parathyroid Flashcards
Calcium Sensing receptor
senses calcium (expressed in Parathyroid gland and kidney), loss of function familial hypocalciuric hypercalcemia (FHH), Gain of function autosomal domiinant hypocalcemia (ADH)
Calcimimetic (cincalcet can be used to treat sever hyperparathyroidism)
Symptoms of hypercalcemia
Related to level and rate of change, fatigue, weakness
Nausea, vomiting, constipation
Anorexia, polyuria, polydipsia, dehydration, memory impairment, drowsiness, confusion, coma, most ambulatory patient - no clear symptoms
Physiology review
GI calcium Absorption: 20-70% highest in children, 90% in duodenum and jejunum,
Energy-dependent, cell-mediated process regulated by 1,25 (OH)2 D
Passive diffusional paracellular pathway
Vitamin D2- plant vitamin D or ergo calciferol is consumed
Vitamin D3- made in skin or consumed (cholecalciferol)
Both 25- hydroxylated to 25OH D at liver in a largely unregulated step (genetic variants may effect this step
Both then 1-hydroxylated in kidney to 1 25 (OH)2 D in a highly regulated step stimulated by PTH
24 hydroxylase deactivated 25D
Calcium disturbances
Primary hyperparathyroidism: parathyroid hyperactivity (usually due to a solitary adenoma) increases PTH secretion–> hypercalcemia, serum PTH concentration can be within the reference range but with such high levels of calcium, it is inapproptiately not suppressed
Hypercalcemia can also be independent of PTH (hypercalcemia of malignancy), where some other factor increases calcium which suppresses secretion of PTH from otherwise normal PT glands
A primary loss of PT gland function (hypoparathyroidism) causes hypocalcemia, a loss of tissue sensitivity to PTH (pseudohypoparathyroidism) leads to hypocalcemia
Hypocalcemia independent of PTH (with decreased serum 1 25 (OH)2 D due to renal failure leads to an increase in PTH secretion (secondary HyperPTHsm)
hypercalcemia
hypercalcemia caused by an increase in PTH secretion, Primary hyperparathyroidism (usually a parathyroid ademona)
hypercalcemia result in a suppression of PTH secretion, vitamin D intoxication hypercalcemia of malignancy (caused by PTH
Hypercalcemia PTH Dependent
Primary hyperparathyroidism (PHPT)- sporadic (single and multiple gland disease, carcinoma) Multiple endocrine neoplasias (MENs) (hyperparathyroidism jaw tumor syndrome
Ca doesnt inhibit PTH secretion (decreased sensitivity), increased/ inappropriately not suppressed serum PTH levels
Hyper Ca due to effects of PTH on bone resorption, calciuma reabsorption, and increase in 1 25 OH 2 D production in the kidneys
Hypophosphatemia due phosphaturic effects of PTH in the proximal tubules
Some patients are hypercalciuric despite PTH mediated increase in Ca reabsorption in the distal tubule because the filtered load of calcium exceeds the ability of the renal tubules to reabsorbs
Brown tumor in severe PHPT- excessive pth bone resorption
The skeleton in Typical PHPT
- It is not known if the relationship between BMD and fractures in PHPT is similar to that in Osteoporosis
Baseline BMD is decreased more at cortical sites with relative sparing of trabecular bone, subset with spinal osteopenia
Fractures may be increased, newer techniques suggest trabecular bone may not be normal
Other forms of PTH dependent hypercalcemia : FHH and ectopic PTH (very rare)
FHH- familial hypocalciuric hypercalcemia (FHH)
FHH1 most families- CaSR (chromosome 3), Codominant- neonatal severe hyperparathyroidism
FHH2 (G protein alpha 11)
FHH3 (Adapter protein 2 sigma 1m not all FHH have CaSR mutations
Usually asymptomatic, modest, lifelong hypercalcemia, PTH not suppressed Parathyroids think Calcium is not high enough, hypocalciuria (renal tubule has CaSR and thinks calcium is low
Autosomal dominant, Surgery is not indicatied
PTH independent hypercalcemia
Maliganancy- bone mets, PTH- related protein, osteoclast activating factor, unregulated calcitriol production, True ectopic PTH
Calcitriol mediated (granulomatous, inflammatory)- calcitriol is a synonym for 1 25 OH2 D
Hyperthyroidism, milk-alkali syndrome, or calcium- alkali syndrome, immobilization, Rare causes
Parathyroid hormone related peptide (PTHrP)
Humoral hypercalcemia of malignancy (breast, lung, kidney, squamous etc)
N- terminal homology with PTH assays
PTHrP assays available
PTHrP found in normal tissue/high concentrations in milk
PTHrP important in Fetal development
Calcitriol 1 25 OH 2 D mediated hypercalcemia
Non-renal/ unregulated expression of 1 hydroxylase
Sarcoid, lyphoma, TB etc
Treatment of hypercalcemia
IV FLUIDS- NORMAL Saline, Patients are frequently dehydrated, high calcium levels compromises renal concentrating mechanism
Loop diuretics- furosemide (loop diuretics augment Ca++excretion and may help the effect of plasma volume expansion by salin, monitor for electrolyte balance
Calcitonin- a rapid reduction in Ca++ can occur, escape, from the hormone commonly occurs within several days, calcitonin can lower serum calcium by 1-2 mg/dl
Bisphosphonates (IV potentially inhibit osteoclastic bone resorption)
Normal response to hypocalcemia
decreased Ca++–> CaSR, increased PTH, bone resorption and increased calcium Efflux, increased Ca++
Increased Kidney 1 25 OH 2 D, increased Ca++ reabsorbtion, decreased PO4- reabsorption same with intestine
Signs and Symptoms of hypocalcemia
related to level and rate of change Neuromuscular irratibility (paresthesias, muscle cramps, tetany) Lowered seizure threshold mental status changes Cardiac- prolonged QT, arrhythmias, CHF Basal ganglia calcification Cataracts Positive Chvostek and Trousseaus signs
hypocalcemia causes
hypocalcemi caused by PTH deficiency (decreased calcium results from low PTH), Iatrogenic, idiopathic, familial hypoparathyroidism
Hypocalcemia results in an increase in PTH - secondary hyperparathyroidism (increased PTH is a response to hypocalcemia), renal failure (kidney cannot produce adequate 1 25 OH2D), malabsorption of vit D, inadequate vit D in the diet
Hypocalcemia caused by resistance to PTH (pseudohypoparathyroidism)
