Lecture 19: PTH and Mineral Metabolism Disorders Flashcards

1
Q

How is PTH secretion controlled via negative feedback?

A

Ionized calcium interacts with calcium sensing receptors (CaSRs) in the parathyroid and kidneys.
High calcium = suppressed PTH secretion.

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2
Q

In what 3 ways can the parathyroid increase its secretion of PTH in response to hypocalcemia?

A
  • Immediate: releasing preformed PTH.
  • Delayed: Expressing PTH mRNA
  • Extended: Parathyroid cell replication by increasing parathyroid gland mass
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3
Q

What are functions of calcium?

A
  • Maintain bone and teeth strength
  • Promote contraction and relaxation of muscle and blood vessels
  • Hormone and enzyme secretion
  • Neurocellular signaling
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4
Q

Where is calcium stored in the body?

A
  • 99% bone
  • Intracellular
  • Blood/ECF (50% of the Ca in this is bound to proteins)
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5
Q

What 3 organs control calcium levels?

A
  • SI/LI: absorbing dietary Ca
  • Kidneys: Reabsorbing Ca
  • Bones: Storing Ca
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6
Q

What secondary mineral has a similar profile to calcium in terms of storage and function?

A

Phosphate

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7
Q

What 3 hormones regulate the balance of calcium and phosphate?

A
  • PTH
  • Vit D-1,25
  • Calcitonin
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8
Q

What is the effect of PTH on the kidneys?

A
  • Reabsorb Ca
  • Excrete phosphate
  • Produce vit D-1,25
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9
Q

What is the effect of PTH on the bones?

A

Stimulates movement of Ca and phosphate from bone to the ECF.

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10
Q

What is the inactive form of Vit D-1,25?

A

Vit D-25

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11
Q

What is the function of Vit D-1,25?

A
  • Increasing intestinal absorption of dietary Ca and Phosphorus
  • Enhancing PTH effect on bone
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12
Q

What hormone opposes PTH? Where is it secreted from?

A

Calcitonin, secreted from C cells in the thyroid.

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13
Q

What triggers the release of calcitonin?

A

Hypercalcemia, overstimulating the C-cell receptors.

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14
Q

What does calcitonin do?

A
  • Suppresses renal absorption of Ca, increasing its excretion.
  • Inhibits osteoclastic activity, increasing bone calcium storage.
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15
Q

What makes up total calcium?

A

Protein bound and free Ca

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16
Q

What can falsely alter serum calcium concentrations?

A

Serum protein counts (esp. albumin)

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17
Q

When do I use a corrected calcium?

A

Patients with abnormal albumin levels or when ionized calcium levels are not available.

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18
Q

What lab test is used to diagnose hyperparathyroidism?

A

Serum PTH

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19
Q

What does increased serum PTH suggest?

A

Primary or secondary hyperparathyroidism.

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20
Q

What are the 2 forms of Vit D measured by a serum 25-hydroxy Vit D test?

A
  • D3 (cholecalciferol), synthesized in the epidermis
  • D2 (ergocalciferol), derived from plants.
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21
Q

What is the active form of vitamin D?

A

Calcitriol, aka 1,25-dihydroxy-Vit D

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22
Q

Disease of what organ can grossly affect Calcitriol levels?

A

Kidney.
Increased renal production in hyperparathyroidism.
Decreased levels with CKD.

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23
Q

What does an elevated serum phosphate suggest?

A

Hypoparathyroidism

Kidneys should be excreting it.

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24
Q

What is Parathyroid Hormone Related Protein (PTHrP)? Why is it significant?

A

Normally found in the body, but pathologically secreted by cancer cells.
Causes a PTH effect on the bone and kidney.

One of the top manifestations of paraneoplastic is hypercalcemia.

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25
Q

What are the 2 main causes of hypercalcemia?

A

Hyperparathyroidism and malignancy

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26
Q

What are the clinical manifestations of hypercalcemia?

A
  • Bones
  • Stones
  • Groans
  • Psychiatric Overtones
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27
Q

How do we treat severe hypercalcemia?

A
  • IV NS w or w/o furosemide and corticosteroids.
28
Q

What are the main causes of hypocalcemia?

A

Impaired PTH or Vit D production.

29
Q

What causes low PTH and hypocalcemia?

A
  • Parathyroid agenesis
  • Parathyroid destruction (surgery)
  • Reduced parathyroid function (hypomagnesemia)

Hypoparathyroidism

30
Q

What causes high PTH but hypocalcemia?

A
  • Vit D def
  • Tissue injury
  • PTH resistance
  • Drugs

Secondary hyperparathyroidism

31
Q

What are the signs of hypocalcemia?

A
  • Chvostek’s
  • Trosseau’s
32
Q

What are the symptoms of hypocalcemia?

A

Paresthesias: fingers, toes, circumoral.

33
Q

What labs should I order in initial eval of hypocalcemia?

A
  • PTH level
  • Albumin, creatinine
  • Phosphorus, Mg
  • Vit D (both 25-hydroxy and 1,25-2D
34
Q

What is the MCC of hypercalcemia?

A

Primary hyperparathyroidism: Excessive PTH secretion leading to hypercalcemia and hypophosphatemia.

MC in females aged 60-70.

35
Q

What is the MCC of primary hyperparathyroidism?

A

Single parathyroid adenoma.

36
Q

How does primary hyperparathyroidism typically present?

A

Asymptomatic, incidental finding on routine screenings.

37
Q

When might a parathyroid mass be palpable? What symptoms does it show?

A

Only if it is a carcinoma (75% of the time)

Symptoms are those of hypercalcemia.

38
Q

What diagnoses primary hyperparathyroidism?

A

Elevated PTH. Generally elevates with size of adenoma, with carcinomas being > 14.0

39
Q

How high is a parathyroid carcinoma’s PTH level usually?

A

5x the ULN.

40
Q

How do we differentiate between FHH and PHPT?

A

24 hour urine calcium collection.
200-300 excludes FHH.
< 200 could be either.

FHH is hypocalciuric, so high calcium = unlikely.

41
Q

How do we differentiate between PHPT and secondary?

A

Serum phosphate
Low = PHPT
High = Secondary dt CKD.

42
Q

What should happen to serum 25-OH Vit D in PHPT?

A

Decreased due to excessive conversion.

43
Q

When is imaging needed for PHPT?

A
  • Neck US needed only if surgery is being considered.
  • Nuclear scan to check which tissue is hyperfunctioning.
  • CT-4D (if other scans are negative)
44
Q

How is asymptomatic PHPT managed by a patient?

A
  • Regular WEIGHT-bearing exercises
  • Avoid immobilization
  • Drinking adequate fluids.

Avoid:
* Thiazides
* Large Vit A doses
* Calcium antacids

45
Q

What labs and imaging can we order to monitor asymptomatic PHPT?

A
  • Serum Ca and Albumin 2x/yr
  • Renal function and urine calcium 1x/yr
  • Serum Vit D 25
  • 3 site DEXA scan (distal radius, hip, and spine) every 2 yrs.
46
Q

How do we manage symptomatic PHPT?

A
  • Surgery (Recommended)
  • Cinacalcet (CaSR binder to decreasing PTH secretion)
  • Oral bisphosphonates (cannot treat hypercalcemia/uria)
  • IV bisphosphonates (can temp treat hypercalcemia)
47
Q

What must a patient do when taking oral bisphosphonates?

A

Stand upright for 30 minutes after ingestion.

48
Q

For postmenopausal women, what medication can help with PHPT?

A

Estrogen replacement, which causes slight reductions in serum calcium.

Raloxifene (agonist in bone, antagonist in breast/uterine tissue)

49
Q

What are the main complications of PHPT?

A
  • Osteopenia/Osteoporosis/Pathological fractures
  • Vit D def
  • Nephrolithiasis
50
Q

What is secondary hyperparathyroidism?

A

Overproduction of PTH due to a chronic abnormal stimulus.

51
Q

What is the MCC of secondary hyperparathyroidism?

A
  • MCC: CKD
  • Second is Vit D def
52
Q

What are the S/S of secondary hyperparathyroidism?

A

Hypocalcemia symptoms

53
Q

What labs would I order to help evaluate secondary hyperparathyroidism?

A
  • BUN/Cr (elevated in CKD)
  • PTH (high)
  • Ca (low-normal)
  • Phosphorus (high in CKD, low in Vit D def)
  • Vit D-1,25 (low in CKD)
54
Q

How do we manage/treat secondary hyperparathyroidism?

A

Refer to nephro if CKD.
Vit D supplementation if deficient

55
Q

What is hypoparathyroidism and its etiologies?

A

Disorder of PTH deficiency.
* Acquired s/p surgery
* Autoimmune hypoparathyroidism
* Parathyroid deficiency (irradiation, riedel thyroiditis, cancer)
* Functional hypoparathyroidism (Severe hypomagnesemia or hypermagnesemia
* Congenital (CaSR dysfunction)

56
Q

What is the hallmark sign of acute hypocalcemia?

A

Tetany due to neuromuscular irritability

57
Q

What signs and symptoms would I expect in hypocalcemia?

A
  • Mild: Paresthesias
  • Severe: Spasms/seizures
  • Trousseau’s
  • Chvostek’s
  • Prolonged QT
58
Q

How do lab tests typically appear for hypoparathyroidism?

A
  • Serum calcium: LOW
  • Serum Phosphorus: HIGH
  • Urinary calcium: LOW
  • PTH: LOW
  • Vit D 1,25: LOW to NORMAL
  • Mg/Vit D-25, Creatinine: NORMAL
  • EKG: Prolonged QT and T wave abnormalities
59
Q

What is the acute management protocol for hypoparathyroidism?

A
  1. AIRWAY
  2. IV Calcium gluconate
  3. Oral Calcium
  4. Magnesium (if hypomagnesemic)
  5. Mg oxide after IV
  6. Vit D therapy once oral calcium is started. (Calcitriol preferred)
60
Q

What is the maintenance therapy for hypoparathyroidism?

A
  • Oral calcium
  • Vit D supplements
  • Monitor Mg
  • Teriparatide SQ (if pt is refractory to Ca/Vit D)
61
Q

When is a cryopreserved parathyroid tissue transplant indicated?

A

Patients undergoing parathyroidectomy. Usually placed into the forearm.

62
Q

What requires more Vit D2, vit D deficiency or hypoparathyroidism?

A

Hypoparathyroidism requires 25x more at minimum with calcium supplements.

63
Q

What is the difference between taking a Vit D2 supplement vs Calcitriol?

A

Calcitriol is the active form, requiring no conversion in the kidneys.

64
Q

What are the indications for calcitriol?

A
  • Hypocalcemia dt hypoparathyroidism
  • Secondary hyperparathyroidism with late stage CKD
65
Q

When is calcium carbonate indicated?

A
  • Hypocalcemia prevention/treatment.
  • Primary osteoporosis prevention.
66
Q

When is calcium gluconate indicated?

A

Severe hypocalcemia.

67
Q

What are the ARs of MgO supplementation?

A

Diarrhea and GI irritation