Hypo- and Hyperparathyroidism
Parathyroid polydipsia/polyuria in cats
(due to calcium inhibition of ADH-dependent resorption of NaCl and to mineralization of renal tissue) --> Cats are often not PU/PD --> Calcium uroliths may be observed in dogs, but not in cats
Clinical signs are mainly due to the hypercalcemia and can include:
- depression - anorexia - vomiting - constipation - polydipsia/polyuria - incontinence - azotemia - weakness - exercise intolerance - diffuse bone disease - most often folding fractures from osteolysis - selected ECG abnormalities (cardiac arrhythmias) - seizures - muscle weakness and twitching - blood calcium values of greater than 16 mg/dl can result in acute renal failure (due to vasoconstriction).
PTH indirectly stimulates intestinal calcium absorption through the mediation of
1,25-dihydroxy vitamin D
PT consists of densely packed cells of 2 types:
1. Chief cells (Principal Cells) - These are the predominant cell type and they manufacture Parathyroid Hormone (PTH). 2. Oxyphil cells - These cells are fewer in number and they are larger than chief cells. They have an unknown function and they may represent degenerate chief cells.
how does Juvenile hyperPTism affect the dogs
Affected dogs will have stunted growth, increased urination and drinking, and muscle weakness
Renal 2ary HyperPT: what can develop due to marrow fibrosis as a consequence of cortical bone remodeling encroaching upon the marrow cavity?
Anemia - PTH also increases the fragility of RBCs making them more susceptible to lysis. All bones are affected, but the lesions in dogs are most striking in the facial bones and mandible aka "renal rickets" or "rubber-jaw"
"rubber jaw"
As bone mineral is reabsorbed under the influence of PTH, fibrous tissue may be deposited in an attempt to "strengthen" the bone weakened by loss of mineral. The most marked gross changes in bone structure occur in young dogs. The bones may become more flexible due to loss of mineral
The dominant regulator of PTH synthesis and release is plasma _______ concentration
Ca++
Hypoparathyroidism Clin Path
Complete blood count and biochemical profile to rule out other possible medical conditions. Only significant abnormality is severe hypocalcemia and, in most dogs and cats, hyperphosphatemia. The only other condition which causes decreased calcium levels and increased phosphate levels is renal failure, in which case elevated creatine and BUN levels should also be present.
Tx of the acute phase of primary hypoparathyroidism
Directed at control of hypocalcemia tetany - IV administration of 10% calcium gluconate - Once the clinical signs of hypocalcemia are controlled, calcium gluconate should be administered SubQ every 6 to 8 hours until oral calcium and vitamin D therapy becomes effective - The acute phase treatment should be discontinued once the serum calcium concentration is greater than 8 mg/dl
Tx of the Maintenance Phase of Primary Hypoparathyroism
Directed at maintaining blood calcium concentration within the low normal range through the daily administration of vitamin D and calcium supplements. Vitamin D supplementation is necessary to assist with the absorption of dietary calcium from the gastrointestinal tract
Dx of Hypoparathyroidism
Documentation of persistent hypocalcemia and ruling out other causes of hypocalcemia Definitive diagnosis is made by measuring the concentration of PTH Most patients have a PTH concentration below normal, or in the mid-normal to low-normal range - A low or low-normal PTH concentration in the presence of hypocalcemia is inappropriate
Primary Hyperparathyroidism
Due to chief cell neoplasia (adenoma or carcinoma) or hyperplasia. There is autonomous PTH secretion, with hypercalcemia, hypophosphatemia and isosthenuria.
Primary HyperPTism Tx: For what reason must the animal be monitored closely after surgery and given calcium if the level becomes too low?
Either surgical removal or chemical ablation of the gland will cause a sudden decrease in the amount of parathyroid hormone, resulting in a corresponding sudden drop in the blood calcium level. - Since the remaining parathyroid glands are normal, they will have been suppressed by hypercalcemia. It usually requires a few days (or longer) for the remaining parathyroid glands to regain function
Overall Canine Signalment for Hypoparathyroidism
Female dogs are more commonly diagnosed than males The average age at diagnosis is 5 years. There appears to be no breed predisposition; however, there may be an increased incidence in the toy poodle, miniature schnauzer, Labrador retriever, and German shepherd
Regulatory feedback mechanism -
Hypocalcium stimulates and hypercalcium inhibits PTH release • A unique calcium receptor within the parathyroid cell plasma membrane senses changes in the extracellular fluid concentration of Ca++ -- Maximum secretion of PTH occurs at plasma Ca++ below 3.5 mg/dl -- At Ca++ above 5.5 mg/dl, PTH secretion is maximally inhibited
Signalment of Hypoparathyroidism
Immune-mediated hypoparathyroiditis can occur at any age, but the average age at occurrence in dogs is about 5 years and in cats about 2 to 3 years The majority of the reported cases in the dog have been in females while male cats are more commonly affected
interpretation of PTH measurements - inc ve dec level
Increased PTH indicates primary or secondary hyperparathyroidism Decreased PTH indicates: - Primary hypoparathyroidism - Hypercalcemia of malignancy may cause decreased blood PTH activity (pseudohyperparathyroidism)
what condition is believed to be inherited as an autosomal recessive trait and is characterized by abnormally increased activity of the PT glands.
Juvenile Hyperparathyroidism
parathyroid gland
Like most domestic species, dogs and cats have two pairs of parathyroid glands generally located at the poles of the two lobes of the thyroid gland and they are located on or in the capsule of the thyroid.
Histo of Renal 2ary HyperPTism
Low-power microscopic view of the kidney of a one-year-old dog. The cortex is fibrotic, the glomeruli are sclerotic, there are scattered chronic inflammatory cell infiltrates, and the arteries are thickened. Tubules are often dilated and filled with pink casts and give an appearance of "thyroidization"
more Histo of Renal 2ary HyperPTism
Low-power microscopic view of the thyroid and parathyroid gland of the same dog. The thyroid and parathyroid are normal, but the parathyroid is four to five times the normal size.
regulation of PTH secretion
NOT under control of hypothalamus not AP controlled by Plasma Ca++ level by -ve feedback mechanism i.e.: ^plasma Ca++ -> dec PTH secretion
Renal Secondary HyperPTism - who is usually affected
Occurs especially in dogs, but also in cats, with chronic renal failure
juvenile hyperPTism on clin path & radiograph
On clinical pathology you will see hypophosphatemia with increased fractional clearance of phosphorus, elevated plasma PTH, hypercalcemia decreased bone density
Symptoms for hypoparathyroidism
Onset of signs tends to be abrupt and severe and to occur more frequently during exercise, excitement, and stress. The symptoms tend to be episodic in occurrence with episodes of clinical hypocalcemia interspersed with relatively normal periods, particularly early on in the course of the disease
Overall Feline Signalment for Hypoparathyroidism
Other than those affected by immune-mediated hypoparathyroidism, cats are typically 12 to 13 years of age at diagnosis. As the most common cause of hypoparathyroidism is due to the accidental removal of the parathyroid gland during removal of the thyroid gland, the mean age of affected cats is the same as those who are diagnosed with hyperthyroidism. This is seen more in mixed breed cats, males are slightly over-represented
Hyperparathyroidism includes the following classifications: Primary, Juvenile, secondary\
Primary hyperparathyroidism due to glandular hyperplasia or neoplasia. Juvenile hyperparathyroidism due to an inherited autosomal recessive trait that is characterized by abnormally increased activity of the parathyroid glands. Secondary hyperparathyroidism which occurs in response to low blood ionized calcium levels most often associated with chronic renal failure.
hypoparathyroidism on EKG
Prolongation of the duration of action potential Increased duration of the S-T and Q-T segments Deep, wide T waves Prolonged Q-T intervals Bradycardia
18-month old Golden Retriever mix male dog with chronic renal failure. The maxilla were firm and enlarged and the jaw bone was slightly pliable and not as rigid as a normal jaw bone.
Renal 2ary HyperPTism - showing thickening of the maxillary region and teeth that are loose and seem to "float" in the gums.
Signalment of Primary Hyperparathyroidism
Reported in both dogs and cats (rare) In dogs, the mean age of onset is 10 years, but ranges from 5 to 15 years old • Equal frequency in male and female dogs. • Appears to affect large breed dogs more often -- it is familial in Keeshonds and inherited in German Shepherd dogs (Juvenile Hyperparathyrodism). -- Other breeds include Golden retrievers, Labrador retrievers and Doberman pinschers Affected cats are middle aged and older • More common in females than in males • Siamese cats may be predisposed • PTH concentrations are elevated in about 50% of cases
where has juvenile HyperPTism been detected
The condition has been identified in the German Shepherd - Parents of affected dogs should not be bred as they are carriers of the disorder. An autosomal-dominant genetic mutation with age-related penetrance has been identified in Keeshond
Diagnosis & of Primary Hyperparathyroidism
The key to diagnosing PHPT using PTH assay results is the recognition of an inappropriate PTH concentration in the presence of hypercalcemia. The parathyroid glands can be visualized with ultrasonography. - Experienced veterinary radiologists can successfully identify 90% to 95% of parathyroid adenomas. Most adenomas in dogs are 4 to 9 mm in diameter and are fairly easy to visualize. However, not all parathyroid nodules are obvious, and the subjectivity of ultrasonography as a diagnostic tool must be taken into account. A more definitive diagnosis is by identifying a parathyroid adenoma/hyperplasia by surgical exploration and biopsy.
A kitten with secondary hyperparathyroidism of nutritional origin
The kitten was reluctant to walk due to bone pain and there was lateral deviation of paws
what is the Px from treating a Primary hyperPT patient
The prognosis for long-term survival after parathyroidectomy is good Parathyroid tumors are usually benign so excision is usually curative Multiple parathyroid tumors are rare, but have been reported and they are typically present concurrently, so they are often removed at the same surgery
Iatrogenic/Secondary Hypoparathyroidism etiology
This is the most common cause of hypoparathyroidism in cats and is usually caused by the accidental damage or removal of the parathyroid glands during surgery to remove the thyroid gland
Transient Hypoparathyroidism etiology
This may develop due to severe magnesium depletion which suppresses secretion and activity of the parathyroid hormone. Magnesium is also required for activation of vitamin D in the kidneys
Incidence of Primary Hyperparathyroidism
Tumors of the parathyroid glands are uncommon; however they can produce serious problems in dogs and cats if the tumors secrete excessive, unregulated amounts of PTH. Excessive PTH causes elevated levels of blood calcium which can have toxic effects on the kidneys, the intestines, and the brain.
other Tx options for Primary HyperPTism
Ultrasound-guided ethanol ablation is a minimally invasive alternative to surgical incision. - requires general anesthesia to ensure that there is no movement during the ablation - The hair on the neck is clipped and the skin is scrubbed similar to surgical preparation
how is the ultrasound-guided ablation done for primary hyperPT treatment
Using ultrasound imaging, the needle is guided into the parathyroid tumor and ethanol is injected into the parathyroid tumor. The ethanol is toxic to the parathyroid tumor and causes rapid necrosis, destroying the tumor. There is a possibility that the ethanol will not destroy the entire tumor and repeat administration would be needed
____________ production is impaired due to renal insufficiency of Renal Secondary hyperPTism
Vitamin D - The reduced formation of Vitamin D results in impaired calcium absorption via the gut and impairs the mobilization of calcium from the bone in response to PTH The PT glands undergo hyperplasia with increased release of PTH and further bone resorption to maintain calcium homeostasis.
____________ inhibits PTH gene expression, providing another level of feedback control of PTH
Vitamin D3
The symptoms associated with hypoparathyroidism are the result of
abnormally low blood calcium level, most notably the effects on the neuromuscular system
The synthesis of parathormone (PTH) by the ____ ______ is similar to that of other protein hormones.
chief cells
Secondary hyperparathyroidism which occurs in response to low blood ionized calcium levels most often associated with:
chronic renal failure - Nutritional secondary hyperparathyroidism is usually caused by dietary mineral imbalances, such as diets that are low in calcium or vitamin D, or diets containing an excessive amount of phosphorus, such as feeding an all-meat diet.
where is the PTH stimulated from during Renal Secondary HyperPTism
from low ionized calcium due to excess phosphate and impaired renal resorption of calcium
clinical path findings of primary hyperparathyroidism
hypercalcemia hypophosphatemia - Phosphate may be low, normal, or even high if the animal has a decreased GFR due to hypercalcemia-induced renal damage. isosthenuria. Other parameters may be affected depending upon the amount of hypercalcemic induced damage to tissues and organs.
PTH acts on kidney to
increase calcium reabsorption (distal tubule), inhibit reaborption of phosphate (proximal convoluted tubule) and to increase conversion of 25-hydroxy vitamin D to 1,25-dihydroxy vitamin D • Increases urinary excretion of K+, HCO3-, Na+, cAMP and amino acids • Decreases urinary excretion of Mg++, ammonia and acids
The overall action of PTH is to
increase plasma Ca++ levels and decrease plasma phosphate levels
Hyperparathyroidism
increased secretion of PTH from the parathyroid glands
Prognosis of Primary Hypoparathyroidism
long-term prognosis depends upon the owner's commitment to the animal and is excellent with proper supplementation and regular monitoring of serum calcium
what is the diagnostic test of choice for the Dx of both Hyperparathyroidism and Hypoparathyroidism
measurement of PTH - Measured in 1.0 ml of serum by RIA - Normal values will differ depending upon the laboratory running the procedure.
during Renal 2ary HyperPT resorption of the bone occurs by
osteoclastic resorption and fibrous replacement and woven bone trabeculae that fail to mineralize are produced excessively
Serum ____________ concentration has no direct regulatory influence on synthesis and release of PTH other than its effect upon Ca/P ratio.
phosphorus
The increase in PTH leads to bone demineralization, which can be viewed as a trade-off of ?
progressive renal disease In this instance, bone demineralization is the price paid for the maintenance of normal calcium and phosphorus homeostasis Clinically, the bones of the head undergo pronounced softening, enlargement, and radiographically detectable rarefaction
Primary Hypoparathyroidism etiology - canine vs feline
rare in dogs and even less common in cats Primary hypoparathyroidism: - Most canine and, less commonly feline, cases of primary hypoparathyroidism are often the result of immune-mediated destruction (immune-mediated parathyroiditis) of the parathyroid glands, or trauma to the neck. - In cats, most cases of primary hypoparathyroidism are idiopathic atrophy/wasting of the parathyroid gland.
juvenile hyperPTism Treatment
removal of 1-3 of the PT glands
surgical Treatment of Primary Hyperparathyroidism
removal of the abnormal or cancerous gland. Surgical excision is done through a midline incision in the neck, just behind the throat. Veterinary surgeons explore both sides of the neck, checking all parathyroid glands. Usually a parathyroid tumor can be excised directly from the thyroid gland, sparing the thyroid gland and leaving the remaining parathyroid glands in place.
Secondary Hyperparatyroidism - 2 etiologies
renal & nutritional
2ary Renal HyperPTism X-ray lateral
reveals very uniformly thin bone. The outer edges of the jaw bone should be nearly as dense as the teeth
2ary Renal HyperPTism X-ray VD
showing very little bone density especially in the upper maxillary bone and "floating" teeth
PTH acts directly on the bones to
stimulate Ca++ and phosphate (effect on bone requires vitamin D3)
Renal 2ary HyperPT Microscopically
the lesions are those of fibrous osteodystrophy and osteomalacia
what are the MC symptoms for hypoPT
• Muscle tremors or twitching • Wobbly, drunken or stiff gain, or loss of coordination • Mental dullness, Seizures • Lethargy/weakness • Loss of appetite - Cardiac abnormalities include paroxysmal tacharrhythmias, bradycardia, muffled heart sounds and weak femoral pulses in dogs and bradycardia in cats. -- Small lenticular cataracts -- Growling, facial rubbing, twitching whiskers • Panting • Hypothermia
