The Case
Mr CA is a 70 year old gentleman who was referred post obliteration of a tracheoesophageal fistula (TOF) with refractory hypocalcaemia secondary to surgical hypoparathyroidism. His background was most significant for transglottic laryngeal squamous cell carcinoma (T4N1) for which he underwent total laryngectomy and partial pharyngectomy in 2017. During this index operation, his right thyroid lobe was removed as were three parathyroid glands however he remained normocalcaemic in the community without calcium or Vitamin D supplementation. Mr CA continues to be in remission of his primary malignancy.
Mr CA developed a TOF in February 2022 and following a failed repair was transferred to a tertiary service for re-do surgery. His pre-operative corrected calcium was 2.34 mmol/L [2.10-2.60] with a normal ionised calcium of 1.12 mmol/L [1.12 – 1.3]. During the re-do TOF repair his last parathyroid gland was unintentionally removed and Mr CA was referred to Endocrinology with a corrected calcium of 1.8, an ionized calcium of 0.77 and a PTH of <0.6 pmol/L [1.7-10]. His QTC segment was also prolonged at 521ms with runs of VT against a past history of a dilated cardiomyopathy. He remained hypocalcaemic requiring IV calcium gluconate despite escalating doses of calcitriol (5mcg QID) and calcium carbonate (5000mg QID) both given via PEG.
A 1, 25 (OH) Vitamin D level was found to be only 144pmol/L [50-190] despite 80 capsules daily of 0.25 mcg of calcitriol and therefore several strategies to improve bioavailability were trialled. Calcitriol was converted to a liquid calcitriol formulation to prevent any losses experienced when the medication was aspirated from the capsules. The PEG was extended to a PEJ due to nausea and this improved Mr CA’s diarrhoea. Thyroxine and enteral nutrition were separated from calcium supplementation. Protein pump inhibition remained necessary in the context of gastrointestinal bleeding and calcium citrate was not readily available. An intravenous formulation of calcitriol was also trialled without significant improvement to hypocalcaemia.
Urinary losses were explored with a 24-hour urine collection, which did demonstrate an elevated calcium excretion 29.7 mmol/d [2.5 – 7.5]. With clinical polyuria of 4L per day, Mr CA likely had a tubular defect but no clear aetiology was determined and this self resolved. Hydrochlorothiazide 12.5mg BD was initiated to counter hypercalcuria and a repeat 24hr hour demonstrated its efficacy (calcium excretion 5.3 mmol/d). For approximately one month, Mr CA’s corrected calcium remained stable with calcitriol 4mcg TDS, calcium carbonate 7000mg QID, calcium citrate 333mg / cholecalciferol 333 IU TDS and hydrochlorothiazide 25mg BD.
Mr CA’s supplementation requirement fell at two major points. When Mr CA was switched from enteral nutrition to total parental nutrition (TPN), his calcitriol doses were down titrated to 3mcg TDS. Two months post initial admission, his calcitriol and calcium supplements were weaned to cessation as his corrected calcium improved (see Table 1). Mr CA was discharged for ongoing monitoring and supplement titration in the community.
Table 1- Calcium changes during admission
|
|
Pre-Op |
Post-Op |
Stable |
Discharge |
|
Corrected Ca |
2.34 |
1.8 |
2.37 |
2.39 |
|
Albumin |
33 |
27 |
31 |
30 |
|
Ionised Ca |
1.12 |
0.77 |
1.19 |
1.28 |
|
PTH |
N/A |
<0.6 |
<0.6 |
<0.6 |
|
Phosphate |
0.99 |
0.91 |
1.54 |
1.77 |
Discussion
This case highlights a number of practical challenges associated with the inpatient management of surgical hypoparathyroidism. Firstly in the setting of enteral nutrition, the percutaneous endoscopic gastrostomy or jejunostomy tubes can interfere with delivery as calcitriol can adhere to the tubing.1 Secondly, there can be multiple gastrointestinal barriers to calcium carbonate absorption including protein pump inhibition,2 the latter of which can be managed with conversion to calcium citrate. A 1, 25 dihydroxycholecalciferol level can be used to prove absorption of calcitriol but should be interpreted in the context of the degree of supplementation, for example a normal level may be relatively low if large doses are being used. Finally, tubular defects resulting in hypercalcuria can prohibit effective calcium supplementation and hydrochlorothiazide can be an effective medication in this scenario.3
Take home messages
In the management of hypoparathyroidism:
- Delivery of calcitriol can be adversely affected by PEG/J administration as the medication can adsorb to the plastic tubing
- Calcium supplement absorption can be limited by diarrhoea, co-administration with enteral nutrition & thyroxine and gastric pH for calcium carbonate
- 1, 25 dihydroxycholecalciferol can be used to prove absorption of calcitriol however needs to be judged in relation to the level of supplementation given to the patient
- Hypercalcuria can limit calcium supplementation in hypoparathyroidism and can be combatted by the use of hydrochlorothiazide