Endocrine Flashcards
What is adiponectin? Does it increase or decrease with obesity and what is the effect?
Anti-inflammatory and insulin sensitising hormone. Decreases with obesity and so contributes to insulin resistance. Produced by adipose tissue
Name an example of a sulfonylurea. What is their MOA? Adverse effects?
Glipizide. Stimulate insulin release by binding to beta cell ATPases. This closes K+ channels and leads to increase Ca2+ in the cell and therefore insulin release. AE: GI upset, liver enzyme elevations and jaundice
Name an example of a meglitinide. What is their MOA?
Nateglitinide. Closes ATP sensitive K+ channels and stimulate insulin release. Short acting.
Name an example of a biguanide. What is their MOA? Side effects?
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). Side effects: potential for lactic acidosis, GI upset
What is the POMC gene in Labradors associated with?
JVIM 2017: Associated with obesity and food motivation. No association found with diabetes
What is the association between PCV and point of care blood glucose?
JAVMA 2015: Lower HCT = high BG, higher HCT = lower BG. This paper developed a formula for correction
How can the accuracy of a POC blood glucose be improved?
JAVMA 2015: separating plasma or serum; difference in this study was 0.3/0.4 compared to 31 for whole blood
What is the average dose required for Detemir?
JAVMA 2015: 0.12iu/kg. Hypoglycemia in 22%, caution in small dogs
How did glargine compare to act rapid CRI for feline DKA management?
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
What mode of inheritance is present for diabetes in American Eskimo dogs?
JVIM 2019: Polygenetic. Theoretically breeding program could address
What is the incidence of cPLI positivity in DKA dogs and what is the significance?
JVIM 2016: 73%. Did not affect duration of hospitalisation or survival
What are some indications for a somatostatin analogue? what is an example? what are some side effects?
Hypoglycemia (insulinoma), gastrinoma. Antagonises insulin release from beta cells and gastrin release from G cells. Eg Octreotide, an injectable. Need 2-3 injections per day. Side effects; GI upset, reduced biliary contraction
What is the reported accuracy for the freestyle libre?
JVIM 2016: 93% accurate at low BG but 99% accurate at other BGs. Mean difference from reference method was 2.3mg/dl (0.12)
What lipid fractions are increased in dogs with DM?
JVIM 2018: All fractions were, but the biggest were LDL-Cholesterols and non-HDL-cholesterol.
Is the CGM accurate in DKA in dogs?
JVIM 2019: found to be clinically but not analytically accurate. BCS, time wearing and metabolic variables did not affect accuracy
What is the incidence of relapse in cats with diabetic remission? What factors can predict this?
JVIM 2015: 30% relapse. Fasting BG 7.5+ and impaired glucose tolerance predicted; taking 5 hours to normalise or BG increasing to 14+
in a study based around an owner survey, feeding what sort of diet was associated with diabetes?
JVIM 2017: Dry food
In an uncontrolled JFMS study, what was the performance of Hills Metabolic in cats?
JFMS 2016: 83% lost weight and 14% reached ideal weight
Which was commonly increased in DM cats? T4, IGF or FPLI?
JFMS 2017: fPLI increased in 43%. T4 uncommonly increased 4.5%, and IGF >1000ng/ml in 17.8%
What is the effect of insulin treatment on IGF in cats and what is the significance?
JVIM 2018: Increased IGF and this was predictive of remission. Was associated with an increase in IGF complexes called ternary complexes (TCs) which is associated with IGF binding proteins.
What are the CT characteristics of cat pancreas’ with diabetes?
JVIM 2018: increased size and volume, increased peak portal enhancement time.
What is acarbose? What is the effect in healthy cats and is this diet dependent?
JFMS 2015: 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, may be less effective with
What is the recommended CHO content of feline DM food?
JFMS consensus: <12-15%/ME
What is the relevance of chromium and vanadium in diabetes?
Cofactor for insulin function. Chromium has improved glucose tolerance in healthy cats and vanadium has improved CSx and fructosamine in cats with DM
What is an incretin? Name an example and how it is degraded. What is its MOA?
GI hormone, such as glucagon like peptide (exenatide). Cleaved by DPP-4 (another drug target; inhibitors). GLP-1 promotes insulin release in response to glucose, inhibit beta cell apoptosis, inhibits glucagon release and delays gastric emptying. Relies on glucose being present. In DM cats also on insulin a long acting exenatide formulation was associated with reduced insulin requirement and higher remission.
What was the impact of exenatide on newly diagnosed DM cats?
JVIM 2016: Reduced appetite and lack of weight gain. Remission in 40% and good control in 89%, compared to 20/58% in placebo group, not statistically significant
What is the benefit of home glucose monitoring in cats?
JFMS 2018: Higher rate of remission 32% vs 10% (though not statistically significant) and improved QOL
What sort of insulin is lispro? how did it compare to regular insulin for DKA in cats?
JVIM 2019: Human analogue insulin, short acting. In this paper found to be safe and in the dose used normalised BG faster than regular insulin.
What % of dogs having abdominal CT had an incidental adrenal mass identified? What were risk factors for this?
JAVMA 2016: 9.3%. Associated with screening for neoplasia and increased age
What was the level of disagreement between a cortisol ELISA and chemilumescent assays?
JAVMA 2018: Clinically important disagreement in 25% of samples, particularly when high or low
What is pasireotide? What is the effect of this drug in conjunction with trilostane or mitotane in PD Cushings?
JAVMA 2018: Somatostatin analogue. PD tumours may express somatostatin receptors (and dopamine receptors). These may be inhibitory.
In this study, pasireotide did NOT improve clinical variables, ACTH stim or plasma ACTH levels. some dogs had increases in PD size and some had decreases
What is the % recurrence of PD in dogs after hypophysectomy? can any post operative variables be used to predict?
JVIM 2015: 28%. Post op cortisol, ACTH were associated with a shorter disease free period but no single cut off could be identified
What dose of ACTH has been recommended for monitoring vs diagnosis
JVIM 2016: 1ug/kg could be used for monitoring (85-108% equivalent to 5ug/kg). Couldn’t be used for diagnosis though, only 73-92% equivalent. Clinical interpretations would have been different for 23% of the dogs
What limitations of the ACTH stimulation test was seen via evaluating it in healthy dogs?
JVIM 2017: Intermediate IoI value, which is a marker of inter-individual variability. This means reference interval may not reflect true normal in all dogs. Cortisol was higher in males. Cd (critical difference for interpretation) was 93
What was the incidence of reported AE in FNA of adrenal masses?
JSAP 2019: only 1/19 dogs had Vtach.
What is the preferred test for Phaeochromocytoma?
JVIM 2015: Urinary normetanephrin:creatinine ratio. No overlap with HAC or healthy dogs
What receptor has been found to be expressed more in adrenal carcinomas?
JVIM 2015: ERBB2 (potential therapeutic target)
What is the Sn and Sp of the LDDST? What pattern of suppression has the highest PPV and which has the second highest?
JVIM 2018: Sn 96 and Sp 67. Lack of suppression had a PPV of 94, followed by partial 67%
How did dogs with atypical HAC differ from control dogs?
JVIM 2015: They had significantly higher hourly and sum cortisol concentrations compared to healthy dogs. Adrenal diameter did not differ between atypical and PDH dogs.
What is the significance of the P/B ratio and UCCr prior to hypophysectomy?
JVIM 2016: Higher of either associated with recurrence. P/B ratio of 0.31+ was associated with significantly shorter survival.
What is the contribution of the basal cortisol to the ACTH stim?
JVIM 2018: Redundant. Post stim cortisol had good discriminatory ability, comparable to the difference in concentration between values. Baseline was redundant.
What is the incidence of concurrent adrenal and pituitary lesions in HAC dogs? What dogs have an increased incidence?
JVIM 2019: 5%. In dogs resistant to dexamethasone suppression, it was 10%
What was the impact of performing an ACTH stem 8-12 hours post trilostane in dogs with low traditional ACTH stims?
JVIM 2015; they had higher cortisol levels. The traditional pre and post ACTH cortisol measurements were lower than the pre-ACTH cortisol 8-12 hours later
What was the median survival for dogs with PDH which did not receive trilostane? How did this compare to dogs treated?
JVIM 2017: MST untreated 506 days. Treated group MST not reached
What is the CYP11B1/2 genes? Do dogs have 1 or 2? What differentiates steroid expression in the adrenals?
JVIM 2016: B2= aldosterone reductase, B1 = 11B-hydroxylase, which makes cortisol in humans. Dogs only have 1 (CYP11B2) and is in both the GF and GR. Another gene, CYP17 is selectively expressed in the Zona Fasciluta and may allow cortisol production
What is the timing of blood collection for a depot of tetracosactide for hypoA diagnosis?
JVIM 2015: 3 hours. No hypoA dogs exceeded the limit of detection for the assay at this time, compared to healthy dogs which increased (>5/>9)
What can the cortisol:ACTH ratio be used for?
JVIM 2015: Diagnosis of hypoA without synacthin, results in a low ratio. Sn 100 and Sp 99 with a CAR of >0.01. a false positive cannot be completely ruled out as there was some overlap with dogs with HA mimicking disease, more studies recommended
How can a basal cortisol be used for diagnosis of hypoA?
JVIM 2016: A cortisol of <55 is 99.4% sensitive for detection of hypoA. A cortisol of <22 is 96% Sn and 95% Sp. If you get a result <5.5 its 99.1% specific.
What dose of synacthen should you use to screen for HypoA?
JVIM 2018: 1ug/kg and 5ug/kg are equivalent
What is the duration of action of DOCP in dogs?
JVIM 2017: 30 days +. Dosing interval was 38-90 days in this study
What is the effect of hypoA on TSH/T4?
JVIM 2017: increased TSH in 11/30 dogs, normalising after up to 4 months of treatment. T4 was normal.
If you want to adjust DOCP dose (rather than interval) what starting dose is appropriate? what dogs tend to need more? what is the average dose?
JVIM 2019:1.5mg/kg, younger dogs tend to need higher doses (< 3). Average dose in this study was 1.1mg/kg
What was the concentration of thyroxine in foods found to cause thyrotoxicosis (c/f normal food)
JAVMA: diet induced hyperthyroidism found from meat containing products. Concentration 1.52ug/g (c/f 0.38ug/g)
What mutation is reponsible for pituitary dwarfism in GSD? What other abnormality may this be associated with in GSD and Czechoslovakian wolfdogs?
JVIM 2015: LHX3 mutation. A-A instability
What may the scintigraphy T/S ratio be predictive of?
JFMS 2018: >5.4 had an increased risk of persistent hyperthyroidism after I131. Sn 73 but Sp only 59
What is the response of thyroid cysts to I 131?
JVIM 2017: 92% achieved euthyroidism but only 50% had their cysts resolve. Some had surgery; 50% of surgical removed cysts were carcinoma
What is the potential contribution of TSH to a diagnosis of hyperthyroidism in a cat?
JVIM 2015: Very sensitive, 98% of hyperthyroid cats have undetectable levels. However poorly specific (69%). Combining with T4/fT4 increases Sp to 98.8%
What is more significantly affected by hyperthyroidism, muscle or fat?
JVIM 2016: Muscle. 35% had low BCS but 77% were sacopenic. increased BCS expected after treatment but sarcopenia persisted in 45%
What is the expected differences between hyperthyroidism of >4-6 years in duration compared to < 1 year?
JFMS 2016: higher T4, higher goitre size, more intrathoracic tissue and increased suspected carcinoma (19.3% vs 0.4%)
What % of cats have their T4 normalise on a low iodine diet and at what time points? what pre-treatment variable affects outcome?
JVIM 2015: Normalised in 42% by day 21-60 and 83% day 61-180. Cats that stayed about RI had higher starting T4
JVIM 2015: All cats in this study had normalisation by 56-112 days
What is the incidence of long term hypothyroidism and recurrent hyperthyroidism in cats having bilateral thyroidectomy in FIRST opinion practice?
JVIM 2019: 17% hypothyroid long term (50% in the first 6 months). 44% developed recurrent hyperthyroidism. This was in first opinion practice, possibility of intracapsular technique. Usual reported recurrence is 5-11%
What is the methylmalonic acid status of hyperthyroid cats with low cobalamin?
JVIM 2016: Normal. Conclusion was that cobalamin supplementation was not required
How did a low dose (2Mi) I 131 treatment compare to standard 4Mi dose?
JVIM 2017: Less hypothyroidism (overt 18% vs 1%) but with no significant difference in hyperthyroidism. Creatinine also increased by more % in the standard dose group
95% cure rate
What are the differences in kidney ultrasound contrast findings in cats pre and post I131?
JVIM 2017; Decreased kidney blood velocity and small decrease in medullary blood volume
Did an I131 fixed dose protocol based on thyroid scintigraphy improve outcomes in cats?
JVIM 2018: No
Did an I131 fixed dose protocol based on thyroid scintigraphy improve outcomes in cats?
JVIM 2018: No
Does administering recombinant TSH to hyperthyroid cats change their % iodine uptake?
JVIM 2018: No
Is SDMA useful in predicting post I 131 azotaemia?
Lu’s paper 2020: SDMA was not able to predict post treatment azotaemia and inconsistently changed after treatment. In most cats SDMA will increase after treatment but in about 28% in this paper it decreased. This was at 3 months
DeMonaco paper: SDMA was specific (94%) for post treatment azotaemia but insensitive (15%) - however, definition for azotaemia was not the same as IRIS (used RI). Used 1, 3 and 6 months
Buresova: SDMA normalised in 4 cats after treatment with I 131 and was not well correlated with GFR. Warned of careful interpretation of increased SDMA in hyperthyroid cats. This was at 1 month.
What form of hypothyroidism is common in adult-onset feline disease?
JVIM 2018: Goitreous
What diseases, apart from DKA, can increase BHB levels above RI in cats?
JVIM 2016: Hepatic lipidosis (can increase moderately), CKD and hyperthyroidism
What tests can be used to diagnose central hypothyroidism (TSH deficiency) and in what breed has this been described?
JVIM 2016: Mini Schnauzers. Can use a TSH stimulation test (3 day protocol) or TRH stim (though this is not completely diagnostic). 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
Can chemiluminescent assays be used reliably for fT4 measurement in dogs with TG-A
JVIM 2015: No - 25-38% of dogs in this study (who had positive antibodies and hypothyroidism) had normal fT4 levels. Need to use ED
What secondary amino acid derangement can happen in hypothyroid dogs?
JVIM 2017: High homocysteine, low folate
What is the effect of hypothyroidism on GH and how might this be used in discriminatory testing?
JVIM 2018: GH is increased in hypothyroidism, presumably due to lack of inhibition by T4 and perhaps also inhibition of somatostatin (and somatostatin suppresses GH).
TRH stimulation testing increased GH in hypothyroid dogs but NOT in normal dogs. May be used for testing as TRH stim is not reliable for differentiating changes in T4
How long do you have to wait after stopping administration of SID levothyroxine to determine the thyroid status of a dog?
JVIM 2017: in this study, healthy dogs were on for 16 weeks and 7 days after stopping were back to baseline values
What type of drug is Bezafibrate? What is its MOA? How effective is it?
JVIM 2017: Peroxisome proliferator-activated receptor - alpha agonist and through this increases lipoprotein lipase -> increases fatty acid uptake and reduces VLDL production in the liver.
Efficacy: Normalised TG in 91% of hyperlipidemic dogs, and cholesterol in 66%.
Hyperlipidemic Schnauzers with proteinuria were not found to be azotaemic or hypertensive. What biochemical variables were increased?
JVIM 2017: Albumin and ALP
What inflammatory marker was increased in Schnauzers with hyperlipidemia and did this respond to diet?
JVIM 2019: Calprotectin. Lipid status improved with diet but calprotectin did not
What are the sulfur containing amino acids (animal protein AAs)
JVIM 2015: Taurine, cysteine and methionine. This paper found vegetarian diets were often not meeting AAFCO standards for AAs.
What is the significance of dietary phosphate in cats?
JVIM 2019: High P (in particular inorganic P) and low Ca;P ratios have been associated with renal damage in cats
What is dirlotapide and what is it associated with?
JVIM 2015: Weight loss drug; inhibits intestinal triglyceride transport proteins. In this study was associated with failure to lose weight
What were the changes to leptin, CSF and microbiome seen in an obese beagle study?
JVIM 2015: higher leptin levels, lower serotonin and adiponectin in the CSF, higher proteobacteria (Firmicutes dominant in the lean group)
What is the effect of obesity on serum adiponectin?
Decreases
What drug can be used to activate lipoprotein lipase in an IV form?
Ettinger: Heparin, used in a liproprotein lipase activity test
What abdominal organ changes can be see in acromegalic cats?
JFMS 2015: Increased kidney length, adrenal thickness and pancreas thickness
What conditions can suppress ghrelin in cats? Is this change reversible?
JVIM 2015: Hypersomatotrophism and DM. RT increased ghrelin levels in the HS cats but did not change IGF so was considered a potential monitoring tool
What conditions can suppress ghrelin in cats? Is this change reversible?
JVIM 2015: Hypersomatotrophism and DM. RT increased ghrelin levels in the HS cats but did not change IGF so was considered a potential monitoring tool
What can Type III Procollagen propeptide be used for? At what cut off? Sn / Sp?
JVIM 2016: Diagnosis of HS in cats. 10.5 differentiated HS from regular DM with a Sn of 87 and Sp of 100. Decreased after hypophysectomy but not RT
What is a medical treatment that has shown efficacy in reducing IGF-1 and insulin requirements in HS cats?
JVIM 2015; Pasireotide
JVIM 2017: Long acting version found to reduce IGF and insulin requirements. Did not affect median BG or fructosamine. 3 cats entered remission. AE: Diarrhoea, hypoglycaemia and polyphagia
What is the preferred assay for PTH determination in dogs?
JSAP 2019: Immunoradiometric assay; either intact or whole PTH. Chemiluminescent assay was not recommended
What is the correlation between pre-hyperparathyroid surgery/ablation calcium and hypocalcaemia post?
JVIM 2017: Moderate correlation; in this study higher = more chance of hypocalcemia
JVIM 2018; Found hypercalcaemia pre-Sx was protective and made an opposing recommendation that calcitriol prior to surgery is not recommended
Can a high tCa predict high iCa? What is this dependent on?
Additionally, what is the sensitivity of a high tCa for high iCa?
JVIM 2019: A high tCa had a high PPV for hypercalcaemia (93%) in dogs WITHOUT hyperphosphatemia. It was only 52% sensitive though; so if you have a normal tCa you can’t rule out ionised hypercalcaemia. But if you have a high tCa with normal PO4 you very much likely have high iCa.
Renal disease causes discordance of tCa and iCa due to PO4 complexes
What vitamin D changes are seen in endurance sled dogs?
JVIM 2015: Sled dogs had increased 25(OH)D3 on Day 2 and Day 8 and 24,25(OH)D also increased by day 8. 1,25(OH)D3 remained the same. The increase in 24,25 indicates enhanced disposal of Vitamin D
What is the association between calcidiol and iCa in dogs with cancer? How about in normal dogs?
JVIM 2017: Dogs with cancer with higher iCa had increased calcidiol concentrations. Healthy dogs had a decrease in calcidiol with higher iCa
Where is the Vitamin D receptor expressed in tissues? Is this affected by chronic enteropathy?
JVIM 2018: Kidney, duodenum, ileum. spleen, skin. Absent gastric and testicular. No reduction in expression in CE dogs
How do you calculate urinary free water clearance? What is the pattern expected with SIADH?
Free water clearance (%) = 1 - (Urine sodium - Urine potassium)/Serum sodium
SIADH = Low Serum Sodium + -ve free water clearance
= patient has low sodium and is conserving water, inappropriate ADH
In which of the following are there breed differences in concentrations: Endothelin, Cortisol and Renin?
JVIM 2016: All 3. Finnish Laphunds had the highest cortisol
What B vitamin derangement is common in Greyhounds and what secondary metabolite increases as a result?
JVIM 2017: Hypofolatemia (B9)and hypocobalaminaemia (often seen together). Associated with increases in homocysteine - these B vitamins are required as cofactors for its metabolism
Has there been an association found between BOAS and CRP/inflammatory profiles?
JVIM 2019: Not in this study. They did find that 76% of these dogs had GI signs though and commonly inflammatory GI lesions
What is a condition that can trigger SIADH?
JVIM 2015: Aspiration pneumonia
Apart from neurological signs, what do the mucopolysaccharidosis (Liposomal storage disease) typically cause?
JVIM 2015: Skeletal and ocular changes
what is a non-neoplastic condition of the pancreas that could cause hypoglycaemia?
JAVMA 2018: Nesidioblastosis (hypertrophy of the endocrine pancreas)
How do you tell the difference histologically between phaeochromocytoma and cortical tumours?
Ettinger; Chromogranin stains medullary tumours. Hard to appreciate if benign or malignant histologically
What neurohormonal marker was different between dogs with PDH and SARDS?
JVIM 2019: PDH higher Urine MT6s: creatinine ratio
