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year 2 endocrine - Robbie > Clinical Calcium Homeostasis > Flashcards

Clinical Calcium Homeostasis Flashcards

1
Q

Name Dietary sources of calcium

A
  • milk, cheese and other dairy foods
  • green leafy vegetables – such as broccoli, cabbage and okra, but not spinach
  • soya beans
  • Tofu
  • nuts
  • bread and anything made with fortified flour
  • fish where you eat the bones – such as sardines and pilchards
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2
Q

what are the functions of calcium?

A
  • Bone formation
  • Cell division & growth
  • Muscle contraction
  • Neurotransmitter release
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3
Q

What percentage of Ca2+ is found where?

A
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4
Q

What proportion of calcium is bound in plasma?

A

45% bound (mainly to albumin)

10% non-ionised or complexed to citrate, PO4 etc.

45% ionised - biologically important (Ionized calcium is calcium in your blood that is not attached to proteins. It is also called free calcium)

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5
Q

what is the normal range of plasma calcium?

A

Normal range 2.20-2.60 mmol/l

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6
Q

how do we calculate and adjust free calcium?

A

Increased albumin decreases free calcium

Decreased albumin increases free calcium

Adjust Ca2+ by 0.1mmol/l for each 5g/l reduction in albumin from 40g/l

Acidosis increases ionised calcium thus predisposing to hypercalcaemia

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7
Q

what are sources of vitamin D?

A
  • Vitamin D is also found in a small number of foods. Good food sources are:
  • oily fish – such as salmon, sardines and mackerel
  • eggs
  • fortified fat spreads
  • fortified breakfast cereals
  • some powdered milks
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8
Q

what cells make up the parathyroid gland?

A

chief cells and the oxyphil cells

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9
Q

what is the role of parathyroid hormone?

A

Chief cells respond directly to changes in calcium concentrations

Alterations in ECF Ca2+ levels are transmitted into the parathyroid cells via calcium-sensing receptor (CaSR)

PTH is secreted in response to a fall in calcium

Chief cells– The role of this cell type is to secrete parathyroid hormone

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10
Q

how does parathyroid hormone increase calcium?

A

PTH has direct effects that promote reabsorbtion of calcium from renal tubules & bone

What bone problem might lengthy exposure to inappropriate levels of PTH lead to? - osteoprosis

PTH mediates the conversion of vitamin D from its inactive to active form

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11
Q

PTH mediates the conversion of vitamin D from its inactive to active form

Where in the body does this conversion take place?

A
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12
Q

Why do some patients need activated vitamin D?

A

if their kidneys do not work

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13
Q

what levels of serum calcium are classed as hypocalcaemia?

A

Serum Calcium <2.20 (reference range 2.20-2.60mmol/L)

Symptoms of hypocalcaemia typically develop when adjusted serum calcium levels fall below 1.9mmol/L. However this threshold does vary and is dependent on the rate of fall

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14
Q

what are the clinical features of hypocalcaemia?

A
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15
Q

what tests can be done to see if someone is hypocalcaemic?

A

Trosseau’s sign - if low calcium then hand goes into spasm when taking blood pressure

Chovstek’s sign

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16
Q

62 years old woman

She presents to a GP practice complaining of muscle spasms

She was discharged from hospital a couple of days ago following a “neck operation”

What operation has she had?

What are the recognised complications of this operation?

What should we do?

Her adjusted calcium is 1.9mmol/L (2.2-2.6)

A

just think about questions form the last slide

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17
Q

whata re the causes of hypocalcaemia?

A

Disruption of parathyroid gland due to total thyroidectomy. May be temporary or permanent

Following selective parathyroidectomy (usually transient & mild)

Severe vitamin D deficiency

Mg2+ deficiency (which drug can cause this?) - PPI

Cytotoxic drug-induced hypocalcaemia

Pancreatitis, rhabdomyolysis and large volume blood tranfusions

Most common cause of low albumin is surgeons doing things to peoples necks

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18
Q

what are the causes of hypocalcaemia with low PTH (hypoparathyroidism)?

Low calcium and low PTH then something wrong with parathyroid gland as PTH should go up

A

Genetic disorders

Post-surgical (thyroidectomy, parathyroidectomy, radical neck dissection)

Autoimmune

Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)

Radiation-induced destruction parathyroid glands

Hungry bone syndrome (post parathyroidectomy)

HIV infection

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19
Q

what are the causes of hypocalcaemia with high PTH (secondary hyperparathyroidism in response to hypocalcemia)

A

Vitamin D deficiency or resistance

Pseudohypoparathyroidism

Hypomagnesemia

Renal disease

Tumor lysis

Acute pancreatitis

Acute respiratory alkalosis

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20
Q

what drugs can cause hypocalcaemia?

A

Inhibitors of bone resorption (bisphosphonates, calcitonin, denosumab)

Cinacalcet

Calcium chelators (EDTA, citrate, phosphate)

Foscarnet (due to intravascular complexing with calcium)

Phenytoin (due to conversion of vitamin D to inactive metabolites)

Fluoride poisoning

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21
Q

what is the diagnostic approach of hypocalcaemai

A

• History:

  • Symptoms
  • Ca & Vit D intake
  • Neck surgery
  • Autoimmune disorders
  • Medications
  • Family history
  • Examination - Neck scars
  • Investigations:
  • ECG - look for a prolonged QT
  • Serum calcium
  • Albumin
  • Phosphate
  • PTH
  • U&Es
  • Vitamin D
  • Magnesium
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22
Q

pictures showing how investigations for hypocalcaemia work

A
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23
Q

how does low magnesium cause hypocalcaemia?

A

Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced (hypocalcemia). The hypocalcemia is described as “secondary” because it occurs as a consequence of hypomagnesemia

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24
Q

hypoarathyroidism may result form what?

A

agenesis (e.g. DiGeorge syndrome)

destruction (neck surgery, autoimmune disease)

Infiltration (e.g. haemochromatosis or Wilson’s disease)

reduced secretion of PTH (neonatal hypocalcaemia, hypomagnesaemia)

Resistance to PTH (discussed on next slide)

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25
Q

What is Pseudohypoparathyroidism?

A

Pseudohypoparathyroidism (PHP) is a genetic disorder in which the body fails to respond to parathyroid hormone

Pseudohypoparathyroidism, which presents in childhood, refers to a group of heterogeneous disorders defined by target organ (kidney and bone) unresponsiveness to PTH. It is characterized by hypocalcemia, hyperphosphatemia and, in contrast to hypoparathyroidism, elevated rather than reduced PTH concentrations

Albright’s heriditary Osteodystrophy (AHO): Obesity, short stature, shortening of the metacarpal bones that can occur in some patients with Pseudohypoparathyroidism

AHO alone without abnormalities of calcium or parathyroid hormone (pseudo-pseudohypoparathyroidism)

26
Q

what is the treatment of “Mild” hypocalcaemia
(Asymptomatic, >1.9mmol/L)?

A

Commence oral calcium tablets

If post thyroidectomy repeat calcium 24 hours later

If vit D deficient, start vitamin D

If low Mg2+, stop any precipitating drug and replace Mg2+

27
Q

what is the treatment of “Severe” hypocalcaemia
(Symptomatic or <1.9mmol/L)?

A

This is a medical emergency

Administer IV calcium gluconate

Initial bolus (10-20ml 10% calcium gluconate in 50-100ml of 5% dextrose IV over 10 minutes with ECG monitoring)

Calcium gluconate infusion

Treat the underlying cause

28
Q

Read this, case study 2:

Mrs Smith is 62 years old

She presents to a GP practice complaining of vague symptoms

GP does some blood tests

Her adjusted calcium is 1.95mmol/L

Her GP phones for advice

What should we do?

History? - She is on a bisphosphonate for osteoporosis, Dietary intake of calcium seems reasonable

Examination?

Investigations? - Low Ca, Low PO4, PTH awaited

Treatment - Vitamin D replacement

A
29
Q

how is vitamin D replacement done in someone with hypocalcaemia?

A

Advice regarding dietary sources

Most tablets contain a combination of vitamin D and calcium

Maintenance dose ~400-1000 international units

Higher loading dose required (e.g. 3200 units daily for 12 weeks)

Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy

30
Q

what levels of calcium is classed as hypercalcaemia?

A

dpeending on how quickly it happens and by how much by determines how symptomatic someone is

31
Q

what are parathyroid mediated causes of hypercalcaemia?

High calcium and inappropriately normal PTH then we know problem is coming form the parathyroid gland

A

Primary hyperparathyroidism (sporadic)

Inherited variants:

  • Multiple endocrine neoplasia (MEN) syndromes
  • Familial isolated hyperparathyroidism
  • Hyperparathyroidism-jaw tumor syndrome

Familial hypocalciuric hypercalcemia

Tertiary hyperparathyroidism (renal failure)

32
Q

what are non-parathyroid mediated causes of hyperglycaemia?

High calcium should be a lowered PTH and if that’s what we find and the parathyroid glands are doing what they are meant to be doing then it is coming form somewhere else

A

Hypercalcaemia of malignancy:

  • PTHrp
  • Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol)
  • Osteolytic bone metastases and local cytokines

Vitamin D intoxication

Chronic granulomatous disorders:

  • Sarcoid, TB, Berylliosis, Histioplasmosis, Wegener’s
33
Q

what medications can cause hypcalcaemia?

A

Thiazide diuretics

Lithium

Teriparatide

Excessive vitamin A

Theophylline toxicity

34
Q

What are miscellaneous causes of hypercalcaemia?

A

Hyperthyroidism

Acromegaly

Pheochromocytoma

Adrenal insufficiency

Immobilisation

Parenteral nutrition

Milk alkali syndrome

35
Q

what are the renal clinical features of hypercalcaemia?

“Bones, stones, groans & psychic moans”

A

Polyuria

Polydipsia

Nephrolithiasis - renal calculi/kindey stones

Nephrocalcinosis

Distal renal tubular acidosis

Nephrogenic diabetes insipidus

Acute & chronic renal dysfunction

36
Q

what are the Gastrointestinal clinical features of hypercalcaemia?

“Bones, stones, groans & psychic moans”

A

Anorexia

Nausea & vomiting

Bowel hypomotility & constipation

Pancreatitis

Peptic ulcer disease

37
Q

what are the Musculoskeletal clinical features of hypercalcaemia?

“Bones, stones, groans & psychic moans”

A

Muscle weakness

Bone pain

Osteopenia/osetoporosis

38
Q

what are the neurological clinical features of hypercalcaemia?

“Bones, stones, groans & psychic moans”

A

Decreased concentration

Confusion

Fatigue

Stupor, coma

39
Q

what are the cardiovascular clinical features of hypercalcaemia?

“Bones, stones, groans & psychic moans”

A

Shortening of the QT interval

Bradycardia

Hypertension

40
Q

read this, case study 3:

Mr Bloggs presented with changed bowel habit and weight loss

Blood tests showed calcium 2.76 (2.20-2.60)

Corrected calcium 2.86

Other tests? Hb, Glucose, TFTs? CXR?

Heavy smoker

Chronic cough on systemic enquiry

Repeat corr calcium was 2.81 (2.20-2.60) and PTH was <0.1 (1.7-9.2)

Most likely diagnosis? Hypercalcaemia of malignancy

A
41
Q

what is the diagnostic approach of hypercalcaemia?

A

• History

  • Symptoms of hypercalcaemia
  • Systemic enquiry
  • Medications
  • Family history

• Examination

  • Lymph nodes
  • Concerns about malignancy (breast, lung etc.)

• Investigations

  • U&Es
  • Ca
  • PO4
  • Alk phos
  • Myeloma screen
  • Serum ACE
  • PTH

• Consider ECG

42
Q

read this, case 4

Mrs Jones - 54 years old

Routine blood test showed adjusted calcium of 3.05mmol/L

She is asymptomatic

Systemic enquiry is unremarkable

Serum calcium was 2.95mmol/L 2 years ago while an inpatient for a choleycystectomy - no malignancy as been going on a while

Diagnosis?

A
43
Q

what is Primary hyperparathyroidism?

A

The parathyroid gland(s) becomes overactive and secretes excess amounts of parathyroid hormone (PTH). As a result, the blood calcium rises to a level that is higher than normal (called hypercalcemia)

44
Q

who is primary hyperparathyroidism common in?

A
  • Female: male = 3:1
  • Incidence peaks 50-60 years
45
Q

primary hyperparathyroidism - most patients are ___________ at diagnosis

A

asymptomatic

46
Q

primary hyperparathyroidism - Most cases are ________ but has been associated with neck irradiation or prolonged lithium use

A

sporadic

47
Q

what are the different causes of primary hyperparathyroidism?

A
  • 85% parathyroid adenoma
  • 15% four gland hyperplasia
  • <1% MEN type 1 or 2A
  • <1% parathyroid carcinoma
  • Often present for years prior to diagnosis
48
Q

what investigations can be done for primary hyperparathyroidism?

A

Ca, PTH

U&Es: check renal function

Abdominal imaging: renal calculi

DEXA (a means of measuring bone mineral density): osteoporosis - too much PTH = taking calcium form bone

24 hour urine collection for calcium: Excl. FHH

Vitamin D

(Para) thyroid ultrasound

SESTAMIBI: After 15mins there is uptake in the thyroid gland (& inferior parathyroid gland), after 2 hours uptake is only evident in the inferior parathyroid gland (shown in the pictures on the right)

49
Q

one treatment of primary hyperparathyroidism is surgery

The presence of what features would be an indication for parathyroid surgery

A

eGFR - Estimated glomerular filtration rate is the best test to measure your level of kidney function and determine your stage of kidney disease

50
Q

what is the medical management of primary hyperparathyroidism?

(treatment of choice is surgery if possible though)

A

Generous fluid intake

Cinacalcet (acts as a calcimetic, i.e. mimics the effect of calcium on the calcium sensing receptor on Chief cells, this leads to a fall in PTH and subsequently calcium levels)

51
Q

is msot tumour associated hypercalcaemia major or not?

A

Most-tumour associated hypercalcaemia is mild

Unless an endocrine tumour, prognosis usually poor

52
Q

what are the types of hypercalcaemia caused by malignancy?

A

High calcium and low PTH so look for malignancy

May be obvious as the person may be known for having a malignancy

May produce a PTH like protein or a direct effect of metastases on bone

53
Q

What is Familial Hypocalciuric Hypercalcaemia?

A

Autosomal dominant disorder of the calcium sensing receptor

an inherited disorder that causes abnormally high levels of calcium in the blood (hypercalcemia) and low to moderate levels of calcium in urine (hypocalciuric). People with FHH usually do not have any symptoms and are often diagnosed by chance during routine bloodwork

Low levels of urinary calcium - High serum calcium then you should have high urinary calcium but in this one your urinary calcium is low

Benign, no therapy indicated

Positive family history, screen young family members for diagnosis

PTH may be normal or slightly elevated

No evidence of abnormal parathyroid tissue on ultrasound or isotope scan

54
Q

What is Multiple Endocrine Neoplasia? and what types is there?

A

Multiple endocrine neoplasia is a group of disorders that affect the body’s network of hormone-producing glands called the endocrine system

MEN type 1

MEN type 2A

55
Q

what is MEN type 1?

A

- Primary hyperparathyroidism

  • Pancreatic
  • Pituitary
  • >95% of MEN 1 will have hyperparathyroidism
  • MENIN mutation (Chr 11)
  • 2-4% of cases of PHP may be MEN 1
  • Usually presents in the 2nd to 4th decade of life
  • Multi-gland involvement, High Recurrence Risk
56
Q

what is MEN type 2A?

A
  • Medullary thyroid cancer
  • Phaeochromocytoma

- Primary hyperparathyroidism

  • RET mutation
  • 20-30 % of MEN2A have hyperparathyroidism
  • Usually milder disease than in MEN 1
57
Q

Is family history very important in patients with primary hyperparathyroidism?

A

yes

58
Q

what is the management of hypercalcaemia?

A

• Rehydration

  • 0.9% Saline 4-6 litres over 24 hours
  • Monitor for fluid overload
  • Consider dialysis if severe renal failure

• After rehydration, intravenous bisphosphonates (Bisphosphonates are a group of drugs that work by slowing bone loss)

  • Zolendronic acid 4mg over 15 mins
  • Give more slowly and consider dose reduction if renal impairment
  • Calcium will reach nadir at 2-4 days
59
Q

what is 2nd line management of hypercalcaemia?

A
60
Q

read this, case study 5:

Mr Arthur - 74 years old

Wife took patient to GP complaining that he appear confused

Under treatment for multiple myeloma (a type of bone marrow cancer)

Adjusted calcium is 3.7mmol/L

What should you do?

A
  • Admit
  • History
  • Examination
  • Investigation
  • Management

year 2 endocrine - Robbie (28 decks)

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