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Q1: What is your differential diagnosis for this case?
The highly sensitive and specific immunometric assays for intact parathyroid hormone (PTH) separates hyperparathyroidism from all other causes of hypercalcaemia.1 With few exceptions, non-parathyroid causes of hypercalcaemia are accompanied by low serum concentrations of intact PTH. Chronic treatment with lithium may produce hypercalcaemia that is associated with high serum intact PTH, a clinical picture indistinguishable from primary hyperparathyroidism.2 Familial hypocalciuric hypercalcaemia must be considered in healthy patients who have had hypercalcaemia since the first decade of life; they usually have hypocalciuria and normal serum concentrations of intact PTH.3
A solitary parathyroid adenoma is the underlying pathology in more than 80% of cases of primary hyperparathyroidism.4 5 Diffuse hyperplasia of all parathyroid glands occurs in about 15%–20% of patients and may in about half of these be part of a multiple endocrine neoplasia (MEN).1 Multiple adenomas and parathyroid cysts are uncommon, and parathyroid carcinoma is very rare (<1%).1 Acute primary hyperparathyroidism is an unusual form of the disease characterised by life threatening hypercalcaemia.6 7
Q2: What further investigations would you perform?
Ultrasonography demonstrated a nodule of 3 cm diameter in the left lower parathyroid gland. Abdominal radiography and ultrasonography did not reveal nephrocalcinosis or nephrolithiasis. Bone series were normal. Plasma calcitonin was 29 ng/l (normal <50 ng/l) and fasting plasma gastrin was 44 ng/l (normal <150 ng/l). The 24 hour urinary free catecholamines, dopamine, epinephrine, and norepinephrine were normal. In our case, there were no family history, clinical or laboratory findings of MEN 1 (primary hyperparathyroidism, tumours of the pituitary and pancreas, often associated with Zollinger-Ellison syndrome) or MEN 2A (primary hyperparathyroidism, pheochromocytoma, and medullary carcinoma of the thyroid).
Q3: What is the therapy for the severe hypercalcaemia in this case?
The patient was treated with saline rehydration, low doses of intravenous frusemide (after rehydration), intravenous clodronate, and subcutaneous calcitonin. Four days after, the blood calcium was 2.2 mmol/l and the creatinine was 61.9 μmol/l. Parathyroid surgical exploration revealed an enlarged left lower parathyroid gland. The other three glands were normal. Removal of the left lower parathyroid gland was performed, and the histopathological examination demonstrated a 3 cm diameter parathyroid adenoma. Seven days after surgery, intact PTH was 43 μg/l and blood calcium remained normal. Six months later, the patient remains asymptomatic and blood calcium and intact PTH are normal.
Surgery, with its risks, for all patients with primary hyperparathyroidism now seems unwise when many will have no features of metabolic bone or renal disease.8 When done by an experienced parathyroid surgeon, parathyroidectomy is curative in more than 90% of cases.1 Medical treatment is intended to lower blood calcium to less dangerous levels. However, it is not necessary to obtain normal levels of calcium, and surgery must be carried out as soon as the patients's clinical condition and metabolism improve sufficiently.7 Emergency neck exploration should be reserved for unusual patients in whom hypercalcaemia cannot be controlled medically and the clinical picture is severe.6
Hypercalcaemia in an adult who is asymptomatic is usually due to primary hyperparathyroidism and severe hypercalcaemia suggests cancer or parathyroid carcinoma.1 The clinical picture of our case suggests malignancy. Muscle weakness is not common in primary hyperparathyroidism but is common in acute primary hyperparathyroidism, due to the severe hypercalcaemia.6 7 The serum creatinine wasn't particularly raised, which is a surprise in view of the very high level of serum calcium; this suggests that our patient's hypercalcaemia was of short duration. The proportion of symptom-free patients with primary hyperparathyroidism has increased since the introduction of the multichannel autoanalyser.4 5 Our case had acute primary hyperparathyroidism caused by a parathyroid adenoma, an unusual form of the disease. Acute primary hyperparathyroidism, also called parathyroid intoxication, parathyroid storm or parathyroid crisis, is characterised by symptomatic marked hypercalcaemia with very high serum PTH levels and with polyuria, dehydration, reduced renal function, and worsening hypercalcaemia.6 7 Most cases of acute primary hyperparathyroidism are due to a parathyroid adenoma.6 7Some authors do not exclude the parathyroid carcinoma from the acute primary hyperparathyroidism.7 Remarkable increases of PTH are characterisitc of acute primary hyperparathyroidism, up to values 30 times normal levels.6 7 It has excluded autonomous PTH secretion as a possible cause of acute primary hyperparathyroidism, and it has been suggested that a sudden increase in the set point of the diseased parathyroid cells in the presence of a huge cell mass accounts in large part for both the marked hypercalcaemia and elevated PTH levels in these patients.9 Infections, recent surgery, immobilisation, dehydration, and trauma appear to play a prominent part in the acute primary hyperparathyroidism.6 7
Frusemide must be used for therapy of the hypercalcaemia after rehydration and with caution as it counteracts the effects of rehydration. Saline rehydration reverses the increased proximal tubular calcium reabsorption, and calcitonin inhibits the distal tubular calcium reabsorption.
Acute primary hyperparathyroidism, caused by a solitary parathyroid adenoma.
Hypercalcaemia with normal or high PTH levels occurs in primary hyperparthyroidism, familial hypocalciuric hypercalcaemia and chronic treatment with lithium
Acute primary hyperparthyroidism is an unusual form of the disease characterised by life threatening hypercalcaemia
Severe hypercalcaemia suggests cancer or parathyroid carcinoma, and acute primary hyperparthyroidism constitutes an exception of this assertion
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