A 44-year-old patient is admitted post thyroidectomy for Graves’ disease. Seven years ago, she had gastric bypass surgery for obesity. Shortly after admission, her serum biochemical findings are:
Parameter |
Patient Value |
Adult Normal Range |
Sodium |
136 mmol/L |
135 – 145 |
Potassium |
5.0 mmol/L |
3.5 – 5.0 |
Chloride |
103 mmol/L |
95 – 105 |
Bicarbonate |
23.0 mmol/L |
22.0 – 26.0 |
Glucose |
5.8 mmol/L |
3.5 – 6.0 |
Urea |
5.5 mmol/L |
3.0 – 8.0 |
Creatinine |
80 μmol/L |
45 – 90 |
Magnesium |
0.60 mmol/L* |
0.75 – 0.95 |
Albumin |
35 g/L |
35 – 50 |
Protein |
74 g/L |
60 – 80 |
Total bilirubin |
12 μmol/L |
< 26 |
Aspartate aminotransferase (AST) |
34 U/L |
< 35 |
Alanine aminotransferase (ALT) |
40 U/L* |
< 35 |
Alkaline phosphatase (ALP) |
188 U/L* |
30 – 110 |
γ-Glutamyl transferase (GGT) |
45 U/L* |
< 40 |
Calcium corrected |
1.80 mmol/L* |
2.12 – 2.62 |
Phosphate |
0.7 mmol/L* |
0.8 – 1.5 |
- Give two potential explanations for the abnormalities seen. (10% marks)
- What clinical features might be associated with these abnormalities? (20% marks)
- Outline your management. (40% marks)
College answer
a) Give two potential explanations for the abnormalities seen.
Vit. D deficiency
Hypoparathyroidism
b) What clinical features might be associated with these abnormalities
Hypocalcaemia is classically associated with
Paraesthesias in perioral and acral areas
Chvostek and Trosseau’s signs
Muscle cramps, laryngeal spasm
Irritability, confusion, seizures
Prolonged QT, arrhythmias
Hypomagnesaemia – some of above, also muscle weakness
Hypophosphatemia – mild, unlikely to be associated with clinical features
c) Briefly describe how you will manage this condition
IV Cal chloride or gluconate, IV Magnesium PO4 replacement
Monitor ionised Ca level, if available. Check ECG for prolonged QT
Avoid alkalosis – as it worsens neuromuscular irritability
Oral Vitamin D3 (cholecalciferol) as soon as oral intake is allowed
Oral Cal supplement (up to 1.5 – 2.0 grams/day) – preferable as Ca citrate Not Ca carbonate Oral Magnesium supplements
If recalcitrant hypoCa, consider s/c parathyroid hormone (confirm adequate vit D level)
Check TFT, TSH – replacement T4 as needed.
Discussion
Unlike a normal data interpretation question which asks the candidate to mindlessly produce a shopping list of abnormalities, this one expects a little more. The shopping list and salient features from the question are:
- Post-thyroidectomy
- Gastric bypass (thus, possible malabsorption)
- Low magnesium, calcium and phosphate
- Raised alkaline phosphatase, suggestive of increased bone turnover
The thyroidectomy story raises the possibility of hypoparathyroidism, which is an easy mark. To produce another differential, one might need to think somewhat laterally. Possibilities relevant to this case might include:
- Hypomagnesemia (after all, it is low)
- Vitamin D deficiency due to malabsorption
More remote possibilities may include:
- Consumption by osteoclastic bone metastases (alk phos)
- Consumption of calcium by coagulopathy (from a massive transfusion? thyroidectomy can be a bloody surgery)
Clinical features, they ask?
Mild hypocalcemia
|
Severe hypocalcemia
|
Symptoms Physical signs
|
ECG changes
Associated biochemical abnormalities
|
Neurological manifestations
Cardiovascular manifestations
Biochemical abnormalities
|
Musculoskeletal manifestations
Haematological abnormalities
|
Management of hypocalcemia might seem as straightforward as replacing the calcium, but the college examiners make the fair point that this process can be more involved and occasionally requires extra thinking. A structured approach might resemble the following, which was borrowed from an excellent article by Cooper and Gittoes (2008):
Acute replacement
- IV replacement of calcium salt
- Calcium chloride or gluconate, doesn't matter
- Ensure magnesium and phosphate are replaced at the same time
Medium term replacement
- Oral calcium replacement
- The college specifically recommend calcium citrate, "Not Ca carbonate", in spite of the fact that the citrate appears to have lower oral bioavailability (Wang et al, 2014). According to UpToDate, both choices are available in exactly the same dose of elemental calcium. One possible reason for this (otherwise unexplainable) preference is the need for normal gastric pH to dissolve calcium carbonate tables, i.e. it is to be taken with food whereas calcium citrate is more suitable to an otherwise fasted post-operative patient.
- Vitamin D replacement
- With intact parathyroid function:
- Cholecalciferol (which is then converted to calcitriol in the kidney, provided parathyroid function is normal)
- With impaired parathyroid function:
- Calcitriol, the hormonally active version of Vitamin D (without PTH around the oral cholecalciferol supplements will not be effective)
- Both drugs will have positive effects:
- Improve gut absorption
- Improve release of calcium from bone
- Decrease renal excretion
So, what might one do if in spite of ongoing calcium infusion the ionised calcium keeps dropping? That would probably be the "recalcitrant hypoCa" described by the examiners, who were presumably too busy to type "hypocalcemia" for the purposes of this model answer. "Recalcitrant hypoCa" is actually a real phenomenon which tends to occur in patients who have previously had gastric bypass procedures (Moore et al, 2013), as the patient in this question has done. It has no scientific definition, but some authors (eg. Ballal et al, 2017) seem to characterise it as a hypocalcemia which fails to respond to either vitamin D supplementation or intravenous calcium. Therre arre some treatment options open to these people:
- Thiazide diuretics (which increase the renal reabsorption of calcium)
- recombinant PTH
References
Cooper, Mark S., and Neil JL Gittoes. "Diagnosis and management of hypocalcaemia." BMJ 336.7656 (2008): 1298-1302.
Wang, Haiyuan, Peter Bua, and Jillian Capodice. "A comparative study of calcium absorption following a single serving administration of calcium carbonate powder versus calcium citrate tablets in healthy premenopausal women." Food & nutrition research 58.1 (2014): 23229.
McKenzie, Travis J., et al. "Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y gastric bypass." Surgery 154.6 (2013): 1300-1306.
Ballal, Devesh Sanjeev, et al. "Persistent recalcitrant hypocalcemia following total thyroidectomy: a management challenge." Malta Medical Journal 29.02 (2017).