Parathyroid disorders: hyperparathyroidism and hypoparathyroidism

PTH does not act on bone in the direct way most diagrams suggest. The osteoclasts that dissolve bone have no PTH receptors. PTH binds receptors on the osteoblasts, the bone-forming cells, and those cells send the signal that recruits and activates osteoclasts; the bone-forming lining is therefore the relay, and continuous exposure to PTH favours resorption while intermittent pulses can favour formation, the principle behind the anabolic drug teriparatide.

In the kidney, PTH increases calcium reabsorption in the distal convoluted tubule and simultaneously blocks the sodium–phosphate cotransporter in the proximal tubule, which is why phosphate leaves the body and the serum phosphate falls. The same kidney cells are stimulated to convert inactive vitamin D into calcitriol, the active hormone, through the enzyme 1-alpha-hydroxylase. Calcitriol then travels to the enterocyte, increases the calcium channels and the calcium-binding protein calbindin, and so raises the fraction of dietary calcium absorbed.

Read the laboratory report against these targets. Total serum calcium is normally about 2.2 to 2.6 mmol/L, and roughly half of it is bound to albumin; ionised calcium, the physiologically active fraction, is about 1.1 to 1.3 mmol/L. When albumin is low the measured total falls without any true change in ionised calcium, so a corrected value is calculated, adding about 0.02 mmol/L for every gram per litre by which the albumin sits below 40 g/L. PTH itself is reported in picomoles or picograms per millilitre, with a normal range of roughly 1.6 to 6.9 pmol/L, and phosphate is normally about 0.8 to 1.5 mmol/L.

Finally, the calcium–phosphate product matters: in conventional units a product above about 55 mg²/dL², equivalent to roughly 4.4 mmol²/L², is the level at which calcium phosphate begins to precipitate in soft tissue. About 99 per cent of the body’s calcium sits in bone, so the skeleton is the buffer that makes the whole arrangement work.

Before accepting a diagnosis of primary hyperparathyroidism, the clinician asks why the calcium is high, because the same number has several quite different meanings. Primary hyperparathyroidism is autonomous secretion from an abnormal gland and is confirmed by a high calcium with a PTH that is raised or, importantly, merely inappropriately normal: in any other cause of hypercalcaemia the parathyroid glands should be suppressed, so a normal PTH in the face of a high calcium is already abnormal. Malignancy is the other common cause. Some tumours secrete PTH-related peptide, a molecule that mimics PTH at the receptor but is not detected by the PTH assay, so the calcium is high and the PTH is suppressed; myeloma and bone metastases raise calcium by destroying bone directly.

Secondary hyperparathyroidism is not autonomous at all. It is a compensation: in chronic kidney disease phosphate is retained and calcitriol production falls, so the glands work harder and PTH rises while calcium may still be low or normal. When that chronically stimulated gland becomes autonomous, the disorder is called tertiary hyperparathyroidism and the calcium finally climbs.

Three traps are worth knowing. Familial hypocalciuric hypercalcaemia is an inactivating mutation of the calcium-sensing receptor: calcium is mildly high and PTH is normal, but urinary calcium is low, the calcium-to-creatinine clearance ratio is below 0.01, and surgery does not help. Thiazide diuretics reduce calcium excretion and can raise the calcium of an otherwise healthy person. Lithium and sarcoidosis also disturb the picture, the latter because granulomas make calcitriol outside the kidney.

Localisation uses ultrasound and a sestamibi scan, with intraoperative PTH measurement confirming that the abnormal tissue has been removed. After a successful parathyroidectomy the calcium can fall sharply as the skeleton, starved for years, suddenly takes calcium up again — the hungry bone syndrome — so postoperative calcium is watched closely.

Two situations turn a chronic calcium problem into an emergency. Severe hypercalcaemia — a calcium above roughly 3.5 mmol/L, or any high calcium with drowsiness, vomiting, dehydration or an arrhythmia — is treated as a crisis. The first step is volume, not diuresis: 0.9 per cent saline is infused rapidly because the dehydrated patient has a contracted circulation, and a loop diuretic is added only once the patient is volume-replete, since giving it first worsens the dehydration and can drop the calcium too abruptly.

Calcitonin acts within hours but briefly; a bisphosphonate such as zoledronic acid is given for a sustained effect and works by inhibiting osteoclast-mediated resorption — that is, by reducing the release of calcium from bone, not by increasing its uptake. They do not increase calcium absorption in bone; they lower serum calcium by blocking bone breakdown. Haemodialysis is reserved for refractory cases or kidney failure.

The nurse watches the electrocardiogram, because hypercalcaemia shortens the QT interval and potentiates digoxin, and watches fluid balance, level of consciousness, constipation and fall risk.

In hypocalcaemia the emergency is the airway and the brain. Intravenous calcium gluconate is given through a large vein over several minutes with cardiac monitoring, because a rapid push can cause bradycardia or arrest; extravasation is dangerous, since calcium salts cause tissue necrosis. Magnesium is checked in every patient whose calcium does not respond, because hypomagnesaemia both impairs PTH secretion and makes the tissues resistant to PTH, so calcium alone cannot correct the problem. Seizure precautions, a quiet environment and the presence of a surgical airway and injectable calcium at the bedside are nursing standards, not formalities. After thyroid surgery the risk period is the first 24 to 72 hours, and the nurse assesses for perioral tingling, carpopedal spasm, a hoarse voice and stridor at every set of observations.