Parathyroid Glands and Calcium Homeostasis

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Questions and Answers

In most species, how many pairs of parathyroid glands are typically present?

  • Two pairs (correct)
  • One pair
  • Four pairs
  • Three pairs

Which of the following chemical types best describes parathyroid hormone (PTH)?

  • Fatty acid derivative
  • Steroid hormone
  • Protein/peptide hormone (correct)
  • Amine hormone

What are the primary cell types found within the parathyroid gland?

  • Follicular and parafollicular cells
  • Basophils and acidophils
  • Chief and oxyphil cells (correct)
  • Alpha and beta cells

What stimulates the release of parathyroid hormone (PTH)?

<p>Decreased blood calcium levels (C)</p> Signup and view all the answers

What is the primary effect of parathyroid hormone (PTH) on phosphate levels in the blood?

<p>Decrease (A)</p> Signup and view all the answers

What is the effect of increased plasma phosphate concentration on ionized calcium?

<p>Decreases the ionized calcium concentration. (C)</p> Signup and view all the answers

Which three organs are primarily involved in the regulation of calcium levels?

<p>Bones, kidneys, and GI tract (B)</p> Signup and view all the answers

What is the role of osteocytes in response to PTH?

<p>Pump calcium from bone fluid to blood. (D)</p> Signup and view all the answers

In the kidneys, what effect does parathyroid hormone (PTH) have on phosphate reabsorption?

<p>Decreases phosphate reabsorption in the proximal convoluted tubules (B)</p> Signup and view all the answers

Which enzyme does parathyroid hormone (PTH) stimulate in the kidneys to activate Vitamin D?

<p>1-alpha-hydroxylase (D)</p> Signup and view all the answers

What is the function of calcitonin?

<p>Decreases bone resorption. (C)</p> Signup and view all the answers

What stimulates the release of calcitonin?

<p>Increased blood calcium levels (C)</p> Signup and view all the answers

Which cells produce calcitonin?

<p>Parafollicular cells (C-cells) in the thyroid gland (B)</p> Signup and view all the answers

What is the primary effect of calcitonin on phosphate?

<p>Movement of phosphate from ECF into bone (B)</p> Signup and view all the answers

Which of the following is a typical finding in primary hyperparathyroidism?

<p>Elevated parathyroid hormone (PTH) (A)</p> Signup and view all the answers

Which of the following most accurately describes the synthesis pathway of PTH?

<p>Preprohormone → Prohormone → Hormone (C)</p> Signup and view all the answers

What is the primary mechanism by which PTH increases serum calcium levels?

<p>Enhancing calcium absorption in the intestines via calcitriol activation (B)</p> Signup and view all the answers

What is the significance of ionized calcium (iCa) in the blood?

<p>It is the biologically active form that is tightly regulated. (C)</p> Signup and view all the answers

What is the effect of PTH on osteoblasts?

<p>PTH binds to osteoblasts and stimulates production of osteoclast-activating factor. (A)</p> Signup and view all the answers

Which of the following best describes the condition known as nutritional secondary hyperparathyroidism (NSHP)?

<p>Elevated PTH levels due to dietary calcium deficiency or imbalanced calcium-to-phosphorus ratio (B)</p> Signup and view all the answers

In hindgut fermenters, how intestinal calcium absorption regulated differently than in other animals?

<p>Calcium absorption is always occurring. (B)</p> Signup and view all the answers

What is the expected urinalysis result of a hindgut fermenter (such as a horse) that is regulating blood Calcium with their urinary loss system?

<p>Chalky white-colored urine (A)</p> Signup and view all the answers

Why is it important to consider calcium homeostasis when internal parasites are suspected as the cause of a prolapse in reptiles?

<p>Because calcium imbalances are frequently ignored during treatment for parasites (B)</p> Signup and view all the answers

Prolonged deficiency of calcium or vitamin D3 is implicated in nutritional secondary hyperparathyroidism due to

<p>Dietary and/or husbandry mismanagement. (D)</p> Signup and view all the answers

Which of the following is a key difference between the actions of calcitonin and parathyroid hormone (PTH)?

<p>Calcitonin decreases bone resorption, while PTH increases it. (A)</p> Signup and view all the answers

For a dog with hypoparathyroidism, which clinical sign would be the most unexpected?

<p>Hypercalcemia (C)</p> Signup and view all the answers

Which of the following statements best describes the role of G-protein coupled receptors in PTH synthesis?

<p>They sense decreasing blood ionized calcium and stimulate PTH release (A)</p> Signup and view all the answers

What is the underlying cause of the cardiac arrhythmias (bradycardia) that can be caused by hypercalcemia during hyperparathyroidism?

<p>Depressed excitability of nervous/cardiac muscle (C)</p> Signup and view all the answers

Why might a patient with advanced kidney disease experience secondary hyperparathyroidism?

<p>Dysfunctional kidneys cannot activate vitamin D, impairing calcium absorption. (A)</p> Signup and view all the answers

Which statement describes an appropriate action to maintain calcium/phosphate homeostasis?

<p>Calcitriol increases absorption of calcium in the GI tract. (B)</p> Signup and view all the answers

After secretion of PTH, what is its half-life?

<p>$5-10$ minutes (A)</p> Signup and view all the answers

Which of the following is a symptom of hypoparathyroidism?

<p>Skeletal deformities (C)</p> Signup and view all the answers

Which of the following is NOT a typical symptom of primary hyperparathyroidism?

<p>Hypocalcemia (A)</p> Signup and view all the answers

What is the role of phosphate in the body?

<p>All of the above (D)</p> Signup and view all the answers

What is the percentage of calcium found in the bone?

<p>99% (B)</p> Signup and view all the answers

What causes Nutritional Secondary hyperparathyroidism?

<p>All of the above (D)</p> Signup and view all the answers

What are the predisposing factors in Nutritional Secondary hyperparathyroidism?

<p>All of the above (D)</p> Signup and view all the answers

In a patient with hypoparathyroidism, which of the following would be seen during diagnosis? Choose the BEST answer

<p>Low ionized calcium (C)</p> Signup and view all the answers

Which factor would cause Gl hormones to stimulate secretion of calcitonin?

<p>Postprandial regulation (C)</p> Signup and view all the answers

Which factor is important to know when thinking about the calcium to phosphate ratio in blood?

<p>If phosphate decreases, the complexed calcium decreases (B)</p> Signup and view all the answers

Which statement about the parathyroid gland is FALSE?

<p>Parathyroid hormone is a steroid hormone (C)</p> Signup and view all the answers

When blood calcium decreases, which of the following does not occur?

<p>Calcium deposition in bone is increased (D)</p> Signup and view all the answers

In a scenario where a patient is experiencing increased blood calcium, and a parathyroidectomy is performed, what would be MOST important to monitor immediately post-op?

<p>Hypocalcemia (C)</p> Signup and view all the answers

Flashcards

Parathyroid Glands

Glands located near the thyroid that produce parathyroid hormone (PTH).

Parathyroid Anatomy

Most species have two pairs of parathyroid glands, but pigs and rats typically have only one pair. The location varies among species.

Parathyroid Cell Types

The two types of parathyroid cells, responsible for hormone production and cellular function, within the glandular tissue.

PTH Secretion

Parathyroid cells are sensitive to changes in ionized calcium levels, which modulate PTH release.

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Parathyroid Function

The parathyroid gland is involved in calcium and phosphate homeostasis.

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Calcium's Roles

Calcium is essential for muscle contraction, nerve cell activity, hormone release, enzyme activation, blood coagulation, membrane stability, and structural integrity of bones and teeth.

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Ionized Calcium (iCa)

The most important pool for physiological control of calcium concentrations in the blood.

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Calcium Regulation

There are three organs and three hormones involved in calcium regulation.

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PTH Actions

PTH effects include increasing calcium and decreasing phosphate concentrations in ECFs.

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Osteoblasts

Cells responsible for forming new bone tissue.

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Osteocytes

Bone cells involved in biomineralization

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PTH on Bone Cells

PTH promotes the transfer of ionized calcium across the osteoblast-osteocyte membrane.

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PTH and Osteoclasts

PTH stimulates the production of osteoclast-activating factor, leading to bone resorption and release of calcium and phosphate into the blood.

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PTH on Kidneys

PTH acts on the distal convoluted tubules to increase calcium reabsorption.

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PTH and Phosphate

PTH acts on the kidneys to decrease renal reabsorption of phosphate.

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PTH and Vitamin D

PTH stimulates the kidney enzyme 1-alfa-hydroxylase which converts calcidiol to calcitriol

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PTH on Kidneys

PTH enhances calcium and phosphate reabsorption in the kidneys and affects bone metabolism.

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Calcitriol Function

Calcitriol helps animals absorb enough calcium from their diet to support normal bone structure.

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PTH Control

PTH secretion is controlled by ionized calcium concentration in the blood.

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Calcitonin

The hormone produced by parafollicular cells in the thyroid gland, which lowers blood calcium levels.

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Calcitonin Release

Increase in blood [iCa] stimulates calcitonin release, counterbalancing the effects of PTH.

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Calcitonin Actions

Calcitonin decreases the movement of calcium from bone by decreasing the action of osteocytes and inhibiting osteoclasts.

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Calcitonin Effects

Calcitonin increases movement of phosphate from ECF into bone and renal excretion of calcium and phosphate.

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Calcitonin Regulation

Secretion regulated by calcium concentration, GI hormones

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Hyperparathyroidism

A condition caused by excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal chief cells of the parathyroid gland.

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Hyperparathyroidism Symptoms

Symptoms are related to hypercalcemia and affect kidneys, GI, and neuromuscular systems.

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Nutritional Hyperparathyroidism

Nutritional secondary hyperparathyroidism in horses is caused by excessive mobilization of calcium from the skeleton due to dietary calcium deficiency.

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NSHP Factors

Causes include low dietary calcium & Vit D3, inverted Ca:P ratio, lack of UV-B light and unappropriated temperatures

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Hypoparathyroidism

A condition caused by absolute or relative deficiency of parathyroid hormone (PTH).

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Hypoparathyroidism Symptoms

Hypoparathyroidism symptoms are related to calcium deficiency and involves muscle weakness, cramps, seizures, neuromuscular and neurologic signs

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Study Notes

Learning Objectives

  • Locate the parathyroid glands and describe their macro and microanatomy
  • Understand the relevance of calcium and phosphate to maintain body homeostasis
  • Understand the synthesis, regulation, and transport of PTH
  • Describe the effects of parathyroid hormones on target tissues/organs
  • Understand the role of PTH on calcitriol activation and its importance on calcium metabolism
  • Understand the relationship between PTH and calcitonin and their effects on calcium and phosphate homeostasis
  • Understand the symptoms of the main pathologies related to parathyroid hormones, including hyperparathyroidism/secondary nutritional hyperparathyroidism, and hypoparathyroidism

Terminology and Abbreviations

  • AMP stands for Adenosine Monophosphate
  • ATP stands for Adenosine Triphosphate.
  • ECF refers to extra cellular fluid
  • GI refers to gastrointestinal
  • iCa is Ionized calcium
  • PTH stands for parathyroid hormone

Parathyroid Gland - Anatomy

  • Most species have two pairs of parathyroid glands
  • Pigs and rats have only one pair of parathyroid glands
  • The location of parathyroid glands varies between species
  • Parathyroid glands are usually at the poles of the two lobes of the thyroid glands

Chemical Structure of Hormones: Protein and Peptide Hormones

  • Protein and peptide hormones comprise the majority of hormones
  • Examples of protein and peptide hormones include insulin, ACTH, PTH, CCK, LH, FSH, and TSH
  • Protein and peptide hormones are synthesized as inactive molecules in the ER, known as pre-prohormones
  • They are cleaved in the Golgi apparatus to form prohormones
  • The hormones are packaged into secretory granules awaiting secretion

Parathyroid Gland Cell Types

  • There are two types of parathyroid cells in the glandular tissue: chief cells and oxyphil cells
  • Chief cells produce PTH (Parathormone or Parathyroid hormone)
  • The function of oxyphil cells is unknown; these cells are larger than chief cells and possess oxidative and hydrolytic enzyme activity

PTH Synthesis

  • Parathyroid cells are very sensitive to a decline in blood ionized calcium [iCa]
  • Calcium-sensing receptors on the gland membrane surface are involved in PTH synthesis
  • G-Protein coupled receptors (cAMP-PKA-gene transcription)
  • A decrease in blood [iCa] (hypocalcemia) stimulates PTH release
  • Normal or increased [iCa] in blood (hypercalcemia) inhibits PTH release
  • Prepro-PTH is synthesized in rER and then cleaved to pro-PTH
  • The "pro" portion is removed in the Golgi apparatus, and the resulting PTH is secreted by exocytosis
  • PTH is metabolized by the liver and the kidneys with a half-life of 5-10 minutes

Parathyroid Gland – Calcium and Phosphate

  • The main gland involved in the Calcium (Ca2+) & Phosphate (PO4) homeostasis
  • Calcium and phosphate ions play a major role in physiological homeostasis
  • Phosphate (PO4) acts as a buffer system
  • Phosphate is a composition of the cell membrane and intracellular components, nucleic acid, Adenosine Triphosphate (ATP), and Adenosine Monophosphate (AMP)
  • 85% of phosphate is found in bones, 14% intracellularly, and 1% in ECF
  • Calcium is required for muscle contraction and nerve cell activity
  • Calcium facilitates the release of hormones by exocytosis and enables the activation of several enzymes
  • Calcium is involved in blood coagulation
  • Calcium ensures the maintenance of membrane stability
  • Calcium provides structural integrity to bones and teeth
  • 99% of calcium is found in bones, less than 1% intracellularly, and 0.1% in ECF

Pool of Calcium

  • 99% of calcium is found in bones in the form of hydroxyapatite crystals, which contain calcium, phosphate, and water
  • Less than 1% of calcium is intracellular and bound to proteins within the ER or mitochondria, and increased intracellular calcium concentrations indicate increased cell activity
  • 0.1% of calcium is found in ECF, which is the interstitial fluid and blood
  • 50% of calcium is ionized (iCa), which is biologically active and precisely regulated
  • 40% of calcium is bound to proteins, mainly albumin
  • 10% of calcium is combined with other anions
  • iCa is the most important pool for physiological control of calcium concentrations in the blood

Calcium: Phosphate Ratio

  • High levels of plasma phosphate concentration means a rise in the fraction of Ca2+ that is complexed (bound) increases which decreases the ionized Ca2+ concentration
  • If the plasma phosphate concentration decreases -> the complexed Ca2+ decreases ionized Ca2+ increases
  • Maintaining the blood Ca:P ratio is essential for homeostasis

Calcium-Phosphate Metabolism

  • Calcium level regulation involves controlling the movement of calcium between the extracellular fluid (ECF) and three organs:
    • Bones
    • Kidneys
    • GI tract
  • Three hormones are involved in this process:
    • PTH (parathyroid hormone)
    • Active Vitamin D (Calcitriol – steroid-like molecule)
    • Calcitonin (thyroid hormone – parafollicular cells/C-cells)

PTH Actions

  • The net effect of PTH is to increase calcium and decrease phosphate concentrations in ECFs
  • PTH has a direct effect on bone and kidney metabolism of calcium
  • PTH has an indirect effect on GI metabolism of calcium (absorption)
  • This indirect effect is conducted via calcitriol

Bones

  • Osteoblasts are responsible for the formation of new bone tissue, which entails bone developing and remodeling
  • Osteocytes enable biomineralization (local mineral deposition at the bone matrix) and are differentiated from osteoblasts (mesenchymal stem cells)
  • Osteoclasts degrade bone tissue and are differentiated from monocytes (hematopoietic stem cells)

PTH Actions – Two Direct Effects on Bone

  • PTH promotes the transfer of iCa across the osteoblast-osteocyte membrane
  • Osteocytes pump iCa from the fluids within bone canaliculi into the extracellular fluid, then into the blood
  • PTH binds to receptors on bone osteoblast cells and stimulates the production of osteoclast-activating factor
  • PTH causes activation of nearby osteoclasts
  • PTH moves toward the bone and begins to digest the organic matrix, resulting in bone resorption
  • PTH releases iCa and PO43- into the blood

PTH Actions - Direct Effects on Kidneys

  • PTH acts on the distal convoluted tubules, increasing reabsorption of calcium
  • PTH acts on the proximal convoluted tubules, decreasing renal reabsorption of phosphate
  • PTH acts on Vitamin D activation by the kidneys
  • Vitamin D must be transformed by the liver and kidneys to become biologically activated
  • PTH stimulates the kidney enzyme 1-alfa-hydroxylase, which converts calcidiol 25(OH)D to calcitriol 1,25(OH)2D
  • Vitamin D becomes an active hormone under PTH action on renal cells
  • Calcitriol increases absorption of calcium by the GI tract and enhances the effects of PTH on bone metabolism of calcium

Vitamin D Metabolism

  • In the presence of UV light, Vitamin D3 (Cholecalciferol) is made in the skin
  • Vitamin D3 can be found in oily fish, egg yolks, and fortified food
  • Vitamin D2 (Ergocalciferol) is found in fortified foods, salmon, mushrooms, and egg yolks
  • The liver converts Vitamin D3 and D2 to 25-hydroxyvitamin D (Calcidiol)
  • The kidney converts 25-hydroxyvitamin D to 1,25 dihydroxyvitamin D (Calcitriol) via 1-alfa-hydroxylase
  • The product is the biologically active form.
  • Due to its lipid nature, calcitriol is carried in plasma by transcalciferin, which is produced in the liver

PTH Actions - Indirect Effect on GI

  • Calcitriol stimulates the active transport of dietary calcium across the intestinal epithelium
  • Without calcitriol, most animals cannot acquire enough calcium from their diet to support normal bone structure
  • An animal can regulate iCa entering the blood from its diet by regulating calcitriol
  • However, hindgut fermenters (horses and rabbits) are exceptions to this rule
  • These animals have intestinal mechanisms to absorb calcium all the time
  • Furthermore, they regulate blood Ca2+ by increasing/decreasing urinary loss
  • These animals can present chalky white-colored urine

PTH Regulation

  • PTH secretion is mainly controlled by free (ionized) calcium concentration in the blood
  • A decrease in [iCa] stimulates PTH secretion
  • An increase in [iCa] inhibits PTH secretion

Calcitonin

  • Calcitonin is produced by parafollicular cells or C-cells in the thyroid gland
  • These cells are scattered throughout the body of the thyroid gland, among the follicles
  • Calcitonin is synthesized as a protein hormone
  • An increase in blood [iCa] stimulates calcitonin release
  • Calcitonin counterbalances the effects of PTH

Calcitonin Actions

  • Calcitonin reduces the movement of calcium from the bone to the ECF
    • It moves against the bone calcium pool (decreasing the action of osteocytes behind the osteoblast-osteocyte barrier)
  • Calcitonin decreases bone resorption through a direct inhibitory effect on osteoclasts
  • Calcitonin increases movement of phosphate from ECF into bone
  • Calcitonin increases renal excretion of calcium and phosphate

Calcitonin Regulation

  • Calcitonin secretion is regulated by calcium concentration in the blood
  • Increased [iCa] stimulates calcitonin secretion
  • GI hormones also stimulate the secretion of calcitonin

Calcium Metabolism

  • PTH increases reabsorption in the kidneys, increases absorption in the GI tract, and increases mobilization from the bones
  • Calcitonin increases excretion in the kidneys and the storage from the bones

Hyperparathyroidism

  • Primary Hyperparathyroidism entails excessive synthesis and secretion of parathyroid hormone (PTH) by abnormal chief cells of the parathyroid gland, or parathyroid adenoma
  • It leads to persistent hypercalcemia, which means negative feedback control is lost, then secretion of PTH is not suppressed by high calcium levels
  • Symptoms related to hypercalcemia mainly affect the kidneys, GI tract, and neuromuscular system
    • These symptoms can include Polydipsia and Polyuria, which decreases the ability of the kidneys to respond to antidiuretic hormone (ADH)
    • Calciuria can result in urolithiasis and secondary urinary tract infection (UTI)
    • Hyperparathyroidism depresses the excitability of the central and peripheral nervous systems, decreases GI smooth muscle excitability, and decreases cell membrane permeability of muscles
    • Cardiac arrhythmias (bradycardia) can be caused by hypercalcemia
  • A diagnosis can be determined via urinalysis (crystalluria – calcium crystals) and serum biochemistry, which will indicate both total and ionized calcium levels are elevated
  • Secondary hyperparathyroidism in horses (Nutritional secondary hyperparathyroidism (NSH), also known big-head disease), is caused by excessive mobilization of calcium from the skeleton under the influence of parathyroid hormone
  • The condition occurs due to:
    • a dietary calcium deficiency
    • excess levels of phosphorus
    • an inverted calcium-to-phosphorus ratio in the total diet
    • high levels of oxalates in forages, which interfere with digestion and absorption of calcium
  • Nutritional metabolic bone disease in reptiles and amphibians (NMBD) includes: Nutritional secondary hyperparathyroidism (NSHP)
  • NSHP predisposing factors:
    • low dietary calcium and vitamin D3
    • inverted Ca:P ratio
    • lack of UV-B light exposure
    • inappropriate temperature gradient
  • This can be caused by unappropriated diet and excessive production of parathyroid hormone (PTH) from the parathyroid gland in response to hypocalcemia
  • Secondary hyperparathyroidism also occurs because of dietary and/or husbandry mismanagement, with the most implicated factors being prolonged deficiency of dietary calcium or vitamin D3, imbalance of the calcium-phosphorus ratio in the diet (usually an excess of phosphorus), and inadequate exposure to ultraviolet (UVB) radiation in diurnal animals

Hypoparathyroidism

  • Hypoparathyroidism is an absolute or relative deficiency of parathyroid hormone (PTH)
  • It can be idiopathic, which is most common, and caused by autoimmune destruction of the parathyroid or other causes, like trauma, agenesis, or surgical destruction of PT gland
  • Inappropriately low levels of PTH classically result in hypocalcemia, decreased calcitriol, and hyperphosphatemia
  • Symptoms may range from mild to severe, and are related to calcium deficiency, including muscle weakness, cramps, seizures, neuromuscular and neurologic signs, hypotension, decreased heart contractility, and skeletal deformities
  • Diagnosis occurs via serum biochemistry: low total and ionized calcium, undetectable PTH concentrations, and hyperphosphatemia is common

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