Hypocalcemia - What's the diagnosis - Answer

This was an interesting case. A woman with a previous history of hyperparathyroidism and multiple neck surgeries who developed severe, symptomatic hypocalcemia 3 hours following a parathyroidectomy was thought to have failed because of a persistently elevated PTH level. This suggests that did in fact successfully remove her parathyroid gland and that there was an issue with the assay.

In the hospital referred to in this case, the assay used was a Roche Elecsys PTH STAT assay. This is an antibody-based assay that uses two murine antibodies - a "capture" antibody and a "signal" antibody. In patients who have been previously exposed to murine tissue, anti-mouse antibodies can be present in the serum that bind to both of these antibodies giving a false positive result on the assay. In this case, the patient had received OKT3 in the past which has been associated with a prevalence of anti-mouse antibodies of up to 26%. Her PTH level was repeated using an alternative assay - her pre-op PTH was 18 pg/ml and her post-op PTH was 5 pg/ml. Unfortunately, she required long-term treatment with vitamin D and calcium supplementation. In retrospect, the normal calcium and phosphate in a patient with this degree of apparent hyperparathyroidism and normal kidney function was a clue that there may have been an issue with the test although, of course, it is easy to say that knowing the answer.

Congratulations to "anonymous" for getting the correct answer. The complete case report can be found here.

Hypocalcemia - What's the Diagnosis?

A 36yr old woman with a history of PCKD was referred for surgical treatment of hyperparathyroidism. She had a history of two prior failed kidney transplants following which she had been on dialysis for more than 10 years. She had a third renal transplant 10 years prior to this presentation which was still functional. At the time of her transplant, she had received OKT3 and was currently maintained on tacrolimus and prednisone. She had a long history of hyperparathyroidism. Six years prior to her transplant, she had a subtotal (3.5 glands) parathyroidectomy. The year of her transplant, she had another neck exploration with the removal of 8 nests of hypercellular parathyroid tissue.

At the time of this presentation, her PTH was 3,300 pg/ml despite treatment with cinacalcet. Her ionized calcium was normal (1.2 mmol/L) but she complained of poor concentration, fatigue and depression. Serum phosphorous and creatinine were normal. She had a normal sestamibi scan but an US revealed hyperplastic parathyroid tissue in her neck.

During the parathyroidectomy, frozen section revealed hypercellular parathyroid tissue that was removed. However, pre-op, intra-op and post-op PTH levels were elevated at >1700 pg/ml. Because of the persistently elevated PTH, it was considered a failed operation and calcium supplementation was not started post-op. However, within 3 hours of the operation, she developed perioral numbness, tetany and muscle spasms in her legs. Her ionized calcium was low (0.9 mmol/L) and her symptoms resolved after treatment with iv calcium. Her PTH remained elevated at 3000 pg/ml.

What is the reason for her acute hypocalcemia in this setting? Answer in the comments please.

Kidney Stones - What's the diagnosis? - Answer

This was an interesting case and all those who responded correctly identified that the patient had bowel pathology. However, only one person figured out that the issue was an ileostomy. This patient had a low urine volume and an extremely low urinary citrate and sodium. The low citrate could indicated a renal tubular acidosis except that the urinary ammonium was high and the urine pH was very low indicating preserved ability to acidify the urine. This points to a metabolic acidosis. The urine sodium in an average US resident is between 100-200 mmol/day. Outside of the amazon, it's hard to imagine that anyone could take in this little salt. This points towards loss of sodium bicarbonate and water from the GI tract.

Finally, in the setting of IBD, generally it is accompanied by hyperoxaluria. There are a number of potential mechanisms for this; decreased metabolism of oxalate by oxalobacter formigenes, decreased calcium binding to oxalate because of the relatively increased binding of calcium to malabsorbed fat in the GI tract. In any case, in order to have hyperoxaluria, it is necessary to have a functioning large bowel. In this case, the patient's urinary oxalate was 28 which is in the low normal range and not suggestive of hyperoxaluria. Thus, the diagnosis is high output of alkaline fluid from an ileostomy.

The treatment in this case is to increase fluids and treat with a combination of sodium and potassium citrate. Even a small rise in urine pH would significantly reduce the risk of uric acid stones while the citrate and increased volume should reduce the calcium oxalate stone risk.

Kidney Stones - What's the diagnosis?

A 65yo man was reviewed in the clinic for assessment of kidney stones. He has a history of stones for at least 8 years and has been passing small calculi on a regular basis for the last few months. His 24 hour urine results are shown below (results are 24 hour total values unless otherwise specified):

Volume, Liters	0.71	Sodium, mmol/day	7
Supersaturation Calcium Oxalate	10.11	Potassium, mmol/day	45
Calcium, mg/day	78	Magnesium, mg/day	52
Oxalate, mg/day	28	Phosphate, mg/day	0.76
Citrate, mg/day	11	NH4, mmol/day	68
Supersaturation Calcium Phosphate	0.71	Chloride, mmol/day	48
Urine pH	5.6	Sulphate, mEq/day	39
Supersaturation Uric Acid	2.71	Urea Nitrogen, g/day	11
Uric Acid, mg/day	0.499	Protein Catabolic Rate	1.2
Creatinine	1292

He has a high risk for calcium oxalate and uric acid stones. His urine citrate and sodium are remarkably low and he has a very low urine volume. His BP in the clinic was normal as were his labs apart from a serum creatinine of 1.3mg/dl

What is the underlying diagnosis (an important  piece has been left out of his background history)?
What is the best approach to treating his kidney stones?

Answers in the comments please (if this proves popular we may make it a regular feature).