Clinical Calcium Homeostasis Flashcards
what is calcium level threshhold for mild hypercalcemia?
<3.0mmol/L
Often asymptomatic and does usually require urgent correction
what is calcium level threshhold for moderate hypercalcemia?
3.0-3.5mmol/L
May be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated
what is calcium level threshhold for severe hypercalcemia?
> 3.5 mmol/L
Requires urgent correction due to risk
of dysrhythmia and coma
what are parathyroid mediated causes of hypercalcaemia?
Primary
hyperparathyroidism
(sporadic)
Inherited variants
*Multiple endocrine
neoplasia (MEN)
syndromes
*Familial isolated
hyperparathyroidism
*Hyperparathyroidismjaw tumor syndrome
Familial hypocalciuric
hypercalcemia
Tertiary
hyperparathyroidism
(renal failure)
what are non-parathyroid mediated causes of hypercalcaemia?
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
what are medication mediated causes of hypercalcaemia?
Thiazide diuretics
lithium
teriparatide
excessive vitamin A
theophylline toxicity
what are mmiscellaneous causes of hypercalcaemia?
hyperthyroidism
acromegaly
pheochromocytoma
adrenal insufficiency
immobalisation
parenteral nutrition
milk alkali syndrome
what are renal clinical features of hypercalcaemia?
polyuria
polydipsia
nephrolithiasis
distal renal tubular acidosis
nephrogenic diabetes insipidus
acute and chronic renal dysfunction
what are gastrointestinal clinical features of hypercalcaemia?
anorexia
vomiting
bowel hypomotility
pancreatitis
peptic ulcer disease
what are musculoskeletal clinical features of hypercalcaemia?
muscle weakness
bone pain
osteopenia/osteoporosis
what are neurological clinical features of hypercalcaemia?
decreased concentration
confusion
fatigue
stupor
coma
what are cardiovascular clinical features of hypercalcaemia?
shortening of QT interval
bradycardia
hypertension
what should be covered in the history in diagnosis of hypercalcaemia?
– Symptoms of
hypercalcaemia
– Systemic enquiry
– Medications
– Family history
what should be covered in examination in diagnosis of hypercalcaemia?
Lymph nodes
– Concerns about
malignancy (breast, lung
etc.)
what should be covered in investigation for diagnosis of hypercalcaemia?
– U&Es
– Ca
– PO4
– Alk phos
– Myeloma screen
– Serum ACE
– PTH
consider ecg
what are the stepwise investigations that should be done for hypercalcaemia?
who does primary hyperparathyroidism most commonly affect?
Female: male = 3:1
* Incidence peaks 50-60
years
- Most patients are
asymptomatic at
diagnosis - Most cases are sporadic
but has been associated
with neck irradiation or
prolonged lithium use
what are causes of primary hyperparathyroidism?
85% parathyroid
adenoma
- 15% four gland
hyperplasia - <1% MEN type 1 or 2A
- <1% parathyroid
carcinoma - Often present for years
prior to diagnosis
Presentation of primary hyperparathyroidism has changed over the decades, the presentation has become much more asymptomatic why is this?
likely due to frequent blood testing previously people would have presented with diseases like osteoporosis and renal caliculi
what investigations are done for primary hyperparathyroidism?
Ca, PTH
- U&Es: check renal function
- Abdominal imaging: renal calculi
- DEXA: osteoporosis
- Spot urinary calcium/creatinine ratio: Excl. FHH
- 24 hour urinary calcium: If elevated, more likely
to be recommended for surgery
* Vitamin D
what imaging can also be done in investigating primary hyperparathyroidism?
para thyroid ultrasound
why is imaging done for primary hyperparathyroidism?
Imaging helps to localise adenoma so surgeon can have a targetted approach with smaller incisions
The purpose is not to confirm the diagnosis which has already been done through biochemical tests
what is first line investigation for adults over 65?
4D CT
what is indication for surgery in primary hyperparathyroidism?
what medical managements are done for primary hyperparathyroidism?
Medical management
– Generous fluid intake
– Vitamin D replacement
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)
what are risks or surgery for primary hyperparathyroidism?
Bleeding, haematoma, wound infection, hypercalcaemia ussually temporary
Sometimes remaining parathyroid glands gone to sleep and takes time to wake up
Recurrent laryngeal nerve injury very rare
what is familial hypocalciuric hypercalcaemia?
Autosomal dominant disorder of the calcium sensing receptor
- 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
what does Hypocalciuric mean?
Low levels of urinary calcium
Most-tumour associated
hypercalcaemia is ____
Unless an endocrine tumour,
prognosis usually _____
mild
poor
what are different malignancies associated with hypercalcaemia?
how many types of multiple endocrine neoplasia are there?
MEN type 1
MEN type 2A
what are features of MEN type 1?
Primary
hyperparathyroidism
Pancreatic
Pituitary
describe incidence and prevalence of MEN type 1?
> 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
describe incidence and prevalence of MEN type 2A?
RET mutation
- 20-30 % of MEN2A have
hyperparathyroidism - Usually milder disease than in
MEN 1
what are features of MEN type 2A?
Medullary thyroid cancer
– Phaeochromocytoma
– Primary
hyperparathyroidism
how is hypercalcaemia primarily managed?
Rehydration
– 0.9% Saline 4-6 litres
over 24 hours
– Monitor for fluid
overload
– Consider dialysis if
severe renal failure
how is hypercalcaemia managed following rehydration treatment?
After rehydration,
intravenous
bisphosphonates
– Zolendronic acid 4mg
over 15 mins
– Give more slowly and
consider dose reduction
if renal impairment
– Calcium will reach nadir
at 2-4 days
what is second line management for hypercalcaemia?
what is the serum calcium range for acute hypocalcaemia?
Serum Calcium <2.20 (reference range 2.20-2.60mmol/L)
what are acute clinical features of hypocalcaemia?
what are chronic features of hypocalcaemia?
what are common signs of hypocalcaemia?
Trosseau’s sign
Chovstek’s sign
what is Chovstek’s sign?
what is Trosseau’s sign?
what are causes of hypocalcaemia?
- 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?)
- Cytotoxic drug-induced hypocalcaemia
- Pancreatitis, rhabdomyolysis and large volume
blood tranfusions
hypoparathyroidism low PTH causes?
High PTH (secondary
hyperparathyroidism in
response to hypocalcemia) causes?
drug causes of hypocalcaemia?
what should be covered in the history in relation to hypocalcaemia?
Symptoms
– Ca & Vit D intake
– Neck surgery
– Autoimmune disorders
– Medications
– Family history
what should be covered in the examination in relation to hypocalcaemia?
Neck scars
what should be covered in the investigations in relation to hypocalcaemia?
ECG
– Serum calcium
– Albumin
– Phosphate
– PTH
– U&Es
– Vitamin D
– Magnesium
what would investigations show in vitamin D deficiency and hypoparathyroidism?
what might hypoparathyroidism result from?
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
what is Pseudohypoparathyroidism,?
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
how is pseudohypoparathyroidism characterised?
It is
characterized by hypocalcemia,
hyperphosphatemia and, in contrast to
hypoparathyroidism, elevated rather than
reduced PTH concentrations
what are clinical features of pseudohypoparathyroidism?
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 (pseudopseudohypoparathyroidism)
what is the treatment for mild hypocalcaemia?
- 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+
what is the calcium serum for mild hypocalcaemia?
Asymptomatic, >1.9mmol/L
what is the treatment for severe hypocalcaemia?
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) - The initial bolus can be repeated until the patient is
asymptomatic and/or calcium levels significantly increased - A Calcium gluconate infusion can then follow (100ml of
10% calcium gluconate in 1litre of 0.9% saline or 5%
dextrose and infuse at 50-100ml/h) - Aim to achieve normocalcaemia
- Treat the underlying cause
what is the serum calcium for severe hypocalcaemia?
Symptomatic or <1.9mmol/L
what advice in relation to vitamin D should be given to those with hypocalcaemia?
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)
what is important to note about vitamin D replacement therapy?
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
what is the scottish governments advice on prevention of hypocalcaemia?
Everyone age 5 years and above should consider taking a daily
supplement of 10 micrograms vitamin D, particularly during the
winter months (October – March).
what are dietary sources of calcium?
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
what are functions of calcium?
Bone formation
* Cell division & growth
* Muscle contraction
* Neurotransmitter
release
describe metabolism of calcium?
what proportion of calcium is bound to plasma?
– 40% bound (mainly to albumin)
– 15% non-ionised or complexed to citrate, PO4 etc.
– 45% ionised (or free)
what is normal range of plasma calcium?
Normal range 2.20-2.60 mmol/l
how do we calculate free calcium?
– 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
how does acidosis affect ionised calciuim?
Acidosis increases
ionised calcium thus
predisposing to
hypercalcaemia
what are sources of vitamin D?
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
describe the parathyroid glands?
Usually 4 glands get their name as they sit beside the thyroid glands
The chief cells secrete parathyroid hormone / PTH
Oxyphil cells are larger but less abundant than chief cells
how is vitamin d metabolised?
Vitamin d is hydroxylated in the liver to its inactive form of vitamin d
This is activated in the kidney which is partly controlled by PTH
Inactive vitamin d is the major circulatinng form of vitamin d, it has a half life of two to three weeks and has seom activity at the bone and in the intestine but is less potent than activated vitamin d
how do cheif cells respond to changes in calcium concentrations?
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
PTJ effects
