Endocrine Flashcards

1
Q

Explain the structure of the thyroid gland

A

Note the thyroid follocles which are cuboidal epithelial cells surrounding colloid.

C-cells are also present (responsible for calcitonin secretion)

Highly vascularised

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2
Q

Outline thyroid hormone synthesis

A
  1. Iodine enters the thyroid gland, co-transported with sodium via NIS
    a - The concentration gradient for sodium is generated via ATPase
  2. Iodine diffuses through the cell and into the colloid mediated by counter-transport with chloride through pendrin (Chloride-iodide anti porter)
  3. Iodine is coupled to thyroglobulin, a glycopeptide containing tyrosine residues produced by the sER/Golgi
  4. Iodide is oxidised by thyroid peroxidase using H2O2
  5. Organification (coupling of Iodine to tyrosine) occurs mediated by thyroid peroxidase
  6. Pinocytosis into the cell occurs and proteases breakdown the colloid droplet to allow active thyroid hormones to be released into the blood.
  7. Deiodinases release tyrosine and iodine from inactive products to allow recycling of these compounds
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3
Q

Outline the different stages of thyroid iodination and number of iodine residues for each molecule

A
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4
Q

What is the majority of thyroid hormone bound to in the blood?

A

Thyroxine binding globulin, it can also bind to pre-albumin and albumin

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5
Q

Why does T4 likely have a longer duration of action than the more potent T3?

A

It takes longer for T4 to unbind from binding proteins in the blood.

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6
Q

How does thyroid hormone expert its effect?

A

Through binding to nuclear thyroid hormone receptors which combine with the retinoid x receptor and then bind to thyroid response elements.

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7
Q

What are the effects of TSH on thyroid production (5 points)

A
  1. Increased proteolysis of TG
  2. Increased NIS activity
  3. Increased iodination of tyrosine
  4. Thyroid hypertrophy
  5. Increased number of thyroid cells
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8
Q

What is the effect of ACTH on the adrenal cortex that results in increased steroid hormone production?

A

It enhances the activity of cholesterol desolate which is the first step in steroid synthesis converting cholesterol to pregnenolone.

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9
Q

Which steps of the steroidogenic pathway does trilostane have an effect on?

A

3B hydroxysteroid dehydrogenase

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10
Q

What is the role of 11BHSD?

A

It converts cortisol, which has some MC activity, into cortisone (which does not) and is present in the renal epithelium. This is why cortisol, in health, does not have a significant MC effect.

Note that 11 beta-HSD 1 has the opposite effect

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11
Q

What food item may inhibit 11BHSD2?

A

Licorice, as it contains glycorrhetinic acid

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12
Q

Outline the effects of MC activation and drugs that may impact on some of these effects?

A
  1. Aldosterone binds to the MR which then stimulates production of NA/KATPase, ENaC and ROMK.
  2. Spironolactone inhibits the MR
  3. Ameloride prevents Na entry into renal cells by antagonising ENaC
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13
Q

Factors and hormones leading to increased vs. decreased insulin secretion

A
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14
Q

At what level of serum phosphate is all filtered PO4 re-absorbed by the kidney?

A

<1mmol/L

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15
Q

What treatments have been used/described for the management of hyposomatotropism in dogs/cats?

A

Use of porcine or human GH products but a problem with these treatments is that antibody development may occur.

Progestin use to stimulate mammary GH production has not been effective in cats.

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16
Q

What is the prevalence of hypersomatotropism in diabetic cats?

A

18 - 32%

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17
Q

What is the gold standard for diagnosis of HS in people?

A

Oral glucose administration followed by GH measurement - this has not been described in cats. The normal response is a suppression of GH secretion in response to testing.

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18
Q

Testing, other than GH/IGF-1 that may be used in diagnosis of fHS?

A

PIIIP - serum type III pro collagen polypeptide, may be up to 5x higher in fHS DM cats compared to DM cats

Gherlin - as a GH secretagogue it is lower in fHS than in healthy cats but may not be lower that DM cats. It has also been shown to increase in response to radiation therapy even when IGF-1 does not change.

GHRG stimulation/SST suppression tests (dogs)
- 1mcg/kg GHRH will NOT stimulate GH release if it is mammary driven (discriminatory test between these types)
- 10mcg/kg SST should suppress GH production in normal animals

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19
Q

What drug may reduce polyphagia in fHS cats?

A

Fluoxitine

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20
Q

In what scenario is gherlin an important secretagogue for GH release?

A

Possibly more important in young animals, compared with GHRH

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21
Q

What phase of reproduction is GH secreted from mammary epithelium in dogs?

A

dioestrus, more often 3 - 5 weeks following oestrus

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22
Q

Treatment for canine acromegaly?

A

MAMMARY DRIVEN:

OVH
Aglepristone

PITUITARY

As for cats
Pegvisomant (GH receptor antagonist)

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23
Q

Which canine breed is predisposed to pituitary dwarfism? What other hormonal deficiencies are noted in this clinical scenario?

A

GSD - autosomal recessive

Will typically have combined GH, TSH and PRL deficiency, however, ACTH production is preserved

Other breeds:
- Czechoslovakian wolfdog
- Karelian Bear Dog
- Lapland reindeer dog
- Lapponian herder
- Saarloos Wolfdog
- Tibetan Terrier
- White Swiss Shepherd

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24
Q

Clinical presentation of hyposomatotropism in dogs

A

Morphological Abnormalities
* Proportionate growth retardation
* Coat changes:
○ Retention of secondary (languno) hairs
○ Lack of primary guard hairs
○ Truncal alopecia (due to loss of languno hairs), sparing trunk and extremities.
○ Hyperpigmentation
○ Scale
○ Secondary bacterial infections
* Pointed muzzle
* LHX3 gene also associated with atlantoaxial joint malformation +/- instability

Reproductive Abnormalities
* Cryptorchidism (due to impaired gonadotrophs)
* Failure to ovulate

Other

May develop reduced demeanour at 2-3 years old due to hypothyroidism and impaired renal function.

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25
What laboratory parameter is possible in congenital hyposomatotropism in dogs?
Increased creatinine
26
Testing to confirm a diagnosis of congenital hyposomatotropism
Basal hormone testing: - IGF-1 (GH) - TSH, TT4 Stimulation testing: Determine basal GH and then re-measure 20 - 30 minutes after: - GHRH - Clonidine or xylaxine - Gherlin Other: TRH stimulation GnRH stimulation Genetic testing: LHX3 mutation
27
What advanced imaging characteristic may be seen in cases with pituitary dwarfism?
Pituitary cysts or hypoplasia
28
Treatment of canine pituitary dwarfism
Porcine GH (human GH results in antibody formation) Progestagens (to stimulate mammary production)
29
Vasopressin structure and sub-hormones
Neurophysin II - involved in the correct processing, transport and cleavage of AVP Copeptin - unknown function n.b. provasopressin is the molecule that is transported down the HPA axons to the PP
30
Half life of AVP
6 minutes
31
Main stimulators for release of AVP
Osmoreceptor stimulation: 1% increase in Osm can stimulate release Sodium - via magnocellular neuron stimulation High pressure baroreceptors - normally inhibit release via glossopharyngeal and vagus nerves Low pressure volume receptors - A drop in blood volume by 10 - 15% will remove inhibition from these systems and result in AVP release.
32
AVP actions based on receptors (renal V2, other V2, V1a, V1b, brain)
33
What breed has CDI been described in a familial fashion?
Afgan Hounds
34
DAMNIT V for central and nephrogenic DI in dogs and cats
Idiopathic Traumatic Inflammation/Infection Cysts Congenital defect Neoplasia: - Carniophayngioma - Meningioma - Chromophobe adenoma/carcinoma - Lymphoma - Metastatic neoplasia
35
What percentage of dogs undergoing hypophysectomy will develop prolonged CDI?
53%, 42% of which will need permanent therapy
36
What breed has primary NDI been reported in and what is the basis of this condition genetically?
Has been suspected in a litter of Siberian Huskeys in which it was suspected to be due to a X-linked mutation (as only males affected?). All the affected dogs had 10x lower binding affinity for AVP. It is thought to be due to reduced AQ2 expression.
37
Clinicopathologic features of DI in dogs and cats?
Low urea, hyposthenuria Dehydration (if water has been restricted)
38
Outline how to perform a MWDT (see printed notes)
(See printed notes)
39
What is the potential risk of performing a DDAVP trial in an animal with psychogenic polydipsia?
Water intoxication and hyponatraemia
40
Indications for and how to perform HH test
Indication: useful to distinguish primary polydipsia from medullary washout from NDI after negative water deprivation and exogenous ADH testing Procedure 1. Instil 20ml/kg water via stomach tube and measure urine flow via urinary catheter (ml/min) 2. Infuse 2.5% NaCl at a rate of 0.25ml/kg/min over 45 minutes 3. Measure urine volume every 15 minutes during infusion followed by every 15 minutes for 45 minutes afterwards Interpretation Normal = Decrease in urine production due to stimulation of ADH release from increase serum osmolality NDI = no real change or even potentially ain increase in urine production PP = Should have a normal response as the hypertonic saline should have Risks * Risky in patients with CHF * May cause hypernatraemia in animals that cannot excrete a sodium load
41
What tests other than DDAVP response, MWDT, HH and ADH administration have been described in diagnosis of DI in dogs/cats/humans?
AVP Measurement * Generally not useful as it is pulsatile * Handing is challending * No widely available assays AQ2 Expression * Not been used clinically although should reflect AVP exposure (experimentally) Copeptin Measurement (Plasma) * Shown to reflect AVP concentrations in people but not evaluated in small animals. Advanced Imaging * Useful if a structural disease process is suspected * Intensity of the PP on T1w MRI has been shown to be proportional to AVP content in dogs (and has been sued to represent phospholipid or secretory granules in people) but has not been evaluated clinically.
42
Treatment for CDI?
DDAVP, although may not always work that well
43
Treatment for NDI
Diet: reduce solute load through low sodium and low protein diets Thiazide diuretics * Decrease Na absorption from distal tubules which will decrease blood volume and therefore increase PCT resorption of Na and water (due to slowed GFR) * Possible that there is also a tubuloglomerular feedback which results in: * Upregulation of AQ2 * Upregulation of DCT Na transporters NSAIDs May have a synergistic effect with thiazide diuretics but side effects are common. Potassium-Sparing Diuretics More for avoiding iatrogenic hypokalaemia Chlorpropamide * Usually for patial CDI * Unknown MoA (may upregulate AVP receptors)
44
What is the reported incidence of iatrogenic hypothyroidism following RAI in cats?
5 - 83%
45
What is a risk factor for development of iatrogenic hypothyroidism following RAI in cats?
Pertechnetiate uptake from both thyroid glands prior to treatment
46
What types of congenital hypothyroidism have and have not been reported in cats?
* Two categories: ○ Dyshormonogenesis ○ Dysmorphogenesis (hypo/aplasia) * Both are likely due to autosomal recessive traits (known to be the case in people) * Dyshormonogenesis is a problem of hormone synthesis therefore there is a lack of negative feedback on the pituitary, TSH is high and the gland enlarges. ○ Defective thyroid peroxidase and impaired iodine organification has been found in related DSH and Abyssinian cats * Dsymorphogenesis does not cause gland enlargement, it has been documented in related cats with an inheritance pattern consistent with an autosomal recessive trait. * There has been a case of hypothyroidism associated with TSH resistance in a family of Japanese cats. * Central congenital hypothyroidism (Hypothalamic or pituitary deficiencies) have not been reported in cats.
47
What dermatologic change associated with hypothyroidism in dogs does not often develop in cats?
Alopecia, however, cats can get coat changes such as a sebbhoraeic coat
48
What is the radiographic feature of congenital hypothyroidism?
Delayed growth plate closure
49
How are cats tested for hypothyroidism.
Both TT4 and fT4 can be used to rule out the condition but given that they can be low for a variety of non-thyroidal reasons they cannot confirm the diagnosis. cTSH can be measured alongside one of the above for diagnosis of iatrogenic hypothyroidism. TSH stimulation testing can be used to rule out euthyroid sick syndrome in cats treated with RAI. - Measure basal TT4 - Administer 25mcg rhTSH IV - Measure TT4 6 hours later
50
Outline how the use of scintigraphy can be useful in the diagnosis of feline hypothyroidism (iatrogenic vs. congenital forms).
* Sensitive and specific * Reduced or absent pertechnetate (99m TcO4-) uptake supports the diagnosis * Use of I123 can help determine between dysmorphogenesis and dyshormonogenesis. ○ Dysmorphogenesis - absent uptake ○ Dyshormonogenesis - may be normal, but since organification is deficient, administration of perchlorate will cause the I123 to be discharged from the gland (perchlorate discharge test)
51
What is the prevalence of hyperthyroidism in cats?
2 - 4 %, although this may rise to >6% in cats >9 years old
52
What is the prevalence of ectopic thyroid tissue and thyroid carcinoma in cats?
Ectopic tissue in <4% cases Prevalence of thyroid carcinoma 1 - 2%
53
What condition should you consider in an older unwell cat with erythrocytosis?
HyperTH - as most other conditions would be expected to cause a mild non-regenerative anaemia
54
What would be expected of TT4 and fT4 concentrations in a cat with euthyroid sick syndrome?
May expect TT4 to be low and fT4 to be high
55
How to perform a T3 suppression test
* d0 Collect a blood sample and separate serum before storing frozen or refridgerated * d1-2 initiate T3 administration 25mcg/cat q8h PO for 2 days (6 doses) * d3 morning give 7th dose of T3 before the cat returns to the clinic for repeat blood sampling * Measure tT3 and tT4 ○ T3 should be higher in the second sample if the owner has been administering it properly (this is why you are measuring this) ○ T4 should be suppressed if the cat is not affected, there is little overlap in results between FHT and unaffected cats so it can be a useful test
56
Indications for and interpretation of thyroid scintigraphy
* Uptake of pertechnetate or radioactive iodine ○ Can calculate pertechnetate uptake or thyroid-to-salivary ratio ○ 99% of FHT cats will have a thyroid to salivary ratio of >1.5 ○ Healthy cats have a ratio <1 * Thyroid-to-background ratio is less sensitive than the thyroid-to-salivary ratio. * Another indication is pre-thyroidectomy to determine unilateral vs. bilateral disease and whether there is thyroid tissue elsewhere, and to increase level of suspicion for thyroid carcinoma. Considered a GOLD STANDARD. It is very useful in animals that are not responding well to anti-thyroid medication as it can detect ectopic thyroid tissue. Uptake of radioactive iodine is compared to that of the salivary gland.
57
Disadvantages of TRH stimulation testing
○ Commercial TRH is not available ○ Lab-grade TRH cannot be recommended for clinical patients ○ Possibly limited usefulness in cats with oncurrent illness ○ Can cause cholinergic and CNS reactions e.g. SLUDGE-M
58
What is the therapuetic target range for TT4 when treating cats with hyperTH with thiourylene anti-thyroid drugs?
Lower half of the RI
59
Frequency of adverse effects of thiourylene anti-thyroid drugs
60
What is the efficacy of Hills y/d in the treatment of hyperTH?
* Heterogenous population of FHT cats given the diet exclusively for 8 weeks * Clinical signs improved significantly by week 4 with no observed adverse effects * TT4 decreased to the RI in 68% of cats by week 4 and in 75% of cats by week 8 but remained in the upper RI (interesting as with other therapies often signs do not resolve until T4 in the lower RI) No change in creatinine - this may be good, or it may indicate that it was not effective.
61
Random treatments for hyperTH and disadvantages
* Ultrasound guided percutaneous radiofrequency heat ablation or intrathyroidal ethanol injections ○ Not recommended!! ○ Questionable efficacy and safety * Iopanic acid ○ An orally administered contrast agent used for cholecystography ○ Can lower serum thyroid hormones ○ Has transient effects so long term treatment not recommended
62
What is the evidence for treatment of iatrogenic hypothyoidism following RAI in cats?
There is no difference in survival between cats that develop azotaemia post RAI vs. those that do not. However, azotaemic hypoTH cats do have a worse prognosis than azotaemic non-hypoTH cats.
63
What handling considerations can affect iCa concentrations?
Prolonged storage will cause lactic acid production from red cell metabolism which will decrease pH and increase iCa Exposure to air results in CO2 loss from the sample, therefore raising the pH of the blood and reducing iCa.
64
Where are the parathyroid glands located in dogs and cats?
4 glands Cranial glands are external to the thyroid capsule Caudal glands are within the thyroid capsule
65
What are the factors that increase and decrease PTH secretion?
Increase: phosphorus, low calcium Decrease: increased calcium, increased vitamin D
66
What is the role of PTHrp in health?
It is involved in foetal calcium regulation, so should be undetectable in adult animals.
67
Enzyme responsible for activation of vitamin D by the kidenys
1-alpha-hydroxylase
68
What is the distribution of malignancy in canine primary hyperparathyroidism?
* Autonomous function of one or more of the parathyroid glands. * Due to: ○ Adenoma (87%) ○ Adenomatous hyperplasia (8%) ○ Carcinoma (5%) * <10% of cases will have more than one gland involved * Metastatic disease has only been reported in 1 dog in the veterinary literature Bear in mind that secondary hyperparathyroidism will also result in hyperplasia of the gland(s) so can sometimes be difficult to distinguish.
69
Breed association to primary hyperparathyroidism
Keeshond - with an OR of 50.7, typically develop increased calcium by 6 - 8 years of age. Autosomal dominant disease. Also reported in an isolated litter of GSD
70
What is the most common clinical sign of hyperparathyroidism?
Urinary tract signs due to urolithiasis (>50% cases). Note that PU/PD is only noted in <10% cases.
71
Percentage of dogs with primary hyperparathyroidism that have CKD
25% - CaxPo does not neccessarily predict this
72
What degree of PTH elevation may be considered 'abnormal' in a case of hypercalcaemia, what are the ain differentials for this pattern?
Upper half of the RI is inappropriate in animal that is hypercalcaemic. DDX: CKD, HyperPTH
73
What percentage of dogs with PTH will have a parathyroid nodiule noted on their neck, what is the normal size of the PT gland
90 - 95% dogs Normal size of PT gland is <3.0mm
74
Mechanisms by which glucocorticoids can reduce calcium
○ Lymphoma cell lysis (useful for this indication) ○ Reduce synthesis and secretion of PTHrP ○ Increase renal calcium loss ○ Decrease intestinal calcium uptake Decrease bone resoption
75
Treatment options for hypercalcaemia (medical options)
NaCl administration Frusemide Bisphosphonates Calcitonin Plicamycin Cinacalcet - CaSR interaction
76
Definitive treatment options for canine primary hyperparathyroidism, number of glands that can be removed, success rates
§ 72% success for ablation (ethanol) § 94% success for surgery 90% for heat ablation Can remove/ablate up to three glands For ablation glands need to be >3mm in size
77
Signalment predispositions to primary hypoPTH
* Females predisposed * Breeds ○ Miniature schnauzers ○ Poodles ○ GSD ○ Terriers St. Bernards in Australia and New Zealand
78
Ocular change that is associated with primary hypoPTH
Lenticular cateracts
79
Weird sequalae of hypoPTH in cats
DCM phenotype
80
What phosphate change would be expected in an animal with primary hypoparathyroidism?
Increased phosphorus
81
With what degree of hypocalcuemiu areclinical signs generally observed in dogs/cats with primary hypoparathyroidism?
<0.8mmol/l iCa
82
What ECG changes could be expected with hypoCa?
Prolonged ST or QT intervals
83
DDx for hypocalcaemia
* Hypomagnesemia * AKI * CKD * Pancreatitis * Diabetes mellitus * Eclampsia * Malabsorption syndromes (e.g. PLE) * Urinary tract obstructions * Phosphate containing enemas Hypoalbuminaemia (only causes reduction in total caclium)
84
Treatment for hypoparathyroidism (chronic)
Aim for iCa within the lower end of the RI - Calcitriol - Ergocalciferol (has much longer duration of action so less good for when you have an overdose) - Oral calcium (likely not to be required long term)
85
What percentage of canine thyroid tumours are benign?
10- 30% and these tend not to have clinical effects
86
Breeds predisposed to thyroid carcinoma
Golden Retrievers Boxers Huskies +/-Malamutes May Have (thyro)GloBulin
87
What are the more common signs of thyroid caricnoma in dogs?
Cervical neck mass palpated incidentally Space occupying signs: dysphagia, dysphonia, dyspnoea, oedema
88
What imaging technique may be useful in determining the extent of a thyroid tumour in a dog and what is the potential disadvantage?
Scintigraphy could be used - CT and MRI are quite specific for thyroid carcinoma, however Scintigraphy is insensitive for detection of pulmonary metastasis and I123 may be superior to Tc99 for this particular indication
89
Prognosis of surgically managed thyroid carinomas and potential complications
Unilateral = 3 years Bilateral = 30 - 39 months Hyppocalcaemia a risk and haemorrhage along with damage to all those neck structures innit
90
Prognosis of thyroid carcinomas treated with RT
PFI 45 months 1 year PFS - 80% 3 year PFD = 72%
91
Which chemotherapeutic has the best evidence in the treatment of thyroid carcinoma (at the time of etts being written)
Cisplatin
92
Side effect of i131 therapy in dogs for thyroid carcinoma
Bone marrow suppression (I believe this is a risk in RAI treated cats as well but just happens quite infrequently)
93
% of insulinomas that are solitary and predilection site
80% solitary, metastasis however occurs in 45 - 64% cases. The most common sites of metastasis are the regional lymph nodes and liver.
94
Biochemical abnormalities that can occur with insulinoma (other than the obvious)
Mild reduction in K+ and increased ALT
95
Sampling consideration in dogs that have episodic neurological signs, where an insulinoma may be suspected and you want to evaluate glucose
Fasting sample is best as feeding can temporarily normalised blood glucose concentrations
96
Which radiolabelled hormone may be used to scintographically detect insilinoma?
SST
97
What percentage of dogs that have surgery for insulinoma will require long-term insulin therapy?
Ettinger says 10% but recent study shows different numbers
98
Medical treatments for insulinoma
Streptozoocin Diazoxide Frequent feeding Glucocorticoids SST analogues
99
MST for insulinoma and prognostic factors
12 - 14 months dependent on clinical stage - Stage - Post-op glucose - Age (young = worse) - tumour size - Ki67 index
100
Staging of insulinoma
1 = solitary tumour 2 = tumour with nodal metastasis 3 = metastatic disease
101
Emerging therapies for diabetes in cats and dogs
- Incretin therapies - Exenatide (GLP-1 agonist) - Amylin - Smart insulin - Bexaglifolozin (GLUT2 inhibnitor, prevents renal glucose reabsorption)
102
Half life of thyroid hormones in dogs - T4 - T3
T4 = 10 - 16 hours T3 = 5 - 6 hours
103
What canine breeds have been reported with the following congenital hypothyroidism? a) Central b) Dyshormonogenesis (type of inheritance pattern) c) Non-genetic reasons for congenital hypothyroidism
a) Giant schnauzers b) Toy fox terriers and rat terriers - fully penetrant autosomal recessive disorder c) Dams fed iodine restricted diets, drugs that reduce thyroid hormone production and in animals that are exposed to iodine deficiencies or excesses when young
104
What breed has been reported to have a spontaneous central hypothyroidism?
Miniature schnauzers
105
What drugs may reduce thyroid hormone levels?
Glucocorticoids Phenobarbital There are actually a load more here
106
How do thyroid histopathology, TGAA status and TSH/T4 concentrations vary with silent, subclinical and clinical hypothyroidism?
107
Why does demonstration of TGAA not usually help in the diagnosis of hypothyroidism?
- 50% of dogs with hypothyroidism will be positive for TgAA - Clinical hypothyroidism does not occur until 75% of thyroid tissue is lost - Although 20% of dogs with TgAA positivity will develop thyroid hormone alterations only 5% will become clinically hypothyroid.
108
Breed predispositions to hypothyroidism
- English Setter - Golden Retriever - Rhodesian Ridgeback - Cocker Spaniel - Boxer
109
What sex predispositions to hypothyroidism have been noted
Intact males and neutered females seem to be at increased risk
110
What description may be given to the facial expression of dogs with hypothyroidism with myxedema?
A tragic facial expression
111
What hair cycle phase are dogs with hypothyroidism likely to have?
A predominance of hairs in the telogen phase
112
What opthalmic disease(s) have been linked to hypothyroidism in dogs and which breed may be overrepresented here?
Arcus lipoides - GSD KCS
113
What are the skeletal radiographic features of congenital hypothyroidism?
Delayed physeal closure Epiphyseal dysgenesis which could lead to DJD
114
What are the morphologic features of disproportionate dwarfism in animals with congenital hypothyroidism?
Wide scull Macroglossia Delay in dental eruption Short limbs Square trunk
115
What is the relationship between TT4 and age (both young and old)?
Tends to reduce with age and dogs <3m can have concentrations that are 3 - 5x higher than adults
116
What breeds may have lower TT4 than other breeds?
o 90% greyhounds o 75% basenjis o 65% Sloughis o 55% Salukis o 25% Whippets o 5% Scottish Deerhounds o Some breeds are so low that an RI cannot be calculated o Dogue de Bordeaux o Giant Schnauzer TSH should not be affected by breed
117
What is the effect of exercise on thyroid hormone testing?
TT4 can be decreased in animals that have prolonged intense excercise and training although brief exercise should not have an effect
118
Conceptually consider the relationship between severity of non-thyroidal illness and its effect on T3, TT4, fT4 and TSH concentrations
The point I want to remember here is that T3 seems to decrease dirst, followed by TT4 and fT4. TSH can be increased in the recovery phase along with decreased TT4/fT4.
119
What drugs may potentially result in a false diagnosis of hypothyroidism?
Phenobarbital - can result in low T4 and increased TSH although normally will remain within the RI Sulfonamides can have the same effect
120
What drug can cause hypothyroidism?
Sulfonamides
121
How long should drug therapy be withdrawn if a drug has been given that is known to impact on thyroid testing, prior to repeat testing
6 weeks, possibly longer for sulfonamides
122
What are the potential changes to TT4 and T3 when TGAA are present?
Expected to increased T4 concentrations but reduce T3 concentrations
123
Why are T3 concentrations generally not useful in the diagnosis of hypothyroidism?
Up to 90% dogs will maintain their T3 concentrations within the RI
124
What testing seems to be reccommended in the following scenarios in the diagnosis of canine hypothyroidism?\ a) Clinical hypoTH with a low TT4 b) Clinical hypoTH with a TT4 in lower half of RI
a) Free T4 (ED preferred but not essential) and TSH b) fT4 by ED and TSH +/- TGAA
125
What are the expected thyroid gland changes on AUS with hypothyroidism?
The gland(s) will have reduced echogenicity, and irregular outline and will be small with a less rounded appearance
126
What is the T 1/2 of levothyroxine in dogs?
9 - 15 hours but this does not necessarily reflect the biologic effect of the hormone
127
What is the target for hyperthyroidism treatment in dogs?
Upper half of the RI
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How should myxedema coma be treated?
Administer T4 at 5mcg/kg q12h IV and commence oral supplementation once the patient has stabilised. Resolution of clinical signs should occur within 30 hours.
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Why might hyperpigmentation be seen in dogs with HAC?
The POMC gene is the parent molecule for ACTH and this also codes for alpha-MSH
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What enxyme does the zona glomerulosa lack which means it only secretes mineralocorticoids?
17-alpha-hydroxylase (which is needed to convery pregnenolone/progesterone to 17-OH versions of these hormones.
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What is the typical USG for dogs with HAC?
≤1.018 - 1.020 possible
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What changes to the calcium/phosphorus system can occur in dogs with HAC?
Decreased phosphorus can occur with increased excretion However, calciuresis can also occur and this can results in secondary hyperparathyroidism and hyperphosphataemia
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What percentage of PDH dogs have a visible pituitary mass?
50 - 60%
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How does mitotane work?
It selectively causes lysis of zona fascilulata and zona reticularis although can result in ZG destruction at higher doses.
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Alternative medical treatments to trilostane?
Mitotane Ketoconazole Selegiline (MOAB which will increased D2) Cabergoline (D2 agonist) Retinoic acid (affects genomic receptors involved in the synthesis of POMC) Pasireotide
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Percentage of cats with HAC that will be diabetic?
80-90%
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What dermatologic change has not been reported in cats with HAC compared to dogs?
Calcinosis cutis
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What AUS features can indicate malignancy vs. non-malignancy in incidentalomas?
Ill-defined mineralisation (but not discrete mineralisations) Invasion (vascular or local tissue) Tortous vessels Heterogenous contrast enhacement on CEUS >2cm
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Reccomended approach to incidentaloma monitoring
Repeat AUS q1m for 3m then q3m therafter
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What are the three main aietiologised for feline hyperaldosteronism?
1. Unilateral aldosteronoma 2. Bilateral adenoma 3. Bilateral adrenocortical hyperplasia
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What are the main clinical consequences of feline hyperaldosteronism?
Weakness due to hypokalaemic myopathy Systmic hypertension (in around 85% of cats)
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What are the clinicopathologic features of hyperaldosteronism?
Hypokalaemia Hypertension Increased urinary FE of K+ Hypernatraemia does not occur (pressure naturesis) Increased CK Metabolic alkalosis (results from aldosterone mediated H+ exhange)
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What is the expected change in PRA with hyperaldosteronism?
It should be decreased due to negative feedback. However in secondary hyperaldosteronism it may be increased
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If PRA is not available, what ancillary tests can be used to confirm feline hyperaldosteronism?
Urinary aldosterone:creatinine Fludrocortisone supression test (measure UACR after 4 days of fludrocortisone which should supress UACR by >50% when hyperaldosteronism is due to secondary causes)
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Medical management for hyperaldosteronism
Potassium supplementation (+/- magnesium) Spironolactone Treatment of hypertension This should all be performed prior to surgery
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Which sex steroid can result in HAC signs?
Progestagens
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What histopathologic change is noted in the adrenal glands of dogs with hypoadrenocorticism?
Lympho-plasmacytic adrenalitis with cortical atrophy (auto 21-alpha-hydroxylase antibodies have not been demonstrated in dogs as in humans)
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Breeds predisposed to hypoadrenocorticism?
Leonburgers Pomeranians Grate Danes Bearded collies Standard Poodles Portugese water dogs Springers and cockers NSDTR
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Definition of classical and atypical hypoadrenocorticism?
Classical - MC and GC deficiency Atypical - GC deficiency with normal electrolyte concentrations
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What breeds have a decreased risk of hypoadrenocorticism?
Golden Retrievers Yorkshire Terriers Pit-bulls Lhasa Apso
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8 conditions that can cause pseudohypoadrenocorticism
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What are the components of Zollinger-Ellinson syndrome?
Gastric antral hypertrophy Hyperacidity Ulceration
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Why is gastric stimulation testing effective in gastrinoma?
Ca and secretin stimulate gastrin release from gastrinomas and these responses to do not occur in normal animals
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Predilection site for gastrinoma?
Right limb or body of the pancrease
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Metastatic rate of gastrinoma
0.85
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What weird manifestation of glucagonaoma is there?
Necrolytic migrateory erythema (I think this can resemble superficial necrolytic dermatitis)
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How is a glucagonoma diagnosed?
Imaging - rarely see a mass Glucagon 1.5 - 5x the RI are reported Measurement of arginine, histadine and lysine which may all be reduced in glucagonoma
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What hormones are produced by intestinal carcinoids?
5-HT or kinins
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What test could be performed in dogs with acromegaly where you are not sure if it is pituitary or mammary dependent?
GHRH stimulation test: - 1mcg/kg GHRH will NOT stimulate GH release if it is mammary driven (discriminatory test between these types)