Endocrine

Question 1

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

Answer 1

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.

Question 2

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

Answer 2

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.

Question 3

Metabolic effects of excessive growth hormone?

Answer 3

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).

Question 4

Vitamin D metabolites?

Answer 4

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.

Question 5

Vitamin D formation pathway?

Answer 5

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).

Question 6

List 8 consequences of chronic hypercortisolism in dogs?

Answer 6

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

Question 7

How to differentiate histologically between phaeochromocytoma and cortical tumours?

Answer 7

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

Question 8

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

Answer 8

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)

Question 9

Abdominal organ changes seen in HST cats?

Answer 9

Increased kidney length, adrenal thickness & pancreas thickness

Question 10

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

Answer 10

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.

Question 11

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

Answer 11

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.

Question 12

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?

Answer 12

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.

Question 13

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

Answer 13

LHX3 mutation
A-A instability

Question 14

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

Answer 14

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

Question 15

Diagnostic utility of TSH for hyperT in cats?

Answer 15

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

Question 16

What is the cortisol:ACTH ratio useful for?

Answer 16

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)

Question 17

What is the preferred test to diagnose phaeochromocytoma in dogs?

Answer 17

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

Question 18

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

Plasma ACTH [ ] - PDH vs ADH?

Answer 18

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)

Question 19

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

Answer 19

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).

Question 20

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

Answer 20

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.

Question 21

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

Answer 21

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

Question 22

What is the recommended CHO content of food for DM cats

Answer 22

JFMS consensus: <12-15% ME

Question 23

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

Answer 23

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.

Question 24

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

Answer 24

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

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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+ >> insulin release. AE: GI signs, liver enzyme elevations, jaundice

Question 27

Name an example of a meglitinide. MOA?

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

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)

Question 30

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

Answer 30

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

Question 31

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

Answer 31

GIT - glucose absorption RBC, kidneys, CNS - glucose utilization. Note neurons only use glucose for energy, thus are highly permeable to glucose.

Question 32

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.

Answer 32

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.

Question 33

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

Answer 33

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

Question 34

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.

Answer 34

(Insulin inhibits lipolysis & FFA oxidation). Lipoprotein lipase decreased Hormone-sensitive lipase activated TG-rich VLDL & chylomicrons FFAs

Question 35

List 5 drugs causing DM/hyperglycemia.

Answer 35

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

Question 36

What factors cause increased vs decreased serum fructosamine?

Answer 36

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

Question 37

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

Answer 37

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

Question 38

Cataract formation in DM dogs - progression?

Answer 38

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

Question 39

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?

Answer 39

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.

Question 40

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

Answer 40

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

Question 41

Name the major glucose counter-regulatory hormones

Answer 41

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.

Question 42

Current dietary recommendations for diabetic cats?

Answer 42

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

Question 43

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

Answer 43

- 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.

Question 44

Which GI hormones can increase insulin secretion?

Answer 44

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

Question 45

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

Answer 45

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

Question 46

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

Answer 46

**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

Question 47

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?

Answer 47

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

Question 48

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

Answer 48

**Secretin stimulation test** - Gastrinoma: marked incr in gastrin (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

Question 49

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

Answer 49

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).

Question 50

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

Answer 50

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

Question 51

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)

Answer 51

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

Question 52

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

Answer 52

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

Question 53

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

Answer 53

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

Question 54

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)?

Answer 54

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

Question 55

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

Answer 55

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

Question 56

Recommended screening test for feline hyperaldosteronism? How does it differentiate primary vs secondary? What 2 other tests can be considered & what results support PHA?

Answer 56

**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.

Question 57

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

Answer 57

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.

Question 58

Factors influencing aldosterone secretion?

Answer 58

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

Question 59

List & explain causes of acquired nephrogenic DI.

Answer 59

- **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

Question 60

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?

Answer 60

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.

Question 61

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

Answer 61

**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 >> 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)

Question 62

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

Answer 62

Tolvaptan. ADH V2-receptor antagonist.

Question 63

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

Answer 63

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).

Question 64

What are the 2 cell populations in the pars intermedia? What is the role of dopamine is regulating secretions from the pars intermedia?

Answer 64

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.

Question 65

What are the 2 cell populations in the pars intermedia? What is the role of dopamine is regulating secretions from the pars intermedia?

Answer 65

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.

Question 66

What changes of the following occur in cats with hypersomatotropism?

Answer 66

- 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.

Question 67

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

Answer 67

- 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

Question 68

Hypersomatotropism - main cause in dogs vs cats?

Answer 68

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

Question 69

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?

Answer 69

Dogs, GH secretion from mammary glands, luteal phase (diestrus). Swedish Elkhounds (Strage JVIM 2014) No (cos of extra-pituitary secretion)

Question 70

List 5 hormones that are inhibited by somatostatin.

Answer 70

GH, TSH, insulin, glucagon, gastrin

Question 71

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

Answer 71

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

Question 72

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

Answer 72

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

Question 73

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

Answer 73

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

Question 74

List 5 characteristics of hyperglycemic hyperosmolar syndrome (HHS)?

Answer 74

- 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)

Question 75

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?

Answer 75

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

Question 76

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

Answer 76

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.

Question 77

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

Answer 77

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)

Question 78

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

Answer 78

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

Question 79

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

Answer 79

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)

Question 80

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

Answer 80

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)

Question 81

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

Answer 81

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

Question 82

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

Answer 82

- 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).

Question 83

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

Answer 83

Autosomal recessive TPO gene mutation. Spanish water dog, Tenterfield terrier Toy Fox Terrier, Rat Terrier Enlarged (goitre/hyperplasia) - if HP-T axis is intact

Question 84

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?

Answer 84

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.

Question 85

Causes for normal TSH in a hypoT dog? Causes for increased TSH in a non-hypoT dog?

Answer 85

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*

Question 86

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?

Answer 86

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

Question 87

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?

Answer 87

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

Question 88

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?

Answer 88

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.