Hypocalcemia


Article Author:
Abhinav Goyal


Article Editor:
Shikha Singh


Editors In Chief:
William Gossman


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
1/21/2019 2:56:04 AM

Introduction

Calcium homeostasis in the body is a complex interplay between several different hormones or hormone-like substances, such as Parathyroid hormone(PTH), Vitamin D, and calcitonin. Disorders of calcium metabolism are encountered pretty frequently in routine clinical practice. Hypocalcemia is not as frequently encountered as hypercalcemia, but it can be potentially life threatening if not appropriately recognized and treated promptly.

Etiology

The causes of hypocalcemia can be divided into three broad categories:

  • Miscellaneous
  • PTH deficiency
  • High PTH

MISCELLANEOUS

  1. 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)
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Acute hyperphosphatemia- An uncommon cause of hypocalcemia which is likely precipitated because of extravascular deposition of calcium.
  7. Drugs- Bisphosphonates, cinacalcet, Denosumab, Foscarnet can all cause hypocalcemia.
  8. 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.

PTH DEFECIENCY (low or low normal serum PTH)

  1. 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.
  2. 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.

High PTH

  1. 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.
  2. 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.
  3. Pseudohypoparathyroidism-This category refers to end organ resistance to the action of PTH. Its a hereditary genetic disorder.

Epidemiology

There is no literature on quantification of hypocalcemia in general. However, the reported prevalence of transient hypocalcemia after thyroidectomy varies between 6.9 to 49% and between 0.4 to 33% for permanent hypocalcemia. In general, renal failure by far remains the most common cause of hypocalcemia followed by vitamin D deficiency, magnesium deficiency, acute pancreatitis, etc.

History and Physical

The history and physical exam of patients with suspected hypocalcemia should be conducted with two underlying principles in mind. First, to uncover the potential manifestations of hypocalcemia like:

  1. Seizures- Can be the sole manifestation or a part of the whole myriad of clinical presentation.
  2. 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.
  3. Paresthesias- can be perioral or otherwise
  4. Psychiatric manifestations- Can be associated with anxiety/depression/emotional lability
  5. 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.
  6. 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.
  7. QTc prolongation- Can lead to Torsades de pointes although extremely rare, it can be fatal.

The second part of history and physical should focus on determining the cause of hypocalcemia such as recent head and neck surgery, family history of similar problems, history of kidney disease, alcohol abuse (hypomagnesemia), psychiatric history, etc.

Evaluation

Work up of hypocalcemia can be thought of in following parts:

  1. 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.
  2. 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.

Treatment / Management

Management of Hypocalcemia can be divided into two broad categories:

  1. 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. 
  2. 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.

Pearls and Other Issues

Check a magnesium level when faced with hypocalcemia since its an important and easily correctable cause of hypocalcemia.


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Hypocalcemia - Questions

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A patient is 1-day status post subtotal parathyroidectomy and reports twitching. What is the best treatment for the suspected underlying cause?



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A patient is taking a calcium supplement to treat hypocalcemia. To facilitate absorption and utilization of the supplement, the patient may be taught to consume foods high in which of the following?



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A patient had abdominal surgery and received six units of blood. Postoperatively, she complains of numbness around her mouth and has carpopedal spasms. An ECG reveals a prolonged QT interval. A reduced level of which of the following is most likely responsible for these findings?



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After a parathyroidectomy, the patient has Chovstek sign. What should be done?



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Which of the following is true of hypocalcemia?



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A patient had abdominal surgery and receives many units of transfused blood. Post surgery he complains of numbness around his mouth and carpopedal spasm. ECG reveals a prolonged QT interval. What is the most appropriate intravenous treatment for this patient?



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A patient undergoes thyroid surgery. The surgery is uneventful and there is minimal blood loss. At night, she complains of tingling in her hands and muscle cramps. What should the initial therapy involve?



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A patient undergoes abdominal surgery for a splenic rupture and receives many units of transfused blood. Post-surgery he complains of numbness around his mouth and a carpopedal spasm. An electrocardiogram reveals a prolonged QT interval. Which of the following would be the best intravenous treatment for this patient?



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What is causing the hypocalcemia in a middle aged alcoholic patient with the following lab values: Ca 7.0 mg/dL, albumin 3.5 g/dL, Mg 0.8 mg/dL, Phos 2.1 mg/dL?



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Which of the following is not a characteristic feature of hypocalcemia?



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Hypocalcemia does NOT cause which of the following symptoms?



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Which is NOT a feature of hypocalcemia?



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Which of the following is NOT a common feature of hypocalcemia?



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In a patient with hypocalcemia, which ECG change is observed?



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What is the treatment for hypocalcemia?



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What is the probable cause of hypocalcemia in a 33-year-old alcoholic male with the following lab values: Ca 6.8 mg/dL, albumin 3.6 g/dL, Mg 0.7 mg/dL, Phos 2.2 mg/dL?



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Which is least likely to be found in a patient with hypocalcemia?



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Bronchospasm may compromise the airway in which of the following electrolyte abnormalities?



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A patient complains of perioral and hand numbness. Trousseau and Chovstek signs are positive. Hypocalcemia is presumed. Which test is most likely to provide the etiology of the hypocalcemia?



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A 22-year-old man sustains a gunshot wound to the abdomen and presents with shock. He requires multiple units of packed red blood cells during resuscitation. Later he reports numbness around his mouth. The physical exam reveals carpopedal spasm and a positive Chvostek sign. An electrocardiogram demonstrates a prolonged QT interval. Which of the following is the most appropriate treatment?



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Which of the following is not seen with hypocalcemia?



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Which of the following is not a clinical feature of hypocalcemia?



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Which of the following children are not at risk of neonatal hypocalcemia?



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Which of the following is not a risk factor for neonatal transient hypocalcemia?



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Which of the following does not cause hypocalcemia?



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Which of the following is not a manifestation of hypocalcemia?



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Which of the following would be the least likely to be found in a patient with a calcium level of 7.1 mg/dL?



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Which is not a clinical feature of hypocalcemia?



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Where does Trousseau sign occur?



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Which is the proper treatment of hypocalcemia?



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Which is not associated with hypocalcemia?



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What is used as emergent treatment for symptomatic hypocalcemia?



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An 17 year old male has acute onset of muscle cramps of both hands and perioral tingling. Exam shows an anxious man with elevated respiratory and ABG showing increased pH and decreased bicarbonate and PCO2. Which of the following is most likely decreased in the serum?



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A 67 year old female complains of bone pain and has hypocalcemia. All four of her parathyroid glands are enlarged. What is the most likely cause?



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A 34 week gestational age infant was born to a mother with pregnancy-induced hypertension and diabetes mellitus. Apgar scores were 8 and 9 at 1 and 5 minutes respectively. One day later, the neonate has a seizure and tetany. Select the most probable cause responsible for the findings.



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What is the most common cause of chronic hypocalcemia?



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Which disease process is characterized by the Chvostek sign?



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An 84-year-old female presents to the emergency department with her daughter. The daughter describes a recent change in her mother's mental status. She reports that her mother seems more confused than usual. She also states that her mother has been complaining of cramps in her legs, which is unusual. A physical examination is positive for increased resistance over the abdomen. You also note that the patient groans when you palpate any quadrant of her abdomen. On auscultation of the abdomen, you note absent bowel sounds. An ECG is obtained which demonstrates QT prolongation. The patient is positive for a Trousseau sign. The patient's gastrointestinal symptoms likely result from a decrease in which of the following?



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During your pediatric rounds, you come across a 7-year old who was admitted the previous night. The resident who admitted the child is not present to provide the history. While waiting for the medical chart, you note that the child‘s right wrist is flexed and there is hyperextension of the middle and index fingers and flexion of the thumb. The medical student states this clinical feature is known as "main d’accoucheur." Based on this clinical finding, which of the following is most likely?



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What serum parathyroid hormone (PTH) level rules out hypoparathyroidism as a cause of hypocalcemia?



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Which one of these electrolyte abnormalities can lead to hypocalcemia?



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What is the preferred treatment of a 74-year-old male patient with a corrected serum calcium level 7.4 mg/dL with positive Chvostek sign and a QTc of 520 ms?



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What ECG finding would be expected with hypocalcemia?



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A client underwent a total thyroidectomy two days ago and the surgeon inadvertently also removed all the parathyroid glands. If this client develops hypocalcemia, what symptoms will the nurse most likely observe? Select all that apply.



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In a patient with hypocalcemia, what is included in the assessment? Select all that apply.



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Which of the following might be present in a patient with hypocalcemia? Select all that apply.



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Hypocalcemia - References

References

Postsurgical Hypoparathyroidism: A Systematic Review., Kakava K,Tournis S,Papadakis G,Karelas I,Stampouloglou P,Kassi E,Triantafillopoulos I,Villiotou V,Karatzas T,, In vivo (Athens, Greece), 2016 May-Jun     [PubMed]
Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia., Edafe O,Antakia R,Laskar N,Uttley L,Balasubramanian SP,, The British journal of surgery, 2014 Mar     [PubMed]
Accuracy of methods to estimate ionized and "corrected" serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support., Dickerson RN,Alexander KH,Minard G,Croce MA,Brown RO,, JPEN. Journal of parenteral and enteral nutrition, 2004 May-Jun     [PubMed]
Diagnosis and management of hypocalcaemia., Cooper MS,Gittoes NJ,, BMJ (Clinical research ed.), 2008 Jun 7     [PubMed]

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