Parathyroid Pathology Flashcards
Which 3 cell types exist in the parathyroid glands?
What is their histology?
Chief cells: central round, uniform nuclei. Light pink/white cytoplasm w/ secretory granules.
Oxyphil cells: smaller, darker nuclei. Eosinophilic granular material (mitochondria). Less endocrinologically active.
Adipose cells
What are the 3 major functions of PTH? How?
Releases Ca++ from bone by activating osteoclast activity (increased [Ca++].
Acts on kidney to hold Ca++ and increase vitamin D levels.
Acts on the SI to increase absorption of Ca++.
What is the relationship between calcium and phosphorus levels?
Inverse correlation
How do the parathyroid glands know when to adjust [Ca++] (to increase or decrease)?
The CaSR (calcium-sensing receptor) regulates the amount of PTH secreted from the gland.
Low serum Ca++ = increased PTH
High serum Ca++ = decreased PTH
What are the 3 major causes of primary hyperparathyroidism? Which is most common?
Adenoma - most common
Primary hyperplasia
Parathyroid carcinoma - least common
What are the levels of PTH and [Ca++] like in primary hyperparathyroidism?
Both are elevated
What are the symptoms of primary hyperparathyroidism?
What is the major cause of these symptoms?
Painful bones: osteoporosis/osteitis fibrosis cystica
Renal stones: nephrolithiasis
Abdominal groans: constipation, gallstones
Psychic moans: depression, lethargy, seizures
Protracted hypercalcemia
Osteitis fibrosis cystica (von Recklinghausen’s disease of bone) include which 4 features?
It may look similar to…
Begins as a brown tumor
Osteoclast-driven bone destruction
Small fractures
Hemorrhage and reactive tissue
May look similar to metastatic disease! This is rare for initial presentation, though.
How is primary hyperparathyroidism detected?
Not usually symptomatically - usually from high Ca++ on normal blood work. PTH is then ordered and found to be high, too.
What cells make up a parathyroid adenoma?
How many are there usually?
They might be surrounded by…
Parathyroid chief or oxyphil cells
Typically solitary
Can be surrounded by a rim of normal parathyroid tissue
What gene mutation may cause parathyroid adenomas? Which type of mutation is most common?
MEN1 - somatic mutations (20-30%) are more common than germline
How many glands does parathyroid hyperplasia typically affect?
What might be responsible for it?
Primary parathyroid hyperplasia is much less common than…
Typically multiple glands
MEN syndromes may be responsible
Secondary > primary parathyroid hyperplasia
What feature is used to distinguish between adenoma and primary hyperplasia?
Adenomas affect 1 gland usually, which primary hyperplasia affects multiple
What is the treatment for parathyroid adenoma?
How can it be predicted to be successful?
Parathyroidectomy
Intraoperative monitoring of PTH
What is the signature sign of parathyroid carcinoma?
Which 3 features are “highly suggestive”?
Metastasis
Invasion of adjacent tissues
Vascular invasion
Elevated PTH post-operation
Which causes of hypercalcemia tend to cause more symptoms?
Non-parathyroid (malignancy) - mental status changes, N/V, EKG changes (shortened QT interval)
What are 4 non-parathyroid-related causes of hypercalcemia?
Malignancy - most common
Vit. D excess - granulomatous disease, hypervitaminosis
Excess calcium ingestion
Medications - thiazide diuretics
What are the levels of PTH and [Ca++] in non-parathyroid-related hyperparathyroidism?
Low/normal PTH, but elevated [Ca++]
What are the 2 mechanisms of hypercalcemia of malignancy?
What are their underlying causes and associated cancers?
Humoral hypercalcemia of malignancy (HHP)
- PTHrP (80%): analogous to PTH and produced in squamous carcinomas (can be others)
- Vit. D-mediated from lymphomas
Local osteolytic hypercalcemia: release of Ca++ due to osteoclastic bone resorption.
- breast carcinoma
- myeloma
What is the main cause of secondary parathyroid hyperplasia?
Kidney disease
What is the mechanism of secondary parathyroid disease?
Poor kidney function leads to decreased calcitrol and increased phosphorus.
This leads to decreased Ca++, which acts on the CaSR: increased PTH, PTH mRNA and proliferation.
All leads to increased serum PTH.
What is renal osteodystrophy?
What is seen on XR? Under what circumstance?
Dissecting osteitis in hyperparathyroidism.
“Rugger jersey sign” in renal osteodystrophy due to secondary hyperparathyroidism.
What causes calciphylaxis? What does it lead to?
Secondary hyperparathyroidism (renal dz), which leads to extensive calcification and occlusion of blood vessels and resultant ischemia.
May lead to clots, infection and ulcers.
What causes tertiary hyperparathyroidism?
Tertiary hyperparathyroidism is a state of excessive secretion of PTH after a long period of secondary hyperparathyroidism and resulting in a high blood calcium level. It reflects development of autonomous (unregulated) parathyroid function following a period of persistent parathyroid stimulation.
