Chapter 10 - Endocrine/metabolic Flashcards
Which is the major, metabolically active thyroid hormone?
T3
Name three things that inhibit TSH secretion
Stress Steroids Dopamine Thyroid hormones Somatostatin
Thyrotropin-releasing hormone stimulates release of TSH and which other hormone?
Prolactin
Which keratinocyte genes are stimulated by T3?
Wound-healing
Myxoedema is due to increased deposition of what?
Mucin
Why do hypothyroid dogs have increased triglyceride levels?
Decreased plasma clearance
What % of euthyroid dogs can have a one-off low T4?
20%
What % of hypothyroid dogs have antithyroglobulin antibodies?
50%
Antithyroglobulin antibodies are more common in which dog breeds?
Great Danes, Borzois, Irish Setters, Old English sheepdogs and Dobermans
Can you see antithyroglobulin antibodies in euthyroid dogs with other endocrine diseases?
Yes
In which zone of the adrenal gland are glucocorticoids produced?
Zona fasciculata
Why do glucocorticoids cause thinning and fragility of the dermis?
They inhibit fibroblast proliferation, collagen and ground substance proliferation
What % of dogs have pituitary dependent hyperadrenocorticism?
80-85%
Which anatomical sites are most commonly affected by calcinosis cutis?
Dorsal neck, rump, axillae and groin
What % of cats have pituitary dependent hyperadrenocorticism?
~80%
Where is growth hormone (somatotropin) produced?
Adenohypophysis (anterior pituitary)
What regulates growth hormone secretion?
GHRH (growth hormone releasing hormone) and somatostatin (produced by hypothalamus)
What impairs insulin-like growth factor-1?
Steroids and oestrogens
Name the anatomical sites most obviously affected by myxoedema with acromegaly
Face and extremities
Do you get hyper- or hypotrichosis with increased growth hormone secretion?
Hypertrichosis
In GSDs, is pituitary dwarfism an autosomal recessive or dominant trait?
Autosomal recessive
Which hormones are deficient in GSDs with pituitary dwarfism?
Growth hormone, TSH, prolactin, gonadotropins
At what age to clinical signs become apparent in GSDs with pituitary dwarfism?
2-3 months
Which zone of the adrenal gland produces androgens and progesterone?
Zona reticularis
Which clinical sign is highly suggestive of hyperoestrogenism in male dogs?
Linear preputial erythema
In which breeds has Alopecia X been reported?
Pomeranians Alaskan Malamutes Chows Keeshonds Min/toy poodles Samoyeds Schipperkes
What are the initial signs of Alopecia X?
Dull, dry coat and loss of primary hairs
Which anatomical sites are spared in Alopecia X?
Head and extremities
Name three cutaneous clinical signs that can be seen with diabetes mellitus in dogs and cats
Bacterial pyoderma
Seborrhoea
Thin and hypotonic skin
Alopecia
What are the differentials for necrolytic migratory erythema/SND?
PF
SLE
Zinc deficiency/responsive dermatosis
Generic dog food dermatosis
What make up the ‘red, white and blue’ layers on histopathology of necrolytic migratory erythema/SND
Red = diffuse parakeratosis White = vacuolaton of keratinocytes and oedema Blue = basal cells hyperplasia superficial interstitial to lichenoid infiltrate
What are the histopathological findings of the skin of dogs with hyperadrenocorticism?
- Thin epidermal and follicular epithelium, which can be 1-3 nucleated cell layers thick.
- If calcinosis cutis is present, the epidermis is frequently hyperplastic and can be ulcerated.
- Orthokeratotic hyperkeratosis; marked follicular keratosis, sometimes with comedone formation.
- Thin dermis.
- Hair follicles that are frequently in telogen or kenogen.
- Sebaceous gland atrophy and/or sebaceous melanosis.
- Dysplastic follicles
- Variable hyperpigmentation.
Mineralization of the external root sheath can be seen in normal old dogs and dogs of which breed?
Poodles
Which treatments have reportedly been effective at reducing/resolving calcinosis cutis in dogs?
DMSO (Tolon et al. 2018)
Minocycline (Jang et al. 2013, Cho et al. 2017)
Tetracycline (Harvima et al. 2020)
Can the hepatopathy, hypoaminoacidemia, and aminoaciduria associated with hepatocutaneous syndrome be seen without NME/SND signs?
Yes - they may appear after diagnosis.
The presence or absence of skin lesions at time of diagnosis does not appear to affect survival (Loftus et al. 2022)
In the study by Loftus et al. (2022), which treatments for HCS were associated with increased survival?
At least two IV amino acid infusions
A home cooked, high protein diet
Supplements targeting depleted AAs essential for collagen synthesis (lysine, proline), supporting the urea cycle (arginine and ornithine), and for glutathione synthesis(cysteine, glycine, and SAMe) are recommended but were not found to significantly affect survival.
Plasma levels of which amino acids are low in dogs with HCS?
Alanine, glutamine, glycine, lysine, proline, threonine, 1-methylhistidine and cystathionine
What is the commonly reported signalment for HCS/SND?
Older, male, small breed dogs e.g. cocker spaniel, Shetland sheepdog, Shih Tzu, and West Highland white terrier
An excess of which amino acid in urine can help to diagnosis HCS?
Lysine and methionine
How does trilostaine treat HAC?
The drug is a competitive inhibitor of the 3β-hydroxysteroiddehydrogenase / isomerase system required to synthesise cortisol, aldosterone, and androstenedione.
Which breeds are more commonly affected by HAC?
Miniature poodle, dachshund, Irish setter, bassett hound, miniature schnauzer and toy poodle (Hoffman et al. 2018) Bichon frise (O'Neill et al. 2016)
Which breeds are least likely to develop HAC?
Dobermann pinscher, rottweiler, collie and great Dane
(Hoffman et al. 2018)
Border collie and Labrador (O’Neill et al. 2016)
In healthy individuals, corticotropin-releasing hormone (CRH), produced by the _________, is the principal simulant of episodic secretion of adrenocorticotropic hormone (ACTH) by the pars ____ which stimulates glucocorticoid production and secretion from the adrenal glands
Hypothalamus
Distalis
True or false; In addition to the pars distalis, ACTH is also produced by the B cells of the pars intermedia where its secretion is regulated by tonic dopaminergic inhibition
True
Have bilateral adrenal tumours been reported in dogs with HAC?
Yes, uncommonly
Which hormone, other than cortisol, can be secreted by adrenal tumours?
17-OH-progesterone
What are the most common non-cutaneous clinical signs of HAC in dogs?
- PU/PD 82–91%
- PP 46–57%
- Abdominal enlargement 67–73%
- Hepatomegaly 50–67%
- Systemic hypertension 31–86%
What are the common biochemical changes in dogs with HAC?
- Increased ALP 76–100% and ALT 80–95%
- Hypercholesterolaemia 73–90%
- Decreased urea concentration 34–56%
- Hyperglycaemia 20–57%
What changes can be seen on urinalysis with HAC?
- SG <1.015
- Proteinuria 62-80%
Which two non-cutaneous diseases have been reported in association with HAC in dogs?
DM 10.5–13.6%
Gall bladder mucocele up to 23%
When interpreting a LDDST, there are several patterns that can be seen at 3-4 and 8 hrs; how do you interpret them?
- Lack of suppression
- Escape
- Partial suppression
- Inverse
- Complete suppression
- Lack of suppression = HAC likely
- Escape = cannot interpret
- Partial suppression = HAC possible, look at other findings
- Inverse = cannot interpret
- Complete suppression = HAC unlikely
The ACTH stimulation test assesses adrenocortical reserve. Serum cortisol concentrations are measured before and at ____ min after administration of a pharmacological dose of synthetic ACTH (also known as tetracosactide or cosyntropin)
60–90
What dose of tetracosactide should be used for ACTH stim testing, 1 or 5 ug/kg?
5 ug/kg
Which test should be used to diagnose iatrogenic HAC?
ACTH stim
How do you interpret ACTH stim testing?
- Post stim cortisol WRI
- Post stim cortisol above RI
- Absent to weak stimulation
- Post stim cortisol WRI - possible HAC, consider other tests
- Post stim cortisol above RI - HAC likely
- Absent to weak stimulation - consider exogenous steroids or cortisol-precursors e.g. 17-OH-progesterone
How can LDDST be used to assess if HAC is pituitary or adrenal dependent?
To confirm PDH:
- Suppression >50% at 3- or 8-h post-dexamethasone administration
- 3-h post-dexamethasone cortisol concentration below the laboratory cut-off
Can HAC present with skin disease only?
Yes - typically non-pruritic, truncal alopecia and/or thin skin and pyoderma (can also present with limb/pedal pruritus!)
Can histopathology be used to determine between iatrogenic and endogenous calcinosis cutis in dogs?
No
What does this image show? Skin biopsy from a dog.
Calcinosis cutis - diffuse mineral deposition from superficial to mid dermis
Seckerdieck and Mueller (2018); what % of dogs with recurrent pyoderma had hypoT4 and HAC?
HypoT4 = 11% HAC = 6%
What are the cutaneous signs of hypothyroidism in cats?
- Unkempt appearance
- Increased shedding
- Dandruff
- Hair thinning
Replacement therapy after hypophysectomy consists of life-long administration of ________ and ________, and temporary administration of _________, a synthetic vasopressin analogue
Glucocorticoids and thyroxine
Desmopressin
Radiotherapy can be used to treat which type of HAC?
Pituitary dependent
Should trilostane be given once or twice daily?
Twice daily, it lasts <12 hours
Trilostane treatment can take months to improve hair/skin signs with HAC; why canthey appear worse initially?
Due to shedding of telogen hairs and dry skin scales
Mitotane causes adrenal necrosis; when might you use this drug over trilostane in dogs?
In cases of adrenocortical carcinomas where cell destruction is preferable (trilostane does not stop tumour growth)
The melanocortin-2 receptor (MC2R) is the receptor for ____ and is expressed only in the adrenal cortex
ACTH
In healthy euthyroid dogs, how long does 16 weeks of levothyroxine supplementation affect T4 and TSH levels?
Up to one week after cessation of treatment
What are the clinical signs of feline HAC?
- PU/PD 81%
- Pot belly 61%
- PP 60%
- Skin atrophy 59%
- Muscle wasting 47%
- Weight loss 47%
- Lethargy 41%
- Alopecia 37%
- Skin fragility 32%
- Unkempt coat 30%
Less commonly weakness/plantigrade stance, weight gain and hepatomegaly
How often is DM seen with HAC in cats?
77%
Why are increased ALP levels less commonly seen in HAC in cats compared to dogs?
Cats lack a glucocorticoid-induced isoenzyme of ALP; increases in ALP activity occur secondarily to diabetes mellitus or other concurrent diseases.
Methimazole can cause what cutaneous signs in cats?
- Most common = severe pruritus and excoriations of the head and neck
- Non-pruritic alopecia with erythema, scales and perilesional yellowish crusts = pyogranulomatous mural folliculitis
Cutaneous ADR has been reported in a dog on levothyroxine supplements, what was suspected to be the cause of the reactions?
The inactive ingredients magnesium stearate and/or polyvinylpyrrolidone as the dog reacted to two products containing these ingredients but not to a third levothyroxine supplement that did not
What biochemical changes are seen in dogs with hypothyroidism?
Hypercholesterolaemia - 75% Hypertriglyceridaemia Hyperlipidaemia Increased aspartate aminotransferase (AST) Increased alanine aminotransferase (ALT) Increased alkaline phosphatase (ALP) Increased creatine kinase (CK) Increased fructosamine
What haematological changes are seen in dogs with hypothyroidism?
Mild normochromic, normocytic, non-regenerative anaemia is the only consistent haematological abnormality, occurring in up to 50% of dogs with hypothyroidism
What % of T4 is ubound (free T4)?
1%
Can thyroglobulin autoantibodies falsely elevate free T4?
No - they can falsely elevate TT4
How does size and breed of dog affect T4 levels?
- Smaller dogs have higher baseline T4 levels than larger breed dogs.
- Sight hounds have lower baseline T4 and FT4 levels
Why are thyroglobulin autoantibodies present before clinical signs of hypothyroidism?
Clinical signs of hypothyroidism are seen only after 75% of the gland is destroyed
Hypothyroidism is most common in which breeds of dog?
Dobermans, Schnauzers, Retrievers, Spaniels, Shetland Sheepdogs, Irish Setters, Dachshunds, Hovawart and Giant Schnauzer
What % of hypothyroid dogs can have a normal TSH and low T4?
20-30%
With short term use of 1mg/kg prednisolone in dogs, how are T4 levels affected?
T4 decreased on daily treatment but not on EOD treatment
Where are thyroid hormone receptors and which thyroid hormone do they bind?
Nuclear thyroid hormone receptors (TRs) bind with 10- to 15-fold greater affinity to T3 than T4; they influence gene expression by binding to specific DNA elements as dimers = thyroid response elements (TREs)
Which hormones are produced in the adenohypophysis (anterior pituitary)?
TSH ACTH FSH LH GH Prolactin
Which hormones are produced by the hypothalamus?
GHRH CRH (corticotropin RH) TRH Gonadotropin RH ADH Oxytocin Dopamine (inhibits prolactin)
The chromophil cells of the adenohypophysis (anterior pituitary) produce which hormones?
Acidophils = somatotropin (GH), prolactin Basophils = FSH, LH, TSH
The chromophobes of the adenohypophysis (anterior pituitary) produce which hormones?
MSH
POMC ( = Corticotopin and beta-lipotropin)
True or false; the TSH receptor is a member of the large superfamily of G-protein-coupled seven-transmembrane receptors
True
How is TSH release controlled?
Free, unbound T3 acts on the anterior pituitary to reduce the release of TSH secretion
What effect do TSH, T3 and T4 have on the hair growth cycle?
They initiate and prolong anagen
What effect do oestrogens have on the hair growth cycle?
They induce premature catagen and telogen and inhibit onset of anagen
What are the primary mechanisms of action of thyroid hormones?
- Stimulation of cytoplasmic protein synthesis
2 Increased tissue oxygen consumption
Thought to be initiated by binding of thyroid hormones to nuclear chromatin and augmentation of gene transcription
Depletion of thyroid hormones results in impaired B and T cell function along with which other WBC?
Neutrophils
Goitrous and nongoitrous congential hypothyroidism have been reported in which breeds of dog?
Bullmastif, GSD and Scottish deerhound
Name causes of secondary hypothyroidism
- Failure of adenohypophysis to secrete TRH - congenital form in giant schnauzers
- Pituitary dwarfism
- Pituitary neoplasia
- GC administration or endogenous hypercortisolism
How are sebaceous glands affected in hypothyroidism?
Sebaceous gland atrophy with reduced sebum excretion (thyroid hormones influence serum fatty acid concentrations and SG function)
Which cutaneous sign is associated with iatrogenic HAC in cats (and not endogenous HAC)?
Medial curling of the pinnae
In pituitary dwarfism, what lesion do most dogs have in the pituitary gland?
A variably sized cyst (Rathke cleft cyst) resulting in varying degrees of pituitary insufficiency
Immunodeficient dwarfism has been reported in an inbred colony of which breed of dog?
Weimeraners (GH deficiency and congenital absence of the thymic cortex)
What are the clinical signs of pituitary dwarfism?
- Fails to grow well after 2-3 months
- Shorter hair coat with no primary hairs (or restricted to face/extremities)
- Hair is soft and woolly and easily epilated (secondary hairs)
- Bilaterally symmetrical alopecia develops especially in areas of friction
- Followed by hyperpigmentation of exposed skin
- Skin becomes thin, hypotonic and scaly
What is a characteristic metabolic abnormality of GH-deficient dogs?
IV injection of regular insulin causes severe, prolonged hypoglycaemia
What can affect GH levels?
Decreased GH: - Hypothyroidism - Hypercortisolism Increased GH: - Pseudopregnancy - Progestogen therapy - Sex hormone imbalances
Can baseline GH levels be used to diagnose GH deficiency?
No - need stimulation testing (e.g. GHRH, clonidine, xylazine)
What are the non-cutaneous clinical signs of acromegaly?
- Inspiratory stridor (ST hyperplasia)
- Increased body size (notably paws and skull)
- Abdominal enlargement
- PU/PD/PP
- Fatigue
- Panting
- Prognathism (projecting lower jaw or chin)
- Widening of interdontal spaces
- Galactorrhea
- Cardiomegaly and failure
What are the cutaneous clinical signs of acromegaly?
- Thickened, myxoedematous skin with excessive folds
- Hypertrichosis
- Thick, hard claws
Skin changes seen in dogs > cats
What is the most common cause of acromegaly in dogs?
Progestational stimulation (intact females)
Which organs/cells produce oestrogens?
- Ovarian follicles
- Zona reticularis of adrenal gland
- Sertoli and interstitial cells of the testes
Can also be made through peripheral aromatization of androgens
What effect do oestrogens have on sebaceous glands?
Reduce size and sebum production
What are the clinical signs of hyperoestrogenism?
Females: - Bilaterally symmetrical alopecia - Enlargement of the vulva and nipples - Oestrus cycle abnormalities Males: - Bilaterally symmetrical alopecia - Enlarged nipples - Decreased libido and spermatogenesis - Possible atrophy of non-neoplastic testicle - Enlarged prostate/prostatitis - Linear preputial erythema - Macular melanosis (rapid onset cf lentigines)
What is the difference in dex dose for LDDST in cats cf dogs?
Cats = 0.1 mg/kg Dogs = 0.01 mg/kg
How do you diagnose acromegaly?
Measure insulin-like growth factor (IGF-1)
Feline growth hormone
Advanced imaging of the brain
Organomegaly
What happens to the hair coat in Schipperkes with alopecia X before hair loss?
Lightening of the coat
What is secondary and what is tertiary acquired central hypothyroidism?
Secondary form arises from a defect in the pituitary and tertiary form arises from a defect in the hypothalamus
What allele is more prevalent in hypothyroid dogs of predisposed breeds?
DLA-DQA1*00101
Which medications influence the concentration of tT4?
Prednisone/prednisolone Phenobarbital Potassium bromide Potentiated sulphonamides Propranolol Clomipramine Aspirin Ketoprofen Carprofen Deracoxib
Is fT4 influenced by medication as well as tT4?
Concentrations of free T4 are potentially lowered by certain drug therapies particularly including glucocorticoids, long-term anticonvulsants and trimethoprim-potentiated sulphonamides
At what age is congenital hypothyroidism usually reported in cats? How do these cats look?
Kittens 2-4 months Disproportionate dwarfism (cretinism)
Describe the physical examination findings and clinicopathological abnormalities in cats with acquired primary hypothyroidism.
- Palpable goiter, unkempt/dull haircoat, hair thinning/hypotrichosis, overweight/obesity, scales/dry skin
- Bradycardia (<150bpm)
- Azotemia, decreased urine specific gravity (<1.035), anaemia, hypercholesterolemia, increased CPK, increased SDMA
What is the most sensitive and specific test to diagnose acquired (and iatrogenic) hypothyroidism in cats?
- TSH
- Serum TSH concentration is the most specific diagnostic test for hypothyroidism: low serum T4 and fT4 concentrations commonly develop in cats with nonthyroidal illness, but high values for TSH have not been reported in these sick, euthyroid cats
What comorbidities are commonly associated with hyperthyroidism in cats?
CKD Thyrotoxic heart disease Hypertension Retinopathy GI disease/malabsorption/cobalamin deficiency (B12) Insulin resistance
What are the treatment options for hyperthyroidism in cats?
Radioactive iodine
Methimazole or carbimazole
Surgical thyroidectomy
Iodine-restricted food
Which dermatological changes can be seen with HAC in cats?
- Non-pruritic alopecia affecting the ventrum and flanks
- Thinning of skin
- Bruising
- Skin fragility (due to steroid-related suppression of fibroblast activity)
- Recurrent cutaneous abscess formation
- Change in hair colour (e.g. black to brown/red)
