Endocrine Articles All Testable Points/ Physio Questions Flashcards
In a 2015 study retrospectively evaluating the risk factors and outcome predictors in cats with DKA (1997-2007) JVECC
DKA cats were compared to cats with uncomplicated DM and nondiabetic cats
Concurrent disorders, initial insulin IV CRI concentration was examined for potential association with outcome
Looked at 93 cats with DKA, 682 cats with uncomplicated DM, and 16926 cats without DM or DKA
Cats with DKA were younger than cats with uncomplicated DM
Siamese cats were overrepresented in the DKA group compared to other groups
AByssinian cats - increased risk for DM and DKA
>50% of cats with DKA had confirmed diagnosis of acute pancreatitis, hepatic lipidosis, CKD, or UTI
Poor outcome (death d/t disease or euthanasia) in 36 cats with DKA (~40%) was associated with increased inital creatinine, BUN, magnesium, and T. Bili concentrations
Cats treated with higher concentrations of insulin (2.2 U/kg/ 240 ml bag) were less likely to have a poor outcome compared to cats treated with a lower concentation of insulin
Recurrence of DKA - 18% of cats
In a 2016 JVECC Sstudy investigating the use of IV insulin aspart for treatment of naturally occuring DKA in dogs…
Objective - To characterize the safety of IV insulin aspart in the treatment of DKA in dogs and determine the times to resolution of hyperglycemia, ketonemia, and acidemia
Prospective noncontrolled single arm study of dogs with DKA
6 dogs with spontaneous DKA
Aspart insulin was administered as a CRI at initial dose of 0.09 U/kg/h, and dose was adjusted according to previously published protocol
Median time to biochemical resolution of DKA — 28 h (range 20-116h)
Mean BG concentration decreased significantly from the time IV fluid resuscitation started until 6 hrs later when IV aspart insulin CRI started
No adverse effects associated with insulin adminsitration were noted
Cost of hospitalization (median) was ~$3500
Start Iv insulin following several hours of IV fluid resuscitation
What average percentage of dogs with DKA will survive to discharge from the hospital? What is the median hospitalization time for dogs with DKA?
70%
6 days
What are factors associated with poor outcome in dogs with DKA?
Degree of acidemia
IV sodium bicarb therapy
Concurrent diagnosis of hyperadrenocorticism
What percentage of dogs with DKA are newly diagnosed diabetics?
> 50%
What are common concurrent disorders in dogs with DKA, and what is the median age of onset of dogs with DKA?
Acute pancreatitis, UTI, hyperadrenocorticism
8 years old
In a 2017 JVECC Study evaluating the immediate effect of transmucosal application of corn syrup or 50% dextrose solutin on blood glucose concentration in healthy dogs …
Randomized controlled trial using 12 healthy client owned dogs >1 YO and >5 kg
Dogs were fasted overnight for min 12 hrs
IV catheter was placed for serial blood sampling, each dog was their own control for one of three treatments
1. Mucosal application of karo syrup, 2. Water, 3. 50% dextrose, each at a dose of 1 ml/kg body weight
BG was measured using a POC glucometer, and samples were taken prior, then 5,10,15,20,30, and 60 min intervals
Statistically significant increase in BG was observed at the 15, 20, 30, 60 minute time points in the corn syrup and 50% dextrose groups as compared with controls, suggesting intestinal absorption (I.e. transmucosal administration of dextrose does not increased BG for approx 15 min, suggesting that in more severely affected hypoglycemic patients, injectable glucose may be necessary)
Plasma GLP-1 measurements may help distinguish between tranmucosal and jejunal absorption
In a pilot study comparing a protocol using intermittent administration of glargin and regular insulin to a CRI of regular insulin in cats with naturally occurring DKA (JVIM 2015)…
Prospective randomized clinical trial, 16 cats with DKA
Randomized to either low dose regular insulin CRI or intermittent short and long acting insulin injections (0.25 U/kg SQ glargine q12 + 1 U IM regular insulin q 6)
~60% of cats survived to discharge with no difference in survival between groups
Times of resolution of hyperglycemia and ketonemia and normalization of pH and bicarbonate were significantly shorter in the SQ/IM group
Cats in the SC/IM group had shorter hospitalization (median 54 hr) vs the CRI group (median 111hr)
Time of first meal was not significantly different between groups
In a retrospective study comparing early vs late insulin therapy regarding effect on time to resolution of DK and DKA in dogs and cats (JVECC 2016)…
Defined ealy insulin as = 6 hours after admission, late defined as >6 hours post admission
60 dogs and cats with DK and DKA
Early group patients had more rapid resolution of DKA/DK after starting short acting insulin therapy (36 hrs vs 55 hrs for late group)
There was no difference in duration of hospitalization or complications between groups
More severe ketonuria resulted in longer time to resolution of DK/DKA after initiation of short acting insulin
In a retrospective study evaluating the impact of early enteral nutrition on clinical outcomes in dogs with pancreatitis (JVECC 2017)…
Evaluated the effect of early enteral nutrition on time ot return to voluntary intake, return to max food consumption, and incidence of Gastrointestinal intolerance and total hospitalization time for dogs with acute pancreatitis.
34 client owner dogs with acute or acute on chronic pancreatitis
Split them into early feeding group/EFG (food offered before 48 hrs) Delayed feeding (after 48 hours)
Dogs in the early feeding group had a decreased time to return of voluntary intake (2.1 vs 2.7 days in the DFG) and time to max intake (3 days EFG vs 3.4 days DFG)
DFG group exhibited more gastrointestinal intolerance than the EFG group regardless of clinical severity index score (60% of DFG had more Gastro intolerance in comparison to 26% of EFG group)
A clinical severity index score >/= 7 was associated with prolonged length of hospitalization
Time to initiation of feeding and diet selection did NOT impact length of hospitalization
What is the reported mortality rate of dogs with severe acute pancreatitis?
27 - 58%
Why is early enteral nutrition considered to be beneficial in critical patients?
Reduced catabolism
Prevention of protein-energy malnutrition
Improved integrity of intestinal epithelial tight junctions
Overall decreased intestinal inflammation
In a study evaluating urine sodium concentrations and their ability to be predictive of hypoadrenocorticism in hyponatremic dogs - JSAP 2018
Retrospective pilot study
Used to determine if urine sodium concentrations could be used to rule OUT hypoadrenocorticism
20 hyponatremic dogs includes - 11 w/ hypoadrenocorticism, and 9 with nonadrenal causes of hyponatremia
No dog with hypoadrenocorticism had a urine sodium concentraiton of < 30 mmol/L
Urine sodium concentration in dogs with hypoadrenocorticism was significantly higher (median 103 mmol/L) than in dogs with non-adrenal illness (median 10 mmol/L
Serum sodium concentrations were not significantly different between dogs with hypoadrenocorticism and those with nonadrenal illness
Urine sodium concentrations could be used to priortize a ddz of hypoadrenocorticism in hyponatremic dogs (I.e. urine sodium < 30 mmol/L makes hypoadrenocorticism unlikely)
Small sample size
Why does classical hypoadrenocorticism result in renal sodium wasting?
Aldosterone deficiency - also results in potassium retention
In a study investigating the use of hydrocortison in the management of acute hypoadrenocorticism in dogs (JSAP 2016)…
Retrospective review of 30 dogs diagnosed with primary hypoadrenocorticism receiving IV hydrocortison and fluid therapy
Excellent clinical response, all dogs survived to discharge within a median of 2 days
23 cases - mean rate of change of sodium over 24 hours was 0.48 mmol/L/hr, mean rate of change of potassium was -0.12 mmol/L/hr
Circulating potassium normalized in 69% of cases in 12 hours and 100% of cases in 24 hrs
Additional treatment for hyperkalemia was not needed
Plasma Na concentration increased by >12 mmol/L/24 hrs in ~31% of cases
One dog developed temporary neuro signs
Hydrocortisone and fluids is associated with rapid resolution of electrolyte derangements, important to carefully monitor lytes
What is the estimated prevalence of primary hypoadrenocorticism?
0.06-0.33%
Why might hydrocortisone a viable alternative to dexamethasone or prednisone in patients in hospital with hypoadrenocorticism?
Synthetic analog of cortisol
Has equipotent mineralocorticoid and glucocorticoid activity
In a study evaluating epidemiology of hyperadrenocorticism among 210,824 dogs attending primary care veterinary practices in the UK from 2009 to 2014 …JSAP 2016
Estimated prevalence for hyperadrenocorticism diagnosis in dogs was 0.28% or 1 in 400 dogs
Four associated risk factors: breed, breed relative body weight, age, insurance status
Other high risk breeds: Dachshund, Yorkie
Bichon frise had 6.5 x the odds of hyperadrenocorticism compared with MBD
Dogs weighing more than or equal to their breed mean body weight had 1.7 x the odds of hyperadrenocorticism compared with dogs weighing less than the breed mean
Dogs <20 kg but above avg breed body weight (I.e. fat little dogs)
Dogs >/= 12 YO had 5.7 x the odds of hyperadrenocorticism compared with younger dogs
Insured dogs had 4x the odds of hyperadrenocorticism compared with uninsured
Overall, fat, bichons, and old dogs that have owners willing to spend money are at higher risk for being diagnosed with Cush
In a study evaluating canine hyperadrenocorticism associations with signalment, selected comorbidities and mortality within north american veterinary teaching hospitals (JSAP 2018)…
Retrospective cohort study of 1519 dogs with hyperadrenocorticism from a population of 70574 dogs
Hyperadrenocorticism was more frequent in females
Neutering was associated with a minor but significant increase in the odds of hyperadrenocorticism
Was the presumed cause of death in ~26% of dogs
Etiology was specified for ~1/3 (527) dogs
PDH 75% of cases where etiology specified (387/527)
ADH noted in 136 (25%)/ 527 cases
Breeds overrepresented: mini poodle, dachshund, Irish setter, Bassett hound
Dogs with HAC were at increased risk for concurrent DM, UTI, urolithiasis, hypertension, GM mucocele, and thromboembolic disease compared to dogs without HAC
In a retrospective study of dogs with atypical hypoadrenocorticism: a diagnostic cutoff or continuum?… JSAP 2017
Objective was to describe the clinicopathologic fundings and outcome in dogs with atypical HAC (group 1) and dogs with suspected atypical HAC whose post ACTH stim cortisol concentrations were greater than 55 nmol/L but below the RI (group 2)
40 dogs group 1, 9 dogs group 2
Most common biochemical abnormalities in dogs with atypical HAC were hypoalbuminemia (87%), hypocholesterolemia (76%). 14% of dogs in this group developed electrolyte abnormalities at 2-51 months post diagnosis
Of the dogs with suspected atypical HAC (I.e. equivocal results where post was >2 but below RR) - steroid therapy was stopped without return of clinical signs in 2/7 dogs, and 4/7 were diagnosed with IBD, 1 dog continued to have c/s despite glucocorticoid treatment
Dogs with concurrent GI signs, hypoalbuminemia and hypocholesterolemia should be assessed for atypical Hypoadrenocorticism, with follow up electrolyte monitoring recommended.
Dogs with equivocal ACTH stim results should be evaluated for other underlying disease (e.g. IBD), could consider endogenous ACTH?
Diagnostic cutoff of post cortisol for dogs with atypical hypoadrenocorticism requires further investigation
What are breeds at risk for hypoadrenocorticism
NSDTR Standard poodle WHWT Soft coated wheaten Rottweiler Great Dane Portuguese water dog Bearded collie
In a study evaluating the use of lispro insulin for treatment of DKA in cats (JFMS 2019)…
Times to resolution of hyperglycemia, ketosis and acidosis were compared between cats treated with CRI of lispo insulin and cats treated with a CRI of regular insulin
18 DKA cats enrolled (9 per group)
No significant difference between groups in median time to resolution of hyperglycemia, ketosis, and acidosis
Two cats in the regular insulin group developed hypoglycemia
One cat in group Lispro and 3 cats in group regular developed hypophosphatemia requiring supplementation
Duration of hospitalization and time to first SQ injection did not differ between groups
What is Lispro insulin?
Genetically engineered analogue of human insulin in which proline at position B28 and lysine at position B29 are inverted in their sequence. This reduces the formation of insulin dimers and hexamers.
The structural change ensures more rapid absorption and elimination from the SQ injection site, resulting in rapid onset and short duration of hypoglycemic activity.
Has similar effects to regular insulin on suppression of endogenous glucose production, glucose uptake and FFA, glycerol and lactate levels in people
Considered valid alternative in people to regular insulin, considered safe and effective IV alternative in dogs
In a study evaluating the survival times for cats with hyperthyroidism treated with 3.35 mCi iodine 131 dose (JFMS 2018)
Study aim - to retrospectively evaluate the efficacy of a fixed 3.35 mCi I131 dose fro teh treatment of 96 hyperthyroid cats with no length estimation for any palpated goiter >/= 20mm, and to assess outcome and identify factors associated with survival
Serum TT4 at diagnosis and at follow up times, survival times and cause of death were recorded
Administration of mean dose of 3.35 mCi I131 was an effective treatment in 94/96 cats, but 2 cats remained hyperthyroid
No hyperthyroid related death recorded
Median survival- 3 year. 1 and 2 year survival rates post I131 were 90% and 78%
Low body weight (<3 kg) and being male were independently associated with death
Age, prior treatment with anti-thyroid drugs, and reason for treatment and pretreatment azotemia were NOT associated with death
~3 Mci fixed dose of I131 is effective when goiter is <2 cm in length
In a study evaluating serum and urinary cystatin C in cats with FIV and cats with hyperthyroidism (JFMS 2016)…
Included 30 cats with FIV
26 hyperthyroid cats
28 healthy cats
Measured serum and urine cystatic C, and urinary cystatic C to creatinine ratio
Routine renal variables (bun, creat, USG, UPCR) also recorded
Cats with hyperthyroidism had significantly higher serum cystatin C and higher urinary cystatin C to creat ratios, lower serum creatinine, and higher UPC than healthy cats
Based on the RR for serum cystatin C, hyperthyroid cats cannot be distinguished from healthy cats, suggesting that serum cystatin C might not be a riliable GFR marker in hyperthyroid cats
Cats with FIV did not show a significantly higher serum cystatin C concentration but had a significantly higher serum creat and UPC than healthy cats
Urinary cystatin C could only be detected in 4/30 cats with FIV
What is cystatin C?
Low molecular mass protein responsible for intracellular catabolism of peptides and proteins
Many properties for endogenous GFR markers apply to cystatin C
Studies in humans and dogs have show that serum cystatin C may be better than creat at detecting early renal impairment, and urinary cystatin C can be used as a tubular marker
In a study investigating the relationship between TT4, thyroid palpation and a clinical index in hyperthyroid and healthy cats and cats with other diseases … (JFMS 2019)
Looked at 55 cats with hyperthyroidism, 45 healthy cats, and 327 euthyroid cats with nonthyroidal disease
~80% of hyperthyroid cats and 20% of healthy cats and cats with non-thyroidal illness had a palpable thyroid gland
Median thyroid palpation score in hyperthyroid cats was 2 (significantly higher compared to other groups)
Thyroid size did not correlate with T4
Thyroid size was smaller (most <5mm) than previously reported
Hyperthyroid cats with lower clinical scores had significantly higher T4 levels compared with hyperthyroid cats with higher scores
Hyperthyroid cats were older and had lower body weight and BCS than other cats
In a study evaluating the incidence of rebound hyperglycemia in diabetic cats (JFMS 2016)…
Background- rebound hyperglycemia aka somogyi
Looked at 10767 BG curves of 55 cats treated with glargine
Biochemical hypoglycemia did occure frequently, but blood glucose curves consistent with rebound hyperglycemia with insulin resistance was confined to 4 single events in 4 different cats .
(14/55 cats - 25%), with a median of 1.5% of BG curves were consistent with rebound hyperglycemia WITHOUT an insulin resistance component
Represented 0.42% of BG curves in both affected and unaffected cats *** Somogyi
Conclusion - rebound hypoglycemia is rare in cats treated with glargine on a protocol aimed at tight glycemic control. Insulin dose should not be reduced when there is hyperglycemia in the absence of biochemical or clinical evidence of hypoglycemia
**note - Bg monitoring was intermittent and all cats were FED after hypoglycemia was noted, then this study likely under or overestimated occurrence of rebound hyperglycemia **
In a study prospectively evaluating a protocol for transitioning porcine lente insulin treated diabetic cats to human recombinant PZI… (JFMS 2018)
Recruited recently diagnosed diabetics treated with >/= 6 weeks of porcine lente insulin q 12
Assessed fructosamine, 24 h BG curve, and QOL assessment, and diabetic control score at enrollment and 2,4, and 12 weeks after transitioning to PZI at a starting dose of 0.2-0.7 U/kg q 12
22 cats recruited
Median porcine lente insulin dose at enrollment was 0.5 U/kg q 12, equaling median PZI starting dose
Transitioning insulin was followed by significant decrease in fructosamine, insulin dose, and diabetic control score and QOL score
Mean BG did not alter significantly
5 cats (23%) achieved remission
Hypoglycemia was noted in 30/190 12 hour BG curves (I.e. 16%), and 5/22 cats experienced clinical hypoglycemia (though proportion of hypoglycemic cats did not differ between porcine lente insulin treatment and PZI treatment
32 % of cats showed a short duration of action of porcine lente insulin, then went on to show duration of action >/= 9 hr on PZI
10.5% of cats showed short duration of PZI
Name three long acting insulins
Glargine
Detemir
Protamine zinc (PZI)
See Picture for study
Investigating prevalence and degree of thyroid pathology in hyperthyroid cats and whether it increases with disease duration
Cross sectional analysis of 2096 cats refered for radioiodine therapy
Objective - to compared serum TT4 concentrations and thyroid scintigraphic characteristics of cats referred for I131 treatment based on disease duration
Methods — Cats were divided into 5 groups based on time from diagnosis
Each thyroid scintigraphic scan was evaluated for pattern (unilateral, bilateral, multifocal), location (cerivcal, thoracic inlet, chest), and size (small, med, large, huge) of the thyroid tumor, as well as features suggesting malignancy
Median TT4 concentration increased with increasing disease duration
Prevalence of unilateral disease decreaed with increasing duration, while multifocal disease increased
Median tumor volume increased with increased disease duration
Prevalence of large and huge thyroid tumors increased from 5.1% to 88.6% with increasing duration, while prevalence of intrathoracic tumor tissue increased from 3.4% to 33%
Prevalence suspected thyroid carcinoma (characterized by severe hyperthyroidism refractory to methimazole, huge intrathoracic multifocal tumors, refractory to methimazole treatment) increased with increasing disease duration from 0.4% to 20%
What is the most common endocrine disease in geriatric cats and what is its approximate prevalence?
Hyperthyroidism, 10% of geriatric cats
98% - benign thyroid adenomatous hyperplasia with ~70 % having bilateral disease
<2% - thyroid carcinoma
In a study evaluating the predictive value of scintigraphic (semi)-quantitative thyroid parameters on radioiodine therapy outcome in hyperthyroid cats (JFMS 2018)…
Background - one factor that may influence outcome of radioiodine therapy in hyperthyroid cats is degree of activty of thyroid gland, represented byuptake of sodium pertechnetate or tracer activities of radioiodine by thyroid gland on scintigraphy. Thyroid gland pertechnetate update can be demonstrated by seiquantitative factors such as thyroid gland to salivary gland ratio and the thyroid to background ratio and the percentage technetium uptake by the thyroid glands
75 cats that had sodium pertechnetate thyroid scans
**Higher thyroid to salivary gland ratios were found to be significantly related to outcome of patient being persistently hyperthyroid. Threshold of 5.4 is a possible indicator of increased risk of persistent hyperthyroidism
Other parameters evaluated (thyroid to background ratio and percentage technitium uptake) were not considered to be significant
For low TT4 outcomes, no significant parameters were found
In a study investigating insulin detemir treatment in diabetic cats in a practice setting (JFMS 2015)
Aim - to evaluate the effect of determir therapy in diabetic cats in a general clinical setting
14 diabetic cats with follow up period of at least 3 months — dose 0.25-0.5 U/kg/BID)
13/14 cats 93% - moderate or excellent control of clinical symptoms within the initial 3 months of therapy, including 5 cats previously treated unsuccesfully with other insulins
Clinical improvements were noted after 1 month and continued with time
3 cats (30%) achieved remission within 3 months, and non experienced a diabetic relapse during the study
1 cat achieve remission after 13 months
Considered safe, with only 2 reported episodes of hypoglycemia
What is the duration of effect of Lente insulin (I.e. Vetsulin) in Cats?
~8 hours (range 8-14 h)
What is detemir?
Long acting isulin analogue, is slowly absorbed from the subcutaneous injection site and displays a prolonged action compared with other types of insulin
Mechanisms of longer DOA - formation of dihexamers and binding of detemir to albumin
In healthy cats - has similar pharmacokinetics to glargine
In a study ingestigating the characteristics of hypoglycemic episodes in cats with diabetes mellitus (JFMS 2018)
Objective - review characteristics of diabetic cats presenting for hypoglycemia and identify factors that may have contributed to hypoglycemic episodes, patient clinical signs, and lab findings, and response to therapy
28 cats presenting a total of 30 times
Majority of cats presented with neurologic attributed to reduced ingestion or subsequent vomiting of a meal after insulin had been administered or accidental double dosing of insulin. Concurrent illnesses that may have affected insulin requirements were also common
Cats that demonstrated clinical improvement within 12 hours of treatment were more likely to recover despite mental status and glucose level on presentation
In a study evaluating the effect of thyroid volume on radioiodine therapy outcome in hyperthyroid cats (JFMS 2016)…
Objective - to relate total thyroid volume calculated by a newly contructed formula for feline patients (0.438 x length x width ^2) to the outcome of i131 therapy
167 cats categorized by dose of I131 given and therapy outcome
Study analysis showed no significant relationship between an increasing total thyroid volume and oddes for a final low TT4 or final hyperthyroid outcome
Did find significant relationship between increased odds for hypothyroid outcome in patients with increased number of foci detected on the thyroid scan, but this was NOT true for a final hyperthyroid outcome
Number of detected foci was associated with total thyroid volume
Did find the largest thyroid volumes in the persistently hyperthyroid group, but no statistical significance
Unlikely to be a testable study
In a study evaluating the effect if acarbose on postprandial blood glucose concentrations in healthy cats fed low and high carbohydrate diets (JFMS 2015)…
Study design - prospective crossover
Population - 12 healthy adult nonobese neutered cats enrolled and glucose assessed over 24 hours after feeding high and low carb diets with and without acarbose during single and multiple meal tests
Testable points — cats fed high carb diet as a single meal had LOWER mean 24 h glucose concentrations when acarbose was given
Mean glucose concentrations were lower in the first 12 h when acarbose was given ONCE daily, but no significant difference was observed in mean results from 12-24 hours — I.e. acarbose may be more effective if given before a meal and BID
Acarbose had little effect in cats eating multiple meals or those being fed a low carb diet
Compared with acarbose + high carb diet, cats fed the low carb diet ALONE had lower mean 24 hours peak glucose
What is acarbose?
Complex oligosaccharide of microbial origin
Competitive alpha glucosidase and alpha amylase inhibitor (enzymes involved in digestion of comple carbs into monosaccharides at the brush border of the SI mucosa). It acts to delay absorption of glucose from the intestinal tract, and in people, reduces postprandial BG and insulin concentrations after a carbohydrate meal
In dogs, helps to improve glycemic control
In a study evaluating cutpoints for screenign blood glucose concentrations in healthy senior cats (JFMS 2017…)
Measured screenin BG at presentation, then again after PE, then measured fasting BG after night of hospitalization
RI for screeing BG was 189 mg/dL
Mean screening BG was higher than mean fasting BG
Breed, body weight, behavior score, fasting BG concentration, and aount of carbohydrate consumed before sampling collectively explained only a small proportion of the variability in screening BG.
Screening BG at presentation should be considered, if >190 and if cat has risk factors for DM, consider additional investigation
In a study comparing health parameters in normal cats fed a limited iodine prescription food vs a conventional diet… (JFMS 2018)
Diet fed for 24 months (either limited iodine n=14 or conventional diet n=12). Performed chem, TT4, CBC, UA, thyroid ultrasound at baseline, 6,12,18,24 months
Median serum concentrations of free and total T4 and TSH were WNL for both groups at all sampling intervals
Median urine iodine concentrations in the limited iodine group declined significantly from baseline and were different from conventional iodine diet group
Ultrasound revealed no significant change in median thyroid height in the limited iodine group at any time
Results suggest that euthyroid cats can be exposed/ eat a limited iodine diet for an extended period of time and remain euthyroid
In a study evaluating coagulation parameters in hyperthyroid cats before and after I131 treatment compared with healthy controls …(JFMS 2019)
15 hyperthyroid and 10 healthy age matched controls
CBC, Chem, T4, PT, PTT, fibrinogen, and TEG were performe in al cats before and 7 and 14 days after I131 therapy. Two weeks post I131, further comparisons were made between cats with normal T4 vs those with low TT4
14 days post successful I131, 7/15 cats had normal TT4, and 8/15 had low TT4
Thrombocytosis was noted in 40%
Fibrinogen was higher and PT shorter in the hyperthyroid cats compared with healthy controls, and these changes persisted post I131
Persistent increases in fibrinogen, Pt, TEG MA and TEG clot rigidity occurred in cats that were euthyroid post therapy
TEG k (time until preset amplitude of 20 mm is reached) and alpha angle (reflecting impaired fibrin cross linking ability prior to I131) significantly increased after therapy
Overall - cats with hyperthyroidism were hypercoagulable compared to controls and had worsening parameters 14 days post treatment, suggesting potential radiation induced thyroiditis - questionable clinical relevance
In a study evaluating clinicopathologic features and comorbidities of cats with mild, moderate, or severe hyperthyroidism in a radioiodine referall population (JFMS 2018)
30% of cats were <10 YO at diagnosis
24% had incidentally diagnosed hyperthyroidism
Time betwen diagnosis and referral for I131 was significantly longer in cats with severe hyperthyroidism at the time of referral
Increase in severity groups between time of diagnosis and referral occurred in ~40% of cats
At referral 54% of cats with mild, 67% of cats with moderate, and 81% of cats with severe hyperthyroidism were unstable despite ongoing medical or dietary management
Prevalence of ardiac abnormalities.was significantly increased in cats with severe hyperthyroidism
No significant different in likelihood of renal disease or hypertension between groups
Earlier I131 therapy should be considered- reduced comorbidities and dose requirements
What is the overall success rate of I131 therapy?
85-95% for cure
In a study evaluating the accuracy of point of care luteinizing hormone test for help in distiguishing between sexually intact and ovariectomize or castrated domestic cats … (JFMS 2018)…
Background - sexually intact females should have low serum LH concetrations until estrus, when it would increase.
LH concentrations increase if there is no negative hormonal feedback from ovarian production of estrogen and progesterone inducing negative feedback on GNRH production. — I.e. high LH in ovariectomized females
Cats or dogs in estrus may yield false positive results due to LH surge
Time of testing relative to time of year can also affect result (cats are seasonally polyestrous increasing likelihood of false positive in the spring)
Both males and females - Overall test sensitivity 90%
Specificity 93%
Accuracy 91%
For differentiating intact vs neutered
Analysis of spayed vs intact females
91% sensitivity, 92% specificity, 92% accuracy
10 intact queens had unexpected positive results, 2/10 were in estrus
Analysis of intact vs neutered males
85% sensitivity
95% specificity
89% accuracy
In a study evaluating owner acceptance of home blood glucose monitoring for recently diagnosed diabetic cats and the impact on the quality of life of the cat and owner (JFMS 2018)..
74% (28/38) cats entered the home blood glucose monitoring group, and the majority considered it to be straightforward (89%)
There was no significant difference between groups in overal qualityof life score or glycemic control parameters at any time point apart from maximal blood glucose at month 6 (max BG was lower in the home blood glucose monitoring group)
Quality of life score (including indicators of owner worry about diabetes, worry about hypoglycemia and costs, and glycemic parameters) all improved at all time points within the home blood glucose monitoring groups but not within the NON-home blood glucose monitoring group
Remission occurred in 32% of the home Bg monitoring group and 10% of the non home BG monitoring group - not statistically significant difference
home BG monitoring is practical and improves QOL of owner and cat with DM
In a study evaluating abdominal ultrasound findings in acromegalic cats (JFMS 2015)
Retrospective case control study
Control group of age matched cats included
24 cats were included in each group
IGF1 concentrations in acromegaly group ranged from >148 - 638 nmol/L
When compared with controls, acromegalic cats had increased median left and right kidney length, increased adrenal gland thickness, and increased pancreatic thickness
Hepatomegaly (63%) and renomegaly (53%) reported in acromegalic cats and no controls
Pancreatic abnormalities described in 88% of acromegalic cats and 8% of controls
Overall - acromegalic cats tends to exhibit signs of organomegaly
What is acromegaly?
Clinical syndrome that results from excessive secretion of growth hormone from a functional somatotrophic adenoma of the pars distalis of the pituitary gland
Clinical signs of the disease are attributed to the catabolic effects of GH and the anabolic effects of IGF1, and space occupying effect of pituitary adenoma
GH —> causes post receptor defect in action of insulin on target cells, leading to decreased carb use, reduced insulin sensitivity, and hyperglycemia
GH also stimulates production of IGF1 from the liver mostly, resulting in increased protein synthesis and excessive tissue growth
In a study evaluating associations between sex, body weight, age and ultrasonographically determined adrenal gland thickness in dogs with non-adrenal gland illness… JAVMA 2016
Design - retrospective cross sectional study
266 dogs with nonadrenal illness
Thickness of the caudal pole of the left and right adrenal glands was measured on longitudinal ultrasonographic images. Dogs were stratified into age and body weight categories to investigate assocations with adrenal thickness
Testable point(S) —
Adrenal thickness was significantly lower in dogs that weighed = 12 kg than in dogs that weight >12 kg
Left adrenal thickness increased with age
Both left and right adrenal thickness were larger in male than in female dogs that weighed > 12 and = 20 kg
Left adrenal thickness was larger in male than in female dogs that weighed > 20 = 30 kg
body weight, age, and sex appear to be significantly associated with adrenal thickness, indicating that these variables should be considered when evaluating adrenal thickness in dgos with non adrenal gland illness and when developing RR for adrenal thickness in dogs
**Dogs that weigh =12kg should have Adrenal thickness no greater that 0.62 cm
Dogs that weigh >12 kg should have an adrenal thickness no greater that 0.72 kg
In a study evaluating combind assessments of serum anti mullerian hormone and progesteron concentratsions for the diagnosis of ovarian remnant syndrome in dogs (JAVMA 2019)…
Prospective case series with 602 bitches that had previously undergone OVH or ovariectomy
AMH and progesterone were measureing in a single serum sample obtained from each dog, and results were classified as positive, negative or inconclusive
55 dogs underwent exploratory laparotomy, and 48 had histologically confirmed ovarian remnant syndrome
25/48 (52%) were positive for both progeseterone and AMH
23/48 (48%) were positive for AMH OR progesterone or test results were inconclusive
No dogs with histologically confirmed ovarian remnant were negative for both AMH and progesterone
5 dogs that tested positive - no ovarian remnant tissue obtained at sx
combined measurement of AMH and progesteron in a single serum sample can be an effective diagnostic test for spayed dogs suspected to have ovarian remnant syndrome. Histologic examination of excised tissue is warranted
What is anti mullerian hormone?
Hormone that the ovaries secrete, and secretion is limited by granulosa cells of ovarian folicles
Gonas are the sole source of AMH, so complete surgical removal of the ovaries should result in the absence of AMH in circulation
**corpora lutea do not express AMH, so an ovarian remnant that is largely occupied by functional luteal tissue might not secrete a sufficient amount of AMH to be detectable, which is why measuring progesterone together with AMH to detect an ovarian remnant is beneficial
In a case report documented resolution of hyperinsulinemic hypoglycemia following partial pancreatectomy in a dog with nesioblastosis .. (JAVMA 2018)
6 MC Australian shepher evaluated for persistent hypoglycemia with high serum insulin to glucose ratio
No pancreatic lesion/ mass found on exlap, so partial left pancreatectomy and hepatic and local lymph node biopsies were performed
Histologic exam revealed islet cell hypertrophy and hyperplasia, with no evidence of neoplasia
Bartonella testing = negative on pancreatic tissue
Clinical signs resolved post sx, and on follow up exasm 8 monthls later the dog was healthy and all b/w was WNL
Consider nesidioblastosis as a ddx in a dog with signs suggestive of insulinoma
What is nesidioblastosis?
Neoformation or neodifferentiation of endocrine cells in the ductal epithelium of the exocrine pancreas.
Results in hyperinsulinemic hypoglycemia
Cause of onset is unknown in people, may be associated with gastric bypass surgery
In a study evaluating outcomes of the addition of pasireotide to traditional adrenal directed treatment for dogs with pituitary dependent hyperadrenocorticism secondary to macroadrenoma… (JAVMA 2018)
9 dogs with PDH + macroadenoma where Cushings signs had been managed with adrenal directed treatment (trilostane/mitotane) — were concurrently given pasireotide (0.03 mg/kg SQ q12) for 6 months while adrenal directed treatment was continued.
No dog developed neuro abnormalities or signs of adverse effects during study
No differences from baseline were found in any clinicopathologic values, ACTH stim results, or plasma ACTH results at the 3 or 6 month post points
***After 6 months of pasireotide treatment, 6/9 dogs (67%) had decreases in MRI measured values, while 3 (33%) had increases in MRI measured values **
no adverse effects of the drug were noted, further studies needed to determine if drug is effective in preventing development of neuro signs or improves outcome in dogs with pituitary macroadenomas
What is the reported incidence of pituitary macroadenomas?
0.2% per year
What is the incidence of pitutiary dependent hyperadrenocorticism?
85-90%
What is Pasireotide and why might it be beneficial in patients with pituitary macroadenoma?
Somatostatin receptor ligand with high binding affinity for multiple receptor isoforms (SST 1, SST2, SST3, SST5)
SST5 and SST2 isoforms are highly expressed in ACTH secreting pituitary adenomas (SST2 is most common in dogs)
Pasireotide has been FDA approved in people with hyperadrenocorticism for whom pituitary surgery is not an options or has not been curative
Previous use in dogs with PDH demonstrated a decrease in plasma ACTH,UCCR and pituitary adenoma size, along with improved clinical signs without adverse effects
What defines a pitutiary MACROadenoma?
Tumor that is > 1 cm in diameter, extends above the sella turcica, or as a pituitary:brain ratio >0.31
What is the mechanism of action of trilostane?
Inhibitor of 3 betahydroxysteroid dehydrogenase
Blocks conversion of 3 beta hydroxysteroids into progesterone/ other steroid precursors to cortisol
I.e. inhibits production of all classes of steroid hormones
What is the MOA of mitotane?
Adrenlytic agent/ adrenal cortex inhibitor
In a case report evaluating management and closure of multiple large cutaneous lesions in a juvenile cat with severe acquired skin fragility secondary to iatrogenic hyperadrenocorticism…JAVMA 2018
Cat had been chronically treated with high dose steroisd
Cat underwent staged wound closure with a combination of daily wound cleaning and debrisement, tension and appositional sutures and wet to dry and nonadherent dressings with triple antibiotic, then with mix of SSD and insulin
Multiple additional lesions developed and were treated in the same way
Complete closure and resolution of all lesions was achieve in 9 weeks
Prognosis in cats that develop acquired skin fragility may be better than previously reported
What are causes of acquired skin fragility syndrome in cats?
Cholangiocarcinoma, cholangiohepatitis, hepatic lipidosis, disseminated histoplasmosis, pancreatic and hepatic carcinoma, FIP, multicentric follicular lymphoma, and spontaneous (most common) or iatrogenic hyperadrenocorticism
What are the histologic characteristics of acquired skin fragility syndrome in cats?
Epidermal thinning
Severe dermal atrophy with wispy attenuated pale staining dermal collagen
Adenexal atrophy, with most follicles in telogen phase
In a case report discussing ischemic necrosis of the digits and hyperlipidemia assocaited with atherosclerosis in a Mini American Shepherd… (JAVMA 2018)
2.5 YO Mini american shepherd referred for 3 week hx of localized crusted skin lesion on the digital pad of digit 3 of the RHL
Chem revealed severe hyperlipidemia
Ultrasonography of the terminal aortal and other major arterial vessels revealed ateeriosclerotic change
Patient was medically managed with atorvastatin calcium, low fat diet, and omega 3 FA, clopidogrel, pentoxifylline, clomipramine and trazodone, gabapentin
Limb was eventually amputated
Response to treatment was poor and patient was euthanized
Necropsy - severe chronic intimal atherosclerosis + CNS changes
What breeds are predisposed to primary hyperlipidemia/ dyslipidemia?
Mini schnauzers, Briards, rough collies, shetland sheepdogs, dobermans, rottweilers, and beagles
In a study reporting exogenous thyrotoxicosis in dogs attributable to consumption of all meat commercial dog food or treats containing excessive thyroid hormone…JAVMA 2015
Retrospective and prospective case series
1 case of thyrotoxicosis was identified retrospectively, the others found prospectively, the remainder of dogs were fed meat based products suspected to cintain excessive thyroid hormone. TT4 measurement and scintigraphy were performed before and after food was discontinued
TT4 was high in all dogs at initial evaluation (median 8.8 ug/dL), and scintigraphy revealed subjectively decreased thyroid gland radionuclide in all dogs
At >/= 4 weeks after feeding was stopped, TT4 was within RR, and all signs associated with thyrotoxicosis if present resolved
Diet analyses revealed median thyroxine concentration for suspected products of 1.52 mcg/g
Commercial foods analyzed contained 0.38 mcg/g
Thyrotoxicosis can occur secondary to consumption of meat based products contaminated by thyroid tissue and can be reversed by switching diets
In a study evaluating outcomes for dogs with primary hyperparathyroidism followign treatment with percutaneous ultrasound guided ethanol ablation of presumed functional parathyroid nodules …(JAVMA 2015)
Retrospective
24 dogs with hyperPTH that underwent 27 ultrasound guided ethanol ablation
3 dogs underwent a second treatment b/c of initial treatment failure of development of another nodule
Hypercalcemia resolved after 23 out of 27 (85%) of procedures
In the 23 treatments, 22 (96%) had resolution of hypercalcemia within 72 hours
Hypocalcemia was noted in 6 (22%) different dogs at 2 (1 dog) 7 (3 dogs), 14 (1 dog), and 21 (1 dog) days after treatment. 5 had mild transient hypocalcemia and 1 developed c/s signs requiring calcium supplementation
2 dogs had delayed adverse effects, overall complication rate was 11%
Long term follow up — sustained normocalcemia in 17/19 dogs
May be beneficial treatment with low complication rate in dogs with significant comorbidities that can’t undergo prolonged anesthesia
What is the incidence of urolithiasis in dogs with primary hyperparathyroidism?
24-29%
What causes primary hyperparathyroidism?
85% parathyroid adenomas
12 % parathyroid hyperplasia
5% parathyroid carcinoma
What are reported complications of ethanol ablation?
Bark change, cough
In a study evaluating the use of detemir insulin for the treatment of DM in dogs… JAVMA 2015
10 Dogs were treated with detemir SQ q 12h for 6 months
Follow up evaluations were done at 1,2,4,12, and 24 weeks and included evaluation of clinical signs and measurement of BG curves and fructosamine
Determir resulted in signficant decrease in BG and fructosamine concentration at 6 months compared with pretreatment values
Median insulin dose at study end was 0.12 U/kg (range 0.05-0.34 U/kg)
hypoglycemia was noted in 22% of BG curvesm and 6 episodes of clinical hypoglycemia were noted in 4 dogs
Subjective clinical improvement in all dogs was noted
Based on clinical improvement, efficacy of detemir was considered good in 5 dogs, moderate in 3, and poor in 2
Detemir is more potent in dogs
In a study evaluating baseline cortisol concentration to monitor efficacy of twice daily administration of trilostane to dogs with potuitary dependent hyperadrenocorticism … (JAVMA 2016)
22 dogs with PDH were retrospectively included
109 ACTH stimulation tests were performed for 22 dogs
Baseline corticsol concentration was >/= 3.2 predicted that ACTH stimulated cortisol concentration would be >/= 2 with 100% certainty
14/64 (22%) tests with a baselin cortisol concentration of >3.2 mcg/dL had an ACTH stimulated cortisol concentration of = 3.2, which suggested inadequate adrenal reserve
There was no correlation between baseline cortisol dose and the subsequent trilostane dose adjustment
**baseline cortisol concentration should not be used as the sole monitoring tool for management of dogs with PDH treated with trilosatne BID **
ACTH stim should be used in conjunction with history and PE to monitor dogs with PDH that are receiving trilostane
In a study evaluating the analytic performance evaluation of a veterinary specific ELISA for measurement of serum cortisol concentration in dogs (JAVMA 2018)
Evaluate agreement of an ELISA and precision for measurement of serum cortisol. — agreement between ELISA and 2 validated chemluminescent assays assessed. Evaluated clinical implications of bias associated with ELISA when measuring Serum cortisol in dogs
75 stored frozen samples
There was a high correlation between ELISA results for all samples combined and the 2 assays used for comparison
Constant and proportional biases between ELISA and the chemiluminescent assays were present at all concentrations
Clinically important disagreement between ELISA and the other assays occurred in 16/63 (25%) of samples, particularly with LOW and HIGH serum cortisol
results suggest that equivocally low or high results obtained by ELISA be confirmed at a reference lab
In a study investigating the prevalence of adrenal gland masses as incidental findings during abdominal CT in dogs … (JAVMA 2016)
Retrospective case series of 270 client owned dogs that underwent abdominal CT
Incidental adrenal gland masses were detected in 25/270 (9.3%) of dogs
Dogs with incidental adrenal gland masses were significantly older (median 12 YO) than dogs without
Dogs examined for neoplsaia were significantly more likely to have an incidental adrenal gland mass (16%) than were dogs examined for any other reason (2.3%)
No other risk factors found
Histologic exam only performed in 3/25 dogs, with 2 having an adenoma, and 1 having a pheo +cortical adenoma
Patient with incidental adrenal mass < 2 cm in any dimension with no c/s - careful monitoring is reasonable q 2-3 months
Patient with incidental mass > 2 cm or <2 cm AND clinical signs or evidence of vascular invasion or contrast enhancement on CT, further testing recommended / consider adrenalectomy
In a study evaluating urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma, hypercortisolism, nonadrenal disease and in healthy dogs … (JVIM 2015)
7 dogs with pheochromocytoma
10 dogs with hypercortisolism
14 dogs with nonadrenal disease
10 healthy dogs
Dogs with pheochromocytoma had significantly higher urinary normetanephrine and metanephrin:creatinine ratios and significantly higher plasma total and free normetanephrine and plasma free metanephrines concentrations compared to the 3 other groups
There were no overlapping results of urinary normetanephrines concentrations between pheo and other groups, and only ONE pheo dog had plasma normetanephrine concentratations in the range of dogs with hypercortisolism and nonadrenal disease
Overlap of epinephrine and norepinrphine results between groups was large
**measurement of normetanephrines is preferred for pheochromocytoma diagnosis and urine is better than plamsa as a sample **
Nonadrenal illness can increase production of catecholamines and metanephrines, so cutoff values of 3-4x normal can be used
What are pheochromocytomas and where do they arise from?
Catecholamine producing tumors
Arise from the chromaffin cells in the adrenal medulla
What are metanephrines (normetanephrine and metaneprhine) ?
O-methoxylated metabolites of catecholamines
In a study evaluating treatment of ionized hypercalcemia in 12 cats using PO administered alendronate… (JVIM 2015)
12 cats with ionized hypercalcemia
Treated with dose of 5-20 mg/cat PO q 7 days - pill followed by 6 ml water on butter
Serum iCa was measured before, and 1,3,6 months of treatment. Dose was adjusted according iCa
Alendronate treatment resulted in a decrease in iCa in all cats
Median % change in iCa was -13.2%, -15.9%, -18.1% at the 1, 3, and 6 month time points
Baseline iCa was significantly different from 1 month, 3, month and 6 months
Median iCa decreased of -0.34 mmolL
8 cats had iCa decrease to within RR at some point during treatment
4 cats did not respond or iCa did not decrease by 20%
Results suggest that increased bone resorption may play a role in idiopathic hypercalcemia
No adverse effects reported
Alendronate was well tolerated and decreased iCa in most cats in 6 months
What is recommended management in a cat with idiopathic hypercalcemia?
Diet change to nonacidifying, high fiber diet to decrease calcium absorption from the GI tract
Prednisolone to promote lowering of serum calcium concentration
What is the mechanism of action of alendronate and what type of drug is it?
Nitrogen containing bisphosphonate
Inhibit osteoclast function by inhibition of enzyme farnesyl diphosphate synthase in the HMG-CoA reductase pathway
The end products of this pathway are required for normal intracellular signaling and cytoskeletal functions requiredfor hydroxyapatite crystal dissolution
Metabolism of nitrogen biosphosphonates also result in the production of an intracellular ATP analog APPPI, which is believed to directly induce apoptosis of osteoclasts
In a study evaluating the prognostic value of perioperative profile of ACTH and cortisol for recurrence after transsphenoidal hypophysectomy in dogs with corticotroph adenomas (JVIM 2015)…
112 dogs with PDH that underwent transsphenoidal hypophysectomy
Hormone concentrations were measured preoperatively and 1-5 hours post
Median follow up and disease free period was 1096 days and 896 days respectively
28% of patients had recurrence, with median disease free period of these patients at 588 days
Absolute and posoperative cortisol concentrations were significantly higher in dogs with recurrence than in dogs without recurrence
High ACTH 5 hours after surgery, high cortisol 1 and 4 hours post surgery, high normalized ACTH 3 hours post surgiery, high normalized cortisol 4 hours post surgery and random slope of cortisol were associated with a shorter disease free period
No cutoff point could be found, so need combine individual perioperative hormone curves with other variables like pituitary height/brain ratio, etc
What is a risk factor for recurrence of PDH following transsphenoidal hypophysectomy in dogs? What is the recurrence rate post op?
25 % recurrence
Large pituitary size
In a study evaluating serum cortisol concentrations in dogs with PDH and atypical hyperadrenocorticism (JVIM 2015)
10 healthy dogs, 7 dogs with PDH, 8 dogs with atypical hyperadrenocorticism
Hourly and sum cortisol concentrations differed significantly between controls and atypical hyperadrenocorticism and PDH dogs
Only hourly cortisol and not sum cortisol was higher in PDH dogs in comparison to atypical hyperadrenocorticism
Hypercortisolism may play a role in the pathogenesis of atypical HAC
Average transverse adrenal gland diameter was significantly less ( 0.53 cm) compared to dogs with PDH (0.64 cm) and atypical hyperadrenocorticism (0.72cm )
Adrenal gland diameter did not differ between dogs with atypical hyperadrenocorticism and those with PDH
Serum cortisol in dogs with atpypical Cush is increased in comparison to healthy dogs, but lower than dogs with PDH, while adrenal gland diameter is similar between dogs with PDH and atypical cushings.
When is atypical hyperadrenocorticism considered a differential? How is it diagnosed?
When dogs have clinical signs of hypercortisolemia, no evidence of sex hormone secreting adrenal tumor, and HAC screening test results are WNL
Adrenal panel - Tenessee
Reveals alterations in concentrations of adrenocortical precursor hormones before and after ACTH stim - e.g. 17- hydroxyprogesterone
In a study evaluating Pasireotide for the medical management of feline hypersomatotropism (JVIM 2015)
12 cats with IGF >1000 ng/mL by RIA and pituitary enlargement
IGF1 decreased in all 12 cats that completed the study (median decreased by ~1000)
Insulin dose was lower on day 5 than on day 1 (median dose reduction of 1.5 U/kg)
Product of insulin dose and area under the BG curve was lower on day 5 than day 1
No clinically relevant adverse effects - small bowel diarrhea (25%), non-symptomatic hypoglycemia (42%)
overall - short acting Pasireotide decreased IGF1 and insulin requirement in cats with hypersomatotropism and DM
In a case report discussing molecular genetic characterization of thyroid dyshormonogenesis in a French Bulldog..(JVIM 2015)
Case of congenital hypothyroidism with goiter in a 9mo french bulldog with signs of cretinism
Thyroid tissue and blood from a CHG-French bulldog and 4 normal controls and buccal brush samples of 125 french bulldogs was studied
The dog had signs of cretinism at 9 mo with otherwise normal skeletal maturation - did well with increasing doses of t4 supplementation
Enlarged thyroid gland had noninflamatory fibrosis and aberrant follicular organization
TPO activity and immunocrossreactive protein were undetectable
What is thyroid peroxidase and why is it important in the pathogenesis of congenital hypothyroidism in dogs and people?
What is it? : multifunctional enzyme required for thyroid hromone synthesis
Lack of TPO causes failure of iodide incorporation into thyroglobulin aka organification defect. This results in failure of thyroid hormone synthesis/ dyshormonogenesis, thus leading to excess TSH stimulation and diffuse thyroid follicular epithelial cell hyperplasia aka goiter
Most common cause of congenital hypothyroidism with goiter in people
In a study longitudinally evaluating serum pancreatic enzymes and ultrasonographic findings in diabetic cats without clinical relevant pancreatitis at diagnosis .. (JVIM 2015)
30 cats with newly diagnosed DM without clinical signs of pancreatitis on admission
Prospective study - at admission, 2, and 6 months later, measured spec fPL, and DGGR lipase and pancreas was ultrasounded
Pancreatitis was suspected if serum markers were increased and >/= 2 ultrasound abnormalities noted
Subclinical pancreatitis at the time of diagnosis was suspected in 33,50, and 31% of cats based on spec fPLI, DGGR lipase, and ultrasound respectively
Suspected in 60% of cats when diagnostics combined
During follow up period, suspected pancreatitis developed in additional 17-30 % of cats
17/30 (57%) of cats achieved diabetic remission
Frequency of abnormal fPl, DGGR, and ultrasound did not differ in cats that achieved remission and those that didn’t
Cats that achieved remission had lower spec fPL at 2 months
Many cats with DM have subclinical pancreatitis. Cats with high fPL might have reduced change of diabetic remission.
In a study evaluating IGF-Phosphatidylinositol 3 kinase signaling in canine cortisol secreting adrenocortical tumors.. (JVIM 2015)
Background - in adrenal carcinomas in people, activation of phosphatidylinositol 3 kinase (PI3K) signaling pathway by IGF signaling or ERBB2 (dimer of epidermal growth factor) represents a promising therapeutic target
36 canine cortisol secreting tumors (11 adenomas, 25 carcinomas) and 15 normal adrenal glands of dogs
Target gene expression indicated PI3K activation in carcinomas, but no adenomas
No amino acid changing mutations were found in genes encoding PTEN or PIK3 catalytic subunit (PIK3ACA)
No significant alterations in IGFII or IGF receptor I expression were detected
In carcinomas, ERBB2 expression tended to be higher than in normal adrenal glands, and higher expression of inhibitor of differentiation 1 and 2 (ID1 and ID2) and IGFBP 5, and lower expression of SGK1 was found in carcinomas with recurrence within 2.5 years post adrenalectomy
ERBB2 expression might be a promising therapeutic target in adrenal tumors in dgogs. ID1 and ID2 might be valuable prognostic markers and therapeutic targets.
What is the phosphatidylinositol 3 koinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway?
Frequently activated pathway in cancers in people
Pathway activation initiated by receptor tyrosine kinases (e.g. IGF1, IGFR1) or dimers of epidermal growth factor (ECG) receptor family (ECFG, ERBB2-4) and counteracted by competitied PI3K inhibitor phosphatase and tensin homolog (PTEN)
Upon activation of the PI3K pathway, phosphorylated AKT and downstream effectors stimulate cell proliferation, survival and growth by transcriptional and posttranslational mechanisms
In a study evaluating the incidence of DM in insured swedish cats in relation to age, breed, and sex…(JVIM 2015)
Overal incidence rate of DM in the cohort of 504688 cats was 11.6 cases per 10,000 cat years at risk
Male cats had 2x higher incidence rate than femalse
DSH at higher risk than purebred
High risk purebreeds: Burmese, Russian Blue, Norwegian forest cat, and Abyssinian
No sex predilection among burmese cats
In a study evaluating Glycemic status and predictors of relapse for diabetic cats in remission… (JVIM 2015)
21 cats in diabetic remission, 28 healthy controls
Of the 21 cats in remission, 19% had impaired fasting glucose concentration and 76% had impaired glucose tolerance
Of cats followed up for 9 months after testing, 30% had relapsed and required insulin treatment
Fasting blood glucose concentration >135 mg/dL and severely impaired glucose tolerance (> 5 hrs to return to normal BG) were significantly associated with relapse - 13 X higher odds of relapse
BG concentration at 3 hrs was significantly assocaited with relapse
Cats with normal fasting BGF and normal glucose tolerance have low risk of relapse
Consider cats in remission as prediabetic long term, most have impaired glucose tolerance
What percentage of cats in diabetic remission are at odds of relapsing?
25-30%
Free T4 by ED and chemiluinescent immunoassays in 13 hypothyroid dogs positive for thyroglobulin antibody… JVIM 2015
13 dogs - each had comprehensive thyroid profile consistent with hypothyroidism
For detection of hypothyroidism, sensitivities of the chemiluminescent assays for FT4human and FT4 vet were 62% and 75% respectively compared to FT4 by ED
38% of dogs had FT4h and 25% of dogs had FT4 v concentrations by chemiluminescent assay that were increased or within RR
Percentage of false negative test results by FT4 by chemiluminescent assay compared to ED was significantly higher than hypothesized false negative rate of 0%.
25-38% of dogs with thyroiglobulin antibodies that are hypothyroid have FT4 concentrations by CLIA that do NOT support a diagnosis of hypothyroidism
In a stuy evaluating TSH, TT4, and fT4 in hyperthyroid cats receiving methimazole (JVIM 2015)
125 serum samples of hyperthyroid cats receiving methimazole and TT4 concentrations <3.9 were included
33% of cats had increased TSH
Of cats with TT4 and FT4 below RR, 68% and 73% respectively had TSH above the RR
18% of cats with normal TSH had increased serum creatinine as compared to 39% of those with increased TSH
Free T4 by ED does not identify more cats with potential iatrogenic hypothyroidism as compared to TT4
The prevalence of iatrogenic hypothyroidism was approximately 20%
Measure of TSH may be helpful in indicating that azotemia, if present is at least in part related to iatrogenic hyperthyroidism
In a study evaluating cortisol to ACTH ratio in dogs with Addisons, dogs with diseases that mimic addisons and healthy dogs… (JVIM 2015)
23 dogs with Addisons, 79 dogs with diseases mimicking addisons, and 30 healthy dogs
Plasma ACTH and baseline Cortisol were measured before 5 mcg/kg ACTH in all dogs
Cortisol to ACTH ratio was calculated and the diagnostic performance of ACTH, baseline cortisol, cortisol to ACTH ratio, and sodium to potassium ratios was assessed
The cortisol to ACTH ratio was significantly lower in dogs with hypoadrenocorticism compared to that in healthy dogs and those with diseases mimicking Addisons
There was an overlap between dogs with hypoadrenocorticism and those with addison’s mimicking diseases, but cortisol to ACTH ratio was still the best parameter for diagnosing hypoadrenocorticism, then ACTH concentration, basal cortisol, and Na/Kratio.
With a cortisol to ACTH ratio of >0.01, the diagnostic sensitivity and specificity were 100% and 99%
**Calculation of the Cortisol to ACTH ratio is a useful screening test, but given the overlap with disease that mimics addison’s can run the risk of misdiagnosis
Unknown reliability of diagnosing secondary hypoadrenocorticism
In a study evaluating serum TSH concentration as a diagnostic test for hyperthyroidism in cats (JVIM 2015)
Objective - investigate the usefulness of cTSH as a diagnostic test in cats with hyperthyroidism
917 cats with untreated hyperthyroidism, 32 euthyroid cats suspected of hyperthyroidism, 131 clinically normal cats
Cats had TT4, FT4, T3 and TSH measured. Scintigraphy was used as gold tandard to confirm or exclude hyperthyroidism
Median TSH concentrations in hyperthyroid cats were significantly lower than clinically normal or euthyroid cats with suspected disease
Only 18 (2%) of cats had measurable TSH concentrations
70% of euthyroid cats with suspected disease had detectable concentrations
**Combining TSH with TT4 or fT4 concentrations lowered sensitivity of TSH from 98 to 97% but increased the spcificity from 70 to 99%
**the TSH assay does a bad job at differentiating low normal TSH from abnormally low TSH
**Serum TSH is suppressed in 98% of hyperthyroid cats, but concentrations are measurable in a few cats with mild to moderate disease. TSH measurement is a sensitive but not specific test for hyperthyroidism diagnosis and is best combined with TT4 and fT4
What percentage of sick euthyroid cats OR clinically normal cats can have increased serum fT4 concentrations?
Up to 20%
In a study evaluating the diagostic potential of serum ghrelin in feline hypersomatotropism and diabetes mellitus (JVIM 2015)
Ghrelin is a GH secretagogue that is down regulated in people with hypersomatotropism and increases after treatment. Also seems to be decreased in people with DM.
20 cats with DM, 20 cats with hypersomatotropism and DM (13 underwent RT), and 20 healthy age matched controls
Retrospective cross sectional study. Differences in serum ghrelin, fructosamine, IGF1 and insulin were evaluated
- *Ghrelin was higher in controls compared to HSDM and DM cats
- *Ghrelin in the HSDM and DM groups was similar - indicates that it should NOT be used as a differentiating diagnostic
- *After RT in the HSDM group, ghrelin increased significantly and post RT ghrelin was not significantly different from controls, indicating that it may be a good marker of treatment success
**Serum IGF1 did not significantly change in the HSDM cats after RT, despite significant decreases in fructosamine and insulin dose requirement.
**ghrelin assay had good analytical performance
In a study evaluating the effect of feeding an iodine restricted diet in cats with spontaneous hyperthyroidism.. (JVIM 2015)
49 client owned cats with spontaneous hyperthyroidism
Retrospective case series, cats were fed a commercially available iodine restricted diet, and clinical response was assessed by weight cahnge, HR and TT4, BUN, creatinine, at various times during diet management (21-60 day, 60-180 days)
**Serum TT4 normalized in 42% of cats at 21-60 day time point and 83% of cats at the 61-180 day time point
Cats in which TT4 was still above RR at days 21-60 had significantly higher starting TT4
Body weight did not significantly increase nor did HR disease
There was a significant decrease in creatinine (1.8 to 1.5)
Cats in the low RR for serum TT4 did not have a significant increase in body weight nor creatinine when compared to those with high RR
**Iodine restricted diets were effective at maintaining serum TT4 concentrations within RR for a majority of cats, though not all c/s of hyperthyroidism improved — retrospective, cats also had other diseases
How much iodine is in an iodine restricted diet?
0.17 -0.28 ppm (mcg/kg) - has been shown to decrease TT4
In a study evaluating the effect of limited iodine diet on iodine uptake by thyroid glands in hyperthyroid cats… (JVIM 2015)
8 cats with hyperthyroidism - prospective study where cats were fed y/d for 6 months. Clinical signes were evaluated and TT4, fT4 were measured during consumption of the diet. I123 uptake was determined before and 8-16 weeks after diet consumption.
**Clinical signs of hyperthyroidism resolved in all cats, but there was no significant increase in body weight
TT4 and fT4 decreased into the RR by 8-16 weeks (9.7 mean at start to 3.1 at finish)
Scientigraphy revealed unilateral isotope uptake in 5 cats and bilateral uptake in 3 cats
Mean percentage of uptake of I123 at 8 hours post isotope was 16.2% before and 34.6 % post diet consumption. Percentage increase was variable between cats
Limited iodine diets increase iodine uptake in autonomous thyroid glands, which could possibly affect sensitivity of thyroid gland to I131 treatment. — I.e. limited iodine diet could be used to decrease dose of I131 needed/ glands may become more ssensitive, may also increase risk of iatrogenic hypothyroidism. Stop limited iodine diets for 2 weeks prior to I131
In a study evaluating cortisol response in healthy and diseased dogs after stimulation with a depot formulation of synthetic ACTH (JVIM 2015)
Objective - to evaluate the poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs.
Population - 22 healthy, 10 dogs with suspected hypoadrenocorticism, 15 dogs with suspected hyperadrenocorticism
Prospective study - ACTH stim performed using synthetic depot IM 5 mcg/kg injection was performed. Samples for cortisol were taken before, and 1,2,3,4,6,24 hours post
Peak cortisol concentrations were reached at 2-4 hours in all dogs
Cortisol concentrations 1 hr post were >9 in all healthy dogs and >5 in all dogs in which hypoadrenocorticism was excluded
None of the dogs with hypoadrenocorticism showed a cortisol increase above the detection limit of the assay
After 6 hrs, cortisol concentrations had decreased in the healthy and hyperadrenocorticism groups, and were at baseline in 24 hours
- *Can use depot formulation in place of short acting ACTH. Blood for peak cortisol concentrations should be drawn at 3 hours post in cases where hyperadrenocorticism is suspected
- In hypoadrenocorticism cases, blood can be pulled at 1 hour post b/c there should not be a detectable response
In a study evaluating cortisol concentrations in well regulated dogs with hyperadrenocorticism treated with trilostane (JVIM 2015)
Background - no guidelines for ogs with clinically well regulated hyperadrenocorticism where serum cortisol pre and post stim performed 3-6 hours post trilostane are <2
Objective - deteremine if serum cortisol measured pre/post at 3-6 hours post pill is lower than cortisol measured 9-12 hours post pill pre/post
13 dogs with clinically well regulated Cushings
**Cortisol concentrations before and after first stimulation were significantly lower than cortisol before second stim. Cortisol concentration before the first stim was also significantly lower than cortisol after second stim.
In dogs with clinically well regulated trilostane treated cushings and cortisol concentrations <2 before and after first stim, a second stim performed 9-12 hours post pill can result in higher cortisol concentrations that could support continued trilostane treatment *. This indicates that it is safe to continue trilostane w/o dose reduction in dogs with clinically well controlled disease. If the dog has low Na/K ratio or no stress leuk, consider ACTH 9-12 hours post to support plan to NOT change dose 31% of dogs in this study had an NA/K ratio <27
In a study evaluating abdominal ultrasound findings in 534 hyperthyroid cats referred for radioiodine treatment … (JVIM 2015)
Objective - to identifyh prevalence of concurrent intraabdominal disease using AUS in hyperthyroid cats referred for radioactive iodine treatment and to determine whether requirement for pretreatment ultrasound is indicated
534 cats with hyperthyroidism
Retrospective
Overall prevalence of concurrent disease: 37% — 23% had renal disease, 2.4 % had neoplasia
Significant differences in USG and BUN were found in cats with abnormal vs normal kidneys on AUS
2.2% of cats were not treated as a result of AUS findings
indicates that pretreatment AUS not needed
In a study evaluating the influence of potuitary size on outcome after transsphenoidal hypophysectomy in a large cohort of dogs with PDH … (JVIM 2016)
306 dogs with PDH
Survival and disease free fractions were evaluated related to pituitary size, dogs with and without recurrence were compared
4 weeks post — 91% of dogs were alive and remission was confirmed in 92% of dogs
median survival time 781 days
Median disease free interval 951 days
27% of dogs developed recurrence of hypercortisolism after median period of 555 days
- *Dogs with disease recurrence had significantly higher pituitary heigh/brain area (P/B ratio) and preoperative basal UCCR than dogs without recurrence — important preoperative prognosticator
- *dogs with a P/B ratio >0.31 have 2x the chance of early death
survival time and disease free interval of dogs with enlarged pituitary glands was significantly shorter than that of dogs with non-enlarged pituitary. Outcome with larger tumors improved over time
What is the remission rate in patients with PDH treated with trilostane?
70-86%
In a study evaluating NTerminal III procollagen propeptide: indicator of GH excess and response to treatment in feline hypersomatotropism (JVIM 2016)
Background - NTerminal type III procollagen propeptide (PIIINP) is a biomarker of soft tissue proliferation. During collagen synthesis, propeptides are cleaved and released into circulation. Hypersomatotropism is associated with ST proliferation - study was done to see if PIINP decreases with treatment of hypersomatotropism
**Serum PIINP concentrations were significantly higher in hypersomatotropism cats compared to DM cats. Cut off of 10.5 ng/mL allowed differentiation between DM and hypersomatotropism with 87% sensitivity and 100% specificity
**After RT, PIIINP INCREASE significantly, with no significant changes in IGF1 concentrations
**After hypophysectomy, serum PIIINP and IGF1 concentrations DECREASED significantly in most hypersomatotropism cats
Serum cobalamin and Methylmalonic acid concentrations in hyperthyroid cats before and after radioiodine treatment (JVIM 2016)
Background - hyperthyroidism has been associated with low seurm cobalamin concentrations. Unclear if functional cobalamin deficiency
39 hyperthyroid cats, prospective observational study — serum cobalamin, methlmalonic acid and clinical scores determined for each cat at enrollement and when euthyroid (60 days post tx)
- *5/39 (13%) had low serum cobalamin, which normalized in 2 cats once euthyroid
- *None of the hyperthyroid/hypocobalaminemic cats had increased serum, methylmalonic acid concentrations
In cats with clinical and biochemical hyperthyroidism, there was no correlation between serum cobalamin concentrations with TT4 concentrationor clinical scores including body weight and BCS
**overall prevalence of hypocobalaminemia was low in this population. Hypocobalaminemia is NOT a functional deficiency requiring supplementation in hyperthyroid cats without GI disease. Investigate for GI disease if hypocobalaminemia persistent once euthyroid **
What important role does vitamin B12 play? What markers indicate functional/ cellular level cobalamin deficiency?
Role in cellular functions involving DNA synthesis and amino acid production
Cofactor required in many enzymatic reactions, including conversion of methylmalonyl-coenzyme A to succinyl coenzyme A and conversion of homocysteine to methionine
Decreased activity of these enzymes leads to increased serum methlmalonic acid (MMA) and homocysteine concentrations
Increased MMA and homocysteine reflect cellular/ functional cobalamin deficiency in people
In a study evaluating PLI in dogs with DKA (JVIM 2016)..
Based on serum PLI activity 45 (73%) of dogs with DKA had evidence of concurrent pancreatic injury — ** pancreatic injury is common in dogs with DKA
Median TCO2 was lower in all dogs with increased PLI compared to dogs with normal PLI
Fair agreement between PLI and AUS.
Pancreatic injury was NOT associated with longer hospital stay (though panc dogs did stay slightly longer) and did not influence short term outcome
Briefly describe the pathophysiology of DKA
Characterized by hyperglycemia, hyperketonemia or ketonuria and metabolic acidosis
Prolonged absolute or relative insulin deficiency results in accelerated lipolysis, hypertriglyceridemia and ketone body production
When ketone production exceeds peripheral utilization, the associated hydrogen ions overwhelm body’s buffering systems and severe metabolic acidosis and electrolyte imbalances ensue
Background — current undertanding of adrenal steroidogenesis is that production of aldosterone or cortisol depends on expression of aldosterone synthase (CYP11B2) and 11beta-hydroxylase cytochromic P450 (CYP11B1). In dogs/ other species, a single CYP11B catalyzes both cortisol and aldosterone formation. Analysis of the canine genome provides data of a single CYP11B gene known as CYP11B2, and a large sequence gap exists near the CYPB11B2 gene.
Equal expression of the CYP11B2 was gound in the zona glomerulosa and zona fasciculata - single gene found.
Expression of 17 alpha hydroxylase/ 17, 20 lyase (CYP17) was significantly higher in the zona fasciculata compared with the zona glomerulosa
**There is only one CYP11B gene in canine adrenals based on RT-qPCR (aldosterone synthase or CYP11B2) in the zona glomerulosa and fasciculata. The zone specific production of aldosterone and cortisol is probably due to zone specific CYP17 expression, making it an attractive target for selective inhibition of cortisol syntehsis ithout affecting mineralocorticoid production in the zona glomerulosa
Name the three layers of the adrenal cortex and what they produce…
Zona glomerulosa - mineralocorticoid/aldosterone production (Regulated by plasma potassium, angiotensin II, and ACTH
Zona fasciculata - functions with reticularis as a unit and are the main source of glucocorticoid, which is strictly regulated by the HPA axis
Zona reticularis - also produces androgens like dehydroepiandrosterone and androstenedione
Uses cholesterol as a uniform precursor, zone dependent enzyme production is needed for distinct steroid production
Objective - to investigate the epidemiological characteristics of naturally occuring adrenocortical insufficiency in a large population of insured dogs
Retrospective cohort study - incidence rates, prevalences and relative risks for dogs iwth naturally occuring adrenocortical insufficiency
Total 534 dogs identified
Overall incidence - 2.3 cases per 10,000 dog years at risk (DYAR)
Relative risk of disease - significantly higher in portuguese water dog, standard poodle, bearded collie, cairn terrier, and cocker spaniel
Female at highter risk than males
Relative risk of death in addisonian dogs - 1.9 x higher than in dogs overally
Objective - to investigate post prandial metabolic and hormonal responses to a high fat mixed meal in dogs and responses of lean vs overweight dogs
Prospective observational study - 12 lean dogs, 10 slightly overweight, 6 overweight. Overnight fasted, collected urine and blood, then fed high fat mixed meal and blood was collected hourly for 4 hours and urine after 3 hours,
Post prandial concentrations of insulin and glucagon were increased at 1 hour, triglycerides at 2 hrs, and glucose at 3 hrs - all remained increase throughout feeding challenge for all groups
Post prandial UCCR was higher than fasting values
There was an overall higher triglyceride response in overweight compared to lean and slightly overweight groups. Overweight dogs also had higher fasting UCCR
**all dogs responded to high fat meal by increase in triglyceride concentrations, but response was higher in overweight dogs (other metabolic and hormonal variables didn’t differ between groups except fasting UCCR being higher in overweight dogs) Increased TG concentrations may suggest metabolic alterations **
Retrospective case series describing 150 cats with EPI
Median age 7.7 YO Median BCS 3/9 77% - hypocobalaminemia 47% - hyperfolatemia 5% - hypofolatemia Clinical signs: 91% weight loss, 62% unformed feces, 50% poor hair coat, 45% anorexia, 42% increased appetite, 40% lethargy, 28% watery diarrhea, 19% vomiting, 58% had concurrent disease
60% had good treatment response, 27% had partial, and 13% had poor response
TLI <4 was assocaited with a positive treatment response, and cobalamin supplementation improved response to treatment
Objective - to investigate body weighy, BCS and muscle condition in hyperthyroid cats
Prospective cross sectional and before/after studies
Pretreatment body weight was lower than premorbid body weight recorded 1-2 years pre-diagnosis
36% of cats were thin or emaciated, 77% had loss of muscle mass
Cats showed increases in body weight, BCS, and MCS after treatment, but mild to moderate muscle wasting persisted in 45% of treated cats
**most hyperthyroid cats lose body weight but maintai an ideal or overweight BCS with only 1/3rd being underweight. Weight loss is generally associated with muscle wasting rather than fat loss (affects >75%) of hyperthyroid cats. Successful treatment leads to weight gain and increase of BCs in most cats, but almost 50% fail to regain normal muscle mass **
Population - 522 dogs: 163 with hypoadrenocorticism, 351 with nonadrenal gland illness, 8 dogs with equivocal results
At a cortisol cut point of 0.8 mcg/dL, sensitivity and specificitry were 97% and 96% respectively
Basal cortisol = 2 - sensitivity 99.4%, specificity 67%
**Basal cortisol = 0.19 mcg/dL resulted in a specificity of 99.1% **, sensitivity 82%
- *similar to previous studies, cortisol >2 ruled out addisons. Lower cut points improved the specificity and PPV for Addison’s disease**
- *Test performance was not influenced by normal/abnormal electrolyte concentrations **
Objective - to estimate the prevalence and identify risk factors for DM ibn a large population of cats in primary care practices
Of 1128 DM cases found among 194563 (period prevalence of 0.58%)
Tonkinese (4.1 x risk), Norwegian forest cats (3.5x risk) , and Burmese (3xrisk) had increased odds of DM compared with crossbred cats
DM odds increased as bodyweight increased above 4 kg, in cats >6 YO, and insured cats
Sex was not significantly associated with DM
Unlikely to be testable
Exenatide extended release is a glucagon like peptide analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type II DM. Exenatide was found to be safe in healthy cats
Prospective placebo controlled clinical trial of 30 cats with DM - cats treated with exenatide ER or saline given SQ once weekly, and both groups received glargine insulin and low carb diet. Exenatide ER was given SQ for 16 weeks. IF cats achieved remission it was given for 4 weeks after discontiuning sinulin.
Cats in both groups had transient adverse signs of decreased appetite (60% exenatide group, 20% placebo) and vomiting (53% exenatide, 40 % placebo)
Body weight increased in the placebo group but not in the exenatide group **
40% of cats in exenatide group achieved remission **
89% achieve good metabolic control**
20% of placebo cats achieved remission
58% achieved good metabolic control
Study suggests that rate of remission in diabetic cats is ~20%, rate of good metabolic control is ~30% **
What are incretins?
Gastrointestinal hormones such as glucagon like peptide 1 (GLP1) and glucose dependent insulinotropic polypeptide (GIP) released in response to food intake that increase glucose dependent insulin secretion
Have been shown to stimulate pancreatic beta cell proliferation in rats
Also inhibit glucagon secretion, slow gastric emptying, induce satiation and promote weight loss
Population - looked at 531 healthy dogs of 9 different breeds
Prospective observational study - measured circulating concentrations of endothelin1 and cortisol, renin activity
Key results - median endothelin 1 concentration was 1.29 pg/ml
Median cortisol concentration was 46 nmol/L
Median renin activity was 0.73 ng/ml/h
Breed differences were found in endothelin 1 and cortisol concentrations and renin activity
67% breed variation — Newfoundlands had the highest median endothelin 1 (3x higher than CKCS, Doberman, and DAchshunds) - ** most prominent difference here, differences in other values were less prominent **
Median renin was highest in DAchshunds
Median cortisol was highest in Finnish Lapphunds
** breed variation may be important when interpreting lap results **
How does the body respond to a decrease in blood pressure?
Decrease in BP —> activates SNS, RAAS, and vasopressin (ADH) —> vasoconstriction
Angiotensin II can stimulate the release of endothelin I = potent vasoconstrictor that is released from vascular endothelium
Endothelin can stimulate the release of norepinephrine, angiotensin II and vasopressin
RAAs and vasopressin stimulate sodium and fluid retention
Objective - compared cortisol response to 1 and 5 mcg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism and in dogs receiving trilostane or mitotane that have PDH
In dogs being treated for PDH with trilostane or mitotane, the 2 doses were pharmacodynamically equivalent
Dogs with suspected hyperadrenocorticism - doses were NOT pharmacodynamically equivalent, and in 23% of the dogs, clinical interpretation of test results was different between doses
**For dogs suspected of having hyperadrenocorticism, 5 mcg/kg cosyntropic IV is still recommended for ACTH stimulation testing, but for monitoring while on trilostane/mitotane, 1 mcg/kg is sufficient making monitoring cheaper **
Why has a lower dose of cosyntropin by evaluated in both cushinoid dogs and dogs with suspected Addison’s?
In healthy dogs, 1 mcg/kg provides the same maximal adrenocortical stimulation
Objective - to describe the occurrence and clinical presentation of central hypothyroidism in mini schnauzers. Possible role of TSH releasing hormone receptor gene and tSH beta gene were investigated
Central hypothyroidism was diagnosed in 7 mini schnauzers based on TSH or TRH stimulation test. Three/seven dogs had disproportionate dwarfism and at least one had combined deficiency of TSH and prolactin.
CT showed no abnormalities
Scintigraphy showed minimal 99m Technetium uptake in the thyroid
No disease causing mutations were found in TSHB genes and exons of the TRHR gene of schnauzers
**Central hypothyroidism could be underdiagnosed in mini schnauzers with hypothyroidism, especially those with normal stature. Could have genetic background in mini schnauzers **
What is central hypothyroidism? What are causes of adult onset central hypothyroidism?
Thyroid glands not affected, but are deprived of TSH. Rare compared to primary hypothyroidism.
Pituitary tumor Lymphocytic adenohypophysitis Head trauma Non-traumatic intracranial hemorhage Hypophysectomy
Prospective observational study. FSL was placed on the neck of 10 client owned diabetic dogs for up to 14 days.
During the 1st-2nd, 6-7th, and 13-14th days from application, interstitial glucose was compared with plasma EDTA glucose
**FSL application was well tolerated. 50% dogs had mild erythema at application site. Good correlation between interstitial and plasma glucose was found (rho 0.94). The FSL was 93,99 and 99% accurate at low, normal, and high BG concentrations.
Prospective randomized masked placebo controlled study - dogs with OA were treated with 2 mg/kg galliprant or placebo and owners completed a survey describing perceived pain level throughout study
**Galliprant/ grapiprant treatment improved pain compared to placebo on day 28 compared to placebo (48% galliprant, 31.3% pacebo treatment success)
Pain interference score and pain severity score improved in the galliprant group compared to placebo.
Veterinary assessments were significantly better in the galliprant treated dogs.
**Galliprant was well tolerated, but 17% of dogs had occasional vomiting as compared to 6% of placebo group
**Galliprant results in owner and veterinary assessed improvement of clinical signs in dogs with OA treated for ~28 days. Minimal adverse events were seen, even in dogs with comorbidities **
What is the mechanism of action of galliprant/ grapiprant?
Potent specific antagonist of the prostaglandin E2 (PGE2) and EP4 receptor.
Member of the piprant drug class, that block prostagland receptors
Used for analgesia
Different from NSAIDs b/c NSAIDs act by inhibiting cyclooxygenase enzymes. EP4 recepto antagonists do not inhibit the production of prostanoids, which are important in a variety of physiological functions and maintain normal homeostatic functions
Objective - to report distinguishing clinical features and treatment responses of cats with thyroid cysts - 40 client owned cats were retrospectively evaluated
40 cats
Cats ranged from 8YO to 20 YO, no breed or sex predilection
93% of cats were hyperthyroid and the majority had long standing hyperthyroidism, remainder had nonfunctional thyroid tumors
Majority of masses (60%) were larger than 8 cm
No association between cystic and serum TT4
Clinical findings: 100% had palpable neck mass, 38% had weight loss, 20% had dysphagia, 13% decreased appetite, 10% dyspnea
Small cysts 40%, large 60%
25 cats treated with I131 - 92% became euthyroid, thyroid cysts resolved in 50%.
I131 resolved small cysts in 62% of cats and large cysts in 36% of cats.
8 cats (including 2 euthyroid cats, underwent thyroid cystectomy. 3 with bilateral thyroid involvement euthanized due to hypocalcemia. Excised thyroid masses were identified as cystadenoma and carcinoma
Cystectomy can be considered in cases of unilateral cyst where euthyroid or if I131 does not resolve cyst
Prospective uncontrolled clinical trial. Dogs were treated with bezafibrate SID using 200 mg tablets (dose range 4-10 mg/kg depending on body weight) for one month
35% of dogs had primary hyperlipidemia
65% of dogs had secondary hyperlipidemia (including hyperadrenocorticism and dogs chronically treated with glucocorticoids)
No difference in baseline triglyceride concentration between the primary and secondary hyperlipidemia group
- *Resulted in normalization of triglycerides in 91% of dogs and cholesterol in 67% WITHOUT raising CK or ALT levels
- *The decrease in triglyceride concentration after treatment was greater in the primary hyperlipidemia group
- *No adverse events observed, but ALT activity decreased significantly after 30 days of treatment
What is the mechanism of action of Bezafibrate/ what type of drug is it?
Fibric acid derivative (other examples - fenofibrate, gemfibrozil)
Used as a lipid lowering drug, specifically effective in treating hypertriglyceridemia
Fibrates are mediated by peroxisome proliferator activated receptor (PPAR) alpha —> induce hepatic fatty acid uptake and decrease hepatic triglyceride and very low density lipoproteins (VLDL) synthesis, increase activity of lipoprotrein lipase, increase gall bladder excertion of hepatic cholesterol, and increase production of high density lipoproteins
Adverse effects: muscle pain, vomiting, diarrhea, increased CK and ALT, predisposition to form gallstones
Background - no genetic predisposition for DM in labradors has been found. A deletion in the pro-opiomelanocortin gene (POMC) in labs is assocaited with increased appetite and risk fo obesity
61 non-diabetic labs aged >6 YO and 57 labs with DM - case control genotyping study to compare the frequency of the POMC deletion in dogs with and without DM
**14 base pair deletion was confirmed and localized to exon 3 of the canine POMC gene. PCR based test for the deletion was successfully developed. There was no association between the presence of the POMC deletion mutation and DM in this population of labs. **
**14 base pair deletion is likely to cause a frameshift in the protein.
**little evidence directly linking obesity and DM in dogs
restriction fragment length polymorphism based genotyping of the mutation can be don using PCR, apaI or Sac II enzyme digestion
What is a single nucleotide polymorphism?
Difference in a single DNA building block/nucleotide. Can act as biological markers and allow for identification of genes that are associated with disease, When they occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function
Which genetic factors have been proven to be potential risk factors for DM in certain breeds?
Certain haplotypes of the canine major histocompatibility complex, polymoprhisms in several other immune response and cytokine genes (e.g. genes encoding IFN gamma, IL10, IL12 beta, IL6, IL4, PTPN22, TNFa)
14 cats with hypersomatotropism diagnosed based on DM, pituitary enlargement, and IGF1 >1000
Uncontrolled prospective cohort study. Cats received long acting release pasireotide 6-8 mg/kg SQ once monthly for 6 months.
8 cats completed the trial
3 cats entered diabetic remission - 37%
Median IGF1, median insulin resistance index (fructosamine x insulin dose) decreased significantly
Median insulin dose requirement significantly decreased (1.5 U/kg decreased to 0.3 U/kg)
No significant change was found in mean fructosamine or mean blood glucose despite significant decreased in median insulin dose.
Adverse events: diarrhea (80%), hypoglycemia, worsening polyphagia
Objective - to evaluate renal perfusion in hyperthyroid cats with contrast enhanced ultrasoubnd
42 hyperthyroid cats included and were evaluated one month before and 1 month after I131 treatment
Renal perfusion was evaluated through contrast enhanced ultrasound and creation of time intensity curves
Increase in multiple time related perfusion parameters was seen following I131 treatment, indicating decreased blood velocity after hyperthyroidism was treated. Small post treatment decrease in peak enhancement was present in renal medulla, suggesting lower medullar blood volume.
reduced renal blood flow following I131 treatment and return to euthyroid state
Why does hyperthyroidism cause increased GFR and mask azotemia?
Increased TT4 causes decreased vsacular resistance and increased cardiac output, leading to increased renal blood flow
Risk factors for DM:
Indoor confinement, being a greedy eater, and being overweight
In cats assessed by owners as being a normal weight, there was an association between eating predominantly dry food and increase risk of DM (odds ratio 3.8)
Objective - to compare efficacy and short term outcomes of low dose I11 vs high standard dose I 131 as treatment for hyperthyroidism
189 hyperthyroid cats with mild to moderate hyperthyroidism (TT4 >4 <13)
**No significant difference in prevalence of cats with persistent hyperthyroidism between standard and low dose treatment groups at 3 (0% high dose, 5.3% low dos) and 6 (0 % high dose, 3.3 % low dose) months post
Overt (18% high dose vs 1% low dose) or subclinical (46% high dose and 21% low dose) hypothyroidism was more common in cats at 6 months after standard dose
No difference in incidence of azotemia was noted between groups, but cats treated with standard 4 mCi dose had higher creatinine concentrations and higher percent rises in creatinine (77% high dose vs 50% low dose)
**97% cure rate of cats treated with low dose, and lower frequency of iatrogenic hypothyroidism and azotemia **
**high TSH together with normal (usually low normal T4) is relatively common in hyperthyroid cats after treatment
Background: - chronic levothyroxine supplementation can suppress the HPA axis and make it difficult to assess thyroid function after withdrawal of levothyroxine
28 euthyroid dogs - prospective randomized study administering levothyroxine (0.026 mg/kg SID) to euthyroid dogs for 8 weeks or 16 weeks. Performed thyroid panels q 4 weeks during supplementation and weekly for 16 weeks once levo stopped
Mean TT4 was higher and TSH was lower during supplementation
Sean serum TT4, fT4, TSH in both groups, starting 1 week post stopping levo wass different compared to values during levothyroxine administration but not compared to baseline
**8 to 16 weeks of treatment, then stopping can result in return to baseline approx 1 week after stopping treatment
What happens if cosyntropic is injected outside a vessel?
Prospective study - each of 20 dogs underwent 2 different ACTH stims (either given perivascular or IV)
No significant difference in results was noted when comparing serum cortisol after IV and perivascular ACTH administration in all 20 dogs
No significant difference was noted when comparing serum cortisol after IV and perivascular ACTH in the 10 healthy dogs OR in the 10 hyperadrenocorticism dogs
***Perivascular administration of ACTH does not significantly alter stimulation test results in healthy dogs or those with hyperadrenocorticism undergoing trilostane therapy
53 dogs with primary hypoadrenocorticism - 24 newly diagnosed, 29 treated
Prospective multicenter clinical trial - DOCP was administered and NA and K concentrations were measured until the dog developed hyponatremia or hyperkalemia or had c/s of electrolyte derangements - defined DOCP duration of action
Individualized dosing interval - DOCP duration of action - 7 days
Duration of action of DOCP in dogs with newly treated hypoadrenocorticism ranged from 32-94 days (median 62 days) Phase II (applying IDI) - mean IDI 58 days (38-90 days) Phase III (IDI long term) - no reduction needed Duration of action of DOCP of previously treated dogs - 41-124 days (median 67 days)
Final DOCP dosing interval for all dogs that completed phase II ranged from 38 to 90 days
No dog that completes phase III required reduction in the individual dosing interval
Median drug cost reduction using individual dosing interval was ~56% per year
**individual dosing interval can be evaluated by measuring plasma sodium and potassium concentrations weekly starting 25-30 days post DOCP to ID duration of action. IDI = duration of action - 7 days
Retrospective cohort study of 43 dogs diagnosed with PDH - 17 trilostane treated and 26 untreated - survival analysis at 2 years post diagnosis was performed
Median survival time for the trilostane group was not reached and was significantly longer than the median survival time of the untreated group of 506 days
Only variable identified associated with increased risk of mortality was being untreated for hyperadrenocorticism
**not treating dogs for PDH might be associated with higher risk of death
Retrospective observational case series of 65 dogs with PDH - each dog treated with trilostane for 3 months before the study. Dogs were separated into three groups based on AUS: normal, cholestasis, gall bladder mucocele
Mucocele group had more severe clinical signs and significantly different total serum cholesterol concentration and post ACTH stim cortisol concentration at diagnosis
Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than other dogs
Optimal trilostane dose for gallbladder mucocele and cholestasis groups were 2.5 x and 1.5 x higher than the normal ultrasound group
**gallbladder mucoceles are a complication of PDH and are related to severity of disease. Dogs with PDH and mucoeles have more severe clnical signs and higher post ACTH stim cortisol concentrations than those without GB mucocele
Pathophysiology of mucocele formation with PDH may include breed, genetic and female sex predisposition, which may be associated with cholesterol metabolism and bile secretion. The significant difference in required trilostane dosing between groups likely because of lipid soluble charcteristic of trilostane
Breeds at DECREASED risk of hyperthyroidism compared to DSH: Burmese, Tonkinese, Persion, Siamese, Abyssinian, and British Shorthair
Domestic longhair - INCREASED risk (odds ratio 1.3)
Coat color and pattern was NOT associated with hyperthyroidism in non-purebred cats
Objectives - to report the biological and analytical variability components in serum cortisol concentration post acth stim in healthy dogs
**Index of individuality was equal to 1.1 (indicator of within and between individual variability)
Critical difference between measurements was 3.3
Number of measurements required to assess homeostatic set points of cortisol with a confidence interval of 90 and 95% were 3 and 15 respectively
Mean cortisol concentration was higher in males than in females
Treatment with cortisone acetate resulted in a dose dependent suppression of cortisol concentration
**false negative test results in hypercortisolism could occur when cortisol concentration is outside of the individual’s homeostatic set point and within the RR
The largest critical difference between sequential measurements emphasizes the iportance of assesing clinically relevant parameters in the diagnosis and monitoring of hyperadrenocorticism
**post ACTH cortisol level has intermiediate individuality that may accound for some false negatives.
54 dogs with primary hyperparathyroidism - enrolled with hypercalcemia and no prior calcitriol treatment leading up to sx. All dogs were treated with parathyroidectomy or percutaneous ultrasound guided heat ablation
There was moderate correlation between before treatment hypercalcemia and after treatment hypocalcemia
All dogs were placed into groups according to their pretreatment iCa
After treatment, the mean lowest iCa was lowest in the group with the highest pretreatment iCa (>1.81 mmol/L)
There was significant association betwween higher group and proportion of dogs with iCa <1 mmol/L
There was no association between PTH concentration or duration of disease before treatment on development of hypocalcemia post op
there are studies that contradict this so it is unlikely to be testable
Background - TSH can be increased in people with primary hypoadrenocorticism before glucocorticoid treatment. Increases in TSH is a typical finding of primary hypothyroidism and both disease can occur together in people
TSH concentrations were increased in 11/30 37% of dogs with hypoadrenocorticism and 0% of dogs with nonadrenal illness. No of the dogs with reduced TSH had low TT4.
There was no difference in TT4 between dogs with increased TSH compared to those with normal TSH and controls
After starting treatment, TSH normalized after 2-4 weeks in 9 dogs and after 3and 4 months in 2 dogs without levothyroxine supplemnentation
Treat hypoadrenocorticism first prior to thyroid function testing
Objective - to characterize the use of IVCRI lispro at an initial dose of 0.09 U/kg/hr and the use of NaCl for resusciation.
12 cats with DKA
Randomized controlled blinded study, 6 cats randomized into each group - lispro group and regular insulin group
All cats received IVCRI fluid resuscitation with NaCl, and solutions with higher than previous electrolyte concentations were used to treat electrolyte deficiencies
**Duration of hospitlization and time time to first SQ insulin injection did not differ betwen groups **
Median time to blood glucose concentration <250 was shorter in the lispro group (median 7hrS) than in the regular insulin group (median 12.5 hours)
Two cats had nonclinical hypoglycemia
Low concentrations of serum sodium, potassium, phosphate, and magnesium were over 3x more common than above normal electrolyte concentrations, despite supplementation with fluids of high electrolyte concentrations , and most rapid sodium change recorded was 0.7 mmol/L/hr - sodium rich fluids are safe to use in DKA
Objective - to investigate heritability and mode of inheritance of DM in the american eskimo dog
Heritability of DM in american eskimo dogs was estimated at 0.62
Predicted DM probability for neutered females was 0.76, intact females 0.11, neutered males 0.63, and intact males 0.12
There was no overlap between 95% posterior intervals of disease probability in any sex/neuter status
Analysis suggested that mode of interitance of DM in american eskimo is polygenic, with no evidence of single gene of large effect
Estimated heritability of DM in American eskimo is high but has low precision. DM transmission appears to follow polygenic mode of inheritance.
Prospective study, 17 dogs with addisons - 12 newly diagnosed, 5 previously treated with florinef
Dogs with newly diagnosed addison’s were treated with a starting dose of 1.5 mg/kg
Dogs previously treated with florinef were started at 1-1.8 mg/kg SQ
Re-evaluations performed at regular intervals for a min of three months. DOCP dose was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval
The starting dose was sufficient in all but 2 dogs, and had to be decreased after 2-3 months to a median dose of 1.1 mg/kg
Dogs = 3 YO needed higher doses compared to older dogs. No dogs needed the listed 2.2 mg/kg SQ
THEY USED ZYCORTAL in this study NOT Percorten
**starting dose of 1.5 mg/kg SQ is effective in controlling c/s and serum electrolyte concentrations in the majority of dogs (88%)
Additional dose reduction is often needed to maintain an injection interval of 28-30 days.
What is desoxycorticosterone pivalate?
Parenteral long acting mineralocorticoid with no glucocorticoid activity
Looked at 40 dogs with hypothyroidism and 20 healthy dogs
Prospective cohort study
Hypothyroid dogs had significantly decreased median or mean HR, P wave amplitude, and T wave amplitude and E point to septal separation normalized to body weight (EPSSn) and transmitral E wave velocity (Emax) at time 0 compared to control dogs
At time 60, significantly increased median or mean HR, P wave amplitude, fractional shortening, and E max and significantly decreased left ventricular and end diastolic volume index, and normalized systolic diameter and EPSSn were found.
overall -hypothyroidism induces some modification of the electromechanical cardiac function in affected dogs, but these changes are usually mild and reversible with treatment. None of the hypothyroid dogs had c/s of heart disease OR echocardiographic features mimicking DCM phenotype. MPI or myocardial performance index (echocariographic index of combined systolic and diastolic function) does not seem to be a useful variable to ID cardiac dysfunction in dogs with spontaneous hypothyroidism
What is the myocardial performance index?
Sum of isovolumetric contractino time plus relaxation time divided by ejection time
Objective - to predict serum iCa concentration from signalment, biochemistry profile, and T4 and compared predicted iCa to tCa
Cross sectional study - attempted to create model by using various variables for 1701 cats to calculate predicted iCa
For hypercalcemia - predicted iCa was highly specific 99% (in hospital), 97% (external set/ out of hospital) but poorly sensitive (in hospital/ test set 30.4%), 43% (External set/ outside hospital)
For hypocalcemia, predictive iCa was highly specific (82% in hospital/test, 99.6% external), but poorly sensitive (58% test/in hospital, 0% external)
These diagnostic performances were comparable to those of tCa.
Upper and lower limits of predicted iCa prediction interval had high sensitivity for detecting ionized hypercalcemia and hypocalcemia.
Model created is useful for ruling IN ionized hyper/hypocalcemia, may get some false negatives
To develop a novel health related quality of life tool to aid assessment of dogs with Cushings and to evaluate factors that impact on dogs living with Cushings
210 dogs with Cushings and 617 dogs without Cushings
19 question tool was developed with good internal consistency
Owners related questions to owner impact (Ie. impact on bond with their pet and how much they worry about their future) as more important than those related to demeanor
There was a positive correlation between tool score of dogs with Cushings and their owner’s assessment of their dog’s QOL
Dogs currently on treatment with trilostane had statistically better QOL scores than those NOT on trilostane.
Objective - to determine how often concurrent pitutiary and adrenal lesions are present in dogs with spontaneous hypercortisolism
In dogs with dexamethasone suppressible hypercortisolism (PDH - 122/201) - 64% had an enlarged pituitary gland (mean P/B ratio 0.43). 2 of these dogs (2%) had concurrent adrenal lesions
In the remaining dogs with PDH based on LDDST (44/122 or 36%), the pituitary gland was NOT enlarged.
In the dexamethasone resistant group (79/201), the pituitary gland was enlarged in 47 (59% - P/B ratio of 0.57). 17% of these dogs had concurrent adrenal lesions
In the remaining dexamethasone resistant dogs (41%), the pituitary gland was not enlarged. 27 of these 32 (84%) had adrenal lesions and suppressed ACTH concentrations consistent with adrenal dependent hypercortisolism and 5 dogs were diagnosed with PDH
Concurrent pituitary and adrenal lesions were present in 5% of all dogs with hypercortisolism and 10% of dogs that did not suppress at all on their LDDST. An enlarged pituitary gland (P/B >0.31) was noted in 70% of dogs with PDH.
Diagnostic imaging of both pituitary and adrenal glands should be included in the evaluation of every dog with Cushings to obtain information needed for estimation of prognosis and choosing the optimal treatment
15 dogs with spontaneous SARDS (median time of vision loss 18 days), 14 normal dogs, 13 dogs with confirmed PDH
Prospective case control study
ELISA on samples obtained in the morning for measurement of plasma melatonin and dopamine, serum esrotonin, urine 6-sulfatoxymelatonin (MT6) and creatinine
There were no significant differences in circulating melatonin, serotonin, or dopamine concentrations between the 3 groups, though the study was underpowered for detection of significant differences in serotonin
Urine MT6:creatinine ratio was higher in dogs with PDH compared with dogs with SARDS, but not compared with normal dogs
What is urine 6-sulfatoxtymelatonin measurement useful?
Reflects more than 70% of melatonin secretion, breakdown product of melatonin, represents accumulated amounts of systemic melatonin over several horus and less affected by fluctuations in circulating concentatinos
Retrospective cross sectional study assessing thyroid hormone concentrations of 68 cats within 6 months of surgery.
Longitudinal study of thyroid status in 23 cats with >18 months follow up post thyroidectomy
68 cats had follow up within 6 months. 22% of cats had persistent or recurrent hyperthyroidism. 33 (49%) were hypothyroid. 23/33 (70%) of the euthyroid/hypothyroid cats had long term follow up. — 4 (17%) remained hypothyroid, 19 (83%) were euthyroid (often transiently) and 9/23 (44%) developed recurrent hyperthyroidism.
SDMA and creatinine were linearly associated, but hyperthyroid cats had higher SDMA concentrations relative to creatinine
**Cats have changes in thyroid function for years after bilateral thyroidectomy, with a high incidence of recurrent hyperthyrooidism. Both SDMA and creatinine are affected by thyroxine concentrations, and the effect is greater in hyperthyroid cats
20 hypothyroid dogs - behavior evaluated at presentation, after 6 weeks, and after 6 months of treatment with levothyroxine (starting dose 0.01 mcg/kg Q12). At each period, circulating serotonin and prolactin were evaluated
After 6 weeks of levothyroxine, behavioral scores significantly improved. No significant change in behavioral scores was observed after 6 months of treatment. No significant difference in circulating concentrations of serotonin and prolactin were noted at any time point
Objective - to assess the association between diabetes and CKD In a population of adult cats — 516 cats
12% of cats had CKD
2.9% of cats had DM
60 cats without DM (11%) had CKD
7 cats with DM (44%) had CKD - both conditions were diagnosed simultaneously in 6/7 cases (86%), DM preceded CKD in the other case
Multivariate analysis showed that D< was significantly associated with CKD (odds 4.47)
Other variables associated with CKD were age and mixed breed
What are the theorized factors that lead to the development of CKD in people with diabetes?
Hyperglycemia, advanced glycation products, oxidative stress, inflammatory cytokines, and profibrotic growth factors are involved in renal injury
Objective - to evaluate SDMA as a biomarker of renal function in hyperthyroid cats before T0 and 1 month post I131 treatment (T1)
47 hyperthyroid nonazotemic cats - measured creat and SDMA pre and post treatment, and estimated GFR by using plasma exogenous crewatinine clearance test
SDMA was elevated in 6/47. (13%) cats at T0 and normalized after treatment in 4 of those cats
All cats remained nonazotemic after treatment
In 10/47 cats (21%) where GFR was measured, correlation between GFR and sSDMA was low and not significant, whereas correlatino between GFR and creatinine was moderate and significant.
**careful interpretation of mildly increased SDMA with normal creat in hyperthyroid cats is warranted, as SDMA values might not normalize after resolution of hyperthyroidism in some cats. SDMA was poorly correlated with GFR in this study. **
What is SDMA?
Symmetric dimethylarginine - byproduct of protein methylation, is minimally protein bound and is freely filtered through the glomerulus.
In people > 90% of SDMA is eliminated by renal clearance, and has been found to be closely correlated with GFR in healthy cats and older cats with CKD
Sensitivity and specificity of SDMA to ID decreased renal function in cats with CKD is 100% sens, 91% specific
In a 2018 study investigating the use of basal and TRH stimulated plasma GH concentrations to differentiate between pituitary hypothyroidism and non thyroidal illness in dogs (JVIM 2018)
Background: a low plasma TT4 in combination with a TSH within RI does not distinguish between hypothyroidism and non thyroidal illness. Hypothyroidism is associated with TSH releasing hormone (TRH) induced increased release of GH.
population - 21 dogs with signs consistent with hypothyroidism, low TT4, and TSH within RI
Thyroid scintigraphy was performed to classify dogs with hypothyroidism or non thyroidal illness. All dogs underwent a TRH stimulation test with GH and TSH measurement before, 30min, and 45 min post IV injection of TRH
11/21 (52%) of dogs were hypothyroid -
basal GH in hypothyroid dogs (3.2) was higher than in non thyroidal illness dogs (0.73), with minimal overlap
GH increased after TRH stimulation test in hypothyroid dogs but didnt change in the non thyroidal illness dogs
plasma TSH did not change significantly in TRH stimulated hypothyroid dogs, while it increased in non thyroidal illness dogs.
10 had non thyroidal illness
**measuring GH and GH + TSH concentrations following TRH stimulation can help differentiate dogs with hypothyroidism and nonthyroidal illness
JVIM 2018 - In a study evaluating the interpretive contribution of the baseline serum cortisol concentration of the ACTH stimulation test in the diagnosis of PDH in dogs …
population - 54 dogs with suspected hyperadrenocorticism
assessed diagnostic performance of: baseline cortisol (BC), post stimulation serum cortisol (PC), post to baseline cortisol concentration (deltaC), and quotient (RatioC) for the diagnosis of hyperadrenocorticism
post cortisol performed best/ AUC was significantly higher than AUCs of BC, and RatioC
post cortisol AUC did not significantly differ from AUC of DeltaC
an Optimal cutoff value of 24.8 mcg/dL for post cortisol yielded sensitivity of 86% and a specificity of 94%. Post cortisol cutoff of 26 yielded specificity of 100% with 81% sensitivity for diagnosis of pituitary dependent HAC
PC was comparable to deltaC for the diagnosis of hyperadrenocorticism. Baseline cortisol and quotient of BC and PC were ineffective. Recommendation for obtaining a baseline cortisol may be redundant when looking to diagnose HAC
JVIM 2018 - In a case series describing spontaneous hypothyroidism in 7 adult cats.. .
prospective case series
cats ranged from 3.5 - 11 YO, with no apparent breed prediction
6/7 cats were male (85%)
2/7 cats were initially tested b/c of signs of hypothyroidism (hair coat changes, lethargy, obesity)
4/7 were azotemic (57%)
6/7 cats had low TT4 and fT4
7/7 had elevated TSH
6/7 cats - thyroid scintigraphy showed bilateral goiter with intense uptake
1/7 - no radio nucleotide uptake/ no thyroid tissue
After levothyroxine treatment, ft4 and TT4 increased, TSH fell, and azotemia resolved in azotemic cats
repeat imaging showed reduction in goiter size
In a study evaluating spectrophotometry and ultracentrifugation for measurement of plasma lipids in dogs with DM… (JVIM 2018)
Objective - to determine lipoprotein lipid content of plasma of dogs with DM and to compare lipoprotein lipid content in diabetic and healthy dogs, and to quantify apolipoprotein B100 in dogs with DM
population - 22 dogs with DM and 9 healthy dogs
Median triglycerides (122) total cholesterol (343.5), HDL-cholesterol (200), VLDL cholesterol (27) LDL cholesterol (68) and non-HDL-cholesterol (114) and ApoB (320) were significantly higher in dogs with DM compared to healthy dogs
A significant association was found between ApoB and LDL cholesterol) and ApoB and non-HDL cholesterol
dyslipidemia of dogs with DM is characterized by pronounced increases of LDL cholesterol and nonHDL cholesterol concentrations, although ALL lipoprotein fractions are significantly increased Statins are typically used in people to lower them in ppl with DM, as LDLC and nonHDLC increase risk of heart disease
JVIM 2018 - In a study evaluating serum concentrations of lipid soluble vitamins in dogs with EPI treated with pancreatic enzymes …
Background - in humans, EPI is associated with deficiencies in lipid soluble vitamins.
This study compared serum concentrations of retinol, 25-hydrocholecalciferol, and alpha tocopherol in dogs with EPI, those with subclinical EPI, and healthy dogs
serum retinol (vitamin A) and alpha tocopherol (vitamin E) was lower in dogs with EPI and dogs with subclinical EPI compared with healthy dogs
dogs with weight loss had significantly lower calcidiol level than dogs with stable weight
What are potential implications of lipid soluble vitamin loss?
vision loss, decreased bone density, coagulopathies
JVIM 2018 - Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formation of pancreatic enzyme supplement in dogs with EPI (Parambeth et al).
In dogs with EPI, there was no difference in percent fecal fat (low value indicates normal fat digestion) between dogs given the enteric coated and standard pancreatic supplement - this may also be due to low power of the study (only 11 dogs with EPI in study)
Why might enteric coated pancreatic enzymes theoretically be better than uncoated for the management of EPI?
less oral bleeding
coating may also reduce inactivation of enzymes in the stomach by gastric acid and proteases
JVIM 2018 - Radioactive iodine uptake in hyperthyroid cats after administration of recombinant human TSH
10 hyperthyroid cats
cats were given either a placebo, 50 mcg TSH, and 100 mcg TSH in randomized crossover design with treatments separated by 10 days
scintigraphy was performed after each treatment - with 123I and assessing uptake 8 and 24 hours post. T 4 was measured at each visit
**thyroid percent iodine uptakes were not different between placebo and the two doses. Independent of TSH administration, percent iodine uptakes were positively correlated with serum T4 concentrations
JVIM 2018 - Low dose ACTH stimulation testing in dogs suspected of hypoadrenocorticism (Botsford et al)
population - 31 dogs with suspected hypoadrenocorticism
prospective study, dogs had ACTH stimulation done using 1 mcg/kg cosyntropin for the first ACTH stir, and the second test was performed 4 hours later and dogs received 5 mcg/kg. Endogenous ACTH was measured at the time of initial blood collection
**No significant difference was observed in basal cortisol concentration before 1 mcg/kg or before 5 mcg/kg
For dogs with suspected Addisons, the ACTH stimulated cortisol in response to both doses of ACTH were equivalent. No cases with partial ACTH deficiency were conclusively identified. Timing of post sample is crucial (exactly 60 min post, cannot use IM/ efficacy unknown)
JVIM 2018 - Investigation of a novel variable dosing protocol for radio iodine treatment of feline hyperthyroidism (Moree et al)
objective - to compare a method of radio iodine dose determination that used thyroid scintigraphy with a standard fixed se for treatment of hyperthyroidism
** No difference in outcome was found between the variable dosing plan based on scintigraphy or fixed dosing.
Euthyroidism developed in 61% of the variable dosing and 58% of the fixed dosing
hypothyroidism developed in 30% of variable and 26% of fixed dosing
persistent hyperthyroidism was noted in 9% of variable and 16% of fixed dosing group
** rates of post treatment hypothyroidism and persistent hyperthyroidism were higher than those founding in other studies investigating modified fixed dosing methods
JVIM 2018 - Glucose concentrations after insulin induced hypoglycemia and glycemic variability in healthy and diabetic cats (Zini et al)
population of 6 healthy and 133 diabetic cats
PZI and degludec insulin was administered and BG curves were performed, and % curves with post hypoglycemic hyperglycemia were documented
in healthy cats, all insulin doses caused hypoglycemia, but post hypoglycemic hyperglycemia was not seen. Glycemic variability did not differ between insulin preparations.
Among diabetic cats
25% had post hypoglycemic hyperglycemia, the remainder did not. PHH cats had higher insulin doses than cats that did not have PHH. They also had higher serum fructosamine, less frequent remission, and higher glycemic variability
JVIM 2018 - CT Angiography of the Pancreas in Cats with Chronic DM compared to normal cats - Secrest et al.
the pancreas in cats with chronic DM was significantly larger, had higher volume, had higher volume to body weight ratio, and shorter time to peak portal enhancement on CT angiogram when compared to normal cats.
These variables can potentially be used to differentiate normal sedated cats from those with chronic DM.
JVIM 2018 - Effect of Insulin treatment on circulating insulin like growth factor I and IGFBP in cats with DM (Strage et al)
prospective study - IGF1, glucose, fructosamine, IGFBP all determined in 14 diabetic and 13 healthy cats
IGF median pre insulin was 300
IGF1 was positively associated with ternary complexes and endogenous insulin and was negatively associated with fructosamine
Median IGF was higher 2-4 weeks after start of insulin treatment compared with baseline and predicted future remission.
In cats that went into remission, the amount of ternary complexes and IGFBP3 increased, suggesting increase in IGF1 is dependent on Ternary complex formation
Effect of prophylactic calcitriol administration on Serum ionized calcium concentrations after parathyroidectomy: 78 cases (2005-2015) (Armstrong et al JVIM 2018)
serial postoperative iCa concentrations measured at 12 hour intervals for 2 days post were positively associated with prep iCA concentrations. The effect of preoperative iCa concentrations on postoperative iCA concentrations decreased as time elapsed.
Prophylactic calcitriol administration was NOT found to be significantly associated with post iCa concentrations or its rate of decrease after parathyroidecomy
** No protective value was found in administering calcitriol prophylactically to prevent hypocalcemia in the immediate postoperative period (48 hours) after parathyroidectomy. Preoperative iCa concentration had a significant positive association with post iCA concentration throughout the monitoring period
JVIM 2018 - Evaluation of individual low dose dexamethasone suppression test patterns in naturally occurring hyperadrenocorticism in dogs (Bennaim et al.)
Objective - to assess the current features of HAC and evaluate if the diagnostic test performance of individual LDDST result patterns differ
48% of dogs had HAC
52% of dogs had non adrenal illness
sensitivity of the LDDST was 96.6%
specificity was 67.2%
PPV 73.1%
NPV 95.6%
Lack of suppression pattern had the highest PPV (94%), followed by partial suppression pattern (68%) and escape or inverse pattern
**I.e. overall LDDST performance remains similar to previously described
JVIM 2018 - Evaluation of Serum SDMA as a marker for masked CKD in cats with hyperthyroidism (Peterson et al)
262 hyperthyroid cats and 206 age matched controls
no hyperthyroid cats were azotemic before treatment
16% became azotemic when rechecked at 4-8 months after I131. Of these 16%, 33% of them had high SDMA concentrations before treatment.
As a diagnostic test for pre-azotemic/masked CKd in untreated hyperthyroid cats, SDMa showed a sensitivity of 33.3% and specificity of 97.7 %
**Finding a high serum SDMA pretreatment can help predict development of azotemia post.
pre-treatment USG <1.035 had the highest sensitivity as a predictor of masked azotemia
At what percent reduction in GFR should SDMA theoretically increase?
40% reduction
