The role of parathyroid hormone
Parathyroid hormone (PTH) works hard all day, every day, to balance or regulate blood calcium (in the same way a thermostat regulates heat) to keep calcium levels in a tightly controlled range by promoting its release from bone (where most of the body’s calcium is stored), increasing the body’s ability to absorb calcium from food, and increasing the kidney’s ability to hold onto calcium that would otherwise be lost in urine. Calcium balance is crucial to the normal functioning of multiple body systems; in particular the heart, nervous system, kidneys and bones. Calcium and PTH work together in a perpetual negative feedback loop. The important factor to consider when looking for PHPT is where in the range both calcium and PTH fall. It is never normal to see both an elevated calcium and PTH. It is also never normal to see both calcium and PTH high within the normal range.
In a healthy individual, a low calcium level will stimulate the release of PTH to increase the release of calcium from bone. When blood calcium is high, the Parathyroid glands stop producing PTH. Symptoms should always be considered. If you have typical symptoms of Hyperparathyroidism and your PTH is inappropriately raised for the level of calcium, your doctor should refer you for further investigations; an ultrasound scan and a sestamibi scan. A dexa bone density scan should be requested to include the non dominant forearm as bone loss in the wrist cortex is indicative of PHPT. Negative scans or adequate bone density should not prevent surgery if you are diagnosed biochemically and symptomatic.
When a pan of water is boiling, we turn down the gas. PHPT is a similar principle. When PTH is unable to balance your calcium, it is malfunctioning and needs to be fixed by removing the malfunctioning parathyroid gland (s). Picture two children on a see-saw. It is never normal to see both children elevated. Think of the bubble in a spirit level when testing if a shelf is straight. The bubble should be in the middle. When it's at one end, the shelf is unbalanced and needs correcting.
If your blood results are questionable, repeat tests two or three times, are recommended to see a trend. Always ask for the ranges used by your lab as they vary from one lab to another. Always check if PTH is tested in EDTA to ensure stability and accuracy of your results.
It is essential for doctors to recognise and understand the relationship between calcium and parathyroid hormone. Levels being 'within the normal range' does not mean you don't have hyperparathyroidism.
If you have high normal calcium and high normal or raised PTH, then you very likely have Primary Hyperparathyroidism.
If your calcium is high normal and you have symptoms, your doctor should retest with corresponding PTH
If you have low calcium with raised PTH, you likely have Secondary Hyperparathyroidism. Your doctor must test your vitamin D (scroll down to the bottom of this page for more information).
This is where it gets complicated and needs a doctor to do his/her research: 20-25% of people with a parathyroid adenoma will have calcium within the normal range and raised PTH. This is classed as Normocalcemic primary hyperparathyroidism (NCPHPT). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127400/ Scroll down to the bottom of this page to read about NCPHPT. Please look at our case stories for positive post-op stories of people with NCPHPT.
22.5% of the primary hyperparathyroid population present with a raised blood calcium and a PTH level that is not above range but inappropriately detectable for its corresponding calcium level; This is classed as Normohormonal PHPT (NHPHPT). The following study explains that NHPHPT: http://www.medscape.com/medline/abstract/27866715
People with recurring PHPT, multiple gland disease or who have been diagnosed with tumours elsewhere like pituitary or pancreas should be genetically tested for MEN. Please scroll down to read the article written by Gill Masters.
Click here to read definitions of PHPT, by people who have it.
Why do so many doctors and endocrinologists still not know how to recognise or diagnose PHPT? Why do so many of them think PHPT is a rare disease when actually it is a very common endocrine disease? Why do they try to treat symptoms independently, but become baffled when they remain unresolved? Why do they still believe PHPT mostly affects post menopausal women? Simply because their knowledge of primary hyperparathyroidism is outdated.
Many Doctors will admit primary hyperparathyroidism was only covered briefly in their training. We campaigned for NICE guidelines in the hope they would encourage doctors to update their knowledge. They were commissioned by RCGP in 2016 and published on 23 May 2019. They are far from perfect, they fail to list the most common symptoms, and fail to cover post op care despite our requests. Your doctor can learn from us about post op remineralisation and supplements as you will be discharged into their care after surgery. Please show them the guidelines: https://www.nice.org.uk/guidance/NG132? and direct them to this site. We created a summary of the guidelines and sent copies to all NHS Trusts. Please join our FB support groups or contact us to obtain a copy.
How is PHPT diagnosed?
PHPT is sometimes diagnosed after finding a raised level of calcium in a blood test, but with increased awareness and education it is important for our doctors to realise that not everybody with PHPT will have an elevated calcium level. Typically, a repeat test should be requested with PTH (which should be tested using EDTA to ensure accuracy) and Vitamin D (to rule out secondary Hyperparathyroidism due to vitamin D deficiency). Some doctors may request a test of 24-hour urine calcium (to exclude a familial condition that mimics PHPT) although this is not always an accurate confirmation.
Once PHPT is diagnosed, bone densitometry scans of the hip, spine and non-dominant forearm may be performed as high bone turnover in PHPT patients is associated with a reduction in bone mineral density specifically in the cortical bone (forearm and hip). A kidney ultrasound will see whether the disease is causing harm to the kidneys.
The next step is an ultrasound scan and sestamibi scan to locate which of the glands has developed an adenoma. A negative scan does not mean you don't have PHPT. We see many cases of positive surgery after negative scans. Please see our article on our Q&A page.
Does PHPT need treatment?
PHPT is a progressive disease. The only definitive cure is to remove the diseased parathyroid gland (s) with surgery called a parathyroidectomy. If you are asymptomatic (without symptoms) you may wish to monitor your calcium levels and bone density, but ideally, surgery should be considered before your health starts to deteriorate. The chance of being cured by a single operation is highest and the risk of complications is lowest, when the surgery is performed by a specialist parathyroid surgeon, which is highly advisable. You should continue to keep a reasonable level of calcium in your diet and stay hydrated until surgery.
Is there a non-surgical treatment?
In a word, No. Whilst a surgical parathyroidectomy is the only cure for PHPT; Cinacalcet is now licensed in the UK as treatment to reduce calcium levels back to normal range (this does not help kidney and bone disease) as a holding measure prior to surgery or in the small number of patients that are considered not fit enough for surgery.
Hyperparathyroidism. How low can you go?
Written by Justin Morgan - Consultant Surgeon
To understand the current thinking around Hyperparathyroidism you need to have a grasp of the history of the disease. The parathyroid glands were the last organs of the body to be discovered in man. A medical student in Uppsala, Sweden, called Ivor Sandstrom, identified parathyroid glands in rodents during a summer anatomy project. He went on to find them in cadavers in the hospital morgue. That was 1880, although in 1851 parathyroid glands had been identified and named by Sir Richard Owen in London. However the animal he identified them in was a rhinoceros that had died in a fight with an elephant in London Zoo. He dissected the rhino over a 2 year period in his front room. After that time the carcass was said to be in an ‘offensive state of decay’!
Nobody knew what the parathyroid glands did until around 1910 and the first operation to remove a parathyroid tumour was not until 1925 in Vienna. A trolleybus driver called Albert was the first patient but unfortunately it was unsuccessful and he sadly died following a second procedure.
Thereafter, a long period of not really knowing what to do about the condition set in. There were no reliable scans to use and the PTH assay was not reliable until the 1980’s. This is where the idea that no one should be considered for surgery until the calcium levels were above 3 came from. Understandably if you have no reliable way to diagnose the problem then you are bound to be quite conservative in what you do. If you wait for the calcium to get above 3 then the parathyroid gland is likely to be quite large and therefore easier to find at operation. Up until the introduction of the reliable PTH assay in the 1980’s very few parathyroidectomies were performed and it remained a bit of a Cinderella specialty.
This also explains another commonly held belief about hyperparathyroidism. If you believe that the condition is one which only needs treatment if the calcium level is above 3 then it follows that any symptoms the patient might have cannot be caused by the calcium if the levels are below 3. In other words the symptoms are only real if the calcium is above 3. We now understand that that is simply not true but it is a bit worrying that many doctors still have it in their mind that the magic number of 3 is the one to wait for. I believe very strongly that the level of calcium is unrelated to the symptoms. I frequently see people who are very symptomatic with calcium levels around the top of the normal range. I also see people with no symptoms who have very high levels of calcium. Sadly patients are still being told that their symptoms cannot be calcium related because the levels are ‘not high enough’. This isn’t acceptable any more in my opinion.
Which brings us to Normocalcaemic Hyperparathyroidism. How low can the calcium be and still be called hyperparathyroidism? This is a really interesting area and it’s a challenge to get it right. We know that the diagnosis of Hyperparathyroidism is made when a raised calcium is accompanied by a raised Parathyroid Hormone (PTH) level. Importantly Vitamin D deficiency and FHH (Familial Hypercalcaemic Hypocalciuria) must be absolutely ruled out because both can look like Hyperparathyroidism biochemically but will not respond to surgery.
So as long as other factors are ruled out then a raised PTH with a calcium level that is at the top end of the normal range (2.2-2.6) now is classified as Normocalcaemic Hyperparathyroidism. It’s a problem to say at what level of calcium, in the normal range, counts as high? 2.5? 2.4? This is where it gets tricky and where it’s true to say that strongly held opinions differ! I am seeing more and more people with this ‘new’ condition. The decision to recommend surgery is a delicate one and needs to be made with full consent and understanding of the risks and benefits. We just don’t know yet what the long term outcomes will be so it’s very difficult to promise success. So far it seems to me that the majority of patients report improvement in symptoms but not all. We must be careful to evaluate the results of surgery as we go along to gain more understanding of the condition. I am however cautiously optimistic so far.
The other current controversial area is around the patients who have calcium levels just above the normal level and PTH levels just within the range. This is also hyperparathyroidism because if the calcium is raised for any reason the PTH should be low. It’s a physiological response so if the PTH is high normal with a high calcium then that may be Hyperparathyroidism. However this comes with a big caveat that in this case it’s doubly important to rule out Vitamin D deficiency and FHH. It may well be that it takes some time to come to the diagnosis of Hyperparathyroidism in this case. Often there have been a number of blood tests and other investigations over months and this is likely to be appropriate given the uncertainty around the diagnosis and potential symptoms. However I have seen a number of patients with this diagnosis and surgery is possible with the right work up.
Primary Hyperparathyroidism is a condition about which there is very much left to discover. The lack of hard evidence makes it easy for opinion to replace facts and for myths and legends to persist. These are of course my opinions! If you ask ten parathyroid surgeons what they think you will probably get eleven different opinions!
PHPT for many people, is not without symptoms (asymptomatic). We remain quite bewildered when PHPT is classed as mostly asymptomatic when so many of our lives are blighted by debilitating symptoms. Why should we wait for a devastating impact on our quality of life before being offered surgery? We shouldn't. There is no good reason to delay surgery for this progressive disease. This diagram illustrates the areas of the body affected, and symptoms.
Primary Hyperparathyroidism untreated can have a devastating impact on quality of life and lead to serious consequences like heart disease, miscarriage and stillbirth, fractures, kidney stones, depression and memory loss.
We conducted surveys to show how peoples lives have been affected. Please be aware the information in our studies represents a small proportion of people. We will continue to collect data for your information, and to raise awareness.
We would like to see blood tests for PHPT become routine as standard when a patient presents with multiple symptoms, at the very least to rule it out. We would also like all pregnant women to be screened early on in their pregnancy to rule out PHPT. As described above, one test result cannot always determine PHPT, a series of blood tests may be needed to identify a trend. levels can fluctuate with hyperparathyroidism. A blood test is only one moment in time and levels can change from one day to the next.
Please click the link below to read why we do what we do.
Age should never be a factor used to rule out a parathyroidectomy.
Out of date literature states PHPT affects mostly post-menopausal women. Our group statistics show in fact many women have had the disease at least 5-10 years before diagnosis, sadly some even up to 20-30 years. Statistics taken from over 1500 group members in 2018, show 31.6% of female members were in the age bracket 45-54 compared to 22.7% aged 55-64, 12.3% over 65, 17.4% aged 35-44 and 6.3% aged 25-34. Only 8 % of the group are men.
HRT treatment may mask calcium levels. Estrogen may falsely lower PTH levels. Please read the case story below of Helen O'Callaghan who battled for 4 years for a diagnosis whilst on HRT with Normohormonal PHPT.
If we add up all the decades lost to this disease, we would have centuries. We will never get those years back but at least we can try to make sure our doctors do not rule out PHPT due to age.
Chart created by Leanne Towse for Hyperparathyroid UK Action 4 Change.
'Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement 2014'
The Fourth International Endocrine Workshop Guideline indicates in Table 1 that only people under 50 are eligible for surgery. The same is also quoted in the Hammersmith Endocrine Bible. Both were quoted to our members, condemning those over 50 to an increasingly poor quality of life as well as impacting unnecessarily on NHS resources, (decades of treatment per person for consequences of untreated hyperparathyroidism), we argued against an age restriction in the NICE guidelines. The benefits of a parathyroidectomy vs years of treatment for the consequences of PHPT, to both patient and the NHS are; as they say a 'no-brainer'. The new NICE guideline makes no reference to age other than to state in their 'Information to the public': https://www.nice.org.uk/guidance/ng132/informationforpublic: 'hyperparathyroidism often goes unrecognised – usually because it’s mistaken for other problems or for age-related changes (it is more common in people over 50).
Age restrictions for surgery should not apply to anybody with PHPT. People over 50 matter too! The fact some literature also states PHPT is most prolific in postmenopausal women should be ringing alarm bells in doctors' and endocrinologists' thought processes if they refuse treatment or referrals based on age, but in most cases, it's the patient who has to reason this point in their fight for surgery to halt the progressive nature of PHPT, or to enable them to continue working until the age of retirement, rather than face the risk of tumours, cancers, heart attack, strokes, osteoporosis, fractures, kidney stones, gallstones, depression, and anxiety. Please read our case story of Vanessa Longstaff who was refused treatment in Scunthorpe because she is over 50, despite her calcium levels being over 2.9mmol/l. She was desperately ill, and we encouraged her to travel to Nottingham to see David Chadwick, who of course agreed to operate. Vanessa got her life back. Surgery for her was positively life changing.
The Fourth international Endocrine Workshop Guidelines do however, include a statement recognising normocalcemic PHPT: 'Normocalcemic PHPT is now a well-recognized variant of PHPT. These subjects have normal total and ionized serum calcium levels without any known etiologies for a secondary elevation of PTH. Knowledge of the natural history of normocalcemic PHPT is incomplete, but some individuals become hypercalcemic, and some show evidence of target organ involvement (eg, reduced BMD). Others, however, appear to be stable over time with persistently elevated PTH levels and normal serum calcium concentrations'. We are somewhat satisfied to see that Normocalcemic PHPT has also been referenced in the NICE Guidelines (although not until page 15), and they have lowered the level of calcium to 2.5mmol/l to compensate for this. although we have seen cases with even lower levels. the guidelines committee also omitted a vital explanation of the negative feedback loop of calcium and PTH and how important it si for doctors to understand in order to make a diagnosis and/or referal to secondary care.
So, you suspect Primary Hyperparathyroidism? - What happens next? - What do you need from your doctor?
We asked our members: Have you had other surgeries believed to be caused by untreated PHPT? :
shock Wave Lithotripsy (ESWL)
Percutaneous Nephrolithotomy (PCNL)
Cholecystectomy (removal of gallbladder)
rods, plates or pins for bones
The results indicate the consequences of delaying a parathyroidectomy is not only costly to the NHS but has a seriously detrimental effect on a patients life quality.
40% ticked options provided, with a further 37.5% adding alternative surgery options.
That is a significant 77.5% of operations that may have been avoided with a timely diagnosis of PHPT.
32.5% needed a hysterectomy, and 32.5% a cholecystectomy (removal of gallbladder).
Kidney stones: 22.5% needed a ureteroscopy. 20% needed a ureteric stent. 17.5% needed shock wave lithotripsy
We have members who have endured up to 30 years of invasive procedures for painful kidney stones which have ceased production after a parathyroidectomy.
Pregnancy: Hyperparathyroidism during pregnancy is associated with high rates of miscarriage, stillbirth, pre-eclampsia, premature birth and neonatal tetany. We have seen cases in our group sadly of all of the above, which is why we would like to see routine testing for PHPT in the early stages of pregnancy.
PTH = EDTA
Parathyroid hormone should be tested in EDTA to ensure stability and accurate results.
Parathyroid hormone is unstable in serum. Therefore it should always be tested using EDTA, without exception. This is more commonly a lavender vacutainer. Whether you are a patient, phlebotomist, or a doctor, please check that PTH is tested under the right conditions to save a delay in diagnosis. PTH should be drawn into a full vacutainer, after calcium to avoid contamination of calcium by EDTA, which can falsely lower the result. The filled vacutainer should be gently rotated 8-10 times to mix the blood with the preservative). Accuracy is more assured when the sample is kept at 4 degrees.
The following Hospitals are all using non-EDTA vacutainers whilst other NHS Trusts specifically request EDTA. We will show them evidence to try to convince them to change their protocol.
North Lincolnshire & Goole
East and North Herts Trust
Guys and St Thomas,
Scunthorpe and Gainsborough
Bupa Cromwell, London
A systematic review by the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) Scientific Division Working Group on PTH:
At room temperature, PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h).
While losses of PTH observed in clotted blood samples may be small within the time frame of a typical working day (e.g., 8%  or 10%  after 8 h; 10% after 12 h ), such differences could contribute to misdiagnosis or changes in management of patients.
We accept that PTH is commonly measured in conjunction with calcium, and sometimes vitamin D, to permit interpretation and that this recommendation will necessitate an additional sample being taken since calcium cannot be measured in EDTA plasma. We recommend blood samples for PTH measurement should be taken into tubes containing EDTA and the plasma separated from the cells within 24 h of venepuncture [Strong recommendation].
I asked expert parathyroid surgeon Dr. Babak Larian from ‘The Parathyroid Education Foundation in LA’, for his opinion. He confirmed all parathyroid hormone tests should be tested in EDTA; 'whilst pathology staff are not concerned with the difference, providing accurate results is beneficial to both patients and consultants'.
He was astonished to hear some NHS Trusts are not concerned that there ‘isn’t much difference’ as it can make the diagnosis process difficult for consultants and patients, and delay treatment.
I wrote to UDBH Trust (Derby and Burton) several times over three years providing much evidence of the benefits to EDTA over serum when testing PTH. Despite this evidence, and a biochemist from another Trust stating 'Does anybody test PTH in serum anymore?' and 'That is just WRONG', UDBH Trust claimed to have evidence PTH is stable in serum for up to 24 hours. They refused to make any changes. However, following communication sent to them in September 2019, I was very happy to see this notice in their blood clinic, which could well impact diagnosis positively for people in Derby, Burton, Tamworth and Lichfield. I hope the remaining Trusts on our list above will also make necessary changes (and not take 3 years to do so).
Please be aware that hypomagnesemia, unregulated glycemic index, estrogen therapy, and biotin can affect calcium and PTH results.
Scientifically flawed diagnostic testing of Primary Hyperparathyroidism
By Kathy Sassoon
The premise of this article is that the indications for diagnostic testing for primary hyperparathyroidism are scientifically flawed. They are flawed in such a way that any research programmes based on them will be inaccurate and unable to further the aims of the National Health Service in improving health outcomes for the population. The normal range for calcium levels in the general population is based on a study of individuals who are healthy. The results are graphed and displayed as a Bell curve with the outlying results removed at both extremes. The lowest and highest levels of calcium found in this random population of healthy people are taken as the extremes of the range at which any person will be healthy. This interpretation is the first and most important error which must be corrected before a correct diagnosis can be made.
The normal range of calcium is taken to be 2.15 – 2.6 at my local laboratory, although this varies from area to area according to local protocols. What this means is that Healthy Person A in the study had a calcium level of 2.15 and Healthy Person Z had a calcium level of 2.6. What it DOES NOT mean is that Healthy Person A will still be healthy if their calcium level rises to 2.6. Nor will Healthy person Z be healthy if their calcium level falls to 2.15. However, this is exactly the distortion that the incorrect interpretation of what a normal range means produces. It is taken for medical diagnosis that any patient is healthy if their calcium level is between 2.15 and 2.6. This goes against all the scientific understanding of the endocrine system.
Calcium must be maintained within a tight balance for the health of any individual. Healthy Parathyroid glands secrete parathyroid hormone in a pulse in response to a slight drop in calcium availability in order to bring calcium back up to that individual’s healthy level. Then PTH hormone drops sharply with a half-life of five minutes as soon as calcium is replenished. This is the suppressive relationship. Evidence of this healthy suppressive relationship being disrupted should be used as the diagnostic criteria. If our Healthy Person A with their healthy calcium level of 2.15 has a rise in calcium to say 2.4 due to an adenoma, their calcium level is seriously elevated but still well within the normal range. So they won’t meet the criteria for a test of parathyroid hormone as they don’t officially present with hypercalcemia. However, if they did get tested the result would show a disrupted suppressive relationship between calcium and PTH hormone, i.e. that PTH remains elevated consistently over three blood tests and is not suppressed by a blood calcium level of 2.4.
Take Healthy Person Z with their individual set level of calcium at 2.6. Their calcium level rises due to an adenoma to 2.7 which is a much lower rise against their healthy level than person A suffers from, but if they are lucky enough to be tested for calcium they are tagged as hypercalcaemic and may well end up being diagnosed promptly. Person A’s disease is more severe and their symptoms may well be more pronounced but they remain undiagnosed and ill and eventually often sadly blamed for their own ‘inexplicable’ disease. This unfortunately often leads to abuse and misdiagnosis in the mental health system. It also uses up exhaustive amounts of NHS resources economically which must be included in any thorough assessment of the economic impact of an increased testing regime.
We have established thus far that each person has their own individual level of calcium in their blood at which they are healthy, and health is maintained by homeostasis through a suppressive relationship with parathyroid hormone. By using the example of two healthy people with individual levels of calcium at different extremes of the population norm, we have shown how diagnosis based on hypercalcemia defined by population range, not by individual range can lead to major misdiagnosis and neglect. There are efforts to avoid this within the endocrinology specialism by defining those with calcium in the normal range but who do have adenomas as evidenced by surgery, as a subset of “Normocalcemic Hyperparathyroidism’ but in reality this is unnecessary if only the reality of individual set calcium levels is recognised and then diagnosis is by evidence of the disruption of homeostasis.
This leads on logically to the need for individuals to have their calcium levels recorded at 18 years old while they are healthy in the same way that babies automatically have their blood group recorded. This would show any elevation in later years accurately in the general population who present with generalised malaise with or without renal and bone disease. Any conclusions through research which uses the incorrect diagnostic methods to analyse blood tests for this condition cannot be considered scientifically accurate or appropriate for use in designing a public health response.
Current estimates in the US are that 5% of the general population have Primary Hyperparathyroidism. The same should hold for the UK. It is reasonable to state therefore that large numbers of patients are not being correctly diagnosed and treated. Even ignoring the individual suffering this entails, the economic burden on the NHS must be significant. Given that diagnostic tests are not ordered until the 2.6 level of hypercalcemia is reached, and even then studies to date are considered weak and inconclusive, I would recommend relevant research based on correct understanding of the endocrine relationship and its disruption immediately.
The present protocols need to be rewritten in their entirety and pathologists and doctors at all levels need to be retrained according to the principles of Endocrinology that are simple once taught correctly, as a matter of urgency. The health crisis in the UK due to unscientific diagnostic methods can then start to be addressed. If there is any doubt as to the existence of a crisis in regards to this condition, the group Hyperparathyroid UK Action4change has hundreds of case studies that can be made available for scrutiny with the permission of the individual patient. We would all be extremely grateful to have this contact in order to work together for the relief of this debilitating. life changing and even life-threatening condition.
Symptoms OF Primary Hyperparathyroidism.
Symptoms of PHPT can vary, sometimes based on the length of time it has remained untreated. By the time many people are diagnosed due to symptoms, they will usually have had PHPT for some time.
Initial symptoms have been reported to be chronic fatigue, depression, migraines, heartburn, mood change, insomnia, aching joints (usually hip and knee) and muscle weakness. As time progresses symptoms can increase to cause blurred vision, severe bone pain, memory loss and confusion, poor coordination, pancreatitis, hair loss, osteopenia/osteoporosis, unstable blood pressure, kidney stones; and in severe cases; strokes, heart attacks and coma.
Hyperparathyroid UK Action 4 Change Symptom Survey 2019.
Mood changes/quick temper
Bone Pain (constant dull ache)
Joint pain & reduced mobility
Hair loss around face
Excessive dry/itchy skin/eczema
Gall bladder disease/gall stones
Kidney Disease/kidney stones
Polyurea (frequent urination)
Polydipsia (unquenchable thirst)
Soft tissue Calcification
Raised BP (needing medication)
Low Blood Pressure
Dental Cavities/teeth breaking
We conducted a survey to ask members if they had been diagnosed coincidentally or from symptoms.
Coincidentally in this case meaning they did not hear from their doctor ', I would like to rule out hyperparathyroidism for these symptoms'. If doctors were more aware of the symptoms attributed to primary hyperparathyroidism. they may have been diagnosed sooner.
60 diagnosed coincidentally
26 diagnosed after reporting symptoms
2 in between (a combination of both)
We also asked: Should the bone profile blood test/calcium/PTH be as standard as cholesterol, blood sugar, haemoglobin etc when we get regular checks?
The response was a resounding YES from all respondents, with comments that GP's need training to be able to understand and act on them.
Too many UK endocrinologists are still letting patients down. They should be able to understand and act on results but we see too many cases where this is not happening and patients are left to be monitored whilst their quality of life and health deteriorates. This is usually after waiting between 4-8 months for an initial appointment. Please see our recommended list of endocrinologists who DO act appropriately.
Please show the following slides to your doctors, endocrinologists, & surgeons:
The spectrum of Primary hyperparathyroidism: Credit to Dr B Larian: http://www.hyperparathyroidmd.com
People with Primary Hyperparathyroidism are often classed by their doctors or endocrinologists as being asymptomatic, which delays their referral for surgery.
Too many doctors fail to consider the quality of life for their patients when deciding on referral for surgery. We conducted a Quality of Life survey for people with Primary Hyperparathyroidism. We hope doctors will look at this survey and consider the impact of poor life quality.
Quality of Life Survey conducted by Hyperparathyroid UK Action 4 Change. May 2017:
We asked one hundred people "What impact has untreated hyperparathyroidism had on your quality of life"? The number of responses in brackets.
I had to give up work (30)
I have had a lot of time off work/I worry I will lose my job (36)
I am afraid of my own mind due to confusion & have become socially withdrawn (46)
I feel I am letting down my family/they do not understand me (63)
I have lost a lot/all of my friends (20)
I have no quality of life other than existing/waiting (46)
My doctors do not understand. They say I am just depressed (29)
The only people who understand what I am going through are in online support groups (60)
I feel lost, isolated and lonely (34)
I feel I have aged before my time (83)
I feel like I am dying (31)
Reading post op stories is the only glimmer of hope keeping me going (47)
Every day is the same. I wake up in pain, I go to bed in pain (51)
I cant sleep at night due to insomnia, pain or needing to urinate, so I am exhausted all day (66)
Hyperparathyroid UK Action 4 Change is a patient to patient support group on Facebook
Members of our support/action group (currently approaching 1800) Hyperparathyroid UK Action 4 Change have found us on Facebook after searching for Hyperparathyroidism, parathyroid or raised calcium. They come to us looking for answers and support, usually after years of consulting their doctors with symptoms such as fatigue, memory loss, bone pain, and aching joints. Many have been turned away year after year, having been told their symptoms cannot be related and are likely caused by fibromyalgia, early menopause, age or lifestyle. Those who have had a raised calcium level picked up are often told their calcium is not high enough to be causing symptoms. This simply is NOT true. the level of calcium does not dictate the severity of symptoms.
Hyperparathyroidism is a progressive disease that will weaken your bones, cause soft tissue calcification, and make you feel very poorly. Our advice is to list all of your symptoms, create a chart of all your recorded calcium, PTH, vitamin D Levels and ask your doctor to read our site or do some research. If you are diagnosed with 'mild' hyperparathyroidism, and your doctor will not refer you to an endocrinologist or surgeon, please consult another doctor with more knowledge about this disease. Your symptoms will likely get progressively worse the longer you have PHPT. The sooner you have surgery the less you will suffer.
NICE guidelines for Primary Hyperparathyroidism were published 23 May 2019. They are far from perfect but please ask your doctors to read them in order to help you. Please join our support group to get a copy of our summary letter to take to your doctors which summarises important sections of the guideline to help you get a diagnosis and referral. Ask them to read this site. Patients have to find the fight within them to keep pushing for diagnosis and treatment which is so hard to do when you are faced with debilitating symptoms. If you have a good experience with your GP, endocrinologist or surgeon, please tell us so that we can share your recommendations.
Normocalcemic Hyperparathyroidism (NCPHPT)
NCPHPT is characterised by high PTH and normal levels of calcium. It was officially recognised in 2008 when an international conference took place for clarifying its nature and relevance (Bilezikian et al., 2009). In order for a diagnosis, certain conditions must be met. In particular, all secondary causes for hyperparathyroidism must be ruled out, and ionized calcium levels should be normal. If ionized calcium levels are above normal, the diagnosis changes to classic primary hyperparathyroidism (PHPT). In true NCPHPT, patients have elevated PTH with normal serum and ionized calcium at all times, not just intermittently. Some doctors make this distinction and some do not.
NCPHPT is a controversial area. Many doctors still believe that unless your calcium is above a certain level, you do not need surgery. However, patients with even low levels of calcium have had successful parathyroidectomy and have benefited from an improvement of symptoms. Each person needs to be assessed on an individual basis. If you have NCPHPT, it is recommended that you build up your own knowledge so that you can ensure you get a correct diagnosis and surgery. The purpose of this document is to help you get started with building your knowledge. Symptoms of NCPHPT can be the same as classic PHPT.
“When diagnosing PHPT, secondary causes must first be ruled out. Drugs such as biophosphenates, anticonvulsants, furosemide, and phosphorus can cause elevated PTH. In addition to drugs, disorders such as renal hypercalciuria, chronic kidney disease (GFR <60 ml/min), malabsorption syndromes (celiac disease and cystic fibrosis), and vitamin D insufficiency with plasma 25-OH vitamin D levels of <50 nmol/L (<20 ng/mL) should be ruled out. Other considerations are hypoalbuminemia, hypomagnesemia, and elevated calcitonin .” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153463/
Vitamin D deficiency is often the first thing that needs to be ruled out. If you have low Vit D, you may be asked to supplement to rule out secondary HPT due to vitamin D deficiency (in which case, magnesium can be helpful). You may also be asked to supplement with calcium (in which case vitamin K2 can be helpful). Gastric bypass due to malabsorption issues, Celiac disease and Crohn's disease (typically severe for many years) and metabolic bone diseases that lead to elevated PTH, e.g. Paget’s disease all need to be ruled out.
Some surgeons will work with high-normal calcium but not low-normal. Our recommended surgeons page highlights surgeons who understand NCPHPT. So, if you have NCPHPT with low-normal calcium, even more research may be needed to find a surgeon. If you learn of surgeons who operate on normocalcemic patients, please do let us know.
Calcium, PTH and Vit D need to be tested at the same time regularly. Adjusted/corrected calcium levels can help with diagnosis. However, the adjustment is an approximation and can be flawed. Adjusted/corrected calcium is attempting to measure what ionised calcium actually measures. For some, it will work against a correct and accurate diagnosis. If you are still having trouble getting diagnosed, an ionised calcium test, where possible, is recommended. The result may still be in normal range but, if it is a higher level or even above the reference range, it can help you move forward with diagnosis and treatment. This can be a significant point for those with NCHPT who are struggling to get correct diagnosis and treatment. If you do get an ionised calcium test, ensure it’s at the same lab and at the same time as serum calcium, PTH and Vit D are drawn.
If your PTH remains elevated, this needs to be explained. Once secondary HPT has been ruled out, ask your specialist; why is my PTH high? Each of us has our own set point for calcium. Reference ranges are based on a bell curve. You may just have a lower set point. This is one possibility.
Mild Primary Hyperparathyroidism: A Literature Review
PTH Best Risk Predictor in Parathyroid Disease
Ionised, Adjusted/Corrected Calcium
https://www.ncbi.nlm.nih.gov/pubmed/15657582 & osteoporosis
Normocalcemic hyperparathyroidism in patients with osteoporosis.
& https://www.ncbi.nlm.nih.gov/pubmed/15657582 calcium.ionised
Bone Mineral Density Evolution After Successful Parathyroidectomy in Patients With NCPHPT:
Normohormonal Primary Hyperparathyroidism (NHPHPT)
NHPHPT is recognised in the UK as a clear distinction of PHPT by only a few conscientious doctors, a few surgeons and even fewer endocrinologists. A fact which is quite beyond comprehension when there is so much evidence. People with Normohormonal NHPHPT, (elevated/high normal calcium with inappropriately suppressed parathyroid hormone), are still greeted with blank medical faces and offered no explanation on the basis their calcium is within range.
Helen O'Callaghan had NHPHPT, although this diagnosis was denied by a London surgeon at Hammersmith Hospital. Helen had to pay to go to Florida. Her is a photograph of the 3cm x 1.5cm adenoma removed. HRT was suppressing her calcium level to 2.61 with a PTH of 4.9.
Helen O' Callaghan:
'After a 4 year battle with this illness; high calcium and high alk phosphate, gerd, bone pain, memory loss, still no further with endocrinologists; I even had a private appt with FP. He said, "I don’t think you have PHPT"!
I’m from a medical background so I knew I had PHPT, I could even feel the discomfort of a tumour in my throat. After lots of consultations and support, I took myself to the USA Tampa under the care of Dr. Norman. What can I say; yes it’s expensive but priceless they are amazing! My tumour has gone and already I feel so much better, just having had a slight calcium crash as I’ve had the illness for so long'.
Please visit our surgeon's page to read the section with educational studies about NHPHPT. Please show them to your doctors:
This is the result of a blood test indicating PHPT in 2011; adjusted calcium of 2.79 picked up with normal parathyroid hormone level of 48 (15-65). calcium levels of 2.91 had been missed in 2006 and 2008 and PTH, not tested. I had a 700mg adenoma removed 2012.
Secondary Hyperparathyroidism is an overproduction of parathyroid hormone with a secondary cause rather than a primary adenoma, often in response to a DECREASED calcium. As the four parathyroid glands only purpose is to maintain normal calcium levels, they will increase production of parathyroid hormone (PTH) if calcium is LOW. Drugs such as biophosphenates, anticonvulsants, furosemide, and phosphorus can cause elevated PTH. In addition to drugs, disorders such as renal hypercalciuria, chronic kidney disease (GFR <60 ml/min), malabsorption syndromes (celiac disease and cystic fibrosis), and vitamin D insufficiency with plasma 25-OH vitamin D levels of <50 nmol/L (<20 ng/mL) should be ruled out. Other considerations are hypoalbuminemia, hypomagnesemia, and elevated calcitonin. We are currently researching boron deficiency as a cause of elevated PTH as well as calcium.
Known causes of secondary Hyperparathyroidism are associated with poor absorption of calcium in the intestines:
Gastric Bypass (GBP)
Vitamin D Deficiency
Kidney Failure Requiring Dialysis
Some medications can interact with vitamin D supplementations such as steroids, (prednisone can reduce calcium absorption, impairing vitamin D metabolism), weight loss and cholesterol-reducing medications can reduce the absorption of vitamin D, and both phenobarbital and phenytoin used to treat epilepsy can reduce calcium absorption.
Supplementation of calcium and/or vitamin D without magnesium can lead to magnesium deficiency symptoms. High doses of vitamin D drains magnesium from its muscle storage sites. The first signs of magnesium deficiency are twitching, leg cramps, and restless legs. Angina and heart attacks affecting the heart muscle are magnesium deficiency symptoms. 600mg of magnesium is recommended with 1/2000 IU of Vitamin D.
There is again so much information about the need for magnesium when supplementing with vitamin or calcium:
Magnesium, Vitamin D, K2, boron and calcium supplements. (update coming very soon).
If you are supplementing with calcium (post op) and/or vitamin D, you will need magnesium. About half of the body's magnesium is found in bone. The other half is found inside cells of body tissues and organs. Magnesium is needed for nearly all chemical processes in the body. It helps maintain normal muscle and nerve function and keeps the bones strong. Magnesium is also needed for the heart to function normally and to help regulate blood pressure. Magnesium also helps the body control blood sugar levels and helps support the body's defense (immune) system. The normal ranges for blood magnesium level are usually 0.7 - 1.00 or 1.7 to 2.2 mg/dl.
If you have low vitamin D pre op and your doctor prescribes large weekly/monthly doses of vitamin D i.e 50,000 iu, refuse it (especially those little blue capsules containing BHT, banned in many countries), because it will only make you nauseous and cause hypomagnesemia. You should instead take a lower daily dose with magnesium which will be more effective in increasing your Vitamin D levels without making you very ill.
Please be aware of the importance of magnesium, the symptoms of low magnesium and the importance of maintaining healthy magnesium levels when supplementing with calcium (although it should be taken about 4 hours before or after calcium, rather than taken together) and vitamin D before and after your parathyroidectomy.
'Since pathologists first started studying the heart, they realised that a connection existed between deposits of calcium and heart disease. Vitamin D inhibits calcium deposition in arteries, and magnesium converts vitamin D into its active form so that it can prevent calcium build up in cholesterol plaque in arteries. The combination of magnesium and vitamin D helps prevent clogged arteries by drawing calcium out of the blood and soft tissues back into the bones where it is needed to build healthy bone structure' Dr. Carolyn Dean MD ND Author of The Magnesium Miracle.
Multiple Endocrine Neoplasia Types 1, 2 and 4.
MEN stands for Multiple Endocrine Neoplasia, of which there are four distinct types – MEN1, MEN2, MEN3 and MEN4. MEN2 was formerly called MEN2a and MEN3 was formerly called MEN2b.
Multiple Endocrine Neoplasia syndromes are inherited disorders – This means that they can be passed down in families, with each child of an affected parent having a 1 in 2 or 50% risk of inheritance.
The main characteristics of each of the disorders are as follows:-
MEN1 – 3 classic signs – Parathyroid Tumours (PHPT), Pancreatic Neuroendocrine Tumours (PNETS) and Pituitary Tumours. https://www.amend.org.uk/flippingbooks/patient-information-books/men1/men1.html
MEN2 – 3 classic signs – Parathyroid Tumours (PHPT), Thyroid Tumours (MTC), and Adrenal tumours (Phaeochromocytoma).
MEN3 – not associated with PHPT
MEN4 – 2 classic signs – Parathyroid Tumours (PHPT), Pituitary Tumours
(No patient booklet available yet, recognised previously as CDKN1B).
90/95% of MEN1 patients will be affected by PHPT, 20-30% of MEN2a patients, and in MEN4 (a relatively ‘new’ MEN1-like mutation but excluding pancreatic involvement), the penetrance is still to be defined, since the number of patients is very small (so far).
Multi-gland hyperplasia and/or multiple adenomas will occur in MEN patients with PHPT and usually presents itself in the third decade of life, although all glands may not be affected at the same time. The symptoms are exactly the same as sporadic (non-familial) PHPT, but a removal of a single gland will NOT cure the condition long-term. Sometimes when a dominant gland is removed calcium and PTH initially return to normal levels if the remaining glands have been dormant but increase again as they ‘wake up’. Sometimes if multi-gland hyperplasia/adenoma is already present, even after removal of the worst affected gland, calcium and PTH will not correct and levels will remain high.
Current UK clinical guidelines for the management of PHPT in MEN is the removal of 3.5 glands, leaving one (least affected) gland in situ to enable the body to self-regulate for as long as possible. The practice of auto-transplanting the remaining half gland into the forearm is usually avoided these days to prevent the gland from failing to function again after being moved. Some surgeons now prefer total parathyroidectomy (removal of all 4 glands and lifelong calcium and Vit D supplements), although there is an argument that HYPOcalcaemia (low calcium) is sometimes difficult to balance and can be just as troublesome as HYPERcalcaemia (high calcium). In addition, it is relatively common for MEN patients to have more than 4 glands, sometimes ‘hidden’ in the thymus or chest, so even 4 gland removal is not a guarantee of a cure. Even after removal of 4 glands, if there is any parathyroid tissue left in situ, it too will eventually become hyperplastic and PHPT will return.
Further education of both patients and medics is essential to ensure that genetic testing is offered to potential MEN patients. Any 2 out of the 3 classic signs of MEN1 and MEN2 constitute a clinical diagnosis (an assumed positive for MEN) even without genetic testing and will enable the patient to have annual screening (bloods and imaging) necessary for the successful management of MEN. In addition, a positive genetic test will enable family members to be tested too. Early diagnosis of these disorders is a huge advantage in ensuring that a pro-active approach can be taken to stay ahead of any issues and live a relatively ‘normal’ life.
PLEASE SEEK ADVICE FROM YOUR MEDICAL TEAM IF YOU HAVE PHPT AND ONE OTHER CLASSIC PRESENTATION OF MEN, particularly if your PHPT hasn’t been rectifed by the removal of a single gland, a possible indicator of multi-gland involvement. Any similar relevant family history is helpful too, ie a parent or sibling also presenting with a classic MEN issue.
www.amend.org.uk – a UK charity providing patient support worldwide
Gill Masters (Amend UK MEN1 representative)
19 March 2019