Disorders of Calcium and Parathyroid Gland Flashcards

(67 cards)

1
Q

Mineral Metabolism Key players

Cellular level

A
– Calcium
– Phosphorous
– PTH
– Vitamin D
– FGF23
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2
Q

Mineral Metabolism Key players

Tissue Level

A
– Parathyroid glands
– Gut
– Kidney
– Bone
– Liver
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3
Q

Mineral Metabolism Minor players

Cellular level

A

– Calcitonin
– Magnesium
– Acid-­‐base state

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4
Q

Mineral Metabolism Minor players

Tissue Level

A

– Skin

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5
Q

Calcium distribution Total body calcium

A

~ 1 kg
– 99% in bone (hydroxyapatite)
– 1% extracellular and soft tissues
– 0.1% intracellular

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6
Q

Calcium distribution Serum calcium

A

– 40% protein bound
– 10% complexed (citrate or phosphate ions)
– 50% ionized – free calcium that is bioavailable

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7
Q

Low Calcium Stimulates release

A

PTH

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8
Q

Increase PTH

A

Increase calcium mobilizaIon from bone
Increase calcium reabsorpIon from DCT
Increase 1α-hydroxylase

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9
Q

Increase in 1α-hydroxylase

A

Increase calcium absorption from intestines from increase 1,25(OH)2D.

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10
Q

increase 1,25(OH)2D

A

stimulates reabsorption of Ca (distal nephron)

inactivates phosphate transporter (PCT)

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11
Q

Calcium-­‐sensing receptor (CaSR) senses

A

Ca++ level

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12
Q

CaSR found in & is a member of?

A

-parathyroid
-kidney
-C cells thyroid
-bone
Member of the GPCR family

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13
Q

Stimulating the calcium sensing receptor results in?

A

an Intra-cellular cascade to reduce PTH secretion

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14
Q

Work up of hypercalcemia (Differential Diagnosis)

Three thing?

A
  1. History and Physical
  2. Check albumin and total calcium x 2
  3. Check a PTH
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15
Q

PTH dependent hypercalcemia

A

− Hyperparathyroidism (primary/tertiary)
− Familial hypocalciuric hypercalcemia
− Medication-induced (Lithium or HCTZ-mediated)

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16
Q

PTH independent hypercalcemia

A
  • Tumor induced (PTHrP or bone metastases)
  • Granulomatous diseases (TB), sarcoidosis, lymphoma - ↑ 1,25 vit.D
  • Multiple myeloma
  • Hyperthyroidism/adrenal failure
  • Immobilization
  • Medication-induced: (vitamin D toxicity, vitamin A, milk-alkali)
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17
Q

Primary Hyperparathyroidism

A

80-85% adenoma
15% hyperplasia (MEN1, MEN2A, HPT-Jaw Tumor Syndrome, familial HPT)
<1% Parathyroid carcinoma

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18
Q

Sporadic Primary Hyperparathyroidism
Risk factors:
Etiology:
Buzz words:

A

age, race (AA>W>H), sex (F>M)
unknown
serendipity: stones, moans (abdominal), groans (psychic), & bones

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19
Q

Symptoms in Primary Hyperparathyroidism

A
Fatigue/weakness
Musculoskeletal pain
Polydipsia/Polyuria
Constipation
Anorexia/nausea/Dyspepsia
Pruritus
Depression/Memory loss
Renal failure/Kidney stones
Osteoporosis/Fracture
Pancreatitis
Hypertension
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20
Q

Symptoms in Primary Hyperparathyroidism Most Common

A
  • Symptoms are non-­‐specific

* Majority of paIents are asymptomaIc

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21
Q

Primary HPT Work up Biochemical:

A
  • calcium, Albumin (ionized calcium),
  • PTH,
  • 25-OH vitamin D,
  • 24-hour urine calcium (to differentiate from FHH)
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22
Q

Primary HPT Work up Imaging:

A
  • Thyroid US (Localization study)
  • 99Tc-sestamibi scan (Localization study)
  • DXA
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23
Q

Management of Primary HPT ConservaIve management

A
  • Adequate hydraIon
  • Use of bisphosphonates in paIents with osteoporosis
  • Maintenance of vitamin D status (20-­‐30 ng/mL)
  • Cinacalcet has been approved by FDA for those who do not qualify for surgery and have moderate hypercalcemia (Ca >12.5 mg/dL)
  • Annual follow up: Ca/PTH, renal function, DXA
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24
Q

Familial Hypocalciuric Hypercalcemia Inactivating mutation causing?

A

Of CaSR, 100% penetrance
Mildly ↑ serum Ca, high-normal/mildly ↑ PTH, hypocalciuria.
Asymptomatic

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25
Familial Hypocalciuric Hypercalcemia Work up:
Serum Ca, PTH, 24-hr urine calcium (<50-100 mg/ | 24 hr). Can also ask relatives to √ serum calcium. Genetic testing
26
Familial Hypocalciuric Hypercalcemia Treatment
No treatment is indicated
27
Tertiary Hyperparathyroidism Occurs in
The face of long standing secondary hyperparathyroidism • At one point, these glands become autonomous (recall Primary HPT) – in the setting of end-stage renal disease – Post-kidney transplant
28
Parathyroid glands develop hyperplasia
Due to chronic low Calcium and/or high | Phosphorous levels
29
Hypercalcemia of malignancy Clinical presentaIon
Consistent with signs & symptoms of hypercalcemia & potenIal diagnosis of malignancy
30
Hypercalcemia of malignancy EIology:
breast, lung, lymphoma, thyroid, kidney, prostate, mulIple myeloma, pancreas… Most common: breast & squamous cell carcinoma
31
Hypercalcemia of malignancy | THE PTH LEVEL WILL BE
SUPPRESSED!!!
32
Hypercalcemia can occur in malignancy without increase in PTHrP
− Bony metastases can increase calcium levels − Humoral factors (cytokines, TNFa) can acIvate osteoclasts − MulIple myeloma can cause significant bone destrucIon resulIng in hypercalcemia
33
Granulomatous disorders causing hypercalcemia
Sarcoid | Lymphoma
34
Granulomatous disorders causing hypercalcemia (sarcoid, lymphoma)
``` Increased 25(OH)D3 Increased1 25(OH)2D3 Decreased VDR (Vitamin D receptor) Increased 1α-hydroxylase Increased PTH Increased Ca Increased PO4 ```
35
Initial Treatment of Acute Hypercalcemia
Address Volume Status: Saline Diuresis ± Furosemide (*only after volume status is corrected) Calcitonin IM/SC (4-6 IU/kg q6-12 hours) – 3-4 days Bisphosphonates (Pamidronate IV over 4 hrs- works for 2-3 wks or Zoledronic acid IV over 15 minutes works for 1-3 months) Glucocorticoids (*useful in myeloma, granulomatous disease, vitamin D toxicity) Phosphate (*rarely used, caution elevated Ca x Phos product) Dialysis
36
Major Causes of Secondary PTH Elevation
1. Hypocalcemia 2. Hyperphosphatemia 3. Vitamin D deficiency
37
Renal Disease
Decrease 1a-hydroxylase Decrease 1,25(OH)2D3 Increase PTH
38
Approach to the patient with Secondary Hyperparathyroidism Symptoms:
Are non-specific and likely related to underlying disease causing elevated PTH but not due to PTH itself
39
Approach to the patient with Secondary Hyperparathyroidism Evaluate key elements of the?
Calcium axis: serum PTH, Calcium (with albumin), Phosphorous, Creatinine, vitamin D. Do not collect 24-hour urine for calcium
40
Approach to the patient with Secondary Hyperparathyroidism if calcium is normal
No indications for imaging studies
41
Approach to the patient with Secondary Hyperparathyroidism Treatment
Treat underlying reason(s). Make sure vitamin D is always replete.
42
Vitamin D Deficiency
1. Severe vitamin D deficiency is rare 2. Presenting complains in mild-to-moderate vit. D deficiency are very non-specific: musculoskeletal pains, fatigue 3. 50% of patients with osteoporosis have vit. D deficiency 4. Vitamin D replacement (>800 units/day) showed ~20% reduction in risk of fractures
43
Hypocalcemia: Clinical signs
``` agitation hyperreflexia convulsions hypertension long QT ```
44
Hypocalcemia: DifferenIal Diagnosis of Hypoparathyroidsm (low PTH)
Primary process as low PTH decreases Calcium 1. Post-thyroidectomy 2. Idiopathic – antibodies to PTH 3. Autoimmune 4. Parathyroid agenesis – e.g. DiGeorge syndrome 5. Hypomagnesaemia, hypermagnesemia, hyperphosphatemia
45
Hypocalcemia: DifferenIal Diagnosis of Hyperparathyrodism (high PTH)
Secondary process or when PTH increases due to low calcium from other reasons. 1. Renal Failure 2. Vitamin D deficiency 3. Vitamin D or PTH resistance syndromes
46
Miscellaneous Causes of Hypocalcemia
1. Acute pancreatitis: free fatty acids chelate calcium 2. Massive transfusion: infusion of citrate will complex with calcium leading to decreased ionized calcium 3. Tumor Lysis Syndrome or rhabdomyolysis: Phosphate release binds to ionized calcium 4. Severe sepsis: Cytokines mediated? 5. Medications: phosphate, bisphosphonates 6. Hungry bone syndrome
47
Work up of hypocalcemia
1. History and Physical 2. Check albumin and total calcium x 2 3. Check PTH
48
Work up of hypocalcemia PTH is low
Hypoparathyroidism Magnesium deficiency Phosphate excess
49
Work up of hypocalcemia PTH is high
Severe vitamin D deficiency Renal failure Vitamin D resistance or PTH resistance
50
Pseudohypoparathyroidism define:
The idiopathic inherited forms of PTH resistance.
51
Pseudohypoparathyroidism PaIents | have
Elevated PTH (1000s), hypocalcaemia, hyperphosphatemia and/or specific morphological features including short stature, rounded face, foreshortened 4th and other metacarpals, obesity.
52
Pseudohypoparathyroidism Molecular defect:
Inability of PTH sImulate intracellular signaling events (cAMP pathway) due to mutaIon in Gsα subunit or elements downstream to cAMP signaling
53
Hypocalcaemia - Treatment Acute Hypocalcemic Crisis:
– Always correct Magnesium if low – Calcium Gluconate (93 mg elemental Ca++/10 ml) • 1 - 2 ampules over ~10 – 20 minutes • 0.5-2.0 mg/kg/hr of elemental Calcium IV
54
Hypocalcaemia - Treatment Long-term Management:
– Oral Calcium salts (up to 3 grams of elemental Ca/day) – Vitamin D • Ergocalciferol/Cholecalciferol (act in 10-14 days) -effective only if PTH is present • Calcitriol - 0.5-1.0 mcg/day – Hydrochlorothiazide – increases reabsorption of Calcium in the distal tubule
55
MEN – Multiple Endocrine Neoplasia
A syndrome in which 2 or more endocrine tumors occur in a single patient
56
MEN Gentics & Tumor Type
1. Autosomal dominant (e.g., DNA deletion) - germline or sporadic mutations (2nd hit hypothesis) 2. Different penetrance (varying phenotype) 3. Benign and malignant 4. Functionally active and inactive
57
MEN1- Affected gene
11q12-13
58
MEN1 Presentation/penetrance
Prevalence up to 20/100,000; 2nd-3rd decade. Remeber Three P's 1.Parathyroid (Primary HPT) – 80-95% 2.Pancreas (insulinoma, gastrinoma, VIPoma) – 50% 3. Pituitary (prolactinoma, Cushing`s disease, acromegaly) - 25%
59
MEN1 Signs/Symptoms
Kidney stones, hypercalcemia, recurrent peptic ulcers, fasting hypoglycemia, hypogonadism, galactorrhea, weight gain, diarrhea
60
MEN1 Screening
- Calcium, PTH - gastrin - insulin,glucose - prolactin - IGF-1 - ACTH, cortisol
61
Timeline of the MEN1 Phenotype
• Hypercalcemia due to Primary HPT manifests by age 40 (19-­‐40) • Pituitary tumors diagnosed on average at age 38 (12-­‐83) • PancreaIc tumors: – Insulinoma at age 25 – Gastrinoma at age 35
62
MEN2A Affected gene
RET 10q11.2 | Mutation at codon Cys634
63
MEN2A Presentation/ penetrance
1/30,000, any age, more in adults, 80% of all MEN2 1. Medullary thyroid carcinoma – almost 100% 2. Pheochromocytoma – 40% 3. Primary HPT – 25%
64
MEN2A Signs/ Symptoms
Thyroid nodule, hypertension, spells, diaphoresis, hypercalcemia,
65
MEN2AB Affected gene
RET 10q11.2 | Mutation at codon Met634
66
MEN2AB Presentation/ penetrance
1/30,000, early onset, 5% of all MEN2 1. Medullary thyroid carcinoma (more malignant) – 100% 2. Mucosal neuromas – 100% 3. Marfanoid habitus – 50% 4. Pheochromocytoma – 50%
67
MEN2AB Signs/Symptoms
Thyroid nodule, skin neuromas, Hirschsprung`s disease, hypertension, spells, diaphoresis,