Calcium Disorders

Laboratory Findings in Calcium Disorders

Ca

PTH

Disease

POa

ft

Hyperparathyroidism (1° and 3°)

I

T or nl

Familial hypocalciuric hypercalcemia

I

t

Malignancy

var.

i

Vitamin D excess

T

Milk-alkali syndrome, thiazides

I

t Bone turnover

t

it

Pseudohypoparathyroidism

t

T

Vitamin D deficiency

I

4

Chronic renal failure (2° hyperpara)

1

van

Acute calcium sequestration

var.

Hypoparathyroidism

Pitfalls in measuring calcium

• Physiologically active Ca is free or ionized (ICa). Serum Ca reflects total calcium

(bound • unbound) and .\ influenced by albumin (main Ca-binding protein).

• Corrected Ca (mg dl) measured Ca (mg dl) - [0.8 x (4 - albumin (gm dl))]

• Alkalosis will cause more Ca to be bound to albumin ( total Ca may be normal but I ICa)

• Best to measure ionized Ca directly

Hypercalcemia

Etiologies of Hypercalcemia

Category

Etiologies

Hyperparathyroidism

1°: adenoma (85%). hyperplasia (15-20%; sponL vs. MEN

1 2A). carcinoma (<1%) 3°: after long-standing 2° hyperparathyroidism (as in renal failure) — autonomous nodule develops, requires surgery Uthium t PTH

Familial hypocalciuric hypercalcemia (FHH)

Mutation in Ca-sensing receptor in parathyroid and kidney -» t Ca set point; i t PTH (and less T than in 1° hyperpara.) Acquired form due to autoAb vs. Ca-sensing receptor (rare)

Malignancy

PTH-related peptide (PTHrP) humoral T Ca of malignancy

(eg. squamous cell cancers, renal, breast, bladder) Cytokines & T 1 ,25-(OH)jDj (eg. hematologic malignancies) Local osteolysis (eg. breast cancer, myeloma)

Vitamin D excess

Granulomas (sarcoid.TB, histo.Wegener's) T 1-OH

T 1.25-(OH),D Vitamin D intoxication

t bone turnover Miscellaneous

Hyperthyroidism, immobilization - Paget's disease, vitamin A Thiazides; Ca-based antacids or massive dairy consumption (milk-alkali syndrome): adrenal insufficiency

(JCEM 2005:90.6316)

(JCEM 2005:90.6316)

Clinical manifestations ("bones, stones, abdominal groans, and psychic moans")

• Hypercalcemic crisis (usually when Ca 13-15): polyuria, dehydration, mental status As

Ca toxic to renal tubules — blocks ADH activity, causes vasoconstriction, and I GFR — polyuria but T Ca reabsorption t serum Ca — ? nephrotoxicity and CNS sx

• Osteopenia, fractures, and osteitis fibrosa cystica (latter seen in severe hyperpara only —

* osteoclast activity cysts, fibrous nodules, salt & pepper appearance on X-ray)

• Nephrolithiasis, nephrocalcinosis. nephrogenic Dl

• Abdominal pain, anorexia, nausea, vomiting, constipation, pancreatitis. PUD

• Fatigue, weakness, depression, confusion, coma, J DTRs. short QT interval

• Calciphylaxis (calcific uremic arteriopathy): calcification of media of small- to medium-sized blood vessels of dermis & SC fat — ischemia and skin necrosis (NEJM 2007:356:1049)

Associated w uremia. T PTH. t Ca. f PO«, and T (Ca x PO^) product. Dx by biopsy. Rx: aggressive wound care, keep Ca & PO* nl (goal < 55). avoid vitamin D & Ca suppl.

IV Na thiosulfate & parathyroidectomy controversial. Overall portends a poor prognosis.

Diagnostic studies

• Hyperparathyroidism and malignancy account for 90% of cases of hypercalcemia hyperparathyroidism more likely if asx or chronic hypercalcemia malignancy more likely if acute or sx; malignancy usually overt or becomes so in mos

• Ca. alb. ICa, PTH (may be inappropriately normal in 1c hyperparathyroidism & FHH). PO«;

based on results consider checking PTHrP. 25-(OH)D. 1.25-(OH)2D. A<t». Uc.

Acute Treatment of Hypercalcemia

Treatment

Onset

Duration

Comments

Normal saline (4-6 L d)

h

during Rx

natriuresis t renal Ca excretion

Furosemide

(IV q6h)

h

during Rx

Start only after intravascularly replete. Promotes natriuresis and 1 Ca excretion.

Bisphosphonates

1-2 d

var.

Inhibit osteoclasts, useful in malignancy, caution in renal failure; risk of jaw osteonecrosis

Calcitonin

h

2-3 d

Quickly develop tachyphylaxis

Glucocorticoids

days

days

? Useful in some malig. & vitamin D intox.

(NEJM 200S:352 373)

(NEJM 200S:352 373)

Hypocalcemia

Etiologies of Hypocalcemia

Category

Etiologies

Hypoparathyroidism

Isolated; familial (PGA 1. activating Ca-sensing receptor mutations; sec 7-2); iatrogenic (s p thyroid, cancer surgery, neck irradiation); Wilson s. hemochromatosis; hypoMg (I secretion and effect); activating Ca-sensing receptor autoAb

Pseudohypoparathyroidism

la and lb: PTH end-organ resistance (.-. Î serum PTH) la: + skeletal abnormalities, short stature. & retardation Pseudopseudohypoparathyroidism la syndrome but nl Ca & PTH

Vitamin D deficiency or resistance

Nutritional sunlight deprivation; Gl disease fat malabs.; drugs (anticonvulsants, rifampin, ketoconazole. 5-FU leucovorin); genetic (1a-hydroxylase.VDR mutations)

Chronic renal failure

1 1.25-(OH)jD production. * PO4 from 1 clearance

Accelerated net bone formation

Post-parathyroidectomy. Rx of severe vit D deficiency or Paget's disease, osteoblastic metastases

Calcium sequestration

Pancreatitis, citrate excess (eg, after blood transfusions), acute it PO* (ARF, rhabdomyolysis. tumor lysis)

Clinical manifestations

• Neuromuscular irritability: perioral paresthesias, cramps. © Chvostek's (tapping facial nerve —contraction of facial muscles). © Trousseau's (inflation of BP cuff — carpal spasm), laryngospasm; irritability, depression, psychosis, t ICR seizures. * QT

• Rickets and or osteomalacia: chronic I vit D -»i Ca, 1 PO< 1 bone cartilage mineralization, growth failure, bone pain, muscle weakness

• Renal osteodystrophy (i vit D & * PTH in renal failure): osteomalacia (I mineralization of bone due to 1 Ca and 1,25-(OH)3D) & osteitis fibrosa cystica (due to 1 PTH) Diagnostic studies

• Ca. alb. ICa. PTH. 25-(OH)D. 1.25-(OH)2D (if renal failure or rickets). Cr. Mg. P04. A<t>. Uo Treatment (also treat concomitant vitamin D deficiency)

• Symptomatic: intravenous Ca gluconate (1-2 g IV over 20 mins) - vitamin D (calcitriol most effective in acute hypocalcemia, but takes h to work) ± Mg (50-100 mEq d)

• Asymptomatic and or chronic oral Ca (1-3 g d) & vitamin D (eg. ergocalciferol 50.000 IU

PO q wk x 8-10 wks). In chronic hypopara. calcitriol is needed, consider also thiazide.

• Chronic renal failure: phosphate binder(s). oral Ca. calcitriol or analog (calcimimetic may be needed later to prevent hypercalcemia)

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