Primary hypoparathyroidism in dogs and cats: Physiology, clinical signs, and initial diagnostic tests - Veterinary Medicine
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Primary hypoparathyroidism in dogs and cats: Physiology, clinical signs, and initial diagnostic tests
To understand this rare condition, you must be familiar with the physiology of calcium regulation. The net effect of a low PTH concentration is hypocalcemia, and the severity of the clinical signs and the timing of their onset are a reflection of the duration and magnitude of the hypocalcemia.


Vitamin D metabolism, including calcitriol

Long-term maintenance of the serum calcium concentration is controlled primarily by calcitriol and its ability to increase intestinal calcium absorption.9 Vitamin D's regulatory role is especially important in managing primary hypoparathyroidism. Multiple forms of vitamin D exist, including vitamin D1 (calciferol), vitamin D2 (ergocalciferol), and vitamin D3 (any of the analogues containing the word cholecalciferol).14 The major source of cholecalciferol in animals is the diet, primarily tissues from animals and fish liver oil; smaller amounts are produced in the skin.4 In the skin, 7-dehydrocholesterol is converted into cholecalciferol with exposure to ultraviolet light (UVB, wavelength 290 to 320 nm); this conversion is more important in people, since other mammals contain only small amounts of 7-dehydrocholesterol in their skin.7,11

Figure 2. Steps in the conversion of vitamin D to its most active form, calcitriol.
Production of a biologically active vitamin D analogue requires multiple steps (Figure 2). Cholecalciferol undergoes several modifications, with the final product, calcitriol, being substantially more potent than its precursors.7 The first conversion occurs within the liver, where cholecalciferol is hydroxylated by a complex interaction of enzymes and cofactors into 25-hydroxycholecalciferol4,11,14 ; this conversion is regulated by negative feedback of 25-hydroxycholecalciferol.7 Unconverted cholecalciferol may be stored in the liver for months.7 In the proximal tubules of the kidneys, 25-hydroxycholecalciferol is converted into the most active form, calcitriol, by the enzyme 1-alpha-hydroxylase, under PTH regulation.4,7,11,13 The presence of sufficient amounts of calcium (directly and indirectly by PTH) or phosphorus (directly) in the plasma inhibits this conversion in the kidneys.5,7 In the absence of PTH, the 25-hydroxycholecalciferol is converted instead to 24,25-dihydroxycholecalciferol, which is biologically inactive.4,7

Calcitriol's primary function is to increase intestinal absorption of calcium and phosphorus.7 In people, about one-third of the dietary calcium is absorbed and the remainder is passed in the feces.7 Calcitriol increases the production of a calcium-binding protein within intestinal epithelial cells.4,7 The rate of intestinal calcium absorption is directly related to the amount of calcium-binding protein present within the enterocytes.7 Calcium-binding protein acts to transport calcium across the brush border into the enterocyte.4,7 Through calcium-binding protein's effect, calcitriol can cause an increase in intestinal calcium absorption within two days, and this effect can last for several weeks.1,7 In addition to its intestinal effects, calcitriol also affects the kidneys and bone. Calcitriol weakly promotes calcium and phosphate retention by the kidneys7 ; supplementation with a vitamin D analogue may also increase serum phosphorus concentrations.15 In small amounts, calcitriol promotes calcification of bone, but in larger amounts, it promotes absorption of bone.7 The effects of PTH on bone are blunted in calcitriol's absence.4,7


Hypomagnesemia decreases both the secretion and activity of PTH, so it can contribute to hypocalcemia.8,16 A decreased PTH concentration also results in hypomagnesemia through decreased release from bone and decreased reabsorption from renal tubules.17 Additionally, vitamin D activation in the kidneys requires magnesium.


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