How is primary hyperparathyroidism treated?
Medical treatment
There was in the past no effective medical treatment to control primary hyperparathyroidism. Conservative management was really little else than a wait and see policy, embarking on surgery when complications occur or bone density deteriorated. If there was no contraindications hormonal replacement was considered advisable in postmenopausal women. When a conservative approach is used the patient must be checked yearly for any deterioration in calcium levels, kidney function and bone density.
Although there is no effective medical treatment for hyperparathyroidism, there are novel developments that involve the parathyroid calcium sensor (calcium receptor). Parathyroid cells detect changes in plasma calcium levels by virtue of a calcium receptor located on the cell surface. Drugs that mimic or potentiate the effects of serum calcium on the calcium receptor are called calcimimetics. A first generation calcimimetic, NPS R-568 was been shown to lower the serum calcium in postmenopausal patients with parathyroid tumours.
The medical treatment of primary hyperparathyroidism has recently been reviewed ( Khan et al February 2009 Journal Clinical Endocrinology and Metabolism 94(2)373-381.
I will summarise their conclusions :-
#1. Long term bisphosphonates therapy may increase bone strength in untreated primary hyperparathyroidism. There is at the moment in 2009 no direct data to confirm this effect.
#2.Two non randomised trials have desaturated that long term use of hormonal oestrogen replacement has exactly the same beneficial effect on axial bone mass as surgical correction of primary hyperparathyroidism.
#3.Raloxifene which is a selective oestrogen receptor modulator (SERM) in a small placebo controlled randomized trial has been shown at 2 months to reduce the serum calcium but not to change the serum PTH.Bone activity markers were improved but not to the extent achieved with oestrogens.
#4.Cinacalcet, a drug that sensitizes the calcium receptor to the ambient serum calcium used long term will reduce the serum calcium to normal levels in primary hyperparathyroidism but as yet has not been shown to significantly increase bone density.
How does all this affect the patient.
In the symptomatic patient surgery is very much the prime choice.Surgery can be done under local anasethetic and is safe with a 99% success rate. Prior to surgery a spell of intravenuous fluids may be necessary combined in patients with bisphosphonates if the serum calcium is very high.Most physcians try to avoid bisphonates pre-operatively as they tend to cause problems in the post-operative period with "hungary bone disease".
If the patient is unfit for surgery (a very rare event) then long term use of oestrogens or bisphosphonates is the treatment of choice especially in patients with reduced bone density.Of the two agents bisphosphonates are preferred because of the long term risks of oestrogens on the cardiovascular system.There is no doubt that in cases where these agents are not effective and surgery is contra-indicted the cinacalcet is the treatment of choice.
Cinacalcet has been shown in patients with primary hyperparathyroidims in a double-blind randomised,placebo controlled trial to cause a fall in the serum calcium in a dose dependant manner. The serum parathyroid hormone also returns to normal.
If there a drugs to treat primary hyperparathyroidism why don't we use them all the time?
Surgery is so successful that most patients prefer that to long term medication. I addition side effects of the drugs such as tingling and nausea can be very troublesome. The most important consideration is cost.Cincacalcet costs £300 per month and must be taken for a lifetime. Over the years costs will drop and further generations of drugs will be produced with less side effects.
There is hope yet for a satisfactory medical treatment for hyperparathyroidism that will make surgery obsolete!
Surgery
This is the best form of treatment for primary hyperparathyroidism. The essential principle is to remove the parathyroid gland or glands that are producing the excess hormone. There are three possible types of operation.
1. Subtotal parathyroidectomy - the abnormal tissue is removed, leaving normal parathyroid tissue behind.
2. Total parathyroidectomy - this is where all the parathyroid tissue is removed.
3. Total parathyroidectomy and autotransplantation - this is where total parathyroidectomy is accompanied by the implantation of some normal parathyroid tissue dissected from the patient's own glands into the patient's forearm. The implant acts as functioning parathyroid tissue.
The type of operation performed depends on what is found during surgery. Details of this are given in the section 'Surgery - what may be found at operation'.
The traditional reasons for doing surgery are listed below:
1. Hypercalcaemia in all patients below 50 years.
2. Hypercalcaemia greater than 3.00 mmol/l in all age groups.
3. Symptomatic hypercalcaemia in all age groups.
4. Deterioration in renal function.
5. Progressive reduction in bone density.
6. Excessive excretion of calcium in the urine.
7. Any suggestion of malignant parathyroid disease.
Before the operation a number of tests must be performed to localise the tumour and assess the wellbeing of the patient. This, together with details of the procedure, can be found in the section 'Parathyroid surgery'.