A solitary parathyroid adenoma is the most common cause of PHPT, causing up to 80% of cases. Other causes may be multiglandular adenoma, parathyroid hyperplasia or carcinoma.1
The diagnosis of PHPT was straight forward in this case upon the demonstration of persistently high levels of serum calcium, associated with a markedly elevated level of iPTH. Malignancy and multiple myeloma could also present with hypercalcaemia, fractures and lytic lesions, but these entities would have low levels of intact PTH.
There are only two entities which may present with hypercalcaemia and high iPTH. These are PHPT and familial hypercalcaemic hypocalciuria. The latter entity is characterised by hypercalcaemia being present early in life, with a similarly affected relative and a low urine calcium excretion, usually <100 mg in 24 h. Our patient did not have hypercalcaemia early in life, had no affected relative and had a urine calcium excretion of 134.4 mg over 24 h.
In the past (1930–1965), nephrolithiasis and skeletal disease were very common in PHPT, being present in as much as 57% and 23% of affected patients, respectively.2
However, due to the advent of routine calcium measurement with the use of multichannel analysers, recent studies have shown that nephrolithiasis is only present in 18% of patients and none had skeletal disease.3
It is for this reason that this case is being reported because the classic complications of nephrolithiasis and skeletal disease are now considered rare entities.
Very striking in this case is the florid skeletal involvement. She presented with multiple repeated fractures in a span of 2 years involving the left humerus, right femoral neck and bilateral femoral shafts. The skeletal survey demonstrated the classic radiographic findings: new fractures of both femoral shafts, old fractures of the right femoral neck and left humerus, the moth-eaten appearance of the skull, the lytic lesions (osteitis fibrosa cystica) of a proximal phalanx, right humerus and distal femur, and generalised osteopenia. A CT scan was performed to determine the anatomic extent of the parathyroid, which also revealed osseous changes in the vertebrae and humeral heads. The bone densitometry quantified the severity of osteoporosis, with a lowest T-score of 4.8 demonstrated at the right radius. Osteoporosis from PHPT affects the cortical bone more than cancellous bone. The lower T-score in the radius, a cortical-rich bone, supports this. In contrast, postmenopausal osteoporosis affects cancellous bone more than the cortical bone, and this would probably not manifest with low T-scores at the radius.
Renal involvement is considered the most common manifestation of PHPT, and the patient was not spared from this.1
Though asymptomatic for renal disease, ultrasound revealed a non-obstructing nephrolithiasis on the left. Other renal manifestations are hypercalciuria (urine excretion >400 mg over 24 h) and nephrocalcinosis, both of which were not seen in this case.
Neuromuscular and cognitive complaints in the form of fatigue, weakness, depression and behavioural changes are also common, but these were not apparent in this case.
Hypertension and left ventricular hypertrophy have been associated with PHPT.1
Interestingly, the patient has a history of hypertension, but this was controlled even without medications. Though the patient did not have symptoms of heart failure, x-ray demonstrated left ventricular cardiomegaly.
Surgery was indicated for this patient due to the skeletal and renal involvement. She also had a serum calcium level that was >1 mg/dl higher than the upper limit of normal (patient's value of 3.05 mmol/l equivalent to 12.2 mg/dl, compared to upper limit of normal which is 2.52 mmol/l or 10.08 mg/d). Had she been asymptomatic, the following are the indications for surgery as enumerated in the 2002 US NIH guidelines: serum calcium >1.0 mg/dl above normal, 24 h urinary calcium >400 mg, creatinine clearance reduced by 30%, T-score at any site of < 2.5 or age <50.1
PHPT is cured by surgical removal of the source of excessive, unregulated, parathyroid hormone. Biochemical cure was demonstrated in this case by the marked return of intact PTH to normal 48 h after surgery (from 820.2 to 26.1 pg/ml).
The patient developed the ‘hungry-bone syndrome’ 7 days after surgery, manifesting with severe signs and symptoms of hypocalcaemia such as grade IV Chvostek's sign, carpopedal spasm and paraesthesias. This syndrome occurs because of extensive calcium deposition into the bone after the levels of PTH have already dropped, causing serum levels of calcium to decrease.4
This was managed with intravenous calcium gluconate, oral calcium carbonate and oral calcitriol.
She was sent home on oral calcium carbonate, oral calcitriol and oral alendronate. On outpatient follow-up, it is recommended that serum calcium and creatinine levels be assessed every 6 months coupled with annual repetition of bone densitometry.1 5
- This case demonstrates the severe skeletal involvement seen in PHPT that is rarely encountered at this modern age, such as moth-eaten appearance of the skull and lytic lesions of bone and osteitis fibrosa cystic.
- It also demonstrates the work-up of a patient presenting with multiple fractures, hypercalcaemia and bony lesions.
- This case also illustrates biochemical cure of PHPT after successful removal of a solitary parathyroid adenoma.
- Also, recognition and appropriate management of the ‘hungry-bone syndrome’ make this case worth reportable.