Hypercalcemia

physiology:

 

·        Adult body has 1 kg of Ca (99 % in bones as hydroxyapatite)

·        Circulating calcium in tight range of 2.25 -2.5 mmol /L

·        50-60 % protein bound (albumin), or complexed with phosphate/citrate

·        40-50 % free or ionized; proportion that is regulated and responsible for symptoms

·        so for every drop in albumin by 10, Calcium drops by .2 mmol /L

 

PTH à from parathyroid glands

·        glands sense [calcium] with calcium sensing receptor

·        low Ca increases secretion and vice versa

actions

·        Kidneys: increases Ca reabsorption + phosphate excretion / stimulates 1-alpha-hydroxylase so more 1, 25 Vit D

·        Bone: activates osteoclasts liberating calcium from skeleton

 

1, 25 Vitamin D: 

·        cholesterol in skin, light converts it to cholecalciferol ? or get from diet, liver converts it to 25- hidroxycholecalciferol, kidney converts it to 1,25-dihydroxycholecalciferol

actions

·        Gut: increases calcium / phosphate absorption

·        Bone: increases bone turnover as well

 

Calcitonin

·        parafollicular cells in thyroid gland secrete it/tries to lower calcium level

 

Signs + Symptoms (moans /bones /stones /psychic overtones)

·        related to degree or rise and absolute value

·        polyuria / polydipsia (due to nephrogenic DI)

·        GI discomfort: anorexia, constipation

·        mental status changes: apathy, fatigue, coma

·        pancreatitis, renal stones, band keratopathy (calcium deposits on cornea), ECG: shortened qt

 

W/U: Do PTH/lytes/extended lytes/cre/ maybe 24 hr urine Ca

 

a. PTH mediated (high / inappropriately normal)

b. non PTH mediated (if suppressed)

 

PTH mediated

·        Hyperparathyroidism (most common cause in outpts): primary when parathyroid out of whack due to adenoma or hyperplasia; secondary when CKD causes low calcium as vit D production impaired, PTH increases; tertiary when autonomous nodule develops in CKD

-        Generally get osteoporosis, in past presented with osteitis fibrosa cystica (skull demineralization/resorption of finger periosteum), kidney stones as more filtered calcium, can lead to nephrocalcinosis

-        Multiparathyroid adenomas generally seen in MEN 1 (pituitary, pancreas) or 2a (med. Thyroid, pheo)

·        FHH (familial hypocalciuric hypocalcemia): autosomal dominant deactivating mutation in Calcium sensing receptor in parathyroids and kidney

Dx with fractional excretion of calcium: (24 hr U Ca / serum Ca) / (24 hr U cre / serum cre)

24 hr U ca < 100 mg / FE_Ca < .01

·        Lithium : increases set point for PTH suppression by calcium

 

Non-PTH mediated

 

·        Malignancy (most common for inpatients), due to local osteolytic activity, PTHrP (humoral), calcitriol..

a.      Osteolytic tumors: myeloma, breast Ca, lymphoma

b.      PTHrP (PTH related peptide): protein produced by malignant cells, generally SCC of head + neck, AdenoCa of breast+ovary, RCC, myeloma. Cells produce small amounts of PTHrP so need a lot of tumor to be the cause.

c.      Increased calcitriol production: B cell lymphoma

 

·        Granulomatous disease (due to increased calcitriol production by autonomous production of 1alpha-hydroxylase): sarcoidosis, tuberculosis, leprosy, wegener’s (GPA)

·        Thyrotoxicosis, prolonged immobilization, paget’s disease: increased turnover

·        Vitamin D intoxication

·        Milk-alkali syndrome: when large amounts of calcium and consumed (> 4 g/day), get polyuria, leads to contraction alkalosis

·        Meds: Thiazides (increase Ca absorption)

 

Management

·        lytes/extended lytes/cre/ maybe 24 hr urine Ca/ calcidiol (25-vit D)/ calcitriol

·        w/u appropriate for underlying cause

·        IV fluids (dry secondary to polyuria)

·        Diuresis? Only if patient is euvolemic to hypervolemic

·        Bisphosphonates: Pamidronate (60-90 mg IV) or zoledronic acid 4 mg IV; calcium begins to decrease at 48-72 hrs; effect lasts for weeks

·        Calcitonin: 4 IU/kg sc q12h; acts quick; tachiphylaxis

·        Glucocorticoids: in Vit D mediated hypercalcemia like lymphoma and granulomatous disease; decrease intestinal absorption, and decrease activity of 1alpha hydroxylase

·        Gallium nitrate, plicamycin

·        Dialysis may be indicated in nothing works

·        Primary hyperparathyroidism:

Indications for surgery: symptoms!, age < 50, Creatinine Cl reduced by > 30 %, Ca > 2.75, high 24hr urine calcium, T score < -2.5

May localize with nuclear scan +- ultrasound; remove adenoma; remove 3.5 glands if hyperplasia (may be guided by intraop PTH levels)

Bisphosphonate increases BMD, but doesn’t lower Ca /PTH

cinacalcet (activates CaSR), lowers PTH, lowers Ca, doesn’t change BMD