Guerin: Parathyroid Flashcards
Chief cells
-they secrete PTH
Oxyphil cells
- acidophilic cytoplasm
- tightly packed with mitochondria
Function of the parathyroid
- regulate calcium
- low calcium…. increased PTH
What does PTH do?
- increased renal tubular reabsorption of calcium
- increases urinary P excretion
- Increases the conversion of Vit D to its active dihydroxy form in the kidney
- release of calcium and P from bone
- net result: raise level of free calcium, inhibit further PTH secretion
What are some causes of Hypercalcemia where PTH is elevated?
- hyperparathyroidism
- familial hypocalciuric hypercercalcemia
What are some causes of hypercalcemia that have decreased PTH
- hypercalcemia of malignancy
- Vit D toxicity
- Immobilization
- thiazide diuretics
- Granulomatous disease (sarcoidosis)
What is primary Hyperparthyroidism?
- autonomous overproduction of parathyroid hormone (PTH)
- Adenoma (85-95%)
- hyperplasia of parathyroid tissue
- rarely parathyroid carcinoma
What is secondary hyperparathyroidism?
- compensatory hypersecretion of PTH in response to prolonged hypocalcemia
- chronic renal failure
What is tertiary hyperparthyroidism?
- Hypersecretion of PTH even after the cause of prolonged hypocalcemia is corrected
- E.g. after renal transplant
Parathyroid adenoma
- Cyclin D1 gene inversions… overexpression
- MEN1 mutations… tumor suppressor gene
- Famlilial syndromes: MEN1 and 2
- familial hypocalciuric hypercalcemia
What mutation does MEN have?
-MEN1 or RET germline mutations
What is familial hypocalciuric hypercalcemia
- rare auto dominant
- mutations in the parathyroid calcium-sensing receptor gene (CASR)
Morphology of the adenoma
- solitary
- well-circumscribed
- glands outside the adenoma are usually normal or shrunken from feedback inhibition by elevated calcium
- hpercellular with little to no fat
- composed of uniform chief cells
- few nests of larger oxyphil cells…. occasionally composed entirely of them
- usually a rim of compressed, parathyroid fland, generally separated by a fibrous capsule
Parathyroid hyperplasia
- occurs sporadically or as a component of MEN syndrome
- calssically ALL FOUR GLANDS INVOLVED
- HYPER CELLULAR WITH LITTLE TO NO FAT
- TYPICALLY SEE CHIEF CELL HYPERPLASIA
Parathyroid carcinoma
- rare
- cells can look like normal parathyroid
- need invasion of surrounding tissues and/or metastasis for dx
Sestamibi scan
- radionucleotide scan
- Sestamibi labeled with the radi-pharmaceutical technetium-99
What are Brown tumors?
- microfactures and secondary hemorrhages…. influx of macrophages and reparative fibrous tissue…. mass lesion in bone
- brown color from vascularity, hemorrhage, and hemosiderin deposition
What is osteitis fibrosa cystica?
- increased osteoclast activity, peritrabecular fibrosis, and cystic brown tumors
- severe hyperparathyroidism, rare
What happens with the other organs in hyperparathyroidism?
-calcification!
What is the most common cause of hyperparathyroidism?
malignancy
Hypercalcemia of malignancy?
- most common cause of symptomatic hypercalcemia
- solid tumors
- hematologic malignancies: multiple myeloma
- typically caused by tumor secretion of PTH-related peptide (PTHrP)… it acts like PTH
- can also be from metastases to the bone and subsequent cytokine-induced bone resorption
What are the labs for primary hyperparathyroidism?
- high calcium levels
- high PTH…. but remember that PTH is low in hypercalcemia causes by non-PT diseases
- hypophosphatemia
Symptoms of primary hyperparathyroidism
- bones, stones, (abdominal) groans, and (psychic) moans
- bone problems
- nephrolithiasis
- GI sx: constipation, nausea, peptic ulcers, pancreatitis, and gallstones
- CNS sx: depression, lethargy, and eventually seizures
- NM weakness and fatigue
- Cardiac: aortic or mitral valve calcifications
Secondary Hyperparathyroidism
- caused by any condition that leads to chronic hypocalcemia…. overactive parathyroid glands
- usually renal failure
- inadequate dietary intake of calcium, steatorrhea, and vitamin D deficiency
- mechanism is not fully understood but related to high serum phophate
Morphology of secondary hyperparathyroidism
- hyperplastic parathyroid glands
- increased number of chief cells
- “metastatic” calcifications can be seen in lungs, heart, stomach, and blood vessels
Clinical course of secondary hyperparathyroidism
- sx not as severe or as prolonged as primary hyperparathyroidism
- Calciphylaxis: vascular calcification… ischemic damage to skin and other organs
Tx of secondary Hyperparathyroidism
-Vit D supplements and phosphate binders
Tertiary hyperparathyroidism
- occasionally in pt with secondary hyperparathyroidism
- parathyroids become autonomous and excessive
Tx of teriary hyperparathyroidism?
-removal of parathyroids
If there is elevated PTH, what will serum calcium and Phosphate look like?
- High calcium
- Low phosphate
Hypoparathyroidism
- uncommon
- surgically induced
- autoimmune
- auto dominant
- Familial isolated
- congenital absence of the parathyroid glands
What is autoimmune hypoparathyroidism associated with?
chronic mucocutaneous candidiasis and primary adrenal insufficincy
-called autoimmune polyendocrine syndrome type 1 APS1
What is Autosomal-dominant hypoparathyroidism?
-GOF in the calcium sensing receptor (CASR) gene
Clinical manifestations of hypocalcemia
- tetany
- numbness and paresthesias of distal extremities
- Chvostek sign
- Trousseau sign: carpal spasms produced by occlusion of circulation tot he forearm
- Mental status changes: anxiety and whatnot
- Heart: prolonged QT
- Dental abnormalities when hhypocalcemia is present during early development
What is a weird finding in hypocalcemia?
- paradoxical calcifications
- Lens and cataract formation
- Basal ganglia…. parkinsonian-like movement disorder
Pseudohypoparathyroidism
- end organ resistance to PTH
- serum PTH levels are normal or elevated
- presents as hypocalcemia and hyperphosphatemia
- can also have end-organ resistance to PTH, TSH, and FSH/LH (from genetic defects in G ptn coupled receptors
What is the most common cause of asymptomatic hypercalcemia
-primary hyperparathyroidism
In the majority of cases, what is primary hyperparathyroidism caused by?
- sporadic parathyroid adenoma
- less commonly by hyperplasia
Parathyroid adenomas vs. Hyperplasia
- adenomas: solitary
- hyperplasia: multiglandular process
What are the skeletal manifestations of hyperparathyroidism?
-bone resorption
-osteitis fibrosa cystica
-brown tumors
(renal changes: stones and nephrocalcinosis)
What are the clinical manifestations of hyperparathyroidism?
- bones
- stones
- groans
- psychic moans
What is secondary hyperparathyroidism most often caused by
- renal failure
- lowers serum calcium levels, resulting in reactive hyperplasia of parathyroid glands
What is the most important cause of symptomatic hypercalcemia?
- malignancies
- results from osteolytic metastases or release of PTHrP from non-parathyroid tumors
How is hypoparathyroidism most commonly induced?
surgically
What are the classic signs of hypoparathyroidism?
- tetany
- Mental status changes
- prolongation of QT interval
