HOSP #	42170712	WARD	Endocrinology OPD
CONSULTANT	Dr. Heleen Vreede	DOB/AGE	37y female

Abnormal Result

• The patient’s calcium measured 2.91 mmol/L on two occasions, with PTH measuring 40.6 pmol/L
• VitD 13.6 (<50 = deficient)
• TFT’s TSH 0.01 T4 26.7pmol/L

Presenting Complaint

Presented at the GIT clinic in Feb 2020 with persistent vomiting and abdominal cramps, which was ongoing since November 2019.

History

• Patient was diagnosed with hypertension in her early 20’s.
• Initiated on HCTZ – subsequently changed to Atenolol 25mg dly – not overweight at the time
• Gastroscopy was normal
• No psychiatric symptoms reported – mood swings are reported occasionally by the family
• Oligomenorrhoea – started in 2019 – nothing else wrong was noted.
• Normal menarche – normal regular menses until the diagnosis of hypertension was made.
• Amenorrhoeic last 4 years on no medication currently

Examination

• Increased BMI – quite significantly increased
• BP 170/90
• Skin: Significant amount of skin tags, acanthosis nigricans
• No striae or bruising
• No Sx of thyroid disease.
• Physical examination unremarkable.
• Normal pulses
• Essentially a normal examination other than the high BMI

Laboratory Investigations

Repeated bloods (5 days after initial presentation): 

• TSH 3.13 T4 12.5
• PTH 28 pmol/L (1.6 -6.9)
• Ca 2.79
• Inorganic phosphate 0.77 L mmol/L (0.78 – 1.42)
• LFT’s: Normal
• Creat Normal
• U-Ca 5.6 (no creatinine to compare ratio)
• FSH 3.2 IU/L
• LH 2.0 IU/L
• E2 244 pmol/L
• Dehydroepiandrosterone sulphate (DHEAS) 2.4 umol/L (1.7 – 9.2)
• Testosterone 0.5 nmol/L (0.3 – 1.7)
• SHBG 25.9 L nmol/L (32.4 – 128.0)
• Prolactin 11.5
• TSH-Receptor antibodies: Negative

Other Investigations

The patient still had occasional vomiting, abdominal cramps and unexplained muscle pain – other electrolytes apart from calcium, magnesium and phosphate is also advised, as is osmolarity as fluid and electrolyte imbalance may be an effect, rather than a cause of the nausea, vomiting and muscle pain – the sodium and potassium was normal however.

See below, for the hypertension, phaeochromocytoma can be excluded by a 24-hour fractionated urinary metanephrines analysis.

Final Diagnosis

• Primary hyperparathyroidism is on top of the differential diagnosis and is likely the cause of the raised total calcium.
• Another cause of the raised blood pressure could very likely be a phaeochromocytoma.
• It was also advised for replacement of Vitamin D, after a repeat measurement.
• Other features of MEN-1 syndrome needs to be excluded.

Take Home Message

For phaeochromocytoma, 3 separate days’ urine collection is recommended if the suspicion is high, which it isn’t in this case. This increases the sensitivity of the test.

Before testing for MEN-1: one needs to correct Calcium first – since the hypercalcemia could exacerbate gastrin levels.

Increased serum calcium and hypophosphatemia is the net-result of increased PTH. Urinary phosphate will also be high if measured.

From other results it is also evident that:

HOSP #		WARD	Nephritic clinic
CONSULTANT	Dr. Heleen Vreede	DOB/AGE	49 y Female

Uric acid nephropathy with hypercalcaemia (Mrs. Linda Meyer) MRN78959694

Abnormal Result

The calcium on 20/02/2019 on bloods taken 14h45 was 3.29 (2.15-2.50 mmol/L).

Presenting Complaint

The patient presented with pain “from loin to groin” which is the typical presentation of passing a renal stone.

History

The patient has chronic renal failure (first creatinine was 362 umol/L with eGFR of 12ml/min – MDRD) on 12 December 2017. Creatinines relatively unchanged since then.

Upon re-evaluation of the case in 2020 it was seen that the baseline creatinine has risen to ~445 umol/L indicating a worsening of the chronic renal failure eGFR now 9 ml/min – by both CKD-EPI and MDRD formulas.

Examination

N/A

Laboratory Investigations

The patient is known with Hyperuricemia, first result 0.50 (0.16-0.36mmol/L) on 16 February 2018.  The response to treatment appears poor due to continuing rising serum uric acid levels (considering whether the patient is on allopurinol).

2. Regarding the hypercalcemia:

Episode	SA04315821	SA03552076	SA03535628	SA02816641	SA02784405	SA02622825	SA02369770	SA02123812	SA01901592
Date	11/11/2020	11/12/2019	04/12/2019	04/03/2019	20/02/2019	12/12/2018	04/09/2018	23/05/2018	16/02/2018
Time	09:44	10:22	17:03	15:48	17:44	17:11	10:31	16:25	15:28
Na			135 L		139	138	139.000	138.000	137.000
K	5,3 H	4,7	4,8		4,8	4,5	4.320	4.400	4.780
Urea			17,2 H		14,3 H	16,2 H	11,3 H	18,8 H	17,1 H
Creat	443 H	484 H	434 H	444 H	446 H	475 H	334 H	408 H	415 H
MDRD	9	8	9	9	9	8	13	10	10
CKD-EPI	9
Ca	2,79 H		2,59 H	3,09 H	3,29 H	2,97 H	2.820 H	2.850 H	3,12 H
Mg			0.94		1,05	1.00		1.060 H	.980
Phos			1,02		1,25	1,33	.980	1.240	1.110
PTH			13,3 H		4,3	4,6

From above results a consistent hypercalcemia with a single raised PTH result can be seen – see “Final Diagnosis” and “Take Home Message” below.

Other Investigations

Uric acid crystals were seen on the urine microscopy reflecting uric acid nephropathy – a possible cause of the chronic renal failure, but I could not find any biopsy result or alternative explanation for the renal failure and assume it is uric acid nephropathy.  The patient also appears to have been for a procedure at Urology (? Renal stone removal).

A serum protein electrophoresis with immunofixation (13/09/2018) showed no monoclonal peaks.

Final Diagnosis

Uric acid nephropathy with renal stones.

Hypercalcemia likely due to tertiary hyperparathyroidism.

Take Home Message

Uric acid nephropathy appears to be an uncommon cause of chronic kidney disease (ref. Up-to-date).

It should however be emphesized that clinicians consider the cause on a differential, as it is a manageable cause.

Hypercalcemia sometimes occur in Chronic Kidney Disease patients due to tertiary hyperparathyroidism. This is due to persistent hyperphosphatemia with resulting hyperparathyroidism leading to hypercalcemia (as opposed to the more commonly occuring hypocalcemia is renal failure).

——Commentary by Nephrologist- Dr. Erika Jones——

WRT the Uric Acid

Difficult to say if it is cause or effect of CKD. We can only really make a diagnosis of uric acid nephropathy on kidney biopsy. But it is definitely a cause that we see on occasion.

The good news is that the creatinine has remained fairly stable in the last couple of years, unlike the UA, but as kidney function deteriorates it is expected the UA will increase.

According to our buff records she had staghorn calculi and that was labelled as the cause of her CKD.

Allopurinol in CKD is challenging as it accumulates with side effects. We have had two patients with full on Steven’s Johnson Syndrome. So if she isn’t symptomatic I wouldn’t give it to her. She is recorded as having Sarcoidosis which explains the hypercalcaemia. I think this stage is too early to have tertiary hyperparathyroidism.