Primary Hyperparathyroidism
So your GP has told you that your blood calcium level is high, and his further investigations has revealed that this is due to a hyperactive parathyroid gland. He has referred you on to an endocrine surgeon to have your hyperactive parathyroid gland removed. You are a bit surprised as you don’t feel that there is anything wrong with you and you cannot quite understand why you need to have surgery. Hopefully by going through this blog you will get a good understanding of primary hyperparathyroidism as well as strategies to treat it.
What are parathyroid glands?
The parathyroid glands are very small bean-shaped glands that are located behind the thyroid gland. There are generally four glands, two behind each thyroid lobe. The glands are normally the size of a grain of rice, tan-coloured, and weigh about 30-40 mg each.
What is the function of parathyroid glands?
Although the parathyroid glands neighbour the thyroid gland, their function is totally separate. The parathyroid glands are responsible to control blood calcium (Ca) level very tightly. They do this by secreting parathyroid hormone (PTH) which is itself controlled by a feedback mechanism through calcium sensors on the surface of parathyroid cells located in the gland. The Ca level is kept within a narrow normal range (2.1 to 2.6 millimoles per litre). When the Ca level goes down, the parathyroid glands secrete more PTH which quickly brings the Ca level back up by acting on three body organs:
Bone: PTH causes release of calcium from bone into the blood stream.
Bowel: PTH increases calcium absorption in the bowel
Kidney: PTH increases calcium resorption in the kidneys.
On the other hand, when the Ca level goes up, PTH secretion is suppressed which quickly brings the Ca level back to normal.
Why is Ca level is so tightly regulated?
Calcium ions play pivotal role in many of the human body’s physiological processes across all organs. Changes in blood calcium level will affect muscle contraction, signal transmission withing the nervous system and the heart, enzymatic metabolic activities, blood clotting, and intracellular signalling leading to changes in cellular secretions and proliferations. Therefor you can see how changes in Ca levels can affect function of many body organs. For example, a low Ca level (hypocalcaemia) causes agitation at a cellular level which can manifest as pins and needles, muscle cramps and spasms, irregularities in heart rhythms, and seizure.
What is primary hyperparathyroidism?
So if the parathyroid glands are functioning normally, a high Ca level should lead to immediate suppression of PTH secretion. When both Ca and PTH level are elevated, it means that one or more of the parathyroid glands have become hyperactive and have not responded to the elevated Ca level by suppressing their PTH secretion. This is called primary hyperparathyroidism (PHP).
The most common underlying pathology is a single parathyroid adenoma (80-90% of the cases). It means that one of the four glands has enlarged due a benign proliferation and secrets excess PTH that is not responding to the elevated Ca level (hypercalcaemia). Removing this single adenoma by surgery will cure the disease.
In about 10% of the cases the cause is multi-gland hyperplasia. It means that two or more of the glands have increased in size and function and therefore surgery should address all these glands to normalise Ca and PTH. Very rarely (<1% of the cases) PHP is due to parathyroid carcinoma, which is a cancerous proliferation of one of the parathyroid glands. This often manifests with a very large parathyroid tumour associated with very high Ca and PTH levels.
What causes primary hyperparathyroidism?
Most cases of PHP are sporadic, i.e., they just happen by chance like most other abnormal growths in the body. About 5% of cases are related to genetic syndromes. Other causes of PHP include radiation exposure (both external radiation to the head and neck and radioactive iodine for treatment of thyroid disease) and prolonged use of a drug called lithium.
What are the symptoms of primary hyperparathyroidism?
The most common presentation of PHP is in fact asymptomatic with incidental finding of elevated Ca on a blood test done by the GP. This is because the rise in Ca level and the damages done by PHP on the musculoskeletal, renal, nervous, and cardiovascular system is often insidious and therefore patients often fail to notice them till later stages. Many patients who are initially labelled as “asymptomatic” report improved in their energy level, mood, irritability, and body aches and pain following surgery! This was most elegantly showed by Professor Paseika in her research using the questionnaire in Table 1. If you are diagnosed with PHP and you score over 200 on this questionnaire you are likely to be affected by the disorder and therefore notice improved symptoms within a year following your surgery.
Table 1. Paseika Questionnaire. No symptoms = 0. Most severe symptoms = 100. A score over 200 in a patient with the diagnosis of PHP is a predictor of significant improvement of symptoms following parathyroidectomy.
Other presentations of PHP include:
Musculoskeletal system: osteoporosis and osteopenia (thinning of bone) leading to fractures
Urinary system: excessive urination leading to thirst, kidney stones, kidney failure
Gastrointestinal system: constipation, stomach ulcers, pancreatitis, loss of appetite, nausea and vomiting
Cardiovascular: high blood pressure, abnormal heart rhythm, heart block
Nervous system: depression, anxiety, headaches, poor memory, confusion, coma
How is primary hyperparathyroidism treated?
Once the blood test confirms the diagnosis of PHP by showing elevated Ca and PTH level, the next step is to identify the underlying pathology. As pointed out above most cases are caused by a single parathyroid adenoma. Therefore, imaging is done to find out which one of the four glands have gone rebellious.
Three imaging modalities are commonly used for the purpose of localising a parathyroid adenoma. These include ultrasound (US), CT scan, and nuclear medicine (NM) scan. The US scan is also done to assess the thyroid gland, as about 25% of patients with PHP also have abnormalities in their thyroid gland. If two of the scans concordantly point out to a single parathyroid adenoma as the culprit, having surgery to remove the gland gives a 98% chance of curing the disease! The operation is called “minimally invasive parathyroidectomy” which is done through a small 2-3cm neck incision often well hidden in a skin crease.
Medical therapy options can be considered in elderly patients who have mild to moderate elevation of Ca, a single adenoma has not been localised on imaging, and are poor surgical candidates. These options include osteoporosis medications such as bisphosphonates and Denosumab, estrogens, diuretics, and Sensipar. These medications are often administered under the supervision of a endocrinologists and need to be continued life-long.