Clinical Calcium Disorders Flashcards by Kyra Porter

normal calcium range

8.4 - 10.2 mg/dL

How well did you know this?

Not at all

Perfectly

hypercalcemia - clinical features

*sings and symptoms vary on degree of hypercalcemia and acuity (chronic vs. acute)
*bones, stones, thrones, groans, psychic overtones, PLUS HEART:
1. bones: osteoporosis, bone pain
2. stones: hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired glomerular filtration
3. thrones: polyuria
4. groans: constipation, anorexia, vomiting, peptic ulcer disease, acute pancreatitis
5. psychic overtones: lethargy, drowsiness, confusion, disorientation, irritability, depression, stupor, coma
6. HEART: shortened QT segment, HTN, bradycardia

How well did you know this?

Not at all

Perfectly

basic rules of hypercalcemia

*PTH is most important lab test in pts with hypercalcemia
*you expect a LOW PTH in presence of HIGH calcium (due to negative feedback)

How well did you know this?

Not at all

Perfectly

PTH-dependent causes of hypercalcemia

primary hyperparathyroidism
familial hypocalciuric hypercalcemia

*PTH-dependent = elevated corrected calcium and normal to elevated PTH levels

How well did you know this?

Not at all

Perfectly

PTH-independent causes of hypercalcemia

CANCER (skeletal metastases, paraneoplastic syndromes)
hyperthyroidism
vitamin D intoxication
granulomatous disease (sarcoidosis, TB, etc)
milk alkali syndrome
lithium therapy
vitamin A intoxication

*PTH-independent = elevated corrected calcium and LOW PTH (PTH levels should be low when serum calcium is high)

How well did you know this?

Not at all

Perfectly

primary hyperparathyroidism - overview

*most common cause of hypercalcemia
*due to increased secretion of PTH; primary means that the problem is at the level of the parathyroid glands
*various forms:
-benign adenoma
-parathyroid hyperplasia (enlargement of all 4 glands)
-parathyroid carcinoma
-MEN syndrome

How well did you know this?

Not at all

Perfectly

primary hyperparathyroidism - laboratory evaluation

*high calcium
*elevated or inappropriately normal PTH
*low phosphate
*high alkaline phosphatase (ALP) from increased bone turnover
*hypercalciuria on 24h urine calcium collection

How well did you know this?

Not at all

Perfectly

primary hyperparathyroidism - imaging evaluation

*goal = localize the gland; can be accomplished via various scans
1. radionuclide scan with technetium-99m (Sestamibi)
2. 4D parathyroid CT scan
3. ultrasound
4. bone density (DXA) to evaluate for surgery indication

How well did you know this?

Not at all

Perfectly

primary hyperparathyroidism - treatment

1) observation
2) surgery (remove the parathyroid(s))
3) cinacalcet: sensitizes calcium sensing receptor (CaSR) in parathyroid gland to circulating calcium to lower PTH secretion; generally reserved for non-surgical candidates

How well did you know this?

Not at all

Perfectly

primary hyperparathyroidism - major indications for surgery

*indications for surgery:
1. calcium 11.5 mg/dL or higher
2. kidney stones, hypercalciuria, declining GFR
3. osteoporosis
4. age < 50 years

How well did you know this?

Not at all

Perfectly

osteitis fibrosa cystica (complication of hyperparathyroidism)

*chronically high PTH = osteoblasts produce RANK-L, which stimulates osteoclasts and increases bone breakdown
*over time, cystic bone spaces fill with brown fibrous tissue or “brown tumor,” consisting of osteoclasts & hemosiderin deposits from hemorrhages
*these cyst-like tumors are painful and classically associated with primary hyperparathyroidism
*findings: lytic lesions on X-ray; fatty infiltration of bone marrow
*aka von Reckinghausen disease of bone

How well did you know this?

Not at all

Perfectly

familial hypocalciuric hypercalcemia (FHH) - overview

*a CaSR (calcium sensing receptor) mutation makes the parathyroid glands less sensitive to Ca2+ levels → a higher-than-usual Ca2+ concentration is required to inhibit PTH release
*autosomal DOMINANT

How well did you know this?

Not at all

Perfectly

familial hypocalciuric hypercalcemia (FHH) - clinical features

*asymptomatic hypercalcemia
*do NOT experience Ca2+-related problems (no osteoporosis, kidney problems, or EKG changes)
*exam tip-off: family history of failed parathyroid surgery in first-degree relatives; genetics = autosomal dominant

How well did you know this?

Not at all

Perfectly

familial hypocalciuric hypercalcemia (FHH) - diagnosis

*very LOW urine Ca2+
*increased serum Ca2+
*normal/mildly elevated PTH

How well did you know this?

Not at all

Perfectly

familial hypocalciuric hypercalcemia (FHH) - treatment

*none
*warn family members to avoid parathyroid surgery for hypercalcemia

How well did you know this?

Not at all

Perfectly

how to differentiate primary hyperparathyroidism vs. familial hypocalciuric hypercalcemia (FHH)

use the URINE CALCIUM to differentiate:
*primary hyperparathyroidism = HYPERCALCIURIA (high levels of calcium in urine)
*familial hypocalciuric hypercalcemia (FHH) = very LOW levels of calcium in urine

How well did you know this?

Not at all

Perfectly

PTH-independent causes of hypercalcemia: HYPERTHYROIDISM

*elevated T4/T3 stimulates osteoclasts to break down bone, releasing calcium into the blood

How well did you know this?

Not at all

Perfectly

PTH-independent causes of hypercalcemia: CANCER

lytic lesions/bony metastases: breast, bone, multiple myeloma
-direct damage to bone causes calcium to leak into circulation
-SPEP + UPEP for multiple myeloma is a standard part of the evaluation of PTH-independent hypercalcemia
paraneoplastic: breast, squamous cell carcinoma of the lung
-some cancers can secrete PTH-rP, which structurally looks and acts like PTH
-PTH-rp (PTH related peptide) stimulates osteoclasts to break down bone

How well did you know this?

Not at all

Perfectly

PTH-independent causes of hypercalcemia: VITAMIN D INTOXICATION

*increased vitamin D = increased calcitriol
*labs: high 25-vit D, high or normal calcitriol

How well did you know this?

Not at all

Perfectly

PTH-independent causes of hypercalcemia: GRANULOMATOUS DISEASE (TB, sarcoidosis, etc)

*increased amount of 1-alpha-hydroxylase (the enzyme that catalyzes the conversion of 25-vit D to calcitriol in the kidney)
*note - for sarcoidosis, ACE level is often elevated

PTH-independent causes of hypercalcemia: other mechanisms

milk alkali syndrome: excessive calcium intake with an alkali (ex. Tums)
lithium therapy: increases PTH release (four-gland hyperplasia)
thiazide treatment: increased renal reabsorption of calcium in the DCT
vitamin A intoxication: increased bone resorption

which diuretic is associated with hypercalcemia

*thiazide diuretics (cause high serum calcium, low urine calcium)
*ex: HCTZ

you can remember this because “Loops LOSE calcium” causing hypocalcemia

lab evaluation of hypercalcemia (general)

*check PTH and calcium (plus albumin for calcium correction)

*if high PTH and high calcium: check a 24h urine calcium (low urine Ca2+ = FHH)

*if LOW PTH and high calcium, check:
-PTHrP
-SPEP and UPEP
-calitriol
-25-vitamin D
-consider: TSH, vitamin A

management of hypercalcemia (general)

*treat underlying cause/avoid exacerbating medications
*acute tx = IV FLUIDS
*other options:
-biphosphonates (zoledronic acid): inhibit bone resorption
-calcitonin: inhibits osteoclast activity and inhibits renal calcium reabsorption (calcium resistance / tachyphylaxis develops after 48-72 hours)
-loop diuretics: LOOPS LOSE CALCIUM
-glucocorticoids for granulomatous disease

hypocalcemia - clinical features

***INCREASED NEUROMUSCULAR EXCITABILITY:** -paresthesias (hands, lips & tongue) -tetany -cramping -muscle spasm -hyperreflexia -seizures -anxiety/depression *physical exam findings: **CHOVSTEK SIGN & TROUSSEAU SIGN**

trousseau sign

*inflation of blood pressure cuff leading to carpal spasm *physical exam finding associated with **hypocalcemia**

Chvostek sign

*ipsilateral facial muscle twitching by tapping the facial nerve *physical exam finding associated with **hypocalcemia**

EKG change associated with hypocalcemia

*QT prolongation *can predispose to Torsades de Pointes

causes of hypocalcemia

*hypoparathyroidism *CKD/hyperphosphatemia *vitamin D deficiency *hypomagnesemia *malabsorption *precipitation/binding: blood transfusions, acute pancreatitis *medications *pseudohypoparathyroidism *pseudo-pseudohypoparathyroidism

hypoparathyroidism - overview

*most common cause of **hypocalcemia** (low PTH, low serum Ca2+, high serum phosphate) *various causes: 1. damage to parathyroid glands during parathyroid and/or thyroid surgery 2. autoimmune destruction (autoimmune polyglandular syndrome) 3. DiGeorge syndrome

hypoparathyroidism - labs

*low PTH *low calcium *high phosphate (less PTH → increased renal reabsorption of phosphate → high phosphate)

DiGeorge Syndrome

*22q11 deletion; associated with: 1. **hypocalcemia (due to parathyroid hypoplasia or absence)** 2. cardiac anomalies (conotruncal); get an echo 3. hypoplastic thymus 4. craniofacial/ENT abnormalities (low set, posteriorly rotated ears; wide-set eyes; bulbous nasal tip; palatal or laryngotracheal abnormalities) 5. developmental delay 6. immunodeficiency (T cells) 7. problem with pharyngeal pouches 3-4

hypocalcemia due to chronic kidney disease (CKD)

*damage to renal tissue → less 1-alpha hydroxylase → decreased conversion of 25-vit D to calcitriol *decreased renal clearance of phosphate: excess phosphate binds to calcium to create deposits of Ca, which removes calcium from the serum → hypocalcemia *secondary & tertiary hyperparathyroidism

hypocalcemia due to secondary hyperparathyroidism in CKD

*low serum calcium in CKD → PTH secretion *over time, this leads to **high PTH and low/normal serum calcium**

tertiary hyperparathyroidism in CKD

*seen only in end-stage renal disease (ESRD) *prolonged secondary hyperparathyroidism → hypertrophy of parathyroid glands *over time, leads to **really high PTH levels, causing high calcium**

hypocalcemia due to vitamin D deficiency

*vitamin D deficiency is very common *mechanism: **low 25-vit D → low calcitriol → inability to increase serum calcium via calcitriol → hypocalcemia** *people with increased skin pigmentation have higher risk *common etiologies of low vitamin D: decreased sun exposure, low dietary intake, liver disease, gut malabsorption, CKD

hypocalcemia due to magnesium deficiency

*magnesium is required for proper PTH secretion and mediates tissue responsiveness to PTH ***low magnesium → reduced PTH secretion and reduced renal responsiveness to PTH** *risk factors: low dietary intake, chronic alcohol use *in patients with hypocalcemia & hypomagnesemia: **serum calcium won't respond until magnesium is corrected**

hypocalcemia due to blood transfusions

*transfused blood contains **citrate** (prevents stored blood from clotting) ***citrate precipitates calcium out of the serum** → hypocalcemia *presents as severe, acute hypocalcemia (seizures)

hypocalcemia due to acute pancreatitis

*release of pancreatic enzymes break down adipose tissue → high serum lipids *lipids decrease magnesium and bind to free calcium, removing calcium from circulation

hypocalcemia due to loop diuretics

***LOOPS LOSE CALCIUM** *loop diuretics such as furosemide → increased renal calcium excretion → increased calcium in urine, decreased calcium in serum

other medications that can cause hypocalcemia

*bisphosphonates *cincalcet *foscarnet

pseudohypoparathyroidism - overview

*mutation in GNAS1 (encodes alpha subunit of G protein): PTH can't activate cAMP when binding to receptor → no signal transduction → **no response to PTH by bone/kidney** *lots of types, but most important = **Type 1a: autosomal dominant, maternal transmission of mutation; example of imprinting** *pts can have resistance to other G-protein coupled hormones *labs: **low Ca2+, high phosphorous, HIGH PTH**

pseudohypoparathyroidism - labs

*serum calcium = LOW *serum phosphorous = HIGH *PTH = HIGH

type 1a pseudohypoparathyroidism - clinical features

*short, broad thumb nails *short 4th and 5th digits *stunted growth

pseudo-pseudohypoparathyroidism - overview

*autosomal dominant *exam findings consistent with type 1a pseudohypoparathyroidism BUT with **normal PTH and calcium** *defective G protein is inherited from father but mom's normal allele can maintain responsiveness to PTH

treatment of hypocalcemia (general)

*correct for albumin if indicated to ensure true hypocalcemia *remember to check for/treat hypomagnesemia *treat underlying cause, if able *acute/symptomatic = **IV calcium gluconate** *chronic/asymptomatic - **oral calcium**

treatment of acute, symptomatic hypocalcemia

***IV calcium gluconate** *hypocalcemia = nerve irritability = ECG changes, seizures, bronchospasm; treat with IV medication to prevent these potentially fatal complications

treatment of chronic, asymptomatic hypocalcemia

*oral calcium: 1. calcium carbonate, calcium acetate (replaces calcium) 2. calcitriol (helps body absorb the calcium replacement)