Definition
Syndrome characterized by clinical effects of excessive parathyroid hormone.
Classification
Primary – resulting from parathyroid adenoma, hyperplasia or carcinoma.
Secondary – due to decreased calcium as in chronic renal failure or malabsorption states.
Tertiary – autonomous parathyroid secretion uncontrolled by calcium levels in patients with long standing secondary hyperparathyroidism.
Calcium
The normal serum calcium level is 2.25-2.65 mmol/L. It circulates in three forms:
- 50% is bound to albumin
- A small amount is bound to citrate and phosphate
- The rest is ionized and free
Intake is via the gut. 20% of ingested calcium is absorbed, via active transport from the duodenum and passive transport in the jejunum. Absorption is inhibited by fat, phosphate, carbonated soft drinks.
Most regulation of calcium reabsorption occurs in the distal convoluted tubule of the kidney, where active calcium transport occurs.
The recommended calcium intake is approximately 1000mg/day, except in pregnant and lactating individuals who should consume 1500mg/day.
Parathyroid hormone
84 amino acid peptide hormone produced by chief cells of parathyroid.
Regulation
Increased by low calcium, low magnesium, high phosphate.
Decreased by high calcium and high calcitriol.
Actions:
- Increased bone resorption. Stimulates osteoblasts to prepare the way for osteoclast action. Osteoclasts are not stimulated directly and have no receptors for parathyroid hormone
- Stimulates calcium resorption in distal tubules of kidney, increased phosphate excretion (by inhibiting its reabsorption in the proximal tubule).
- Stimulates production of 1,25 dihydroxycholecalciferol by the kidney.
- Thus indirectly stimulates absorption of calcium from the small intestine
Overall effect is to increase serum calcium and decrease serum phosphate. There is also an increase in urinary calcium, because the increase in filtered calcium overwhelms the ability of the distal tubules to reabsorb the calcium.
Metabolism
Half life of 20 minutes, broken down by Kupffer cells of liver.
Primary hyperparathyroidism
Definition
Primary hyperparathyroidism is the hypersecretion of parathyroid hormone despite an elevation of serum ionized calcium.
Epidemiology
Common, found in 1 per 1000.
Affects patients in 3rd to 5th decade
Women 2:1
Aetiology
Adenoma 80%
Hyperplasia 19%
Carcinoma 1%
Pathology in bone
The increased osteoclast activity in hyperparathyroidism affects cortical bone more than cancellous bone.
As bone resorption occurs microfractures and microhaemorrhages occur. Highly vascular fibrous tissue begins to fill up the marrow spaces, and macrophages accumulate in the fibrous tissue, laden with haemosiderin from the microhaemorrhages. Cysts develop in the fibrous tissue, resulting in osteitis fibrosa cystica (a.k.a. von Recklinghausen’s disease of bone).
Focal haemorrhages may develop after subclinical fractures and become organized with accumulation of macrophages, deposition of haemosiderin and the formation of multinucleated giant cells – this constitutes the brown tumour of hyperparathyroidism.
Osteoclasts tunnel and penetrate into the central parts of trabeculae, as well as the surface of the bone. The disorganized osteoclastic tunnels leave behind increased numbers of poorly organized cement lines resulting in a pseudo-mosaic pattern (akin to Pagets).
Clinical findings
“Stones – kidney stones, polyuria, hypertension
Bones – bone pain, joint pains from chondrocalcinosis
Groans – abdominal pain, peptic ulceration, pancreatitis
Moans – depression, emotional lability”
The commonest presentation is with renal colic.
Skeletal manifestations are seen in 10-15% of patients.
Proximal muscle weakness.
Secondary hyperparathyroidism has been implicated in flexor and extensor tendon rupture, as well as quadriceps, patella and triceps tendon rupture.
Lab findings
Increased calcium, decreased phosphate in blood
Calciuria and increased urinary phosphate levels
Increased parathyroid hormone levels
Radiology
Early finding is generalized osteoporosis
Subperiosteal resorption in middle phalanges of fingers, particularly affecting radial side and particularly affecting the middle and index fingers. Extensive erosion can also be seen at the symphysis pubis, distal clavicles, vertebral end plates.
Brown tumours – particularly in the diaphysis of long bones, jaw or skull.
Chondrocalcinosis
The skull can demonstrate a granular demineralization, the so-called “salt and pepper” appearance.
Loss of the lamina dura of the teeth can occur.
Treatment
Medical treatment
Hypercalcaemia is treated with rehydration and bisphosphonate (e.g.Pamidronate) infusion. The pamidronate is given in doses of 60 to 90mg over an hour, and takes 1-2 days to produce its effect of lowering the serum calcium for a week. Addition of a loop diuretic will favour calcium excretion.
Calcitonin may be used in doses of 50 to 100U every 6 hours.
Surgical treatment
Patients with renal stones or osteitis fibrosa cystica need surgical treatment.
This consists of sub total parathyroidectomy. There is controversy over the optimal amount of parathyroid tissue to remove. In patients with one clearly demonstrated adenoma, the surgeon may find this lesion, and then also find one other parathyroid gland. If this gland is normal it may be presumed other glands are normal, and this assumption will result in success in 90% of patients.
Post surgery marked hypocalcaemia may develop. Bone hunger refers to the marked uptake of calcium by bones that have been released from the effects of excessive parathyroid hormone.