The video version of this podcast can be found here:

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This episode makes reference to guidelines produced by the "National Institute for Health and Care Excellence" in the UK, also referred to as "NICE". The content on this channel reflects my professional interpretation/summary of the guidance and I am in no way affiliated with, employed by or funded/sponsored by NICE.

NICE stands for "National Institute for Health and Care Excellence" and is an independent organization within the UK healthcare system that produces evidence-based guidelines and recommendations to help healthcare professionals deliver the best possible care to patients, particularly within the NHS (National Health Service) by assessing new health technologies and treatments and determining their cost-effectiveness; essentially guiding best practices for patient care across the country.

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I go through the NICE guideline on Primary Hyperparathyroidism, focusing on what is relevant to Primary Care only. Make sure to stay for the entirety of the episode because, at the end, I will also explain the pathophysiology of secondary and tertiary hyperparathyroidism.

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

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There is a podcast version of this and other videos that you can access here:

Primary Care guidelines podcast:

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

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There is a YouTube version of this and other videos that you can access here: 

• The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

The Full NICE guideline Hyperparathyroidism (primary): diagnosis, assessment and initial management or [NG132] can be found here:

·      https://www.nice.org.uk/guidance/ng132

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we are looking at the NICE guideline on Primary Hyperparathyroidism, or NG132, focusing on what is relevant to Primary Care only. Make sure to stay for the entirety of the episode because, at the end, I will also touch on secondary and tertiary hyperparathyroidism.

Right, let’s jump into it.

What features could indicate primary hyperparathyroidism?

Well, experience suggests that hypercalcaemia in primary hyperparathyroidism is commonly associated with symptoms such as thirst, frequent or excessive urination, and constipation, and with conditions such as osteoporosis, fragility fractures and renal stones. So, these are the prime clues to look for.

However, sometimes there are also chronic non-specific symptoms, including fatigue, anxiety and depression, confusion, irritability and digestive problems.

And, of course, primary hyperparathyroidism can also be asymptomatic showing simply as hypercalcaemia. Hypercalcaemia is defined as a corrected calcium of 2.6 mmol/litre or more. 

What diagnostic testing should we do in primary care?

The main initial test is the albumin-adjusted serum calcium, which, from now on and for simplicity, I will refer to as just corrected calcium. We should not rely on ionised calcium. This is because calcium that is bound to albumin is not active and does not have clinical effects, so adjusting for albumin is a better measurement. Furthermore, ionised calcium is not subject to the same stringency of laboratory testing and the sample has to be handled very quickly, making it unreliable.

And when should we check corrected calcium?

We will definitely check it if we suspect primary hyperparathyroidism because of, as we have just said:

·      symptoms of hypercalcaemia, primarily thirst, frequent or excessive urination, or constipation but also those with chronic non-specific symptoms.

• Or if there are conditions like osteoporosis
• a previous fragility fracture or
• a renal stone

Then we should repeat the corrected calcium if the level is either:

• high, that is, 2.6 mmol/litre or above or
• if it is 2.5 mmol/litre or above and features of primary hyperparathyroidism are present.

And you may ask yourselves? Should we be checking parathyroid hormone or PTH with this second blood test?

Well, NICE says, not yet. This is because calcium levels can vary with changes in blood pH or albumin, and the cost of the test is low, so it should be checked at least twice before moving on to more expensive tests like PTH.

So, then, we will check PTH if the corrected calcium level continues to be either:

• high, that is, 2.6 mmol/litre or above on at least 2 separate occasions or
• if it is 2.5 mmol/litre or above on at least 2 separate occasions and primary hyperparathyroidism is suspected.

But you may be thinking: a corrected calcium of 2.5 is in the normal range. Should we be even thinking of primary hyperparathyroidism in these cases? Well, NICE explains that although most people with primary hyperparathyroidism have hypercalcaemia, there is a smaller number of people that develop 'normocalcaemic primary hyperparathyroidism' which often goes unrecognised, so this is the reason for this lower calcium threshold.

When measuring PTH, we will check the corrected calcium again at the same time. To check PTH we can use a random sample at any time of day because, although there is a marginal diurnal difference, it is not enough to need adjusting for. Once checked, we should not routinely repeat the PTH in primary care

Once we have the results, we will conclude that primary hyperparathyroidism is unlikely if:

• the PTH is below the midpoint of the reference range and
• the corrected calcium is below 2.6 mmol/litre.

However, we will refer to a specialist if the PTH is either:

• below the midpoint of the reference range but with a concurrent corrected calcium level of 2.6 mmol/litre or above or
• if PTH is above the midpoint of the reference range and primary hyperparathyroidism is suspected. Considering that we should not be checking PTH unless we suspect hyperparathyroidism, this means that we may have refer patients even if their PTH level is within the normal range, as long as it is above the midpoint of the reference range. 

Do we need to worry about low PTH levels? Well, NICE says that we should look for alternative diagnoses, including malignancy, if the PTH is below the lower limit of normal.

Why is this? A low PTH or hypoparathyroidism, can have several causes including autoimmune diseases, genetic disorders and low magnesium but also malignancy. Certain cancers, particularly those that metastasise to the bones, can disrupt the normal function of the parathyroid glands. Additionally, some cancers can produce substances that mimic PTH, causing hypercalcemia of malignancy, which can suppress the normal parathyroid function.

Now, moving on, although NICE recommends the following tests in secondary care, some of them can be done in Primary Care, so we can use our clinical judgement in this respect. These tests are:

·      Vitamin D. This is because vitamin D deficiency can lead to a rise in PTH level and exacerbate bone disease. Therefore, assessing and correcting vitamin D in important. However, NICE also considers that waiting for vitamin D to be checked, and corrected, if necessary, could delay the diagnosis of primary hyperparathyroidism. So, although we could indeed check it, we should not delay referral because of it.

·      The other tests that we can consider are less common in Primary Care. They are tests to check urine calcium excretion, for example with a 24-hour urinary calcium excretion. They are used to exclude familial hypocalciuric hypercalcaemia so perhaps they are really best left for secondary care.

Now, secondary care will decide which cases of primary hyperparathyroidism need referral for surgery and which follow up is needed after it depending on whether the surgery is deemed to have been successful or not.

However, we need to be aware that patients who haven’t had successful surgery should be monitored by checking:

·      corrected calcium and renal function at least once a year

·      a renal ultrasound scan at diagnosis and if a renal stone is suspected and

·      a DXA scan at diagnosis and then every 2 to 3 years until the hyperparathyroidism has been corrected.

Whilst a bisphosphonate can be considered for those with an increased fracture risk, it should not be used just to treat the hypercalcaemia of primary hyperparathyroidism.

And of course, primary hyperparathyroidism in pregnancy should be managed in secondary care being aware that these patients are at increased risk of hypertensive disease in pregnancy.

Now, as promised, I am going to tell you a little about secondary and tertiary hyperparathyroidism.

But before, let’s go through some definitions:

Primary hyperparathyroidism is when the parathyroid glands produce excessive amounts of parathyroid hormone without any external trigger, that is, it is an intrinsic problem within the parathyroid glands and the most common cause is a benign tumour or adenoma.

Secondary hyperparathyroidism is when the parathyroid glands overproduce PTH as a compensatory response to low calcium and it is the body's attempt to normalise the levels. Possible causes are chronic kidney disease and vitamin D deficiency.

And, finally, tertiary hyperparathyroidism is when hyperplastic parathyroid glands overproduce PTH autonomously, that is, not responding to normal regulatory feedback. This is generally seen after prolonged secondary hyperparathyroidism in patients with CKD.

And let’s quickly look at the pathophysiology of tertiary hyperparathyroidism:

In CKD, the kidneys lose their ability to excrete phosphate, leading to hyperphosphatemia.

In CKD, the kidneys also produce less active vitamin D, resulting in decreased calcium absorption and hypocalcemia.

Both hypocalcemia and hyperphosphatemia stimulate the parathyroid glands to produce more PTH to maintain calcium levels. This is the secondary hyperparathyroidism stage.

However, over time, the continuous stimulation of the parathyroid glands leads to glandular hyperplasia and, as it progresses, the parathyroid glands become less responsive to normal feedback mechanisms.

So, in some patients, particularly in those after prolonged and severe secondary hyperparathyroidism, the parathyroid glands can become autonomous, meaning that they secrete PTH independently of blood calcium levels. At this stage, even when the initial cause of secondary hyperparathyroidism is corrected (for example, after a kidney transplant), the overactive parathyroid glands continue to produce excessive PTH which will lead to hypercalcemia. This is when we talk about tertiary hyperparathyroidism.

So that is it, a quick review of the different types of hyperparathyroidism.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.