Lit Endocrine Flashcards
Which tests were used to differentiate PDH from cortisol-producing adrenal tumors (CPAT) dogs, and what were the test sensitivities & specificities?
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.
At what time points were median interstitial glucose (IG) concentrations found to be significantly increased when evaluating circadian fluctuations in DM dogs?
Shea JVIM 2021
Night time (1-6am)
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?
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.
Which pre-treatment factors were helpful in predicting persistent hyperT and iatrogenic hypoT post-I131 treatment in hyperT cats respectively?
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.
What was the advantage of administering insulin glargine 300 U/mL (IGla300) or insulin degludec (IDG) vs porcine lente (PL) in DM dogs?
Miller JVIM 2021
Lower day-to-day variability – so advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.
What were the accuracies of insulin devices (pens vs syringes) when delivering various insulin doses (small </=2U vs 8-16U)?
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.
Progesterone concentrations were …. in cats with hyperaldosteronism (HA), and occurred in ……% cats. Serum cortisol concentration was ……. in HA cats, likely indicating …….
Langlois JVIM 2021
Increased, 32%
Decreased, HPA axis suppression
Canine TLI was decreased in DM dogs compared to healthy controls. (T/F)
CTLI negatively correlated with DM duration. (T/F)
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.
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 ….
Harro JVIM 2021
Diabetes mellitus, diabetic remission, hypoadrenocorticism.
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.
Howard JVIM 2021
a) 39.1%, 81.7%
b) 80.1% (basically double), 80.1% (similar)
*IG concentrations fail to reliably detect hypoglycemia.
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?
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
How does long-acting recombinant insulin work in the treatment of DM cats?
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.
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?
Del Magno JVIM 2021
a) HyperNa 46.5% dogs»_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.
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.
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)
(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.
Malerba JVIM 2020
False – poor analytical but good clinical accuracy.
True
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?
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.
Exenatide = GLP-1 agonist
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?
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.
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?
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).
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.
Hauck JVIM 2020
4%
Melena, hematochezia
28%, 6%
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.
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
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)?
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).
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?
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.
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?
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.
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?
Bermejo JVIM 2020
a) No variables (study assessed USG, UCCR, ACTH stim, serum cortisol concentrations (SCCs))
b) Within 1hr.
c) <8 hours.
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?
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.
- What was the diagnostic utility of serum cortisol (SC) to predict prognosis in critically ill dogs?
- The optimum cutoff of SC concentration was …… ug/dL; with an OR of ……, sensitivity ……% and specificity of ….% to predict non-survival.
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)
What was the prognostic value of serum TT4 concentration at admission in critically ill dogs?
Neiman JAVMA 2020
Not useful as prognostic indicator in critically ill dogs.
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?
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.
Is SDMA useful in predicting azotemia post-I131 in hyperT cats?
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.
What is the incidence of 1. long term hypothyroidism and 2. recurrent hyperthyroidism in cats that had undergone bilateral thyroidectomy in FIRST OPINION practice?
Covey JVIM 2019
Renal parameters assessed at 6mths post sx (thyroid status deemed stable then with likely minimal influence on SDMA & SCr.)
- 50% hypoT at 6 months, 17% hypothyroid long term.
- 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).
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?
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.
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)?
Morré JVIM 2018
99m Tc-pertechnetate. % 99m Tc uptake of thyroid glands.
No
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?
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.
What is a non-neoplastic condition of the pancreas that could cause hypoglycaemia in dogs?
Polansky JAVMA 2018
Nesidioblastosis (islet cell hypertrophy of the endocrine pancreas on histo).
Results in hyperinsulinism. Hypoglycaemia resolved with partial pancreatectomy (case report).
What is the correlation between iCa levels preceding parathyroidectomy or heat ablation, and risk of post-treatment hypoCa in dogs with hyperPTH?
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.
Which assay is preferred (vs not recommended) for PTH determination in dogs?
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).
What secondary amino acid derangement can occur in hypothyroid dogs?
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.
What is the effect of hypothyroidism on GH? How might this be used diagnostically to discriminate hypoT from non-thyroidal illness in dogs?
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.
