Lit Endocrine

Question 1

Which tests were used to differentiate PDH from cortisol-producing adrenal tumors (CPAT) dogs, and what were the test sensitivities & specificities?

Answer 1

Tanaka JVIM 2021
PDH dogs: expect high eACTH, lack of suppression with CRH stim - continuous ACTH pdtn.

Cut-off values:
1) eACTH: 26.3 pg/mL. Sens 90.62%, spec 87.50%, AUC 0.95.
2) Post-CRH stim [ACTH] (PAC): 54.5 pg/mL. 100% sens, 66.67% spec.

No significant correlations noted between PBR and CRHT, nor adrenal size and CRHT.

Question 2

At what time points were median interstitial glucose (IG) concentrations found to be significantly increased when evaluating circadian fluctuations in DM dogs?

Answer 2

Shea JVIM 2021
Night time (1-6am)

Question 3

1) Which factors were considered in the generation of a novel 131 dosing algorithm for the treatment of hyperT cats?
2) What was the outcome/benefit of using this algorithm?

Answer 3

Peterson JVIM 2021
1) Initial I131 dose calculated by averaging dose scores for T4/T3 concentrations, thyroid volume, and % uptake of 99mTc-pertechnatate (TcTU).
2) 75% euthyroid, 4% overtly hypoT, 17% subclincially hypoT, 4% persistently hyperT.
More overtly (72%) and subclinically (40%) hypoT cats developed azotemia cf euthyroid cats (14%).
Overall similar to historical treatment rates, but much lower I131 doses needed –> lower prevalence of both I131-induced overt hypoT & azotemia.

Question 4

Which pre-treatment factors were helpful in predicting persistent hyperT and iatrogenic hypoT post-I131 treatment in hyperT cats respectively?

Answer 4

Peterson JVIM 2021
Iatrogenic hypoT: older, female, detectable serum [TSH], bilateral thyroid nodules, homogeneous bilateral distribution of 99mTc-pertechnetate uptake, milder severity score, higher I131 uptake.
Persistent hyperT: younger, higher severity score, lower I131 uptake.

Question 5

What was the advantage of administering insulin glargine 300 U/mL (IGla300) or insulin degludec (IDG) vs porcine lente (PL) in DM dogs?

Answer 5

Miller JVIM 2021
Lower day-to-day variability – so advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.

Question 6

What were the accuracies of insulin devices (pens vs syringes) when delivering various insulin doses (small </=2U vs 8-16U)?

Answer 6

Malerba JVIM 2021
JuniorSTAR and VetPen 0.5-8 U more accurate when delivering ≤2U doses.
40 U/mL syringes more accurate when delivering 8-16U doses.
Overall all pens underdosed (less underdosage with increasing insulin dose), and increased precision with higher insulin doses for all devices.

Question 7

Progesterone concentrations were …. in cats with hyperaldosteronism (HA), and occurred in ……% cats. Serum cortisol concentration was ……. in HA cats, likely indicating …….

Answer 7

Langlois JVIM 2021
Increased, 32%
Decreased, HPA axis suppression

Question 8

Canine TLI was decreased in DM dogs compared to healthy controls. (T/F)

CTLI negatively correlated with DM duration. (T/F)

Answer 8

Hamilton JVIM 2021
False for both..
No sig differences in [cTLI] between DM vs control dogs. No correlation between DM duration & cTLI.

*NB: concurrent increases in cPLI suggest cTLI might not be the optimal indicator of exocrine pancreatic dysfunction in DM dogs.

Question 9

In cats with aldosterone & progesterone-secreting adrenal tumors, ….. was present in all cats. Both surgical and medical treatment may result in long-term survival, although ……was documented only in cats that underwent adrenalectomy. A post-operative complication included ….

Answer 9

Harro JVIM 2021
Diabetes mellitus, diabetic remission, hypoadrenocorticism.

Question 10

The agreement with interstitial glucose (Freestyle Libre/FGMS) measurements vs portable BG meter (PBGM) and peripheral BG measurements were:
a) At hypoglycemic ranges (BG <100mg/dl): …… for FGMS & …. for PBGM.
b) At normal BG ranges: …… for FGMS & …. for PBGM.

Answer 10

Howard JVIM 2021
a) 39.1%, 81.7%
b) 80.1% (basically double), 80.1% (similar)
*IG concentrations fail to reliably detect hypoglycemia.

Question 11

Of 12 methods evaluated to monitor efficacy of trilostane treatment in HAC dogs, which 3 variables were most useful to identify well-controlled or under-controlled dogs?

Answer 11

Golinelli JVIM 2021
1) Haptoglobin - significantly associated with clinical score, cut-off of 151mg/dL had 90% spec (% of correctly identified well-controlled dogs) & 65.6% sens (% of under-controlled dogs)
2) ALT- sig higher in undercontrolled dogs, cut-off >86U/L
3) GGT - sig higher in undercontrolled dogs, cut-off >5.8U/L

Question 12

How does long-acting recombinant insulin work in the treatment of DM cats?

Answer 12

Chen JVIM 2021
Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells where it is protected from proteolysis. AKS-267c.
Administered SQ weekly.

Question 13

a) Which electrolyte changes occurred after transsphenoidal hypophysectomy in dogs & incidence?

b) Any associations with post-op outcome?

c) Risk factor(s) and associations with persistent DI post-sx?

Answer 13

Del Magno JVIM 2021
a) HyperNa 46.5% dogs&raquo_space; hypoNa 6.3% dogs.
Plasma K+ increased but remained within RI.

b) No associations between hyperNa or K+ changes with post-op outcome.

c) Enlarged pituitary glands. Sig longer sx time in dogs with persistent DI.

Question 14

When comparing markers of calcium & phosphate homeostasis in dogs with naturally occurring hypercortisolism (NOHC) and healthy dogs, NOHC dogs had higher a) ……………..(list 3), lower b) …………….. (list 2). No differences in c) ………… (list 4) were observed between groups.

Answer 14

Corsini JVIM 2021

a) Mean serum [phosphate], median fractional excretion of Ca (FECa), median serum [wPTH]
b) Lower serum [25-(OH)D] & plasma [FGF-23]
c) tCa, iCa, calcitriol, fractional excretion of phosphate (FEP)

Question 15

(T/F)
Use of the Freestyle glucose monitoring device had poor analytical & clinical accuracy when applied on dogs in DKA.

The severity of ketosis & acidosis, lactate concentration, BCS, and amount of time wearing the FGMS did not appear to impact agreement between interstitial glucose & BG.

Answer 15

Malerba JVIM 2020

False – poor analytical but good clinical accuracy.

True

Question 16

What were the 2 main findings in a study that evaluated glycemic variability (GV) in newly diagnosed DM cats receiving exenatide extended-release (EER) treatment in conjunction with insulin glargine & low CHO diet?

Answer 16

Krämer JVIM 2020

1) Lower GV in EER cats (at wks 6, 10, 16) cf baseline & cats receiving placebo tx.

2) Cats achieving DM remission had lower GV at wk 6.

Question 17

a) What was the outcome of using an initial low dose (1.5mg/kg) DOCP in the treatment of primary hypoA in dogs compared to manufacturer recommended dose (2.2mg/kg)?

b) Which 2 patient groups typically required higher DOCP dosages?

Answer 17

Sieber-Ruckstuhl JVIM 2019
a) Initial dose of 1.5 mg/kg DOCP was effective in controlling clinical signs & maintaining serum electrolytes WRI in 88% dogs with PHA. A significant dose reduction was often needed after 2-3 months to a median dose of 1.1 mg/kg to maintain an injection interval of 28-30d.
No dogs required 2.2 mg/kg DOCP (manufacturer recc dose).

b) Young (</= 3yo) & growing animals required higher dosages.

Question 18

What 2 parameters were used to assess overtreatment in DOCP-treated hypoA dogs?

What were the adverse effects of standard (2.2mg/kg) vs low dose (1.1mg/kg) DOCP treatment for dogs with primary hypoA?

Answer 18

Vincent JVIM 2021
a) Plasma K+ (hypoK) & plasma renin activity (plasma renin oversuppression - indicates high aldosterone)

b)
- Low-dose DOCP protocols - appear safe & effective for treatment of HA in most dogs. HypoK in 33% dogs.
- Standard-dose protocols - more likely to result in biochemical evidence of overtreatment (overly suppressed plasma renin activity in 80% dogs, hypoK in 50% dogs).

Question 19

Prevalence of hypoA in dogs with chronic GI signs?
2 common GI signs noted in HA dogs?
Basal serum cortisol was <2ug/dL (55nmol/L) in ……% dogs and <1ug/dL (28nmol/L) in …..% dogs with GI disease.

Answer 19

Hauck JVIM 2020
4%
Melena, hematochezia
28%, 6%

Question 20

State the
- Prevalence of systemic hypertension (SH) in dogs with spontaneous HAC
- Proportion of HAC dogs with SH & risk of TOD

List 3 clinical parameters that may predict SH & 1 co-morbidity that may reduce risk of SH.

Answer 20

San José JVIM 2020
82%
46% with SBP ≥180 mmHg
Predictors - thrombocytosis (platelet count ≥438K = 100% specific & 61.1% sensitive to predict SH), proteinuria (UPC ≥0.5), low K+ concentrations
Concurrent DM - lower risk of SH

Question 21

Prevalence of systemic hypertension (SH) in PDH dogs before & after 1 year of trilostane treatment?

(T/F) BP was associated with control of PDH.
(T/F) SBP measurements at all follow ups are recommended as SH can develop anytime throughout the disease course & require anti-hypertensive treatment.
What proportion of HAC dogs required anti-hypertensive tx (monotherapy vs dual therapy)?

Answer 21

San José JVIM 2020
70% pre-tx, 46% after 1 year of tx.
False.
True.
60% dogs required anti-hypertensive tx. 42% of these dogs required dual therapy (benazepril + amlodipine).

Question 22

How did the FGMS compare to the portable blood glucose meter (PBGM) for
a) decisions on insulin dose adjustments
b) detection of nadir & hypoglycemic episodes, and
c) day-to-day variations in glycemic control?

Answer 22

Del Baldo JVIM 2020
a) Suboptimal for PBGM. Good concordance between 2 devices in different environments on 2 consecutive days.
b) FGMS & PBGM identified 60% & 9% of hypoglycemic episodes; and 79% & 41% of glucose nadirs respectively
c) FGMS reflects large day-to-day variations in glycemic control - almost ZERO concordance between FGMS IGCs on 2 consecutive days at home.

Question 23

a) Which 2 variables were associated with greater odds of relapse & decreased survival time in dogs with insulinoma undergoing surgical treatment?

b) What was the MST in dogs with insulinoma undergoing surgical treatment?

c) What was the main post-op complication noted in these dogs, and proportion of dogs affcted?
d) What were the risk factors for this complication?

Answer 23

Del Busto JVIM 2020
a) Stage of disease & post-op hypoglycemia
b) Overall MST 372d. Stage I – MST 652d; stage II or III – MST 320d.
c) Post-op hyperglycemia in 33% dogs. 19% developed persistent DM.
d) No risk factors identified.

Question 24

a) Which clinical variables were useful in differentiating clinically controlled vs persistently symptomatic HAC dogs treated with trilostane?
b) Time to cortisol suppression following trilostane administration?
c) Duration of action of trilostane in most PDH dogs?

Answer 24

Bermejo JVIM 2020
a) No variables (study assessed USG, UCCR, ACTH stim, serum cortisol concentrations (SCCs))
b) Within 1hr.
c) <8 hours.

Question 25

a) What is procalcitonin (PCT)? b) Why is PCT a reliable biomarker of sepsis in people? c) What were the changes in PCT expression at different timepoints in response to sepsis in a cohort of dogs with endotoxemia induced by single lipopolysaccharide (LPS) injection?

Answer 25

Easley JVIM 2020 a) PCT = precursor of calcitonin, primarily produced in the C cells of the thyroid gland during upregulation of the calcitonin I (CALC-I) gene in response to increased plasma Ca2+. PCT is then cleaved into 3 products (katacalcin, calcitonin, and an N terminal fragment) in the thyroid gland --> releases calcitonin into the bloodstream. b) CALC-I gene expression increases in response to infection --> subsequent PCT production by extra-thyroidal tissues including the liver, kidneys, pancreas, spleen & adipocytes. **CALC-I gene expression & PCT production is activated specifically in response to PAMPs (e.g. LPS).** (NB: in people, PCT also useful in guiding abx tx) c) PCT was significantly increased from baseline by 2hrs after LPS injection, remained significantly increased for 12hrs, and returned to baseline by 48hrs.

Question 26

1. What was the diagnostic utility of serum cortisol (SC) to predict prognosis in critically ill dogs? 2. The optimum cutoff of SC concentration was ...... ug/dL; with an OR of ......, sensitivity ......% and specificity of ....% to predict non-survival.

Answer 26

Swales JAVMA 2021 1. Higher median SC concentration in non-survivors to discharge (8.5ug/dL vs 4.5ug/dL). 2. 7.6ug/dL (210nmol/L). OR 5.4, sens 58%, spec 80%. *(Poor sens - so even if cortisol < cutoff may still have a 44% chance of non-survival)*

Question 27

What was the prognostic value of serum TT4 concentration at admission in critically ill dogs?

Answer 27

Neiman JAVMA 2020 Not useful as prognostic indicator in critically ill dogs.

Question 28

What class of medications have shown efficacy in reducing IGF-1 & insulin requirements in HST cats? Name 3 examples & discuss the proposed reason for difference in clinical response in some cats between these 2 drugs (hint: MOA of these drugs). How often is the long acting release version of the drug mentioned above administered, and what was the effect on serum IGF-1 & insulin requirements in HST cats? Adverse drug effects?

Answer 28

Gostelow JVIM 2017 Somatostatin analogues. Octreotide, Lanreotide, Pasireotide. Somatostatin binds to 5 receptor subtypes (somatostatin receptors (STTR) 1-5) which are variably expressed in feline pituitary tissue - studies show cats have greater expression of STTR 1 & 5 vs 2. Octreotide & lanreotide (1st generation STT analogues) predominantly bind to STTR 2 - may explain poor response in some cats. Pasireotide is multireceptor-binding so binds to a wider range of STTR (1,2,3,5) & with much higher affinity for most receptors cf 1st gen drugs (except STTR2 - slightly lower affinity). Pasireotide is given as 6-8mg/kg SQ once monthly (for 8 months in the study). Significantly reduced median IGF-1 & insulin dose requirements (insulin resistance index) but DID NOT affect median BG or fructosamine. 37.5% (3/8) cats entered diabetic remission. AE: D+ (most common), hypoglycaemia, worsening polyphagia.

Question 29

Is SDMA useful in predicting azotemia post-I131 in hyperT cats?

Answer 29

Yu JVIM 2020 No, SDMA was not able to predict post treatment azotemia & inconsistently changed after treatment. In most cats SDMA will increase post I131; decreased in 28% cats at 3mths post-I131 in this study. DeMonaco JFMS 2020 Increased SDMA (above RI) was specific (94%) for post-131 azotemia but insensitive (15%) for predicting post-to azotemia. Post-tx SDMA increased in 19-32% cats - assessed at 1, 3 & 6mths post-I131. Limitation: definition for azotemia did not follow IRIS guidelines (used RI). Buresova JVIM 2019 SDMA assessed at baseline & 1mth post-I131. Warned of careful interpretation of mildly increased SDMA in hyperT cats with normal sCr, as sSDMA might normalize after resolution of hyperT in some cats (at 1mth post-I131). sCr correlated with GFR (but not sSDMA) in this study population.

Question 30

What is the incidence of 1. long term hypothyroidism and 2. recurrent hyperthyroidism in cats that had undergone bilateral thyroidectomy in FIRST OPINION practice?

Answer 30

Covey JVIM 2019 Renal parameters assessed at 6mths post sx (thyroid status deemed stable then with likely minimal influence on SDMA & SCr.) 1. 50% hypoT at 6 months, 17% hypothyroid long term. 2. Of 23 cats with long term FU (>6mths), 22% persistent/recurrent hyperT at 6mths, 83% euthyroid (often transiently), fluctuating between euthyroid/hypothyroid. 44% developed recurrent hyperT long term - high incidence! This was in first opinion practice, possibility of intracapsular technique. Usual reported hyperT recurrence is 5-11%. SDMA & crea were linearly associated & both affected by thyroxine [ ], but effect in greater in hyperT cats (higher SDMA concentrations relative to sCr).

Question 31

What is the effect of primary hypoA on TSH/T4 in dogs? What is the name of the condition in people/dogs with concurrent hypoA & hypoT?

Answer 31

Reusch JVIM 2017 Increased TSH in 37% (11/30) dogs but no difference in T4 between dogs with normal & increased TSH. TSH normalisation may take between 2 weeks & 4 months after starting glucocorticoid tx - without need for thyroxine supplementation. Care: avoid misdiagnosis of hypoT (based on increased TSH) in hypoA dogs before starting tx - monitor thyroid function. Schmidt’s syndrome (autoimmune polyglandular endocrinopathy type II). HypoA usually follows hypoT.

Question 32

What radioisotope is used for thyroid scintigraphy? What measured variable on scintigraphy is used to determine I131 dose for hyperT cats? Did an I131 variable dose protocol based on thyroid scintigraphy improve outcomes in cats (compared to fixed dose protocols)?

Answer 32

Morré JVIM 2018 99m Tc-pertechnetate. % 99m Tc uptake of thyroid glands. No

Question 33

Dysregulation in which neurohormonal marker is thought to contribute to the development of SARDS/ What neurohormonal marker was different between dogs with PDH and SARDS?

Answer 33

Oh JVIM 2019 Dysregulation in melatonin thought to contribute to photoreceptor apoptosis observed in SARDS. In the retina, melatonin is almost exclusively produced by photoreceptor cells. PDH dogs had higher urine MT6s: creatinine ratio vs SARDS dogs, but was not sig diff from normal dogs. (MT6 = 6-sulfatoxymelatonin) NB: Urine 6-sulfatoxymelatonin(MT6s) concentrations represent accumulated amounts of systemic melatonin over several hours - thus less affected by fluctuationsin circulating concentrations. Also urine MT6s accounts for >70% of melatonin secreted, and its concentration in urine is 2-3x higher vs urine melatonin.

Question 34

What is a non-neoplastic condition of the pancreas that could cause hypoglycaemia in dogs?

Answer 34

Polansky JAVMA 2018 Nesidioblastosis (islet cell hypertrophy of the endocrine pancreas on histo). Results in hyperinsulinism. Hypoglycaemia resolved with partial pancreatectomy (case report).

Question 35

What is the correlation between iCa levels preceding parathyroidectomy or heat ablation, and risk of post-treatment hypoCa in dogs with hyperPTH?

Answer 35

Dear JVIM 2017 Moderate correlation (in this study higher iCa —> more chance of post-tx hypoCa). Dogs with baseline iCa >1.81mmol/L had mean post-iCa of <1.00mmol/L. Recommended treating dogs with higher initial iCa to prevent rapid decline & development of clinical hypoCa. Armstrong JVIM 2018 Found no protective value of prophylactic calcitriol administration in the immediate (48hrs) post-op period - was not significantly associated with post-op iCa or rate of decrease after parathyroidectomy. Actually found hyperCa pre-op protective (positive association with post-op iCa). Made an opposing recommendation that pre-op calcitriol is not recommended.

Question 36

Which assay is preferred (vs not recommended) for PTH determination in dogs?

Answer 36

Mooney JSAP 2019 Immunoradiometric assay preferred; either intact or whole PTH. Chemiluminescent assay NOT recommended (81% samples had [PTH] at/below reported limit of detection of assay).

Question 37

What secondary amino acid derangement can occur in hypothyroid dogs?

Answer 37

Gołyński JVIM 2017 High homocysteine, low folate (usually mild, may be result of high homocysteine) Remember folate = co-factor for cystathionine-beta-synthase enzyme - which is needed transsulfuration of homocysteine to cysteine.

Question 38

What is the effect of hypothyroidism on GH? How might this be used diagnostically to discriminate hypoT from non-thyroidal illness in dogs?

Answer 38

Pijnacker JVIM 2018 TSH-induced GH release occurs in hypoT - thus increased GH levels. Presumably due to lack of inhibition by T4 (on TSH) +/- inhibition of somatostatin (latter suppresses GH). TRH stimulation testing increased GH levels in hypoT dogs but NOT in euthyroid/NTI dogs. (Think TRH > TSH > GH-release + lack of inhibition from low T4 in hypoT dogs. TSH won’t increase with stimulation test in these dogs). May be used to discriminate hypoT, as TRH stimulation is not reliable for differentiating changes in T4 levels.

Question 39

How long do you have to wait after stopping administration of levothyroxine SID to assess thyroid function in dogs?

Answer 39

Ziglioli JVIM 2017 7 days after stopping (thyroid function parameters were back to baseline values) - in this study healthy dogs received thyroxine SID for 16 weeks.

Question 40

1. In what canine breed has central hypothyroidism (TSH deficiency) been described? 2. What tests can be used to diagnose central hypothyroidism? 3. What other hormonal imbalances may occur concurrently?

Answer 40

Voorbij JVIM 2016 1. Miniature Schnauzers. 2. TSH stimulation test (3 day protocol) - see increase in plasma T4 or TRH stimulation test (though this is not completely diagnostic due to variable increases in TSH). Difficult to diagnose as these dogs have low T4 and small thyroid on scintigraphy AND low TSH - but TSH is inconsistently increased in dogs with primary (thyroid gland) dependent hypothyroidism. So you have to prove that it is the absence of TSH which is the problem. NB: some dogs present with disproportionate dwarfism, but some dogs may have normal stature - so possibly this disease is underdiagnosed. 3. Prolactin deficiency.

Question 41

What form of hypothyroidism is common in adult-onset feline disease? Did improve with thyroxine supplementation?

Answer 41

Peterson JVIM 2018 Goitreous (reflective of thyroid hyperplasia, thyroid atrophy less common vs dogs). Goitre reduction & improvement in clinical & lab abnormalities (eg azotemia) observed with levothyroxine tx.

Question 42

What diseases, apart from DKA, can increase BHB levels above RI in cats? Were these non-DKA cats ketonuric?

Answer 42

Gorman JVIM 2016 Hepatic lipidosis (can increase moderately), CKD, hyperT. Basically increased BHB reflects catabolic state (negative energy balance & decreased glucose utilization) Ketonuria not documented.

Question 43

Does administering rhTSH to hyperthyroid cats change their % iodine uptake, and if so is this dose-dependent?

Answer 43

Oberstadt JVIM 2018 No, no difference in uptake even at high doses. (In people, administration of rh-TSH in cases of thyroid neoplasia or nodular goiter can increase thyroidal iodine uptake, thereby allowing the use of lower radioactive iodine doses for tx.)

Question 44

What changes in renal perfusion (assessed by contrast-enhanced ultrasound) were detected in cats pre & post I131?

Answer 44

Stock JVIM 2017 Decreased renal blood velocity & small decrease in medullary blood volume (reduced peak enhancement) with resolution of hyperT state at 1 month post-I131.

Question 45

How did a low dose (2Mi) I 131 treatment compare to standard 4Mi dose for cats with mild to moderate hyperT?

Answer 45

Lucy JVIM 2017 Overall low dose was safe & had similar success rates with additional advantages. Low dose had similar rates of achieving euthyroidism (>95%), but caused lower rates of hypothyroidism (overt 1% vs 18% with standard; subclinical 21% vs 46% with standard). Also although low & high I131 doses were associated with similar incidences of azotemia, 2mi dose was associated with lower creatinine & lower % rise in creatinine post-I131. Also no significant difference in prevalence of cats with persistent hyperT with low vs standard doses. (NB: 2Mi = 75mBq, 4Mi = 150mBq)

Question 46

What is the prevalence of hyperT cats with hypocobalaminemia & their methylmalonic acid status? Did this change with achievement of euthyroidism?

Answer 46

Geesaman JVIM 2016 13% prevalence (B12 <150 to 290 ng/L). B12 normalised in small % of these cats once euthyroid. All cats had normal MMA concentrations (NB: increased MMA with B12 deficiency). In cases where concurrent GI disease is unlikely, B12 supplementation is not required.

Question 47

What are the expected differences between cats with hyperT of >4-6 years in duration compared to <1 year?

Answer 47

Peterson JFMS 2016 Cats with long standing hyperT had: Higher T4 Increased prevalence of multifocal disease (3 or more tumor nodules) vs unilateral Increased goitre size - increased median tumor volume + significantly increased prevalence of large (4-8cm) & huge (>8cm) thyroid tumors Increased intrathoracic masses Increased suspicion of carcinoma (19.3% vs 0.4%) - severe hyperT, huge intrathoracic multifocal tumors, refractory to methimazole treatment).

Question 48

What is more significantly affected by hyperthyroidism in cats - muscle or fat? Did loss of muscle/fat improve with successful treatment?

Answer 48

Peterson JVIM 2016 Muscle. 77% hyperT cats lose weight (associated with muscle wasting) but 66% maintain ideal/overweight BCS (remaining 35% thin/emaciated). Euthyroidism leads to weight gain & increased BCS, but mild-moderate sarcopenia persisted in 45% cats.

Question 49

What % of hyperT cats with thyroid cysts have hyperT, and what % of hyperT cats have malignant disease? What is the response of thyroid cysts to I131? When should surgical removal of cysts be considered?

Answer 49

Miller JVIM 2017 93% hyperT, 50% carcinoma. I131 tx alone had high success rate (92% became euthyroid) but inconsistently resolved thyroid cysts (only 50%). Consider thyroid-cystectomy in cats with unilateral thyroid disease, or when symptomatic cysts persist despite successful I131 tx.

Question 50

What does the scintigraphy T/S ratio represent? What can this parameter be predictive of?

Answer 50

Volckaert JFMS 2018 Ratio of thyroid to salivary gland pertechnetate uptake. Cats with T/S ratio of 5.4+ had an increased risk of persistent hyperT post-I131. Sn 73% but poor Sp 59%.

Question 51

What co-morbidity was significantly more common in cats with severe hyperT (vs mild-moderate)?

Answer 51

Watson JFMS 2018 Cardiac abnormalities - thyrotoxic cardiomyopathy. (No sig diff in likelihood of renal disease or systemic hypertension)

Question 52

What is the duration of action of DOCP in dogs?

Answer 52

Jaffey JVIM 2017 >30 days. Dosing interval was 38-90 days in this study.

Question 53

What are the differences in using a lower vs recommended dose of synacthen (cosyntropin) to screen for primary hypoA in dogs? What is the lower dose used?

Answer 53

Botsford JVIM 2018 1ug/kg IV Equivalent to 5ug/kg for screening dogs

Question 54

Is measuring a basal cortisol essential when performing an ACTH stimulation test for the diagnosis of PDH in dogs? Why/why not? What cut-offs for post-stim cortisol yielded the optimal Sn & Sp to diagnose PDH?

Answer 54

Nivy JVIM 2018 No. Basal cortisol deemed redundant from this study, as post-stim cortisol had good discriminatory ability for the diagnosis of HAC (AUC 92%). Optimal cut-off = 683nmol/L (24.8 μg/dL) with Sn 86% & Sp 94%. (Cut-off of 718nmol/L had Sp 100% but poorer Sn 81%).

Question 55

What is the utility of basal cortisol for the diagnosis of hypoA in dogs?

Answer 55

Gold JVIM 2016 Basal cortisol 55 effectively excludes hypoA) Cortisol <22nmol/L (0.8ug/dl) = 96% Sn & 95% Sp Cortisol <5.5nmol/L (0.19ug/dl) = 99.1% Sp (effectively rules IN hypoA)

Question 56

What are the functions of the CYP11B1/2 genes? Do dogs have 1 or 2 genes? What differentiates steroid expression in the adrenals in dogs?

Answer 56

Sanders JVIM 2016 B2 = aldosterone reductase --> produces aldosterone B1 = 11B-hydroxylase --> produces cortisol (only in people) Dogs only have 1 gene (B2) which is equally expressed in both the GF & GR. Dogs have another gene CYP17 (17a-hydroxylase/17,20-lyase) which is selectively expressed in the ZF (much lower in ZG) & may account for ZF-specific cortisol production. CYP17 may be a good therapeutic target for selective inhibition of cortisol synthesis without affecting mineralocorticoid production in the ZG.

Question 57

What derangements in the oxidative status of RBCS were observed in cats with diabetes mellitus? Did these change during treatment and/or at remission?

Answer 57

Zini JVIM 2020 At baseline, RBCs of DM cats had higher median membrane carbonyls (protein oxidation by-products) & lower cytoplasmic TBAR (thiobarbituric acid reactive substances = lipid peroxidation by-products). With treatment, mild improvement in protein oxidation occurs (carbonyls decreased by 13%) but remained higher + lower TBAR vs controls. No differences in markers with DM remission. *NB: Short-term hyperglycemia or hyperlipidemia does not cause oxidative stress.*

Question 58

What was the median survival for dogs with PDH which did not receive trilostane? How did this compare to dogs treated?

Answer 58

Nagata JVIM 2017 Untreated MST 506 days. Treated group MST not reached. Concluded that withholding tx for dogs with PDH might be associated with a higher risk of death. (Cause of death in untreated dogs mostly unrelated to PDH, but 4/17 had dyspnea & 2/17 had neuro signs which could be PDH-associated).

Question 59

What is the incidence of concurrent adrenal and pituitary lesions in HAC dogs? Which dogs have an increased incidence?

Answer 59

van Bokhorst JVIM 2019 5%. Dogs resistant to dexamethasone suppression (10% incidence).

Question 60

What was the disease recurrence rate in PDH dog undergoing transsphenoidal hypophysectomy? What is the significance of the P/B ratio & UCCr pre-operatively in these dogs? P/B ratio = pituitary height (mm) /brain area (mm2) UCCr = basal urinary corticoid-to-creatinine ratio

Answer 60

van Rijn JVIM 2016 27% recurrent hypercortisolism, median 555d. Higher P/B ratio and/or UCCr associated with recurrence. P/B ratio of 0.31+ (cut off for definition of enlarged pituitary gland) was associated with significantly shorter survival.

Question 61

What is the Sn and Sp of the LDDST? What pattern of suppression has the highest PPV & which has the second highest?

Answer 61

Bennaim JVIM 2018 Sn 96% & Sp 67%. Lack of suppression had the highest PPV (94%), followed by partial suppression (67%). In contrast, escape or inverse pattern provided limited support of HAC.

Question 62

What was the incidence of reported AE in FNA of adrenal masses?

Answer 62

Sumner JSAP 2019 US-guided FNA of adrenal masses appear safe. Only 1/19 dogs had VTach (dx phaeo).

Question 63

What limitations does the ACTH stimulation test have when evaluated in healthy dogs?

Answer 63

Gal JVIM 2017 Intermediate IoI (index of individuality) value for post-ACTH stim [cortisol], which means the RI may not reflect true normal in all dogs. So false negatives to diagnose HAC may occur when post-ACTH [cortisol] is outside of the individual’s homeostatic set point but WRI. Cortisol was higher in males. Cd (critical difference for interpretation) was 93. * *Definition: smallest difference between sequential lab results in a patient which is likely to indicate a true change in the patient.*

Question 64

What dose of ACTH has been recommended for monitoring vs diagnosis of HAC in dogs?

Answer 64

Alridge JVIM 2016 1ug/kg could be used for monitoring (85-108% equivalent to 5ug/kg) for dogs receiving mitotane OR trilostane. Couldn't be used for diagnosis though, only 73-92% equivalent. Clinical interpretations would have been different for 23% dogs.

Question 65

What is pasireotide? What is the effect of this drug in conjunction with trilostane/mitotane in PDH dogs?

Answer 65

Lottati JAVMA 2018 Pasireotide = somatostatin analogue. Pituitary corticotroph tumours may express somatostatin (and dopamine type 2) receptors. Somatostatin has inhibitory effects on pituitary hormone secretion. In this study, pasireotide did NOT improve clinical variables, ACTH stim or plasma ACTH levels at 3 & 6 mths. Some dogs had increases in pituitary size while some had decreases.

Question 66

What was the level of disagreement between an ELISA vs validated chemilumescent assay to evaluate serum cortisol?

Answer 66

Lane JAVMA 2018 Clinically important disagreement in 25% of samples, particularly for very high or very low serum cortisol [ ]s.

Question 67

What % of dogs having abdominal CT had an incidental adrenal mass identified? What were risk factors for this?

Answer 67

Baum JAVMA 2016 9.3%. Associated with screening for neoplasia (15.9%) & increased age (median 12yo).

Question 68

What % of dogs having abdominal CT had an incidental adrenal mass identified? What were risk factors for this?

Answer 68

Baum JAVMA 2016 9.3%. Associated with screening for neoplasia (15.9%) & increased age (median 12yo).

Question 69

What sort of insulin is Lispro? How did it compare to regular insulin to treat DKA in cats?

Answer 69

Anderson JVIM 2019 Human analogue insulin, short acting. In this paper found to be safe at starting dose of 0.09U/kg/hr. Normalised BG faster than regular insulin (7hrs vs 12.5hrs).

Question 70

What is the benefit of home glucose monitoring in cats?

Answer 70

Hazuchova JFMS 2018 Higher rate of remission 32% vs 10% (though not stat significant) & improved QOL.

Question 71

What is the MOA of exenatide? What was the impact of exenatide on newly diagnosed DM cats?

Answer 71

Riederer JVIM 2016 MOA - glucagon like peptide (GLP-1) analogue. *Placebo group = low CHO diet + glargine + saline SQ* Reduced appetite (60%) & did not lead to weight gain. V+ (53%). DM remission in 40%, good control in 89% (vs 20/58% in placebo group); not stat significant.

Question 72

*IMPT* Treatment options for hypersomatotropism (HST) in cats? (List 6) Include drug MOA.

Answer 72

1) Medical management - Pasireotide (somatostatin analogue) (Gostelow JVIM 2017) 2) Linear-accelerator-based modified radiosurgery 3) Hypofractionated RT 4) SRT (Wormhoudt JVIM 2018) 5) Cryohypophysectomy (single report) 6) Transsphenoidal hypophysectomy (Fenn JVIM 2021)

Question 73

What condition can N-Terminal Type III Procollagen propeptide be used to diagnose and/or monitor? What cut-off was established, and Sn/Sp of this?

Answer 73

Keyte JVIM 2016 Diagnosis of hypersomatropism in cats. NB: PIIINP = biomarker of soft tissue proliferation, increased [ ] reflects effects of excess GH on soft tissue. Collagen is synthesized with propeptides at both ends of the molecule, and cleavage of these propeptides promotes formation of collagen fibrils and fibrosis. Stable; measurement avoids fluctuations due to pulsatile release (as with GH). Correlates with GH concentrations in humans. Serum [PIIINP] sig higher in HS+DM cf DM cats. Cut-off of 10.5ng/mL differentiated HS from regular DM with Sn 87% & Sp 100% (AUC 91%). Serum [PIIINP] sig decreased after hypophysectomy (in conjunction with IGF-1) in most cats. Though post-RT, increased significantly (IGF-1 remained unchanged).

Question 74

**Impt** What was the impact of SRT for treatment of functional pituitary adenomas in acromegalic+ poorly controlled DM cats in terms of disease control & survival? What was the incidence of hypothyroidism post SRT?

Answer 74

Wormhoudt JVIM 2018 Overall improved survival + DM control. 95% had lower insulin requirements - median 9.5mths to lowest insulin dose required. 32% achieved DM remission (permanent in 62%). 14% developed hypoT requiring supplementation. MST 1072d.

Question 75

(2 papers) Hypophysectomy for treatment of HST in DM cats. List: a) Complications b) % improved glycemic control c) % DM remission d) % DM recurrence e) Long term treatments required

Answer 75

Fenn JVIM 2021 a) Hypoglycemia (13%), electrolyte imbalance (13%), transient CHF (7%) b) 81% c) 60%, insulin stopped after median 9d d) 12% (after median 248d) e) 100% cats received long-term levothyroxine & hydrocortisone PO. DDAVP (conj) 72% cats. van Bokhorst JVIM 2021 Plasma GH sig decreased by ~17x within 5hrs post-sx. 95% HST remission (normalised plasma IGF-1) 92% DM remission, remaining 8% had improved (excellent) DM control requiring lower insulin doses MST 1374d. All-cause survival rates 76% (at 1 & 2yrs), 52% (3yrs).

Question 76

(3 papers) Can HST occur without concurrent DM in cats? Is an elevated serum IGF-1 diagnostic for HST in cats? Are there any other conditions which could elevate serum IGF-1? What cut-off concentration has a 95% PPV to detect HST in cats? What conditions could cause DECREASED serum IGF-1 in cats?

Answer 76

Fletcher JVIM 2016 & Fracassi JFMS 2016 Yes, case reports. Not diagnostic, elevated serum IGF-1 can be found in non-HST cats. Also need pituitary mass/enlargement. Serum IGF-1 >1000ng/mL (800-1000ng/mL gray zone) Steele JFMS 2021 Increased IGF-1 >1000ng/mL noted in 6.7% non-DM cats with HCM. Decreased IGF-1: LSA, DM, renal dz

Question 77

What is the MOA of cabergoline? Indications other than HST in cats? Mechanism & efficacy in treatment of HST in cats?

Answer 77

Miceli JVIM 2021 Cabergoline = long-acting dopamine agonist (DA), with a high affinity for dopamine receptor 2 (D2R). Indications - Pseudopregnancy in dogs, PDH (to reduce ACTH production & pituitary adenoma proliferation). - HAC+DM in a cat (case report Miceli JFMS 2021) - skin changes & abdo distension improve + DM remission concurrently. Mechanism - somatotrophinomas have dopamine receptor expression. Variable efficacy - previous study showed ineffective. But this study showed efficacy at 10ug/kg q48h - reduced insulin requirements; eventual DM remission in all 3 cats at 2 & 3 months of tx with persistence at 14-38mths.

Question 78

What is the MOA of cabergoline? Indications other than HST in cats? Mechanism & efficacy in treatment of HST in cats?

Answer 78

Miceli JVIM 2021 Cabergoline = long-acting dopamine agonist (DA), with a high affinity for dopamine receptor 2 (D2R). Indications - pseudopregnancy in dogs, PDH (to reduce ACTH production & pituitary adenoma proliferation). Mechanism - somatotrophinomas have dopamine receptor expression. Variable efficacy - previous study showed ineffective. But this study showed efficacy at 10ug/kg q48h - reduced insulin requirements; eventual DM remission in all 3 cats at 2 & 3 months of tx with persistence at 14-38mths.

Question 79

In a UK epidemiological study, what was the prevalence of DM? What risk factors were identified for the development of DM in cats?

Answer 79

O'Neill JVIM 2016 Overall prevalence 0.58% (1 in 200 cats). Breeds - Tonkinese (OR 4.1), Norwegian Forest (OR 3.5), Burmese (OR 3.0). BW >4kg, cats >6yo, insured cats. Not sex.

Question 80

What is the effect of insulin treatment on IGF-1 in cats & what is the significance?

Answer 80

Strage JVIM 2018 Increased IGF-1 & this was predictive of DM remission. Was associated with an increase in IGF complexes called ternary complexes (TCs) which is associated with IGF-binding proteins (IGFBPs).

Question 81

What are the CT characteristics of the pancreas in chronic DM cats?

Answer 81

Secrest JVIM 2018 Increased pancreatic size & volume, volume:BW ratio & increased peak portal enhancement time.

Question 82

What is the reported accuracy for the freestyle libre in dogs?

Answer 82

Corradini JVIM 2016 93% accurate at low BG but 99% accurate at normal-high BGs. Mean difference from reference method (EDTA plasma glucose) was 2.3mg/dl (0.12mmol/L).

Question 83

What lipid fractions are increased in dogs with DM?

Answer 83

Seage JVIM 2018 All lipoprotein fractions were, but the biggest were LDL-cholesterols and non-HDL-cholesterol.

Question 84

In a study based around an owner survey, feeding what sort of diet was associated with DM in cats?

Answer 84

Öhlund JVIM 2017 Dry food (OR 3.8). Other risk factors - Indoor confinement, being a greedy eater, overweight status.

Question 85

Which was commonly increased in DM cats? T4, IGF-1 or FPLI?

Answer 85

Schaefer JFMS 2017 fPLI increased in 43%. IGF-1 >1000ng/ml in 17.8% (lower cf other studies) UCCR increased in 15% (may reflect HPA axis activation as with DM people). T4 uncommonly increased 4.5%.

Question 86

In a non-controlled JFMS study, what was the effect of feeding Hills Metabolic diet on weight control in cats?

Answer 86

Christmann JFMS 2016 83% lost weight, 14% reached ideal BW.

Question 87

What is the incidence of cPLI positivity in DKA dogs? What is the clinical or prognostic significance?

Answer 87

Bolton JVIM 2016 73% - concurrent pancreatic injury common. Did not affect duration of hospitalisation or survival

Question 88

What mode of inheritance is present for diabetes in American Eskimo dogs?

Answer 88

Cai JVIM 2019 Polygenetic. Theoretically breeding program could decrease incidence.

Question 89

xx How did glargine compare to act rapid CRI for feline DKA management?

Answer 89

JVECC 2019 No difference in survival. Median times to resolution of ketonaemia were shorter in the glargine group, but was not statistically significant. Faster improvement in hyperglycaemia and faster discharge for glargine treated cats

Question 90

Did insulin-induced hypoglycemia incite posthypoglycemic hyperglycemia (PHH) in DM cats? What are the clinical implications on DM control/remission?

Answer 90

Zini JVIM 2018 PHH not associated with insulin, but occurred in 25% of DM cats with hypoglycemia, especially when DM control was poor. PHH associated with higher insulin doses, higher serum fructosamine, metabolic control, lower risk of remission & increased glycemic variability (GV). Similar GV with insulin degludec (ultra long acting basal insulin ) vs PZI.

Question 91

Based on an epidemiological study in Sweden, what are the risk factors for adrenocortical insufficiency in dogs?

Answer 91

Hanson JVIM 2016 Portuguese Water Dogs, Standard Poodle, Bearded Collie, Cairn Terrier, Cocker Spaniels. Females. Relative risk of death = 1.9x cf normal dogs.

Question 92

How did a lower cut-off basal cortisol concentration compare to the traditionally used cut-off for diagnosing hypoA in dogs?

Answer 92

Gold JVIM 2016 Cut-off of > 22nmol/L had high Sn 96.9% & high Sp 95.9% in excluding hypoA - comparable to traditional cut off of > 55nmol/L (Sn 99.1%) Cut-off of <= 5.5nmol/L had Sp 99.1% of ruling in hypoA.

Question 93

Based on a study evaluating hepatic tumor portal perfision in dogs with incomplete resectable hepatic tumors, where does most of the tumor blood supply arise from?

Answer 93

Goode JVIM 2019 Hepatic artery (not portal vein)

Question 94

What echocardiographic changes may be observed following thyroxine supplementation in hypothyroid dogs?

Answer 94

Guglielmini JVIM 2019 Hypothyroidism in dogs induces mild & reversible changes of electromechanical cardiac function. Increased median HR, P wave amplitude, FS, E max. Decreased LVIDd, normalised LVIDs & EPSS Myocardial performance index (MPI) used in people does not have clinical imptance in identifying cardiac dysfunction in hypoT dogs

Question 95

Did hypothyroid dogs have changes in neurohormonal status after 6 monhts of levothyroxine supplementation?

Answer 95

Hrovat JVIM 2019 None observed in this study (no diff in circulating serotonin), though study noted increase in activity post-supplementation.

Question 96

What autoantibodies may be associated with feline limbic encephalitis?

Answer 96

Hasegawa JVIM 2019 DCC (deleted in colorectal carcinoma) aka netrin-1 receptor

Question 97

What endocrinopathy may be introduced by ketoconazole at high doses? What are the possible mechanisms?

Answer 97

Hernandez-Bures JVIM 2019 Hypoadrenocorticism (adrenal insufficiency). Dose-dependent, idiosyncratic, or cumulative in nature.

Question 98

Does accidental injection of ACTH perivascularly affect ACTH stimulation test results for diagnosis (HAC) or treatment monitoring (trilostane)?

Answer 98

Johnson JVIM 2017 No for both.

Question 99

What is the main limitation of using basal cortisol to monitor efficacy of BID trilostane in PDH dogs?

Answer 99

Woolcock JAVMA 2016 14/64 dogs with basal cortisol >3.2ug/dL or 28nmol/L) had ACTH stim normal basal cortisol will miss significant no of dogs with dose suggesting inadequate cortisol reserves.

Question 100

Is adrenal gland thickness (AT) affected by BW, age & sex in dogs with non-adrenal illness?

Answer 100

Bento JAVMA 2016 Yes. Larger AT in dogs 12kg+, larger left AT with age. Larger L & R AT in males > females. Study concluded that dogs 12kg - AT <0.72cm.