This document discusses hypocalcemia, beginning with an overview of calcium homeostasis. It then covers the etiology of low and high parathyroid hormone levels as causes of hypocalcemia. Specific conditions that can cause hypocalcemia like post-thyroidectomy, autoimmune disorders, chronic kidney disease, and vitamin D deficiency are described. Other potential causes like pseudohypocalcemia, acid-base abnormalities, pancreatitis, and sepsis are also reviewed. The clinical features, evaluation, and management of hypocalcemia are summarized.

1. HYPOCALCEMIA
Ade Wijaya, MD – January 2020

2. CALCIUM HOMEOSTASIS
Song, Lu. (2017). Calcium and Bone Metabolism Indices. 10.1016/bs.acc.2017.06.005.

3. ETIOLOGY
Low
PTH
Others
High
PTH

4. LOW PTH
• Post thyroidectomy- It's not uncommon after thyroid or other head
and neck surgeries to get transient or permanent hypoparathyroidism
leading to hypocalcemis. This can be a result of unintentional removal of
parathyroid hormones or a loss of blood supply in some cases.
• Autoimmune- Auto antibodies against the parathyroid gland or
activating antibodies against Calcium-sensing receptors can both cause
hypocalcemia. Hypoparathyroidism can also occur as a part of MEN
sydromes.

5. HIGH PTH
• Chronic Kidney Disease (CKD)- CKD leads to impaired phosphate
excretion which drives PTH secretion and can cause secondary
hyperparathyroidism. However, due to impaired Vitamin D metabolism
and high phosphorus level, the serum calcium remains low despite the
high PTH.
• Absolute or relative Vitamin D defeciency- This includes lack of active
metabolite of vitamin D due to inadequate sun exposure or liver disease
or kidney disease. Also, included in this category are familial causes of
vitamin D resistance.
• Pseudohypoparathyroidism-This category refers to end organ
resistance to the action of PTH. Its a hereditary genetic disorder.

6. OTHERS
• Pseudohypocalcemia- Serum calcium is normally bound to protiens in the blood
most prominently albumin and therefore low albumin states can give a falsely low total
serum calcium level. Ionized calcium level is usually normal in these states and thus a
correction of adding 0.8 mg/dL to serum calcium level is usually recommended for
every 1gm drop in serum albumin below normal (4 gm/dL)
• Acidosis/Aklalosis- Calcium binding to albumin is dependent on the serum pH and
thus in states of severe acidosis ionized calcium is increased and viceversa in sever
alkalosis. There is no reliable correction factor to estimate this shift in ionized calcium
level and direct measurement of ionized calcium is recommended in these cases to
guide therapy.
• Acute pancreatitis- Hypocalcemia is often seen in the setting of acute pancreatitis
due to calcium deposition in abdominal cavity as a result of ongoing inflamation.
• Severe sepsis- Severe sepsis can also lead to hypocalcemia through unclear
mechanisms. Impaired PTH secretion, dysregulation of magnesium metabolism,
impaired calcitriol secretion have all been outlines as potential mechanisms but none
have been definitely proven as yet.

7. OTHERS
• Hypomagnesemia/hypermagnesemia- Low serum magnesium can be
commonly associated with hypocalcemia due to induced PTH resistance. It is
uncommon above a serum magnesium level of 1mg/dL. Severe
hypermagnesemia although rare, can also cause hypocalcemia by
suppressing PTH secretion thorough a decreased sensitivity of calcium-
sensing receptors.
• Acute hyperphosphatemia- An uncommon cause of hypocalcemia which is
likely precipitated because of extravascular deposition of calcium.
• Drugs- Bisphosphonates, cinacalcet, Denosumab, Foscarnet can all cause
hypocalcemia.
• Massive Blood transfusion- Massive blood transfusion can cause an acute
decline in ionized calcium due to calcium binding with citrate which is used
to prevent the stored blood from clotting.

8. CLINICAL FEATURES
• Seizures- Can be the sole manifestation or a part of the whole myriad of clinical presentation.
• Tetany- Generally induced by a rapid decline in serum ionized calcium. Tetany is usually most
dangerous and most commonly seen in the presence of respiratory alkalosis causing
hypocalcemia.
• Paresthesias- can be perioral or otherwise
• Psychiatric manifestations- Can be associated with anxiety/depression/emotional lability
• Carpopedal spasm- Also referred to as Trousseau's sign. It represents increased
neuromuscular excitability which may be related to the gating function of calcium ion for ion
channels at a cellular level (particularly in neurons). This manifests as a spasm of hand upon
routine BP check.
• Chvostek's sign- Another manifestation of heightened neuromuscular excitability. It is the
spasm of facial muscles in response to tapping the facial nerve near the angle of the jaw.
• QTc prolongation- Can lead to Torsades de pointes although extremely rare, it can be fatal.

9. EVALUATION
• Confirming the hypocalcemia: First part of evaluation should focus on
confirming the hypocalcemia and requires checking a serum albumin level to
correct the total calcium, or measuring directly the ionized calcium level
(where available). An EKG should also be obtained for all suspected cases of
hypocalcemia to look for QTc prolongation which if present is a risk factor
for Torsades de pointes.
• Etiology of hypocalcemia: This part can be driven by the clinical picture
obtained during previous steps. Usually entails checking electrolytes such as
serum magnesium and phosphorus levels and at least a serum PTH level. If
suspicion for vitamin D deficiency is high based on history then Vitamin D2
level should be measured as vitamin D3 can be affected by PTH levels. Other
biomarkers may be obtained as indicated by history and physical eg. serum
lipase in suspected pancreatitis.

10. MANAGEMENT
• Symptomatic hypocalcemia: intravenous calcium is recommended for rapid repletion if
there is any evidence of neuromuscular excitability. If the symptoms are mild such as
paresthesias or psychiatric oral calcium can be attempted. Calcium gluconate is the
preferred solution and can be given over 10-30 minutes depending on the severity of
symptoms. Calcium chloride can be used if central venous access is available. Alkaline
solution like bicarbonate and phosphorus containing solution need to be avoided
through the same iv to avoid precipitation of calcium salts.
• Asymptomatic hypocalcemia: if corrected total serum calcium is below 7.5mg/dL, iv
calcium should still be the preferred method. However, if corrected serum calcium is
>7.5 mg/dL and patient is asymptomatic oral calcium can be used. Vitamin D
supplementation is often recommended with calcium to promote absorption and
because vitamin D deficiency is commonly encountered in most clinical scenarios
leading to hypocalcemia. It is also important to address disease-specific problems and
correct co-exiting electrolyte disturbances eg. hypomagnesemia.

11. REFERENCES:
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surgery, 2014 Mar
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[4] Diagnosis and management of hypocalcaemia., Cooper MS,Gittoes NJ,, BMJ (Clinical research ed.), 2008 Jun 7

12. THANK YOU