause).
SE: potential lactic acidosis, GI signs

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29
Q

What is C peptide? What does it presence in circulation indicate?

A

C peptide is part of the proinsulin molecule (along with polypeptides A & B). It is packaged together with insulin into secretory granules & secreted in minute amounts (but in itself has no insulin activity).
Presence in circulation indicates presence of functional beta cells (so low to absent in Type 1 DM)

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30
Q

Glucose uptake & utilisation in which 4 organs/body systems is not influenced by insulin?

A

GIT - glucose absorption
RBC, kidneys, CNS - glucose utilization

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31
Q

T/F
Obesity induces an insulin-resistant state, and can predispose to development of DM in dogs.

Adipokine concentrations are decreased in DM dogs, like in people.

A

False - obesity does cause insulin resistance but not reported to directly cause DM in dogs.

False - not reported. BUT adiponectin may still protect beta cells against FA-induced apoptosis in dogs.

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32
Q

In what scenarios are dogs most likely to achieve diabetic remission?

A

DM associated with diestrus, pregnancy or ovarian remnant syndrome when serum GH & progesterone concentrations are increased.
* Impt to recognize & correct insulin resistant state EARLY; otherwise progressive loss of beta-cells increases risk of permanent insulin deficiency.
* Also, bitches that undergo DM remission following diestrus have high likelihood of developing permanent IDDM next estrus; so spay ASAP after DM diagnosis in these dogs.

Stopping insulin antagonist drugs (glucocorticoids, progestogens)
* Note these animals likely do not have normal beta-cell populations & are probably subclinical/pre-diabetic

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33
Q

During DM, …..lipase is decreased while ….lipase is activated. As a result hepatocytes produce more …….due to decreased clearance, and release of ……from adipocytes into circulation.

A

(Insulin inhibits lipolysis & FFA oxidation).

Lipoprotein lipase decreased
Hormone-sensitive lipase activated
TG-rich VLDL & chylomicrons
FFAs

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34
Q

List 5 drugs causing DM/hyperglycemia.

A

Glucocorticoids
Progestagens
Thyroxine (thyroid hormone)
Thiazide diuretics
Beta adrenergic agonists

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35
Q

What factors cause increased vs decreased serum fructosamine?

A

DECREASED: hypoproteinemia, azotemia, hemolysis, prolonged storage at room temp (decrease), hyperlipidemia (mild/minimal), hyperT (increase protein catabolism)

INCREASED: hypoT (reduced protein turnover), chronic stress (rare), oxytetracycline, levodopa (dopamine precursor)

NO EFFECT: icterus

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36
Q

What is the mechanism of diabetic nephropathy in dogs? And complications?

A

Glucose has a central role in development of microvascular damage –> thickening of glomerular/tubular capillary basement membrane, glomerular fibrosis, glomerulosclerosis.
Eventual azotemia, uremia, significant proteinuria

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37
Q

Cataract formation in DM dogs - progression?

A

14% at time of dx; 50% at 6mths; 75% at 1yr.

38
Q

What is the relapse rate in DM cats, and what % of these cats achieve a 2nd remission?
What factors reduce possibility of remission? Is DKA a negative predictive factor?

A

Feldman & Nelson
25-30% relapse rates within 1-2yrs , <25% of these cats achieve a 2nd remission

Remember that most cats in DM remission are pre-diabetic as they do not have normal beta-cell function/numbers of or sufficient insulin to maintain normal glucose tolerance

Factors
- Peripheral neuropathy (seen in later course of disease, likely associated with greater beta-cell damage)
- Increased serum cholesterol
DKA is NOT a negative predictive factor, remission can still occur in these cats.

39
Q

What is the critical difference in serum fructosamine to be considered a significant change in glycemic control?

A

50umol/L difference between 2 consecutive measurements (assessed when changing insulin dose/type)

40
Q

Name the major glucose counter-regulatory hormones

A

Acute - glucagon, epinephrine
Chronic - GH, cortisol

Epinephrine acts differently to other hormones - increases plasma FFAs + decrease glucose utilization by cells, increases glycogenolysis + hepatic gluconeogenesis in the liver.

41
Q

Current dietary recommendations for diabetic cats?

A

1st choice:
- High protein (min 5.2g/kg/d, >40-45% ME), low CHO (<12-15% ME or as low as the cat will tolerate)
- Canned

2nd choice
- High fibre, moderate carb
- Mix canned + dry

42
Q

When to measure serum IGF-1 in a diabetic cat? What can cause low IGF-1 concentrations in a diabetic cat?

A
  • Measure IGF-1 levels only 6-8 weeks AFTER initiating insulin tx. Use cat-validated assay.
  • IGF-1 [ ] are often low in newly diagnosed DM (+/- HST) cats & increase markedly after initiating insulin therapy. As high insulin concentrations required in the portal vein for the expression and function of GH receptors on hepatocytes, thus mechanism is impaired in initial insulin-deficient states.
43
Q

Which GI hormones can increase insulin secretion?

A

Gastrin, secretin, cholecystokinin
Incretins (most potent) - glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP)

44
Q

Glucose transporters - where are they located? Differences in affinity?

A

GLUT-1 all tissues, brain vasculature, RBCs – HIGH affinity
GLUT-2 beta-cells, (liver, serosal surface of GIT & kidneys) – low affinity
GLUT-3 neuronal cells (also all tissues) – HIGHEST affinity
GLUT-4 skeletal muscle & adipocytes – medium affinity

45
Q

List 3 drugs (apart from glucocorticoids) that may be used to medically manage insulinomas. What is their efficacy & safety profile?

A

Diazoxide
- MOA: benzothiadiazide diuretic. Inhibits closure of ATP-dependent K+ channels in pancreatic beta cells > inhibits opening of voltage-gated Ca2+ channels, Ca2+ influx & decreases exocytosis of insulin vesicles. Also inhibits glucose utilization by peripheral tissues, stimulates hepatic gluconeogenesis & glycogenolysis.
- 70% dogs respond
- Good in early disease (adjunct to low-dose GCS), late disease (adjunct to GCS when attempting to reduce GCS dose due to intolerable SE, and/or if CSx persist)
- SE: ptyalism, anorexia, V+ (give with food or reduce dose)

Octreotide
- Somatostatin analogue
- Inhibits insulin synthesis and secretion of insulin by both normal & neoplastic β cells > net effect is hyperglycemia
- Variable response – depends on presence of somatostatin membrane receptors on tumor cells. In some dogs may actually worsen hypoglycemia.
- 40-50% dogs respond
- SE uncommon – steatorrhea, nausea, V+, abdominal pain, constipation

Streptozotocin
- MOA: naturally occurring nitrosourea, selectively destroys pancreatic β cells (uptake by GLUT-2 only)
- AE: DM, nephrotoxicosis, severe V+, acute pancreatitis
- Not commonly used due to variable effectiveness & severe AE

46
Q

xxx
What is the effect of diabetes mellitus on hormone sensitive lipase (HSL) activity? What other conditions may cause similar effects on HSL? What are the roles of HSL?

A

Upregulates HSL activity. (Especially by counterregulatory hormones cortisol & Epi).
Other endocrinopathies (HAC) xxx
HSL:
- Mediates the hydrolysis of TG to glycerol + FFAs in adipose tissue –> increased circulating FFAs

47
Q

What provocative tests can be used to diagnose gastrinoma in dogs?

A

Secretin stimulation test
- Gastrinoma: marked incr in gastrin at 2 & 5min (enhanced responsiveness of tissue). - 2x elevation in serum gastrin diagnostic in people.

Ca gluconate stimulation test
- In people, slow infusion over 3hrs with serum gastrin measured at set points > expect substantial increase in serum gastrin
- SE: cardiac effects during infusion

111iridium-octreotide test
Not used really in vet med
- Octreotide = somatostatin analogue; binds to somatostatin receptors that can be found in a gastrinoma
- Sensitivity is dependent on size of tumor
- In people, use somatostatin-receptor scintigraphy (Octreoscan) to look for tumor foci

48
Q

What cut-off for serum gastrin is currently considered diagnostic for gastrinoma in dogs?
What other factors can increase serum gastrin?

A

TAMU lab: cut-off value of 10x URI (>278 ng/L) diagnostic for gastrinoma in dogs (normal should be <27.8, mostly undetectable).

CKD, chronic gastritis/GI disease or other causes of gastric outflow obstruction, hypochlorhydria (deficiency of gastric acid), atrophic gastritis, SI resection, GDV, liver disease, PPIs, immunoproliferative enteorapthy (Basenjis).

49
Q

In health, what is the effect of glucocorticoid administration on pancreatic beta cells?

A

GCS reduces peripheral insulin sensitivity&raquo_space; balanced by increasing beta cell function. If compensation is not fully effective, leads to hyperglycemia (esp in DM or pre-DM patients).

50
Q

Name other medical options apart from trilostane or mitotane for the treatment of HAC in dogs? (May or may not be commonly used in vet med)

A

Drugs that block steroidogenesis:
- Metyrapone
- Ketoconazole
- Aminoglutethimide

Drugs that inhibit ACTH secretion (PDH)
- Serotonin antagonists
- GABA- transaminase inhibitors.
- Cyproheptadine.
- Bromocriptine - dopamine agonist.
- Selegiline (L-Deprenyl) - dopamine agonist.FDA approved for uncomplicated PDH 10-15% response rate.
- RU-486

Pituitary RT

51
Q

In a dog receiving phenobarbitone with supportive signs of HAC, which adrenal function test should be performed? Disadv vs adv?

A

ACTH stim - lower Sn (60% AT, 80% PDH) but higher Sp (60-90%). Not LDDST as pheno interferes > false pos.

52
Q

Dogs with alopecia X or other causes of occult HAC may have a deficiency in which enzyme, and what does it result in?

A

Partial deficiency in 21-beta hydroxylase > accumulation of 17-OH progesterone > see increased [ ]. Normal cortisol.

53
Q

What manifestations of water imbalance is observed post hypophysectomy? How soon after surgery?
Why can this imbalance be transient?
What % of dogs is this water imbalance permanent, and what are the risk factor(s)?

A

Central DI. Occurs within 1-4hrs post-op.
Can observe dramatic UOP (>10 mL/kg/h), USG hyposthenuric (frequently <1.005); serum Na+ rapidly increases (>160 mEq/L)

ADH produced in the hypothalamus can still be secreted into the systemic circulation via the portal capillaries in the median eminence

20-22%
P/B ratio >0.31 (i.e. larger masses)
Location of tumor
Extent of surgical manipulation > direct damage to the neurohypophysis or hypothalamic nuclei

54
Q

What parameter is used to assess pituitary size, and what is the established cut-off for normal vs enlarged pituitary glands?

A

Pituitary height (mm) to brain area (cm2) height ratio - allows for correction of patient size.
P:B ratio >0.31

On imaging:
Generally 3-7mm > monitor
<3mm may miss on imaging (40% missed on CT)
8mm+ > consider sx/RT

55
Q

Recommended screening test for feline hyperaldosteronism? How does it differentiate primary vs secondary?

What 2 other tests can be considered & what results support PHA?

A

Plasma aldosterone: renin ratio. Primary - high ratio (aldo incr, renin low/undetectable). Secondary - normal? (aldos incr, renin incr)

Urine aldosterone: creatinine ratio
- High UACR supports PHA, but large overlap between healthy & PHA cats
- Can be combined with fludrocortisone PO suppression test. Administer fludrocortisone 0.05mg/kg PO q12hr x 4d & collect urine daily. PHA cats - escape from suppression. PHA excluded if UACR on day 4 suppresses >50% from baseline.

56
Q

What are the differences in enzyme expression between the different zones of the adrenal cortex?

A

ZG = low expression of CYP17, only zone to express aldosterone synthase (CYP11B1) (cholesterol –> aldosterone)
ZF & ZR - express 17a-hydroxylase (17,20-lyase aka CYP 17) –> catalyzes 17a-hydroxylation of pregnenolone & progesterone –> cortisol & androgens.

57
Q

Factors influencing aldosterone secretion?

A

Low blood volume, serum K+ (hyperK stimulates), serum Na+ (hypoNa), RAAS
ACTH (potent acute secretagogue), natriuretic peptides, some NTRs

58
Q

List & explain causes of acquired nephrogenic DI.

A
  • HyperCa
  • HypoNa. E.g. hypoA – chronic Na wasting, also medullary washout, loss of [ ] gradient
  • HypoK: decreased response to AVP, downregulation of aquaporins. E.g. primary hyperaldosteronism.

-** Bacterial endotoxins** – E. coli, reversible, prevents aquaporin insertion & cell function; pyometra
- Pyelonephritis – infxn/inflam destroys countercurrent mechanisms; endotoxins

  • Hepatic insuff, PSS – MOA unclear
    - HAC – steroids inhibit ADH release by direct effect in hypothalamus/ neurohypophysis; increase GFR, Na transport, ADH resistance. Pituitary macroadenoma may also prevent ADH pdtn.
  • HyperT - MOA unclear
  • Acromegaly – excess GH, DM
  • Polycythemia – increased ADH threshold, delayed ADH response – may be due to increased ANP which inhibits ADH
59
Q

How does a DDAVP treatment trial help to differentiate causes of PUPD in an animal? What condition should be ruled out prior to conducting this and why?

A

Helps to differentiate central DI (will respond with decreased PUPD & 50+% in USG from baseline, esp >1.030 if complete, less if partial) vs nephrogenic DI (no response to ADH). Psychogenic potentially slight decreased PUPD (impaired ADH secretion from chronic medullary washout).

Rule out HAC first before conducting tx trial, as HAC causes ADH suppression & thus mimics partial central DI –> false positive response to DDAVP.

60
Q

Which 2 drugs may be used for diabetes insipidus (and which forms)? Describe MOA & AE.

A

Both for partial central DI & nephrogenic DI.

**1. Chlorpropramide: sulfonylurea. **
- 1-2 weeks for effects.
- Potentiates ADH action at DT/CTs; possibly due to reduction of PGE which normally inhibits ADH.
AE - hypoglycemia (incr insulin secretion).

2. Thiazide diuretics
- Causes a paradoxical decrease in UOP. MOA = Na reduction. Drugs reduce Na & Cl reabsorption in DTs&raquo_space; initially causes Na loss & ECF volume contraction. Overtime, INCREASES Na & H2O reabsorption in the PTs, so less filtrate is presented to the distal nephron & CDs for urine excretion.
- Use with low Na diet.
- AE: hypoK, hyperglycemia, hypercalciuria (hyperCa)

61
Q

What medication has been trialled for treatment of SIADH in dogs? MOA?

A

Tolvaptan. ADH V2-receptor antagonist.

62
Q

What are the 5 cell types found in the pars distalis & their roles?

A

Pars distalis = anterior pituitary
1. Somatotrophs: 30-40% of gland mass. Acidophils. Secrete GH.
2. Lactotrophs: 3-5% gland mass. Secrete prolactin > promotes mammary gland development and milk production.
3. Gonadotrophs: 3-5% gland mass. Secrete FSH, LH.
4. Thyrotrophs: 3-5% gland mass. Secrete TSH > controls secretion rate of T3 & T4 by thyroid glands
5. Corticotrophs: 20% gland mass. Produce pro-opiomelanocortin (POMC) > most converts into ACTH via prohormone convertase I (post-translational processing).

63
Q

What are the 2 cell populations in the pars intermedia?

What is the role of dopamine is regulating secretions from the pars intermedia?

A
  1. A cells - predominant. Stain for a-MSH (melanocyte-stimulating hormone).
  2. B cells - stain for ACTH.

Dopamine = main regulator of pars intermediate secretions, via tonic inhibition; interacts at D2 receptors of melanotropes to decrease POMC production.

64
Q

What changes of the following occur in cats with hypersomatotropism?

A
  • Ghrelin (lower in HST cats) GH secretagogue so downregulated in HST. Secretion also impaired in DM.
  • PIIINP (Serum N-terminal type III procollagen propeptide): measures turnover of collagen. 5x increases in FeHS DM cats cf DM cats alone.
65
Q

Canine hyposomatotropism.
- Pathogenesis
- Gene mutation & prediposed breed(s)
- Deficiencies in which hormones?
- Diagnosis
- Treatment

A
  • Patho: failure of complete differentiation of the craniopharyngeal ectoderm of Rathke’s pouch into healthy functioning AP, OR cyst formation in Rathke’s pouch causing pressure necrosis of AP.
  • LHX3 gene mutation, GSDs
  • TSH, LH, FSH, prolactin deficiencies. But normal ACTH.
  • Dx GH stimulation test with xylazine or GHRH, or exclusion test with ghrelin. May see low IGF-1.
  • Tx porcine GH SQ
66
Q

Hypersomatotropism - main cause in dogs vs cats?

A

Dogs - GH-producing mammary tumors (primary hypoT less common)
Cats - pituitary adenoma > carcinoma > hyperplasia

67
Q

In which species does progestogens play a role in stimulating GH secretion, and from where?

WHich breed is predisposed to progesterone-related insulin resistance (and DM)?

Does plasma GH concentration decrease after hypophysectomy?

A

Dogs, GH secretion from mammary glands, luteal phase (diestrus).

Swedish Elkhounds (Strage JVIM 2014)

No (cos of extra-pituitary secretion)

68
Q

List 5 hormones that are inhibited by somatostatin.

A

GH, TSH, insulin, glucagon, gastrin

69
Q

What is the prevalence of an elevated IGF-1 in DM cats?

A

‘Normal’ DM cats (10-15%), poorly controlled DM cats (30+%)

70
Q

Which somatostatin receptors does pasireotide vs octreotide have binding affinity for?

A

Scudder JVIM 2015
Pasireotide exhibits high affinity binding to SSTR1, 2, 3 & 5.
Octreotide preferentially binds to SSTR2.

71
Q

Survival outcome & clinical response of HST-DM cats post-hypophysectomy?

A

85% DM remission within 2mths post-op, remainder have good glycemic control with reduced insulin reqts. 10% mortality rate.

72
Q

List 5 characteristics of hyperglycemic hyperosmolar syndrome (HHS)?

A
  • BG >540- 600mg/dL; 30-34mmol/L
  • Serum osmolality >325-350mOsm/Kg
  • Profound dehydration, with progressive CNS depression
  • +/- mild acidosis, but usually blood pH >7.3 & [HCO3-] >15mEq/L
  • Variable ketosis (not a key feature)

Similar to DKA: relative or absolute insulin def, excess counterregulatory hormones (glucagon, catecholamine, cortisol)

73
Q

What 3 membrane pumps present in the thyroid gland (1 on luminal surface, 2 on apical surface) are responsible for iodine uptake?

What can increase the efficacy of 1 of these pumps?

A

Apical (facing circulation):
- Na+/K+ ATPase pump (Na+ efflux against [ ] gradient to generate gradient for I- transport)
- 2Na+/I- symporter –> iodide trapping in TG. TSH can incr efficacy of this pump. I131 uptake occurs by this pump.
Luminal (facing follicular lumen):
- Cl-/I- counter transporter aka pendrin

74
Q

What is the MOA of methimazole? Which enzyme in the TG does it act on, and which drug may reversibly inhibit this enzyme?

A

Inhibits thyroid peroxidase (TPO) in the follicular lumen > thus inhibits I- oxidation (I- > I0 or I3) for corporation with tyrosine AA of thyroglobulin (coupling) to form T3 & T4. Note NO effects on release or activity of thyroid hormones already formed or in circulation.

Sulfonamides may reversibly inhibit TPO.

75
Q

HyperT cats can develop what nutritional deficiencies?
What haemogram changes may be observed in hyperT cats?
What is the effect of hyperT on:
- Liver function tests
- Cortisol secretion

A

Thiamine (B1) & B12

~50% mild erythrocytosis (TH stimulates EPO release), macrocytosis, Heinz bodies. Normal WBC & platelets (+/- eosinopenia/lymphopenia - BM effects, L shift if thyroid storm)

  • May see incr NH3 but normal BAST - NH3 normalises post-tx.
  • ACTH-stimulated cortisol secretion higher in hyperT, cortisol & adrenal size may be increased (consider HAC, similar CSx)
76
Q

What diagnostic challenge may arise when differentiating cause of hyperglycemia in a hyperT cat?

A

hyperT significantly decreases serum fructosamine (due to increased metabolism/turnover) so may be difficult to differentiate between concurrent DM vs stress)

77
Q

What diagnostic tests are recommended to screen for occult hyperT in cats with high-normal TT4?

A

fT4, T3 suppression test (check baseline T3 & T4, give 7 doses T3 PO q8hr, check T3 & T4 after - hyperT cats no effect on T4) and/or scintigraphy
Or…waiting and repeating TT4 in a few weeks

NOT TSH response test (poor Sn), TRH response (AE common)

78
Q

What % of thyroid tumors in dogs are functional? What IHC stains can be used to differentiate origin of thyroid tumors in dogs?

A

Mostly non-functional, 10-20% hyperT, rarely hypoT.
- Thyroglobulin stain = follicular origin - differentiated follicular cell thyroid carcinoma (dFTC).
- Calcitonin = parafollicular/C cells origin = medullary thyroid carcinoma (MTC)

79
Q

What diagnostic tests are recommended for diagnosis of hypoT in cats?

A

Combined TT4 & fT4 by ED + cTSH
If equivocal results, FU with rhTSH stimulation test (hypoT cats - no incr T4, NTI/normal 2-3x incr T4) or thyroid scintigraphy

80
Q

What is the potential utility of thyroid scintigraphy in differentiating cause of congenital hypoT in cats?

A
  • Dysmorphogenesis: abnormal TG structure > absence of 123I uptake
  • Dyshormonogenesis: 123I uptake may be normal in cases with thyroid peroxidase deficiency, but organification (incorporation of iodine) is deficient > abnormal 123I discharge is observed after administration of perchlorate (perchlorate discharge test). Abyssinians, related DSH - defective TPO activity
81
Q

List breeds affected by congenital hypoT (dyshormonogenesis) and the causal gene mutation? What is the expected size of the thyroid glands?

A

Autosomal recessive TPO gene mutation.
Spanish water dog, Tenterfield terrier
Toy Fox Terrier, Rat Terrier

Enlarged (goitre/hyperplasia) - if HP-T axis is intact

82
Q

What cut-off serum TT4 measurement using RIA may be helpful to differentiate between dogs with NTI vs hypoT?

What may cause falsely increased TT4 in hypoT dogs, and what % of hypoT dogs are affected?

What may cause low TT4 level in a non-hyperT dog?

Does hemolysis or hyperlipidemia interfere with this assay?

A

TT4 <1.5ug/dL more likely hypoT.

Presence of anti-thyroid antibodies. 2% dogs with CSx, 15% of all hypoT dogs. (NB may also cause decreased T4). Overall rare cause.
Note TG autoAb interfere with RIA but not chemiluminescent or ED assays.

Low TT4 - drugs (glucocorticoids; TMPS?, phenobarb etc.), severe NTI, breed diff - sighthounds, Nordic breeds, Eng Setters etc

No for both.

83
Q

Causes for normal TSH in a hypoT dog?

Causes for increased TSH in a non-hypoT dog?

A

Test Sn (20-40% hypoT dogs have normal TSH)
Pulsatile secretion
Secondary hypoT (pituitary dz)
Reduced sensitivity of TGs to TRH & TSH secretion over time

NTI, drugs (esp TMPS)
NB: GCS tx can cause reduced thyroid gland isotope uptake, but typically normal with TMPS

84
Q

Thyroid autoantibodies develop most commonly against which component of thyroid hormones?

What is 1 potential advantage of T3/T4 autoAb over thyroglobulin autoAb? What signalment has increased OR of T3/T4 autoAb?

A

Thyroglobulin (can be antigenic)
TPO enzyme less common
Not T3 or T4 alone (indirectly via their attachment to TG)

TG autoAb much more common (50%) but doesn’t predict if these dogs will develop clinical hypoT in the future. Whereas T3/T4 may be a better predictor.
Females, neutered dogs, Pointers, Skye terrier, GWP, Old English, Boxers have higher odds

85
Q

What are the effects of the following drugs on thyroid hormone concentration interpretations?
- Phenobarb
- GCS
- Sulfonamides

What can sulfonamides reversibly inhibit? Name 1 other drug that can also do this?

A

GCS & pheno: normal-decr T4, normal fT4 , normal/incr/decr TSH
Sulfonamides: basically mimics hypoT (decr T4, decr fT4, incr TSH). Differentiate by scintigraphy (normla uptake)/drug hx.
- May even induce myxedema coma due to the ability to reversibly inhibit TPO.
- Clomipramine can also inhibit TPO (& alter I- uptake) - see decr TT4 & fT4, but normal TSH

86
Q

Why is T3 supplementation not routinely recommended to treat hypoT dogs? When might this be indicated instead of levothyroxine supplementation & what thyroid hormone levels are expected during monitoring?

A

T3 admin circumvents the normal physiological process of deiodination, may cause alterations in HPT axis? Also incr risk of thyrotoxicosis (more potent), shorter T 1/2 so require multiple doses daily.

Indication for T3: dogs with severe GI disease - decreased T4 absorption > tx failure (T4 inherently has poor GI absorption).
Expect low T4 & TSH while on T3 tx.

87
Q

Where is calcitonin produced & what are its roles? What factors stimulate or inhibit its release?

A

C cells (parafollicular cells) of thyroid gland.
Roles in limiting postprandial rise in Ca2+ + emergency control of hyperCa.

Stimulate: ↑ iCa2+, Mg2+, gastrin, cholecystokinin, glucagon.
Inhibit: ↓ iCa2+, ↑ somatostatin

88
Q

PTH has effects on bone via the …..pathway. Discuss the mechanisms involved in this pathway. Name 1 drug each that can increase or decrease components of this pathway.

A

OPG-RANKL
- RANKL receptor = OPGL (binding site for OPG)
- Found on OBs
- PTH binds to PTH receptors on OBs & releases RANKL to bind to OC precursors > OC differentiation to OCs
- Note OCs have no PTH receptors

OPG = osteoprotegerin
- Produced by OBs
- Opposes PTH actions, PTH can also block this
- Binds to RANKL/OPGL receptor on osteoblasts, prevents binding to OC precursors & thus OC differentiation & bone resorption

Glucocorticoids: incr RANKL, decr OPG
Oestrogen: incr OPG

89
Q

Treatment options for primary hyperPTH?

A
  • Surgical parathyroidectomy = tx of choice, 95% success. Leave min 1 gland to prevent permanent hypoCa.
  • US-guided heat ablation (similar success as sx)
  • Ethanol ablation (72% success)
  • Calcimimetic: cinacalcet (increases sensitivity of Ca-sensing receptors in PT glands to activation by ECF Ca2+ > release less PTH; AE: GI signs, $$)
  • Calcitonin (emergency tx for hyperCa)
90
Q

DDx for low calcium & high phosphate?

A
  • Primary hypoPTH
  • Nutritional hyperPTH
  • Renal 2’ hyperPTH
  • Phosphate containing enemas
  • Tumour lysis syndrome

ACVIM Specialty Exam (20 decks)

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