Endocrine Flashcards
Describe blood supply to the adrenal gland and how the right and left glands differ.
Arterial: 20-30 branches from the renal, arota, cranial abdominal and phenicoabdominal aa.
Venous: single branch
Left: renal v.
Right: vena cava
Describe the embryonic development of the adrenal gland?
Medulla: neural crest - essentially a symphathetic post synaptic ganglion
Cortex: mesdodermal cells from the genital ridges
Describe the layers of the adrenal gland and what they produce.
Zona glomerulosa - mineralocorticoids
zona fasciculata - glucocorticoids
zona reticularis - androgens (testosterone, androstenedione converted to estrogens and DHT in periperheral tissues)
Location of the left and right adrenal glands?
Left: Poas minor, transverse process L2
Right ventral to T13
Describe how corticosteroids and mineralocorticoids are transported in the blood.
Protein bound.
Cortisol: 75% transcortin, 10% albumin, 10% unbound
Aldosterone: 10% tanscortin, 50% albumin, 40% unbound
Pregnancy decreased transcortin
What is the half life of cortisol and aldosterone?
Cortisol: 60 minutes
Aldosterone: 20minutes
Both metabolized via liver
Effects of glucocorticoids (9)?
Stimulate: Inhibit:
hepatic gluconeogensis glucose uptake in perhiperal tissues
lipolysis protein synthesis
protein catabolism vasopressin (synthetic ADH)
increase GFR immune system
gastric acid secreation
Describe RAS and how related to aldosterone secretion?
How are catecholamines made?
In chromaffin cells:
Tyrosine and phenylalinine ⇒ dopa ⇒ dopamine ⇒ norepinephrine (20%) ⇒ epinephrine (80% excreated when symphathetic activation)
Metabolize by liver and kidney with 10 minute activity
What is the width of a normal adrenal gland on US?
Large breed dogs: 7.5mm
Small breed dogs: 6.0mm - (75% sens, 94% specific for PDH , Cho JVetSci 2011)
US criteria for an adrenal mass?
Maximum width > 1.5cm
Loses typical kidney bean shape
Asymetric in size
What characteristics of a functional cortisol secreating tumor?
Large size poss
Poss invasion/compression of vessels
CS of hyperadrenocorticism
Contralateral gland small, if not doesnt rule out
When is an ACTH stim test recommend?
Diagnose iatrogenic Cushings, Addisons or for trilostane testing.
Most specific test but not very sensitive - 20% in normal range, 20-30% in borderline range.
Name 3 tests for HAC testing.
Name 3 tests that can potentially differeniate PDH from adrenal.
HAC testing: LDDST, ACTH stim, UCCR
Differenitating: LDDST, HDDST, Baseling endogenous ACTH
Post-operative complications of cortisol secreating adrenal tumors
Cortisol induced immunosupression
Impaired wound healing
systemic hypertension
hypercoagulation
post-op Addisons
Pancreatitis
What is the MOA trilostane?
Competitive inhibitor of 3-ß-hydroxysteroid dehydrogenase (mediates adrenal conversion of pregnenolone to 17alpha-hydrooxyprogesterone = cortisol precursor)
Proposed mechanism of hyperadrenocortisim hypertension?
How to treat?
- Increased activation of angiotensin I
- Increased vascular responsiveness to cathecholamines
- decreased conc. of vasodilator prostaglandins
Treat with ACE inhibitors ⇒ decrease vasoconstriction and aldosterone
MOA phenoxybenazamine and recommended dose.
Side effects?
Alpha 2 Antagonist (aka receptor block)
Start at 0.5mg/kg and increase upto 2.5mg/kg or until blood pressure normal
GI, syncope, hypotension, lethargy/weakness
What anesthetic drugs should be avoided with suspected pheochromocytomas?
Potentiate catecholamines
arrhythmogenic
anticholenergics
affect apha receptors
Describe the flank approach to the adrenal gland
For unilateral uncomplicated masses:
10cm paracostal incision caudal to last rib - ventrally from the epaixal muscles
Grid incision - external and internal oblique, transverse abdominus
Ventrally retract kidney
May need to transect/retract the caudal most rib
% frequencies of vena cava thromus in adrenal cortical tumors and in pheos?
Cortical: 11-16%
Pheos: 35-55%
What does acute occulsion of the supra-renal vena cava result in in normal dogs?
60% decrease CO
renal dysfunction - temp or permanant
death
What are the reported mortalitly rate for adrenal tumors?
Pheos specifically?
all tumors 19-60%
pheos only - 18-47%
With current anesthetic procols more like 20%
Outcome of bilateral adrenalectomy for HAC in cats?
High postop mortality: 3/8 died within 5 weeks, 2 more died from adrenal insuffiencty at 3 and 6 months.
Barrera 2013 JAVMA: what were risk factors associated with adrenalectomy?
Poor short-term (<14 day) surviaval:
Intraop: caval invasion, extent of thrombus (most important,), pheo, transfusion
Post-op: DIC, pancreatitis, renal failure, hypotension, hypoxemia
Normal size of the thryoid gland dog vs cat?
Dog: 5cm x 1.5cm x 0.5cm
Cat: 1cm x 4mm x 1-2mm
Describe location of the right gland vs. the left
Left: more caudal, rings 3-8, in contact with the esophagus (NOT carotid sheath)
Right: caudal cricoid to 5th ring, in contact with carotid sheath (common carotid, internal jugular, vagosympathethic trunk) and tracheal duct.
Vascular supply of the thyroid
- cranial carotid a. = br. of common carotid a.
- Caudal thyroid a. = br. of brachycephalic a. = absent in most cats
- Cr. and cd. thyroid v. = internal jugular v. (caudal larynx and caudal neck)
- Some dogs middle segment left thyroid vessel near midline trachea that drains into the brachycephalic v.
Lymphatic drainage of thyroid glands?
Left: left tracheal duct
Right: right lymphatic duct
Drain to cr. and caudal deep cervical lymph nodes or retropharyngeal lymph node
Thyroid innervation?
thyroid n. (runs along cr. thyroid a.) = br. cranial laryngeal n. = branch of vagal n.
What is the freqency of ectopic parathyroid tissue in the dog and in the cat?
Dog: 3-6% (found in thymus)
Cat: 35-50% (found histologically)
Describe thyroid hormone synthesis
Thyroid gland produces thyroglobulin (glycoprotien containing iodotyrosines) - stored in follicular lumen
Iodine actively transported into follicular cell
Iodine oxidized and organificaiton occurs in the lumen
Thyroglobulin hydrolyzed into thyroxine (T4) and triodothyronine (T3) which is released into the blood
Thyroid hormones are largely protein bound. Less than 1% is free (metabolically active) and the rest is a resovior.
How is the secreation and metabolic activity of T4 and T3 different?
T4 is the major secratory product but T3 has several times the metabolic activity. Only 20% T3 made in the cells. The rest is from monodeiodination of T4 in peripheral cells.
How is throid hormone regulated?
Extrathyroidal: TSH (inhibited by free thyroid hormone) also modulated by TRH (thyroid releasing hormone)
Intrathyroidal??
Explain the actions of parathyroid hormone?
Secreated by Cheif cells = Increase Ca and decrease phosphorus
- Bone: Increased BOTH Ca and Phos absorption
- Kidney:
- Decrease Ca excreation, Increase phos secreation (greater than bone absorption).
- Vitamin D to calciriol (1,25 -dihydroxycholecalciferol)
- Increases absorption Ca and phosphorus in the intestine
What does Calcitonin do and what secreates it?
Secreated by C cells (parafolicular cells of the thyroid)
Prevent post prandial hypercalcemia = decrease bone resportion but no effect on kidneys or intestine.
What is the 1/2 life of parathyroid hormone?
3-5 minutes
What is the metastatic rate of thyroid carcinomas in cats?
71%
What percent of hyperthyroid cats have bilateral involement?
70-91%
Hyperfuncitonal ectopic tissue is found in what percent of hyperthyroid cats?
9-23%
What is apathetic hyperthyroidism and what percent of cats present with this?
Decreased appetite and lethargic
14%
What is the estimated prevalence of pre-exsisting renal disease in hyperthyroid cats?
40%
What percent of hyperthyroid cats have hypokalemia and what are possible causes?
Hypokalemia 32%
Causes:
- loss through vomiting, diarrhea, polyuria, anorxia
- thyrotoxicosis ⇒ increased sens. to catecholamines and thyroid hormone causes K to move from extracellular to intracellular
What is the MOA of methimazole?
inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to iodine (I2), hypoiodous acid (HOI), enzyme linked hypoiodate (EOI) facilitating iodine’s addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4)
What is the radionucleotide used in scintigraphy? Where is it trapped? Is it affected by methimazole?
Technetium 99m (pertechnetate)
Salivary glands, thyroid and gastric mucosa - normal have 1:1 ratio uptake in salivary:thyroid
All normal tissue should be atrophied so ANY scintigraphic thyroid activity should be interpreted as cancerous tissue
No effect by methimazole
What are the 4 techniques for thyroidectomy?
- Extracapsular technique - loose parathyroids
- Modified extracapular technique
- Modified intracapsular technique
- Intracapsular technique
With autotransplantation of the parathyroid, how long does it take to funciton and what percent of cats require post-op calcium supplemenation with bilateral thyroparathyroidectomy?
7-21 days
87% do not require supplemenation, without median duration of hypocalcemia is 71 days (range 17-84 days).
What are options for treatment of acute hypocalcemia?
- IV 10% calcium gluconate 0.25-1.5ml/kg over 20-30min
- 5-15 mg/kg/hr CRI 10% calcium gluconate
- 10ml calcium gluconate in 250ml saline: give 60ml/kg/day
What is the recurrence rate of hyperthyroidism in cats with bilateral thyroidectomy?
5-11% within 2-3 years
For thyroid carcinoma (marginal thyroidectomy and radiation) in cats, what is the survival time and what percent developed hypothyroidism?
10-41 months
57% develop hypothyroidism
(6/8 treated with only high dose radiation did not develop clinical hypothyroidism and became euthyroid and survived 6-78m)
What side effects of methimazole?
- GI signs
- hepatopathy
- hematologic changes ( increased eios and lymps, decreased WBCs and platelets), agranulocytosis
Percent of dogs with malignant tumors, percent benign found on necropsy?
90% malignant
30-50% found on histo
What is the metastatic rate of thyroid carcinoma? and what is the most common lymph node?
Up to 40% at diagnosis, up to 80% in lifetime (medulary carcinomas potentially lower rate)
medial retropharyngeal
Percent of canine thyroid tumors that are hyperthyroid or hypothyroid?
Hyperthyroid 10% - do not get renal insufficiently like dogs
Hypothyroid 30%
% canine thyroid tumors that are bilateral?
30-60%
(cats 70%)
What are potential uses of sintigraphy related to canine thyroid tumors?
- ID metastatic disease: specific but not sensative
- Helpful to determine the dose required
- Can help to determine response to I131 but only if use a radionucleotide that is incorporated into the organic thyroid hormone (AKA not pertechnetate)
What is the MST for thyroid carcinoma if mobile, invasive or no treatment?
Mobile 3 years
Fixed 6-12 moths
Untreated 3 months
What is the metastatic rate of thyroid carcinoma related to size?
<23cm^3 = 14%
23-100cm^3 = 74%
>100cm^3 = 100%
Bilateral tumors are 16x more likely to metastasize
What survival times with radiation for thyroid carcinoma?
Non-resectable tumors: MST 24.5.
Progression free: 80% at 1yr, 72% at 3 years
Clinpath changes associated with hypothyroidism?
Normocytic, normochromic anemia
hypercholesterolemia
What are the four stages of thyroiditis?
- Subclinical thyroiditis: no CS, normal T4/3, normal TSH, postive autoantibodies tyroglobulin
- Subclinical hypothyroidism: no CS, normal T4/3, decreased TSH, postive autoantibodies tyroglobulin
- Overt hypothyroidism: CS, decreased T4/3, decreased TSH, postive autoantibodies tyroglobulin
- Noninflammatory atrophic hypothyroidism: CS, decreased T4/3, decreased TSH, NEGATIVE autoantibodies tyroglobulin
What are the cardiovascular effects of hypothyroidism?
Decreased myocardial contractility, vascular volume
Increased SVR
Atherosclerosis
What are 3 systems effected by hypothyroidism?
- Cardiac - decreased CO
- Coagulation - VonWillebrands (factor VIII related antigen)
- Wound healing and increased risk infection
What dog and cat breed is at risk for primary hyperparathyroidism?
Keeshound - OR 50.7 - autosomal dominant trait
Siamese cats
How can primary hyperparathyroidism be differeniated from renal?
Increased total Ca and PTH = renal or Primary
Renal
- Must be azotemic
- >94% have a normal or decreased ionized calcium
- Increased phos = renal, decreased - primary
What are methods of intraop detection of parathyroid glands?
- Rapid chemiluminescent assay - decrease <50% still gland present - not sens
- intraop methylene blue - 3mg/kg IV = heniz body anemia and ARF (not recommeded)
- Removal of 1 thyroid-parathyroid complex
What percent of primary hyperparathryoid dogs develop hypocalcemia post-op and when should treatment be institued?
33%
- TCa <8mg/dL
- ICa <0.8mmol/L
- Clinical signs
What is the dose of calcitriol for hypocalemia maintainence?
20-30 nanograms/kg/day divided for 3-4 days, then 5-15 nanograms/kg/day divided.
