- 13 Dec 2019
- 20 min
- 13 Dec 2019
- 20 min
Justin Coleman interviews Christian Girgis about the latest updates from Therapeutic Guidelines on bone and metabolism, including osteoporosis, vitamin D and calcium deficiency, and thyroid and adrenal disorders.
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Welcome to this Australian Prescriber Podcast. I'm Dr Justin Coleman, a GP on the Tiwi islands, north of Darwin, and a medical educator with Northern Territory General Practice Education. Today we're talking bones, minerals, vitamins, and those little glands that are so small and squidgy, yet seem to exert such control over our lives. I'm speaking today with Dr Christian Girgis, a Sydney endocrinologist who's dedicated his life to the squishy bits. Welcome, Christian.
Thank you, Justin. It's great to be here.
Lovely. Well, we're talking today about the latest version of Therapeutic Guidelines for bone and metabolism, which you have recently helped update and this is the go-to guideline for Australian clinicians making medical treatment decisions. We'll have a look at bones, thyroid, vitamin D screening, and as many glands as I can remember from medical school. But happily, Christian, your primary field of expertise is bones. Because they're the things that fracture, I do know the names of most of those. Tell me, what do you find particularly interesting about bone metabolism?
Thank you, Justin. I've been interested in bones now for many, many years. Now, you see, bones aren't just these important structures that help us to stand up and help us to move around, they're very dynamic organs that are made of multiple cell types, different compartments. They make hormones, they respond to hormones.
Well, that's a wonderful endocrinologist answer. I think if I asked an orthopaedic surgeon, they'd say they're the things that help us stand and walk around, but I like the complexity. Let's talk about osteoporosis and bone fractures. One statement struck me when it said that fewer than 20% of patients who present with a minimal trauma fracture are investigated for osteoporosis. That surprises me. I know some of us are reluctant to do broader screening for osteoporosis, but I would have thought when there's a minimal trauma fracture, that would kick us off.
I think this is a really important point, Justin. When you have a patient who goes to hospital with a heart attack, you'll find that in the majority, they're sent home with a plan for an exercise stress test. They're started on a beta blocker and a statin and an aspirin, whereas a minimal number of people, in fact, the minority, less than 20% with a fracture, are sent home with a plan for a DEXA scan or to start therapy. The vast majority won't even have a vitamin D test when they're in hospital.
Once a person's had a fracture, the primary focus is on the fracture itself. The healing of the fracture, whether this involves plaster, immobilisation or the insertion of rods or prosthesis, and not much thought goes on to what else could happen, could this person fracture again?
So to answer your question, the first indication for a DEXA scan is in a person who sustained a fracture, which was experienced under minimal trauma, and that means fall from a standing height. But increasingly, we're also understanding and recognising that a fracture that might not be simply minimal, but may in fact be a bit more than minimal, such as a moderate form of fracture, may also be an indication of osteoporosis.
So I would say in any individual who's had a fracture that has not occurred after major trauma, that a bone density scan will be important, especially in those people who are older than 50 years. Now, 50's an important age cut off, because women on average experience menopause at the age of 51, at which point there'll be a decline in their bone density or after the age of menopause. Men in general can have a gradual decline in their bone density, which starts usually from the age of about 40 or 45 onwards.
Then we would consider primary screening for osteoporosis in people who have significant risk factors. For example, women with an early menopause, whether they've had a hysterectomy with an oophorectomy at an age less than 50 in whom the drop in bone density would occur sooner than it would otherwise, or other risk factors, for example, long-term steroid therapy. We know that steroids, which are used for all sorts of inflammatory conditions, can be very nasty for bone, can cause big drops in bone density.
Certainly there are other risk factors such as malabsorption, like coeliac disease or people who have had major surgery on their intestines and are not absorbing enough nutrients, that could also cause osteoporosis. There are several other risk factors. For example, long-term treatment with antiepileptic therapy, an eating disorder or amenorrhea in younger women due to weight loss, can also be a significant risk factor for osteoporosis.
So these are risk factors that would be red flags in considering possibility of osteoporosis in the individual who's not had a fracture as yet, but who could be at high risk of osteoporosis in whom a DEXA would be appropriate.
Thanks for that summary, Christian. Listeners can of course look up a table which is neatly laid out in the Therapeutic Guidelines. Just thinking while we're on screening, then thinking of vitamin D screening. Vitamin D sort of reached almost its peak excitement five or six years ago after a long build-up, where everyone seemed to be recommending vitamin D for everything. But these days, the evidence is slightly turning against it, and I noticed that the newer guidelines say that routine screening for vitamin D deficiency in healthy people with no risk factors is not recommended. Are we looking at a particular subgroup who have a specific reason that they might be vitamin D deficient?
So we've moved away from the idea of screening vitamin D en masse and the population at large towards a more targeted approach in testing vitamin D in people who may be at risk of a low vitamin D and in whom treatment of a low vitamin D would actually cause some sort of benefit in them.
So, certainly anyone with osteoporosis or who's had a fracture in whom you may be considering treatment with an osteoporosis therapy should have the vitamin D tested. You've got to make sure that a person who's about to start an osteoporosis therapy has an adequate vitamin D, because there can be a risk of hypocalcaemia in the setting of a person, for example, on intravenous bisphosphonate with a low vitamin D or on denosumab.
Then you might also test vitamin D in people who are at risk of a low vitamin D. For example, people who, for some cultural reason, may have their skin covered most of the day and not have exposure to the sun or people who are darker skinned for that same reason may also have a higher risk of a low vitamin D. Then we would consider also people with malabsorption, who don't absorb enough vitamin D adequately, they should also have vitamin D tested. For example, people with long history of pancreatitis or pancreatic insufficiency, you may have fat malabsorption, because vitamin D is a fat-soluble vitamin.
That take-home message is that there seems a bit less use in screening broadly, and so a targeted approach is necessary. In terms of when we should start treating, so the guidelines said that we should consider treatment of vitamin D if the result comes back as less than 30, particularly if they're symptomatic, or as you said, if you're going to be treating for osteopetrosis, you'd have a higher threshold. So they suggested if the result comes back it’s less than 50.
Yes, that's exactly right. So you might test level of vitamin D in a person who doesn't fit in the categories that I just mentioned, and you might find that they may indeed have deficient state, of what's known as deficient state with a level less than 30. The question is, will they benefit from being started on vitamin D supplementation? When, seasonally, when are they being tested? Because it might be okay to have a level of less than 30 in winter, which may then actually increase in the warmer months. Which is why testing en masse probably doesn't help, because if you identify low vitamin D in someone who doesn't fall under these categories, then perhaps treating the low vitamin D wouldn't make any impact or any difference to their outcomes.
Dr Christian Girgis, it's lovely to talk to someone who's a sceptic after my own heart. Talking with scepticism, let's move onto calcium. I note that the data demonstrating a correlation between fracture risk and calcium intake alone is lacking and it turns out that in most of the studies of treatments for osteoporosis, adequate calcium and vitamin D were entry requirements to the study. There's a bit of a move now towards encouraging patients with a low dietary calcium to increase their calcium-rich foods rather than necessarily putting them straight onto a supplement.
Yeah. Look, at the moment, Justin, there is a bit of a move away from calcium supplementation, towards more in the way of advising people to increase their intake, to consume at least two or three servings of calcium daily and at least trying to get about 1000 mg of elemental calcium daily through dietary sources. The reason for this move away from calcium supplementation on mass is the possible link between calcium supplements and coronary artery calcification, coronary artery disease.
Now it's a very complex and controversial area, but the jury is out at the moment as to whether or not calcium supplements do indeed increase one's risk of coronary artery disease. Question is, do they help, I suppose? Do they help in improving bone density, independent of the effects of the osteoporosis treatment that they're associated with? The data are not clear. They probably help a little bit, but for the large majority of people, we advise people to instead increase their dietary intake of calcium.
If they're not able to reach that sort of requisite 800 to 1000mg, then we may supplement them minimally with perhaps 600 mg a day elemental calcium. The other consideration is, Justin, that a lot of people that we see take proton pump inhibitors for reflux. There can be issues with the absorption of certain kinds of calcium compounds. In that population, you might instead, if they're needing a supplement, advise them to take calcium citrate, because it doesn't require gastric acidity or a low gastric pH for absorption.
So for most people, encourage calcium rich foods. Yet another reason to have a cappuccino or two each day, as I enjoy. Just before we move from osteoporosis, I gather there are some concerns about the potential skeletal adverse effects associated with withdrawal of denosumab.
So denosumab, which is under the trade name, Prolia, is a widely prescribed medication for osteoporosis. The uptake has been really, really high with this medication, especially amongst GPs. I think the reason for that is that it's simple, it's an easy drug to give. It's given subcutaneously every six months and you really do see big increases in bone density. It's the only treatment we have, in fact, at this stage where you see ongoing continued increases in bone density, but we need to recognise some of the long-term effects of this drug.
So people who suddenly stopped because they've forgotten to take an injection or they've travelled overseas and missed a dose, or people who have been advised to skip a dose because they've seen their dentist and they're concerned about the risk of osteonecrosis of the jaw and advised to stop, can have a significant drop in their bone density. Such that if they've been on the drug for say three years and they've gained say 5% in the vertebral spine bone density in that period of time, they can drop that 5% within a year of ceasing treatment, if not sooner. So what's taken three years to gain on treatment, can come down in a period of one year.
The concern is that there've been some isolated reports that have been examined in more detail of fractures that occur in the offset period. So in essence, a person may catch up with their fracture risk. Hence, it's really, really vital that when you start a person on denosumab, that they're advised this is an ongoing indefinite treatment, six monthly without discontinuation.
It's not like a bisphosphonate, which you can use for five years and then stop and then have a drug holiday, so to speak. This is an ongoing treatment and a drug holiday cannot be afforded. You would be back to where you started a year after ceasing treatment and not much would have been achieved of being on treatment to start with.
Let's move onto thyroids now. We GPs are fairly used to treating people long term with thyroxine, but let's look at the grey area in the middle. When should we start thyroxine replacement therapy? What's the thinking there?
At the moment, there are really two kinds of hypothyroidism. There's subclinical hypothyroidism and clinical hypothyroidism. What this essentially refers to is the level of the different hormones that we might test for in thyroid function tests. So you've got your thyroid stimulating hormone, which is a TSH, and this is really the most sensitive marker of a person's thyroid state. So if the TSH is between four to about 10 and a person's free T4 is normal, then that would be in an early stage of subclinical hypothyroidism. But when it crosses that 10 threshold, it's more likely to be associated with symptoms at some point.
So when do we treat a person with hypothyroidism? Well, firstly, the obvious case is in a person who's got clinical overt hypothyroidism, high TSH, a low T4 and a low T3. Very likely to have symptoms of hyperthyroidism, lethargy, fatigue, constipation, weight gain. Those with subclinical hypothyroidism, it's more nuanced. If a person's TSH is increased in the intermediate range of four to about 10 and the free T4 and free T3 are normal as they usually are, that person usually will be asymptomatic, because it's very early stages of hypothyroidism. In that case, you generally wouldn't commence treatment, unless the person comes to you and says they have symptoms which you may attribute to that thyroid state.
The other consideration is in a person whose TSH is more than 10, who doesn't have symptoms, with a normal free T4 and free T3. So it's subclinical, a bit more severe. In this situation, you'd repeat the TSH a few weeks later and, if it's still increased or if it's increasing, you would talk to the person about starting on some therapy, even in the absence of symptoms, because it is likely in due course, TSH will rise further and they will develop symptoms at some point.
Is that more likely to be the case when their thyroid antibodies are positive?
Yes. So that also is an important indication that helps, because it indicates the person is likely to be developing an autoimmune form of thyroiditis, what's known as Hashimoto thyroiditis. So the antibodies can be a very helpful clue in determining that a person's likely to progress to frank hypothyroidism, because it indicates the underlying autoimmune process. That's the cause of the hypothyroidism.
So when we start thyroid replacement, I've traditionally started with the start low, go slow approach, but is that still the case?
What we've decided in this latest edition of Therapeutic Guidelines, Justin, is to treat people to target right away. This is because there's no evidence that the start low, go slow approach is necessary in people who are otherwise healthy, who, frankly, are overtly hypothyroid, should be treated to target with a weight-based dose. So if you look in the guidelines, the recommendation is for 1.6 microgram/kg to the nearest 25 microgram given daily. You would then repeat the thyroid function every four to eight weeks and you would adjust as appropriate.
Now the half-life of thyroxine is about seven days, so you can make changes to the dose of the thyroxine on a weekly basis. Which means that some days of the week you might be on one dose and other days of the week you might be on a higher dose to change the weekly rather than the daily dose. Those in whom you would start low and go slow are older people, people with a history of heart failure. We know the heart is acutely sensitive to the effects of thyroid hormones, and with people with a history of arrhythmia.
It's also important to consider what you're trying to target the TSH to. So the person who's younger and otherwise healthy and active, you might target the TSH to the lower end of the reference range, to 0.5 to 2.0 mIU/L. Whereas someone who's a bit older, you might accept a slightly higher TSH at around about 3.0 to 4.0. There's evidence to suggest that inducing a hyperthyroid state in an older person may have adverse consequences, may be associated with a high risk of coronary artery disease, and also cardiac events and strokes. So the gentler approach in the older population or those with heart failure is a sensible approach.
Let's finish now with adrenal and pituitary functions, which aren't front and centre in the minds of GPs and often are under specialist care. But just looking at what population groups we should be considering testing for things like Conn's syndrome and Cushing's.
A lot of the time we have people with hypertension who we see and we put on one medication, a second and a third, and they're not well-controlled with their blood pressure, in spite of being on, perhaps, an ACE inhibitor, a calcium channel blocker, and a beta blocker. In this population, we need to consider secondary causes of hypertension. Now, although the majority of hypertension is essential hypertension, there are a subset of people who have undiagnosed and underdiagnosed secondary causes that might need attention and may help greatly in being able to treat the hypertension and lower the risk of end organ effects of hypertension.
So the first to consider is Conn's syndrome. Now Conn's syndrome apparently is pretty underdiagnosed. There are some studies that suggest that one in 50 people with hypertension may have Conn's and not know about it. The adrenals hypersecrete aldosterone, so it's hyperaldosteronism. It can be caused by one of two things, either a single lesion in one of the adrenals, like an adenoma, which is secreting aldosterone, or hyperplasia of both adrenals, so both adrenals are hypersecreting aldosterone. Important to differentiate one from the other, because one's treated surgically and the other's treated medically.
Now when would Conn's be worth considering? So if you have a younger person, a person perhaps in their midlife who is on multiple antihypertensives and may potentially have low potassium as well, that would raise alarm bells for Conn's syndrome. However, low potassium, it's only really seen in one or two cases of Conn's, so you wouldn't hang your hat just on the potassium.
The problem with Conn's though is that it's a very tricky diagnosis to make. You've got to be off any drug that might influence aldosterone or renin. Most antihypertensives such as ACE inhibitors and angiotensin receptor blockers, calcium channel blockers, and even beta blockers have effects on this pathway and it would need to be stopped for six weeks prior to testing.
On the other side, Cushing's disease, pituitary gland is hypersecreting ACTH, which is a precursor hormone for cortisol made in the adrenals. Increased cortisol results in hypertension. So in a person who has other features of hypercortisolism, obesity, weight gain, and diabetes, which is perhaps poorly controlled, plus hypertension's poorly controlled, then that constellation of findings might draw you to considering Cushing's disease and, once again, a referral to a specialist to consider this further.
Christian Girgis, that, I think, is all we have time for today. It's been a great thing talking to you and running us through the latest edition of the Therapeutic Guidelines for bone and metabolism. Thanks so much for your input today.
Thanks so much, Justin. It was a real pleasure to be on your program. I really enjoyed it and I hope that people find the latest edition of Therapeutic Guidelines very useful.
My guests’ views are their own and don't represent Australian Prescriber, and my views are certainly all mine.