Flashcards in Hyperparathyroidism Week 6 Deck (39)
What is hyperparathyroidism?
it is the result of excessive parathyroid hormone (PTH) secretion, PTH-induced bone resorption, and hypercalcemia. 3 types- primary, secondary, tertiary
Primary HPT is characterized by?
abnormal regulation of PTH secretion by calcium, resulting in excessive PTH secretion and hypercalcemia.
causes of primary HPT?
a single parathyroid adenoma mostly (85%)
four-gland hyperplasia (10%)
multiple adenomas (5%)
parathyroid carcinomas- rare (<5%).
How do you diagnose primary HPT?
Persistent hypercalcemia with increased or high-normal serum PTH levels confirms the diagnosis of primary HPT.
diagnosis primarily on laboratory studies since sx usually non- specific or absent
normal lab values- PTH and calcium
PTH 10-65 pg/mL- increase with age- unknown why
calcium 8.5-10.5 mg/dL
How might you make the diagnosis of primary HPT more certain before recommending parathyroidectomy?
Get at least 3 fasting serum calcium levels, ideally with no venous occlusion, and 2 PTH measurements at least several weeks apart. Ensure that the patient has normal renal function. Discontinue any thiazide diuretics for at least 1 week before measurement. Discontinue lithium if safe to do so.
2 major hormones modulating calcium and phosphate homeostasis
PTH and calcitrol (1,25-dihydroxyvitamin D)
diagnostic of primary hyperparathyroid
elevated PTH and elevated serum calcium (because of hyper secretion of PTH relative to the serum calcium concentration)
a decrease in serum calcium would do what to the PTH?
stimulates the release of PTH from the parathyroid gland
PTH increases the activity of ____ leading to _____.
1α-hydroxylase in the kidney; increased activation of
PTH increases _____ and decreases_____.
the reabsorption of calcium (into blood); the reabsorption of inorganic phosphate (Pi)
Elevations in plasma Pi levels stimulate what?
the release of PTH
In bone, PTH stimulates ? Which leads to what?
bone resorption. which leads to an increase in plasma calcium levels
clinical manifestations of primary hyperparathyroidism
elevated intact PTH levels
increased plasma calcium levels (hypercalcemia)
increased urinary calcium excretion (hypercalciuria) which may lead to kidney stones (urolithiasis)
and decreased plasma phosphate
symptoms and signs of excess PTH secretion/ hyperparathyroid
s/s of hypercalcemia
increased production of calcitrol
proximal renal tubular acidosis
hyperuricemia and gout
most patients with primary hyperthyroid present with calcium levels of?
10- 11mg/dL, often discovered on routine testing
SX: Renal: hypercalciuria, nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, renal insufficiency probable cause in hyperparathyroid ?
Parathyroid hormone (PTH) stimulates bone resorption, hypercalcemia, bicarbonaturia, and phosphaturia, causing decreased tubular responsiveness to antidiuretic hormone (ADH), polyuria, calcium oxalate
and phosphate crystallization, nephrocalcinosis, and renal insufficiency
SX: Neuromuscular: weakness, myalgia probable cause in hyperparathyroid?
Prolonged excessive PTH arguably causes direct neuropathy with abnormal nerve conduction velocities (NCVs) and characteristic electromyographic changes and myopathic features on muscle biopsy
SX: Neurologic and psychiatric: memory loss, depression, psychoses, neuroses, confusion, lethargy, fatigue, paresthesias probable cause in hyperparathyroid?
PTH and calcium cause peripheral neuropathy with abnormal NCVs and central nervous system damage with abnormal electroencephalographic changes
SX: Skeletal: bone pain, osteitis fibrosa, osteoporosis, and subperiosteal skeletal resorption probable cause in hyperparathyroid?
PTH increases bone resorption and acidosis with subsequent bone buffering and bone loss of calcium and phosphate
SX: Gastrointestinal: abdominal pain, nausea, peptic ulcer, constipation, and pancreatitis probable cause in hyperparathyroid?
Hypercalcemia stimulates gastrin secretion, decreases peristalsis, and increases the calcium-phosphate product with calcium-phosphate deposition in and obstruction of pancreatic ducts
SX: Hypertension probable cause in hyperparathyroid?
Hypercalcemia causes vasoconstriction, and parathyroid hypertensive factor (PHF) may raise blood pressure
SX: Arthralgia, synovitis, arthritis probable cause in hyperparathyroid?
HPT is associated with increased crystal deposition from calcium phosphate (para-articular calcification), calcium pyrophosphate (pseudogout), and uric acid/urate (gout)
SX: Band keratopathy probable cause in hyperparathyroid? (classic but unusual sign of HPT)
Calcium-phosphate precipitation in medial and limbic margins of cornea
SX: Anemia probable cause in hyperparathyroid?
Primary hyperparathyroidism (HPT) is associated with what? (major things)
hypercalcemia, osteoporosis, nephrolithiasis, and symptoms associated with these conditions
The new recommendations for surgery in patients with asymptomatic HPT are ?
serum calcium more than 1 mg/dL above the upper normal limit, decreased estimated GFR to less than 60 mL/min, reduced bone density with T-score less than –2.5, age less than 50 years, and calcium nephrolithiasis
Advantages of parathyroid surgery include ?
cure of HPT and hypercalcemia in most cases with a single operation, no need for regular prolonged follow-up, decreased fracture rate, and increased bone mass in most patients.
What are the classic radiographic findings in HPT?
often no radiographic findings related to HPT (since pts diagnosed early). If HPT is prolonged, osteopenia or osteoporosis develops. However, the classic radiographic finding is subperiosteal bone resorption along the radial aspect of the middle and distal phalanges and distal clavicles. Salt-and-pepper skull is another classic finding.
differential diagnosis of primary HPT?
Because the main abnormality in primary HPT is hypercalcemia, the differential diagnosis initially is that of hypercalcemia- 2 most common causes of hypercalcemia are primary HPT and malignancy.
What lab tests help to distinguish the three types of HPT?
primary= PTH normal or high and calcium high
secondary= PTH high and calcium low or normal
tertiary= PTH very high and calcium high
What pathophysiologic changes occur in secondary HPT? most common cause?
Secondary HPT is excessive PTH secretion occurring as a compensatory response to absolute or relative hyperphosphatemia, hypocalcemia, or low calcitriol levels. Renal failure is the most common cause of secondary HPT, often producing PTH hypersecretion by means of all three of these stimuli. In renal failure, phosphorus increases because of decreased renal function. The increased phosphorous stimulates PTH secretion and decreases calcium and 1,25(OH) 2 D levels. The lower calcium and vitamin D levels also increase PTH synthesis and secretion. Thus, controlling phosphorus levels with diet and phosphate binders and appropriate calcitriol supplementation may delay onset of the secondary HPT of renal failure.
What pathophysiologic changes occur in tertiary HPT?
Tertiary HPT results from progression of secondary HPT. In tertiary HPT, prolonged hyperphosphatemia and/or hypocalcemia cause further parathyroid hyperplasia with eventual development of autonomous parathyroid function and hypercalcemia. (most common in chronic renal failure) PTH levels usually approximately 15- 30 times normal
early manifestation of surgical removal of parathyroid glands?
classic sign for hypocalcemic tetany
Chvostek sign= twitching or contraction of the facial muscles in response to tapping the facial nerve at a point anterior to the ear and above the zygomatic bone
not bc of decreased PTH levels but because of an abnormal response to the PTH because of a congenital defect in the G protein associated with PTHR1
pseudohypoparathyroidism type 1a
Characterized by a generalized hormone resistance to PTH, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone, is associated with
abnormal physical features including short stature and skeletal anomalies
pseudohypoparathyroidism type 1b
Characterized by renal resistance to PTH and normal
appearance. The PTHR1 has decreased Gαs activity, and this can be tested by measuring the increase in
urinary cAMP in response to PTH administration (which should be low in patients with defective Gαs activity).