hypercalcemia, hyperparathyroidism, and other imbalances Flashcards

1
Q

When is hypercalcemia usually found?

- what accounts for most cases?

A
  • relatively clinical problem that is often incidentally found on screening labs
  • hyperparathyroidism and malignancy account for 90% of cases
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2
Q

What occurs in primary HPT that causes hypercalcemia?

A
  • increase bone resorption and usually small elevations in Ca
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3
Q

What occurs in malignancy that causes hypercalcemia?

A
  • occurs with solid tumors and leukemias
  • Ca values are high
  • in nonmetastatic solid tumors secretion of PTHrP
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4
Q

What occurs in Milk-Alkali syndrome that causes hypercalcemia?

A
  • high intake of milk or Ca carbonate (tums)

- metabolic alkalosis stimulates Ca2+ reabsorption

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5
Q

What medications cause hypercalcemia?

A
  • lithium (increased secretion of PTH)
  • Thiazide diuretics (lower urinary Ca2+ excretion)
  • thyroid hormone
  • estrogens and progesterones
  • Hypervit A and hypervit D (this increases calcitriol)
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6
Q

What is pseudohypercalcemia?

A
  • elevation in total Ca2+, but not the ionized form:
    thyrotoxicosis, pheochromcytoma, adrenal insufficiency, islet cell tumors of the pancreas, and elevated platelet count
    (more bound Ca2+ but not true elevation of active Ca2+)
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7
Q

Manifestations of Hypercalcemia?

A
  • bones, stones, abdominal pain and psychic overtones
  • bones: bone pain and muscle weakness
  • stones: nephrolithiasis: used to be most common presentation, will see high Ca on CMP
  • abdominal pain: constipation, nausea and anorexia
  • psychic: anxiety, depression and cognitive dysfunction
  • renal: polydipsia, and polyuria which will result in dehydration
  • CV: bradycardia, shortening of QT interval, and varying arrhythmias
  • CNS depression
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8
Q

Work up of calcium disorders?

A
  • serum calcium level: will be artificially elevated if tourniquet left on too long or if pt is dehydrated
  • can be artificially increased by elevated albumin or decreased if albumin is decreased
  • normal: 8.2-10.2 mg/dL
  • ionized calcium: 50% of calcium in this form, changed by blood pH (look at arterial blood gas)
  • normal: 1.15-1.35 mg/dL
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9
Q

When will there be falsely elevated Ca in asymptomatic pt?

A
  • when albumin levels are elevated

- need to confirm elevated Ca2+ with 2 readings with albumin

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10
Q

What else will you see in hypercalcemic lab findings?

A
  • phosphate usually is slightly decreased
  • ALP may be slightly increased because bone is getting turned over
  • need to rule out thyroid dysfunction
  • check PTH level and if that is normal check PTHrP
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11
Q

When would 24 hr urinary Ca excretion be low?

A
  • in Milk-alkali sydrome, thiazide diuretic use and familial hypocalciruic hypercalcemia
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12
Q

Tx of hypercalcemia?

A
  • depends on etiology

- tx underlying etiology will correct hypercalcemia

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13
Q

Lab findings in primaray hyperparathyroidism?

A
  • serum Ca will be high, elevated PTH is also present, high urine phosphate and low serum phosphate levels, ALP will be elevated, urine calcium will be high because hypercalcemia in blood overwhelms absorptive capacity of kidneys for calcium
  • increased urinary cAMP
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14
Q

What happens in a hypercalcemic crisis?

A
  • saline diuresis: Ca2+ > 14 mg/dL
  • pt is usually dehydrated - so hydrate the personto decrease Ca; infuse 250-500 ml/hr of saline to rehydrate
  • give IV synthetic calcitonin
  • give IV biphosphonates (stop leaching of bone): max effect in 2-4 days, zoledronic acid or pamidronate
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15
Q

Etiologies of primary HPT

A
  • 80%: parathyroid adenoma (enlarged gland)
  • ## 15%: hyperplasia
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16
Q

Presentation of a parathyroid carcinoma?

A
  • rare:
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17
Q

2 criteria dx PT cancer?

A
  • local invasion of contiguous structures

- lymph node or metastatic spread

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18
Q

What is primary method of tx of parathyroid cancer?

A
  • surgery
  • chemo and radiation not very helpful
    3 outcomes: 1/3 cured at surgery, 1/3 recur and may be cured with reoperation, other 1/3: short, aggressive course
  • if not surgically tx: manage hypercalcemia
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19
Q

Presentation of primary HPT?

A
  • hypercalcemia (asymptomatic)
  • PTH mediated bone resorption: decreased bone resorption: decreased bone mineral density, and increased risk of vertebral fractures
  • CV: HTN and left ventricular hypertrophy and diastolic dysfunction
  • often aren’t a lot of physical findings unless malignancy is underlying cause -> then you have to search for a tumor, metastases and nodes should be carried out
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20
Q

What is secondary HPT due to?

A
  • maligancy:
    etiologies: multiple myeloma, lung, kidney, esophagus, head and neck, breast, skin and bladder cancers are some of the more common
  • work up: PTHrP
  • chronic to advanced renal disease: hypocalcemia/hyperphosphatemia, Cr/BUM elevated, PTH increased b/c of hypocalcemia
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21
Q

Levels of PTH and Ca in blood if primary HPT?

A
  • blood PTH levels: 30-180

- blood calcium: 9-14

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22
Q

Levels of PTH and Ca in blood if malignancy?

A
  • low blood PTH levels (less than 20) but PTHrP would be high
  • high blood calcium levels (11-14)
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23
Q

Work up of HPT

A
  • intact PTH: normal - 10-50 pg/mL
  • serum creatinine: assess renal fxn
  • bone-specific alkaline phosphate: assess bone turnonver
  • calcitrol: Vit D metabolites- suppressed in hypercalcemia: normal 1.5 pmol/L
24
Q

How do you measure bone density?

A
  • DEXA-scan: dual energy x-ray absorption

- most common, used to measure bone density of the femoral neck, lumbar spine and wrist

25
Q

Management of primary HPT?

A
  • pts with sx or progressive disease: surgical tx

- general surgeons usually, although ENT also can do surgery

26
Q

Preop localization for PHPT?

A
  • use technetium-99m-sestamibi schintigraphy w/ SPECT imaging
  • ultrasonography
  • CT scan or MRI
  • used prior to minimally invasive parathyroidectomy
  • used if 1st surgery unsuccessful and need to do more extensive procedure or locate ectopic tissue
27
Q

MIP?

A
  • minimally invasive parathyroidectomy
  • must do preop imaging, limits the operative field to localize 2-4 cm incision, intraoperative PTH assay, 84-99% success rate based somewhat on surgeons experience
  • post surgical complication: hypocalcemia, vocal cord paralysis (recurrent laryngeal nerve)
28
Q

Reoperation for PHPT

A
  • 1st determine correct dx of PHPT
  • then may need to use localizing modalities again, aberrant location
  • need to do bilateral neck exploration to find causative gland(s)
29
Q

Surgery indications in Asx pts?

A
  • serum Ca2+: 1.0 mg/dL > then normal

- creatinine clearance

30
Q

Asx pts - nonsurgical management?

A
  • pts with only mild increase in Ca2+, pts who are unfit for surgery
  • pts who refuse surgery, and pts who are asx
  • avoid meds that make hypercalcemia worse
  • low Ca2+ diet: get rid of excessive Ca2+
31
Q

Med management for Asx pts?

A
  • bisphosphonates: IV - effects last for a week, pamidronate and zoledronate
  • be aware of renal problems and jaw necrosis
  • calcimimetic: cinacalcet: activates Ca sensing receptor in PT gland inhibiting PTH secretion
  • used in pts with parathyroid carcinoma or those with secondary hyperparathyroidism
  • dialysis is a last resort
32
Q

Bisphosphonates SE

A
  • flu like sxs
  • ocular inflammation (uveitis)
  • hypocalcemia
  • hypophosphatemia
  • impaired renal fxn (nephrotic syndrome)
  • osteonecrosis of the jaw (more common in cancer pts)
  • nephrotoxic
33
Q

Hypercalcemia of malignancy tx?

A
  • tx underlying malignancy
  • use bisphophonates
  • calcitonin: SQ or IM, rapid antiresorptive agent
  • dialysis in Ca2+ free bath for pts in renal failure (secondary HPT)
34
Q

Etiologies of hypocalcemia?

A
  • hypoparathyroidism: usually from surgery for thyroid disease or for surgery for hyperparathyroidism, autoimmune
  • hypovitaminosis D
  • hyperphosphatemia: usually secondary to renal failure
35
Q

Sxs of mild hypocalcemia?

A
  • circumoral parethesias, hyperventilation
  • myalgias, muscle cramps
  • fatigue, hyperirritability, anxiety
36
Q

Sxs of severe hypocalcemia?

A
  • tetany/laryngospasm
  • seizures
  • myopathy
  • prolonged QT interval on EKG
  • papilledema, hypotension
37
Q

what is trousseau’s sign?

A

blood pressure cuff on arm -> inflating cuff causes a tetanic spasm of wrist
- this indicates hypocalcemia

38
Q

Work up of hypocalcemia?

A
  • decreased serum Ca2+ (need to check albumin levels, may need to use corrected form)
  • increased serum phosphate
  • 1, 25 (OH) 2D levels can be low
  • usually high PTH levels
39
Q

Tx of hypocalcemia?

A
  • Vit D and Ca supplement
  • Ca: 600-1200 mg elemental Ca
  • Thiazide diuretic: because increase Ca reabsorption
  • Calcitriol can be given as itincreases levels more rapidly
  • watch Ca2+ levels carefully as they can get hypercalcemic
40
Q

Etiologies of hyperphosphotemia?

A
  • marked tissue breakdown: sepsis, rhabdomyolysis
  • can induce hypocalcemia b/c Ca/phosphate precipitation in tissue
  • lactic acidosis/DKA
  • renal failure!!!!
  • hypoparathyroidism: also will have hypocalcemia
  • Vit D toxicity
41
Q

Work up of hyperphosphatemia?

A
  • serum phosphate: measured on whole blood, level usually inverse of Ca when abnormal values, normal: 2.5-4.5 mg/dL
  • CMP: check renal fxn, glucose
  • ABG for pH
  • urinalysis
42
Q

Tx of hyperphosphatemia?

A
  • acute: saline infusion to increase phosphate excretion, but can lower Ca2+ even more
  • hemodialysis

Chronic: low phosphate diet: 900 mg a day, phosphate binders

43
Q

Etiologies of hypophosphatemia?

A
  • redistribution of phosphate from ECF into cells: admin of insulin in tx DKA, refeeding malnourished pts such as alcoholics and those with anorexia nervosa, acute respiratory alkalosis
  • decreasd intestinal absorption
  • increased urinary excretion
44
Q

How does decreased intestinal absorption lead to hypophosphatemia?

A
  • poor intake combined with chronic diarrhea or steatorrhea, Vit D deficiency, antacids w/ aluminum, or magnesium
45
Q

How does increased urinary excretion lead to hypophosphatemia?

A
  • primary and secondary hyperparathyroidism
  • primary renal phosphate wasting (rare)
  • osmotic diuresis (usually secondary to glucosuria)
46
Q

Signs and sxs of hypophosphatemia?

A
  • CNS: paresthesias, irritability, can progress to seizures and coma
  • CV: decreased contractility may lead to CHF
  • MS: proximal myopathy, dysphagia, may progress to rhabdomyolysis
  • lungs: decreased ventilation
  • releases PH04 from bone and with it Ca2+ resulting in hypercalcemia
47
Q

Work up of hypophosphatemia?

A
  • serum phosphate level
  • CMP
  • measure 24 hr urine phosphate excretion:
    low: DKA, refeeding, intestinal malabsorptio
    high: hyperparathyroidism, or renal tubular defect
48
Q

Tx of hypophosphatemia?

A
  • with DKA the phosphate will correct on its own

- if phosphate is

49
Q

What is usually the culprit of Vit D toxicity?

A
  • usually due to those taking megadoses of Vit D

- D is a fat soluble vitamin and in excess is stored in liver and adipose tissue

50
Q

Main presenting sxs of Vit D toxicity?

A
  • hypercalcemia
  • with hypophosphatemia
  • confusion (dehydrated), anorexia, and vomiting
  • extreme: muscle weakness and bone demineralization from being hypercalcemic
  • kidney stones
51
Q

Work up of Vit D toxicity?

A
  • Vit D level

- hypercalcemia work up

52
Q

Tx of Vit D toxicity?

A
  • if not severe: IV saline

- if more severe: glucocorticosteroids, IV bisphosphonates

53
Q

Etiologies of Vit D deficiency

A
  • elderly
  • winter months/houseboubd
  • northern climate
  • chronic renal disease
  • GI disease- malabsorption (celiac, gastric bypass, inflammatory bowel disease (crohns and ulcerative colitis)
  • liver failure
  • drugs: phenytoin, phenobarbitol, caracbomezepine, isoniazid, rifampin (TB), and prolonged glucocorticoid use
54
Q

Presentation of Vit D deficiency?

A
  • initially reduced absorption of Ca2+ and PO4-
  • leding to hypophosphotemia > hypocalcemia
  • with persistent deficiency: hypocalcemia will result in HPT -> phophoturia -> demineralization of bone and w/o t it will manifest as osteomalacia/osteoporosis
    (adults) , rickets (children)

sxs: bone pain, muscle weakness: difficulty walking, and fractures

55
Q

Work up of Vit D deficiency

A
  • Vit D level
  • serum Ca2+
  • phosphorus
  • PTH
  • ALP
  • electrolytes
  • BUN and creatinine
56
Q

Tx of Vit D deficiency

A
  • depending on how low level of serum vitamin D determines dosing of supplement
  • oral replacement of Vit D and not it’s metabolites is recommended
  • there is an IM version in some countries: quite painful no added benefit
  • for those with malabsorption sometime metabolites are given or just sun is Rx