Loss of function seen in FHH is
ADH acts on CaSR of the parathyroid cell to cause release of:
What can we use to treate severe hyperparathyroidism
A calcimimetic; cinacalcet
Excess PTH leads to excess Calcium... what are symptoms of excess Ca?
• Fatigue, weakness • Nausea, vomiting, constipation • Anorexia • Polyuria, polydipsia • Dehydration • Memory impairment • Drowsiness, confusion, coma
Hypercalcemia is caused by an increase in PTH secretion, we see this in:
Primary hyperparathyroidism (usually a parathyroid adenoma)
Hypercalcemia results in a suppression of PTH secretion; what are some causes
Vitamin D intoxication, Hypercalcemia of malignancy (caused by PTHrp)
Hypercalcemia that is PTH Dependent is:
Primary hyperparathyroidism (PHPT)
Some causes of Primary hyperPT
–Sporadic (single and multiple gland disease, carcinoma) – Multiple endocrine neoplasias (MENs) – will be discussed in a subsequent session – Hyperparathyroidism jaw tumor syndrome
HOw do PTH secreating cells respond to high Ca++ in Primary HyperPT?
Decreased sensitivity of PTH-secreting cells to inhibition by plasma Ca++ and
Increased or “inappropriately not suppressed” serum PTH levels.
What kind of Ca++ and Phosphate levels do we see in pts with Primary HyperPT?
Hypercalcemia (due to effects of PTH on bone resorption, calcium reabsorption, and increase in 1,25(OH)2D production in the kidneys).
• Hypophosphatemia due to phosphaturic effects of PTH in the proximal tubules.
Some patients with PHPT are hypercalciuric despite PTHmediated increase in Ca++ reabsorption in the distal tubules because
the filtered load of calcium exceeds the Tm for reabsorption.
Causes of Hypercalcemia PTH DEPENDENT
• Familial isolated hyperparathyroidism
• Familial hypocalciuric hypercalcemia (FHH)
• Ectopic PTH – RARE!
• Asymptomatic, modest, lifelong hypercalcemia
• PTH not suppressed
• Autosomal dominant
• Surgery not indicated
Familial Hypocalciuric Hypercalcemia (FHH)
Mutation seen in FHH
- CaSR (chromosome 3) (~2/3)
• Codominant - neonatal severe hyperparathyroidism
Two findings in the bone you see with severe Primary Hyper Parathyroidism
Hyperpara osteitis: fibrous tissue in bone
Brown tumor: see lytic lesion anf ofteh multinucleated osteoclasts
What does a scanning EM of the bone look like in pt with PHPT
see cortical bone is thinned out, controverys over wheter trabeculated bone is spared or not
Causes of PTH-INDEPENDent Hypercalcemia
Calcitiro mediated; granulmos or inflammation
milk alkali or calcium alkali syndrome
Has – N-terminal homology with PTH, use in assays, found in high conc in normal tissue and key for fetal development
Parathyroid-Hormone-Related Peptide (PTHrP)
Calcitriol (1,25[OH]2D)-Mediated Hypercalcemia can be caused by:
sarciod and lympohma
Your pt has elevated Ca+ levels, what test do you order next?
Hypercalcemic pt had PTH labs done, they have elevated PTH, what is our next step?
Most likely dx – primary hyperparathyroidism
Measure 24 hour urine calcium & creatinine to rule out FHH
A primary process causing too much____ (primary hyperparathyroidism) will cause hypercalcemia [increased bone resorption and increased production of 1,25(OH)2D)].
A process which raises the serum calcium independent of PTH (for example a tumor producing PTH related protein or lytic bone lesions) will suppress ____
Pt has Hypercalcemia and LOW PTH, what could be going on?
PTH independent HyperPT;
excess 1,25-D suggets cancer, sarcoid or hyperthyroidism
How do you tx pt with Hypercalcemia?
IV fluids; normal saline
Loop diuretics; furosemide but waith till AFTER pt is rehydrated
used to tx hypercalcemia, potently inhibit osteoclastic bone resorption.
A drug to tx hypercalcemia: see a rapid reduction in Ca2+ can occur. “Escape" from the hormone commonly occurs within several days. Calcitonin can lower serum calcium by 1-2 mg/dL