Parathyroid Gland Pathology Flashcards
3 predominant cell types of parathyroid gland
Chief cells — central round, uniform nuclei; light pink or white cytoplasm, secretory granules
Oxyphil cells — smaller darker nuclei, eosinophilic granular material, less endocrinologically active
Adipocytes
2 major functions of parathyroid hormone released from parathyroid glands
Directly releases calcium from bone
Promotes synthesis of 1,25-dihydroxyvitamin D in kidney (further mobilizes calcium from bone and intestine)
3 major causes of primary hyperparathyroidism
Adenoma (85-95%)
Primary hyperplasia (5-10%)
Parathyroid carcinoma (1%)
Parathyroid adenomas are benign neoplasms of parathyroid ______ or ______ cells. They are typically solitary and can be surrounded by a rim of normal parathyroid tissue
Chief; oxyphil
Germline mutations in the tumor suppressor gene ______ can manifest with parathyroid adenomas
MEN1
T/F: sporadic parathyroid adenomas with somatic MEN1 mutations are less common than parathyroid adenomas in the setting of familial MEN1
False, they are more common
T/F: Parathyroid hyperplasia almost always presents in multiple glands and may be caused by MEN syndromes, but secondary hyperplasia is MUCH more common
True
T/F: in cases of parathyroid hyperplasia, NO normal rim of parathyroid tissue is present
True
Intraoperative monitoring of ____ predicts a successful outcome in parathyroidectomy
PTH
Most telltale sign of parathyroid carcinoma
Metastasis
The most telltale sign of parathyroid carcinoma is metastasis. However, what are some highly suggestive features?
Invasion of adjacent tissues
Vascular invasion
Elevated PTH that doesn’t go down after surgery
Symptoms of primary hyperparathyroidism
Symptoms largely derive from hypercalcemia — bones, stones, groans, psychic moans —
Osteoporosis/osteitis fibrosis cystica
Nephrolithiasis
Constipation, gallstones
Depression, lethargy, seizures
Others: weakness, fatigue, heart valve calcifications
Although you may see/diagnose primary hyperparathyroidism based on symptoms of hypercalcemia, what is the far more common way it is diagnosed?
Hypercalcemia discovered as incidental finding on routine lab work
Brown “tumor” (although not technically a neoplasm) that forms d/t osteoclast-driven bone destruction leading to small fractures, hemorrhage, and reactive tissue
Osteitis fibrosis cystica
[note osteitis fibrosis cystica is rarely the initial presentation; it also may look like metastatic disease]
In the setting of asymptomatic hypercalcemia, it is important to consider _____________
In the setting of symptomatic hypercalcemia, it is important to consider __________
Primary hyperparathyroidism
Malignancy
How is hypercalcemia due to primary hyperparathryoidism differentiated from hypercalcemia due to malignancy (based on labs)
Primary hyperparathyroidism = hypercalcemia with raised [PTH] (similar presentation to familial hypocalciuric hypercalcemia)
Malignancy = hypercalcemia with decreased [PTH] (similar presentation to people on thiazide diuretics or with granulomatous disease like sarcoidosis)
What is secondary hyperparathyroidism?
Hypocalcemia due to renal failure, vitamin D deficiency, or pseudohypoparathyroidism —> increased parathyroidal volume as an adaptive process
What causes tertiary hyperparathyroidism?
Prolonged hypocalcemia —> autonomous function of parathyroid glands
What is Rugger Jersey sign?
Dissecting osteitis in hyperparathyroidism — specifically secondary hyperparathyroidism in which there is renal osteodystrophy
Condition in secondary hyperparathyroidism characterized by extensive calcification and occlusion of blood vessels with resultant ischemia; patients are susceptible to necrosis leading to infection and sepsis
Calciphylaxis
2 major mechanisms of hypercalcemia of malignancy
Humoral hypercalcemia of malignancy (HHM) [d/t PTHrP release (often in squamous carcinoma) or Vitamin D-mediated (often in lymphoma)]
Local osteolytic hypercalcemia [release of calcium d/t osteoclastic bone resorption]
Causes of acquired hypoparathyroidism
Iatrogenic (surgical)
Autoimmune
Causes of congenital hypoparathyroidism
DiGeorge Syndrome — developmental defects in 3rd to 4th pharyngeal pouches [parathyroid glands may be absent or underdeveloped]
CASR germline mutations — familial hypocalcemic hypercalciuria [hyperactive calcium-sensing receptors]
Familial isolated hypoparathyroidism [precursor PTH can’t get all the way to functional PTH]
Signs/symptoms of hypocalcemia
Muscle cramps and spasms (tetany)
Trousseau sign positive
Chvostek sign positive
[others include behavioral disturbance and stupor, numbness and parasthesias, laryngeal stridor, cataracts, basal ganglia calcification, papillaedema, prolonged QT interval on ECG]
What is pseudohypoparathryoidism?
Hypoparathyroidism that occurs because of end-organ resistance to the actions of PTH (related to GPCR pathways)
Serum PTH is typically elevated; presents with hypocalcemia and hyperphosphatemia
Can affect other hormone pathways: TSH, LH/FSH
