Tag: Parathyroid hormone-related protein

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Hypercalcaemia

Definition:-

Calcium is a mineral that’s vital for the development of healthy bones and teeth – 99 per cent of the calcium in our bodies is found here. It’s also needed for muscle contraction, regulation of the heartbeat and formation of blood clots. A long-term shortage of calcium can lead to osteoporosis (brittle-bone disease).

The four pea-sized parathyroid glands (found at the front of the neck) are responsible for regulating the body’s calcium levels. These small glands, which are embedded in the tissue of the thyroid gland in the neck, detect fluctuations in the level of calcium in the blood.

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There are times when this delicate balance is upset and too much calcium enters the blood. If levels rise too much, the glands decrease the secretion of the parathyroid hormone (PTH) and calcium levels return to normal again.
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Hypercalcaemia  is an elevated calcium level in the blood. (Normal range: 9–10.5 mg/dL or 2.2–2.6 mmol/L). It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a diagnosis should be undertaken if it persists. It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion.

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Symptoms:–
There is a general mnemonic for remembering the effects of hypercalcaemia: “groans (constipation), moans (psychic moans (e.g., fatigue, lethargy, depression)), bones (bone pain, especially if PTH is elevated), stones (kidney stones), and psychiatric overtones (including depression and confusion).”

Other symptoms can include fatigue, anorexia, nausea,abdominal pain, weightloss,loss of appetite, vomiting,constipation, pancreatitis and increased urination.

Abnormal heart rhythms can result, and ECG findings of a short QT interval and a widened T wave suggest hypercalcaemia. Significant hypercalcaemia can cause ECG changes mimicking an acute myocardial infarction.

Peptic ulcers may also occur.

Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l). Severe hypercalcaemia (above 15–16 mg/dL or 3.75–4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result.

Causes:-
One of the commonest causes of hypercalcaemia is cancer. Up to 20% of people with cancer have high calcium levels, especially with cancers of the breast, lung, head and neck, and certain blood cancers.

Abnormal parathyroid gland function:
*primary hyperparathyroidism
*solitary parathyroid adenoma
*primary parathyroid hyperplasia
*parathyroid carcinoma
*multiple endocrine neoplasia (MEN)
*familial isolated hyperparathyroidism
*lithium use
*familial hypocalciuric hypercalcaemia/familial benign hypercalcaemia

Malignancy:
*solid tumour with metastasis (e.g. breast cancer or classically squamous cell carcinoma, which can be PTHrP-mediated)
*solid tumour with humoral mediation of hypercalcaemia (e.g. lung cancer [in turn, most commonly of the small cell lung cancer type] or kidney cancer, pheochromocytoma)
*haematologic malignancy (multiple myeloma, lymphoma, leukaemia)

Vitamin-D metabolic disordershyper:
*vitaminosis D (vitamin D intoxication)
*elevated 1,25(OH)2D (see calcitriol under Vitamin D) levels (e.g. sarcoidosis and other granulomatous diseases)
*idiopathic hypercalcaemia of infancy
*rebound hypercalcaemia after rhabdomyolysis

Disorders related to high bone-turnover rateshyperthyroidism:
*prolonged immobilization
*thiazide use
*vitamin A intoxication
*Paget’s disease of the bone
*multiple myeloma

Renal failure
*severe secondary hyperparathyroidism:
*aluminium intoxication
*milk-alkali syndrome

Risk Factors:
An overproduction of PTH may also responsible for hypercalcaemia; this is often caused by a tumour in one or more of the parathyroid glands. Excess production of PTH may occur to compensate for a malfunction in one of the body’s other calcium-balancing mechanisms; for example, when the kidneys aren’t working properly or when there’s a deficiency of vitamin D.

Women over the age of 50 are most likely to have hypercalcemia, usually due to primary hyperparathyroidism.

Diagnosis:
Hypercalcaemia is diagnosed by laboratory tests including: serum calcium, albumin, phosphate, alkaline phosphate, BUN, creatinine, electrolytes and PTH level. These investigations assist in diagnosing the cause of hypercalcaemia and give a baseline indication of renal function. Urinary calcium should be measured as hypercalciuria may be detected. Other investigations may include an ECG and radiology examinations such as x-ray or bone scans which may show bone metastases

Treatment:
The treatment of hypercalcaemia is determined by the underlying disease, the degree of the hypercalcaemia and the patient’s clinical presentation. The aim of treatment is directed at decreasing serum calcium levels by increasing urinary excretion of calcium and decreasing bone resorption of calcium. Immobilization should be avoided as inactivity will cause an increase in bone resorption of calcium. The level of activity will be appropriate for the patient’s physical condition and other measures such as pain control may need to be considered prior to undertaking any physical activities. A review of the patient’s medications will need to be considered. Drugs that inhibit urinary calcium excretion, such as thiazide diuretics, should be ceased. NSAID and H2-receptor drugs, such as Ranitidine which decrease renal blood flow, should also be avoided if possible. Any calcium, Vitamin A and D supplements should also be ceased. Dietary restrictions of calcium have not been proven to be of any benefit to patients that are hypercalcaemic, or at risk of hypercalcaemia. Currently there is no data to suggest that hypercalcaemia has been attributed to food. However, some dietary supplements can cause abnormally hight levels of calcium in the blood. Patients with chronic renal failure are at risk of becoming hypercalacemic due to calcium intake.

This is due to decreased urine production, in combination with high calcium intake). Intravenous fluids (0.9% sodium chloride) will be administered to rehydrate the patient, the volume of fluid given will depend on the extent of the patients dehydration and cardiovascular and renal functions. At least 4-6 litres of saline on day 1, and 3-4 litres for several days thereafter is usual. Diuretics such as frusemide may also be given. Repeat blood tests should be taken several hours after treatment and reassessed. Cardiac status and urinary output should also be assessed, thus a strict fluid balance chart should be maintained on the patient. Oral phosphates, which inhibit bone resorption, may be administered. Diarrhoea is a common side effect and may lead to non-compliance. Bisphosphonates, which are given intravenously, inhibit osteoclast activity that contributes to bone resorption may also be administered. The two most common drugs used are Pamidronate/Aredia (60-90mg IV over 2 hours) and Zoledronic Acid/Zometa (4mg IV over 15 minutes). Both of these agents are generally well tolerated with limited side effects such as mild fever and irritation at the infusion site.

Prognosis:
The prognosis of hypercalcaemia depends upon the cause of increased calcium levels. When the underlying cause is treatable and the treatment is initiated promptly, hypercalcaemia can have a good prognosis. However, when associated with malignancy that has progressed into development of hypercalcemia, prognosis is poor. Hypercalcaemia is potentially fatal. Early diagnosis is important, as the cause of high blood calcium is usually identified and treated to avoid long-term complications. Signs and symptoms may be confused with those of end stage disease in terminal patients. In some patients, symptoms may be non-specific and have a slow onset.Some examples of these are:
•Anorexia
•Weakness
•Nausea
•Vomiting
•Constipation

In other cases, symptoms such as dehydration, renal failure and coma may develop very quickly resulting from very rapidly rising calcium levels. This may result in a life threatening situation. Symptoms do not always correlate with serum calcium levels. These must be closely compared with an in-depth patient history, examination and laboratory report. Signs and symptoms of hypercalcaemia can be numerous and nonspecific. They depend on the underlying cause and how quickly the calcium level rises. Mild hypercalcaemia may be asymptomatic but as the calcium levels rise, the symptoms begin to appear in all body systems. Some non-specific findings associated with hypercalcaemia include: decreased heart rate, hypertension, proximal muscle weakness (chronic hypercalcaemia), bony tenderness, increased tendon reflexes, unwanted tongue movements, dehydration and even coma.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/hypercalcaemia1.shtml
http://en.wikipedia.org/wiki/Hypercalcaemia
http://www.virtualmedicalcentre.com/symptoms.asp?sid=31&title=Hypercalcaemia#C3

http://erc.endocrinology-journals.org/content/12/3/549.full

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