1 : en07a.jpg
2 : en07aa02.jpg
3 : en07aa02.jpg
4 : en07aa10.jpg
5 : en07aa40.jpg
6 : en07ab10.jpg
7 : en07ab40.jpg
Read-Only Case Details Reviewed: Feb 2013



MARCH 2016



Signalment (JPC #1697323): An 11-year-old German shepherd dog


HISTORY: Incidental finding


HISTOPATHOLOGIC DESCRIPTION (Slide a): Parathyroid gland: Expanding and compressing the surrounding parathyroid parenchyma, there is a partially encapsulated, 5 x 7mm, densely cellular neoplasm composed of polygonal cells arranged in cords which often palisade around small caliber blood vessels (pseudorosettes), supported by a fine fibrovascular stroma. Neoplastic cells have indistinct cell borders, scant amounts of finely granular, eosinophilic cytoplasm, and round, often antibasilar nuclei with finely stippled chromatin and 1-2 indistinct basophilic nucleoli. Mitotic figures average 1 per 10 HPF.


MORPHOLOGIC DIAGNOSIS: Parathyroid gland: Adenoma, German shepherd dog, canine.


Signalment (JPC #1877305): An 11-year-old German shepherd dog


HISTORY: This dog was in chronic renal failure.


HISTOPATHOLOGIC DESCRIPTION (Slide b): Parathyroid gland: Minimally compressing the adjacent thyroid gland are multiple hyperplastic parathyroid glands that are enlarged 2-3 times normal and are composed of a uniform population of densely packed hyperplastic chief cells arranged in nests and cords, supported by a fine fibrovascular stroma which extend to the glandular capsule. Chief cells have indistinct cell borders with moderate amounts of pale eosinophilic cytoplasm with occasional distinct vacuoles. Mitotic figures are rare.


Thyroid gland: No significant lesions


Trachea: Focally extensively there is mineralization of the tracheal cartilage (old age change).


MORPHOLOGIC DIAGNOSIS: Parathyroid gland, multiple: Hyperplasia, diffuse, moderate, German shepherd dog, canine.


ETIOLOGIC DIAGNOSIS: Secondary hyperparathyroidism


·      The parathyroid glands are of endodermal origin and are derived from the 3rd and 4th pharyngeal pouches

·      The glands contain:

o   Chief cells: Single purpose cells, produce parathyroid hormone (PTH). The majority of chief cells are inactive in healthy animals

o   Oxyphil cells: Do not have an active role in biosynthesis of PTH, purpose unknown

o   Transitional oxyphil cells: Have cytoplasmic characteristic of both chief and oxyphil cells, represent a transition of chief cells to oxyphil cells, and do not have an active role in biosynthesis of PTH. Purpose is unknown

·      Primary hyperparathyroidism

o   Focal (nodular) or diffuse hyperplasia: increase in functioning chief cells, resulting in the secretion of excess amounts of parathyroid hormone (PTH)

·      Secondary hyperparathyroidism results from increased production of PTH secondary to nutritional deficiencies or chronic renal disease

·      Persistently elevated PTH results in fibrous osteodystrophy



·      Primary hyperparathyroidism:

o   Due to functional parathyroid adenomas, carcinomas or primary parathyroid hyperplasia (nodular or diffuse); described in German Shepherd puppies

o   All secrete excess PTH, resulting in persistent hypercalcemia

·      Nutritional secondary hyperparathyroidism:

o   Common in horses (bran disease), dogs & cats fed meat-only or offal, some primates, goats on high concentrate diets, birds, reptiles, and pigs fed unsupplemented grain rations

o   Induced by:

§  Diets low in calcium (results in osteoporosis and less severe fibrous osteodystrophy)

§  Diets high in phosphorus with normal or low calcium (more severe fibrous osteodystrophy)

§  Diets with excessive oxalate content

§  Inadequate vitamin D3 (more severe fibrous osteodystrophy)

o   All of the above cause hypocalcemia, resulting in parathyroid stimulation and PTH secretion

o   With chronicity, stimulated chief cells undergo hypertrophy and eventually hyperplasia

·      Renal secondary hyperparathyroidism (renal osteodystrophy):

o   Decreased number of functional nephrons in chronic renal failure:

§  GFR <25% of normal > phosphorus retention > hyperphosphatemia > increased formation of hydroxyapatite crystals (mass law) > hypocalcemia > increased secretion of PTH > chief cell hypertrophy and hyperplasia (most important mechanism) Decreased number of cells with 1-α-hydroxylase activity > decreased active vitamin D (1,25-hydroxycholecalciferol) > decreased intestinal and renal absorption of calcium > hypocalcemia > increased secretion of PTH > chief cell hypertrophy and hyperplasia

§  Decreased GFR à metabolic acidosisà ↑iCaà ↓serum Caà PTH

o   Decreased calcitriol in CKD causes increased production of PTH by causing chief cell hyperplasia

o   Serum FGF23 increases early in process, which decreases renal 1-α-hydroxylase activity, before the cells producing 1-α-hydroxylase have actually decrease in number (FGF23 also acts in the parathyroid gland where it decreases secretion of PTH

o   Increased PTH stimulates increased 1-α-hydroxylase in attempt to maintain normal calcitriol (active vitamin D levels)

·      Neoplasm of parathyroid gland

o   Functional adenoma or carcinoma will cause primary hyperparathyroidism

o   Adenoma: older dogs and cats

1.    Single/unilateral parathyroid gland enlargement in Chief cell adenoma

·      PTH increases blood calcium levels through 3 mechanisms:

o   Bone resorption via increased osteoclast activity (direct)

o   With chronic hyperparathyroidism, reabsorption of bone through osteoclastic activity can result in fibrous osteodystrophy of mandible/maxilla (“rubber jaw”) or osteoporosis of skull

§  Increased reabsorption of calcium in the distal convoluted tubules and decreased reabsorption of phosphorus in the proximal convoluted tubules (direct)

§  Increased absorption of calcium from the intestine by regulating hydroxylation of 25-hydroxycholecalciferol to 1, 25-dihydroxycholecalciferol (active Vitamin D) by 1-α-hydroxylase in the kidney (indirect)

·      Metastatic and dystrophic mineralization incorporating the hydroxyapatite crystal in multiple tissues occurs

o   Mass Law: Total Ca x inorganic P (expressed in mg/dL) = >70 often results in metastatic mineralization of tissues (lungs and kidneys)



·      Primary hyperparathyroidism:

o   Increased parathyroid hormone (PTH)

o   Hypercalcemia

o   Hypophosphatemia

o   Elevated alkaline phosphatase (bone resorption)

·      Nutritional secondary hyperparathyroidism:

o   Increased PTH

o   Normocalcemia or hypocalcemia

o   Variable phosphorus (depends on underlying dietary cause)

o   Weakness, anorexia, polydipsia, polyuria, depression, constipation

o   Clinical signs of fibrous osteodystrophy include lameness and pathologic fractures

·      Renal secondary hyperparathyroidism:

o   Signs of kidney failure predominate: Increased BUN, creatinine and hyperphosphatemia, nonregenerative anemia (end-stage renal failure and decreased erythropoietin production)

o   Low serum bicarbonate, and hypocalcemia to normocalcemia with increased PTH

o   Clinical signs of fibrous osteodystrophy include lameness and pathologic fractures

·      Enlarged parathyroid glands are rarely palpable, except in the cat



·      Primary hyperparathyroidism:

o   Adenoma: Single enlarged red to light brown parathyroid gland; atrophied remaining glands

o   Carcinoma: Unencapsulated, invasive

·      Nutritional secondary hyperparathyroidism:

o   All parathyroid glands are uniformly enlarged

o   Soft or pliable, sometimes thickened bones, often in maxilla, mandible, and subperiosteal areas of long bones; Bilateral swelling of bones of the head (hyperostosis), especially dogs and horses (big head); loose teeth; increased fractures; osteopenia; detachment of ligaments & tendons

·      Renal secondary hyperparathyroidism:

o   All parathyroid glands are uniformly enlarged

o   Shrunken, pale kidney characteristic of chronic renal disease

o   Calcification of the subpleural intercostal musculature, gastrointestinal mucosa, lung, and vascular subintima

o   Soft or pliable, often in maxilla, mandible, (“rubber jaw”) and subperiosteal areas of long bones; loose teeth; increased fractures; osteopenia; detachment of ligaments & tendons



·      Primary hyperparathyroidism:

o   Nodular hyperplasia: multiple nodules of uniform cellularity, minimal compression, no fibrous encapsulation; both parathyroid gland affected

o   Diffuse hyperplasia: uniform cellularity and cells extend to capsule of the gland

o   Adenomas: Closely packed chief cells often arranged in nests and packets with lightly eosinophilic cytoplasm, antibasilar nuclei, pseudorosettes, delicate fibrovascular stroma, thin fibrous capsule, compression of adjacent parathyroid parenchyma +/- thyroid gland

o   Carcinoma: Larger, invasive, unencapsulated, can metastasize to lymph nodes and lung

·      Nutritional secondary hyperparathyroidism:

o   Hyperplasia and hypertrophy of chief cells will often have narrowing of perivascular spaces with cytoplasmic vacuolation and clearing; poorly demarcated, unencapsulated, no compression of surrounding tissue

·      Neoplasm of parathyroid gland

o   Adenoma: presence of compression rim of parathyroid parenchyma and partial to complete fibrous capsule

o   Carcinoma: larger than adenoma and there is invasion of capsule and adjacent structure, with possible metastasis to draining lymph node

·      Renal secondary hyperparathyroidism:

o   Combined with histologic lesions of chronic renal disease there is hyperplasia and hypertrophy of parathyroid chief cells with narrowing of perivascular spaces, cytoplasmic vacuolation and clearing; poorly demarcated, unencapsulated, no compression of surrounding tissue

o   Mineralization of the subpleural intercostal musculature, gastrointestinal mucosa, lung, and vascular subintima

·      Fibrous osteodystrophy: Osteoclastic resorption, fibrous replacement and failure of mineralization of woven bone



·      Chief cells are immunohistochemically positive for chromogranin A and synaptophysin

·      The appearance and number of affected glands at surgery/necropsy is helpful in distinguishing adenoma from hyperplasia



·      Causes of hypercalcemia:

o   Hyperparathyroidism

o   Acidosis, Addison’s (Hypoadrenocorticism)

o   Renal Failure: in the horse and in young dogs with familial renal disease (e.g. lhasa apso)

o   Vitamin D elevation: Due to calciferol containing rodenticides, hypervitaminosis D, vitamin D glycoside-containing plants (Cestrum sp., Solanum sp., and Trisetum sp.) or granulomatous disease ( macrophage secretion of activated Vitamin D, such as with blastomycosis)

o   Thiazide diuretics

o   Immobilization

o   Osteolytic lesions (e.g.- osteomyelitis)

o   Neoplasia: (CLAP)

§  Carcinoma metastasis to the bone (ie. squamous cell carcinoma in the horse)

§  Lymphoma

§  Apocrine cell adenocarcinoma of the anal sac

o   Plasma cell myeloma

o   Spurious: Hemoconcentration, Hyperproteinemia (including paraproteinemia), and Granulomatous disease



·      Primary and secondary hyperparathyroidism are described in most domestic and exotic species

·      Parathyroid adenoma and nodular hyperplasia associated with CRD reported in nondomestic felids (leopards, tigers, cougars)

·      Nutritional hypocalcemia with secondary hyperthyroidism reported rabbits fed calcium deficient diet



1.    Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:314.

2.    Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1, 6th ed. Philadelphia, PA: Elsevier-Saunders; 2016:61-63,74-80.

3.    Feldman E, Nelson R. Canine and Feline Endocrinology and Reproduction. 3rd ed. Philadelphia, PA: WB Saunders;2003:660-715.

4.    Ferguson DC, Hoenig M. Endocrine system. In: Latimer KS, ed. Duncan and Prasse’s Veterinary Laboratory Medicine Clinical Pathology. 5th ed. Ames, IA:Iowa State University Press; 2003:295-304.

5.    Miller MA. Endocrine System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:703-704.

6.    Pope JP, Steeil J, Ramsay EC, et al. Spontaneous Proliferative and Neoplastic Lesions in Thyroid and Parathyroid Glands of Nondomestic Felids. J Vet Diagn Invest. 2017;29(1):8-13.

7.    Rosol TJ, Grone A. Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier-Saunders; 2016:299-309.

8.    Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed., Ames, IA: Blackwell Publishing Professional;2008:593-638.

Click the slide to view.

Click on image for diagnostic series.

Back | Home | Contact Us | Links | Help |