Dear AchillesHeel …
Thank you for your question and you have very nicely set out the salient features of your problem.
The following is broken into two parts: a shorter answer to your query, and a longer explanation of the complexity of the PTH conundrum.
The key issue, in your case, is the difference between:
(A) a condition called primary hyperparathyroidism: where independently from chronic kidney disease (CKD), one of the (usually) 4 parathyroid glands spontaneously develops a benign overgrowth of normal parathyroid gland tissue … a ‘lump’ that is called an adenoma. Adenomas are benign tumours … but pesky!
The development of an adenoma - and common sites for adenomas to develop are the parathyroid and adrenal glands - is a quite common ‘out-of-the-blue’ thing to happen in humans. In the case of parathyroid adenomas, lots of people who do NOT have kidney disease have (or will develop) a small parathyroid adenoma. These are not commonly linked to CKD, and simply ‘happen by chance’ or, possibly, via genetic influences.
Less commonly, but also unrelated to CKD, two or more of the parathyroid glands can become rather more diffusely (generally) over-active (or ‘hyperplastic’). In both cases, the gland (or glands) over-produce parathyroid hormone (PTH).
This results in changes in the blood and, later, in bone.
… or …
(B) a state arising WITHIN the context of CKD, called secondary hyperparathyroidism. Here, as a result of a vastly complex interplay between FIVE seemingly separate body tissues/regions (= the gut, the blood, the bones, the kidneys, and the parathyroid glands), a chain of events results in a ‘syndrome’ that ultimately induces renal bone disease … see below …
© Finally, there are even more complex outcomes … tertiary, and even quaternary hyperparathyroidism … but I won’t go there!
While you don’t state your actual eGFR level of CKD, or whether your ‘normal’ calcium is low or high normal … and though, on balance, you probably DO have CKD-related hyperparathyroidism … a search for an adenoma seems still worthwhile as sometimes relatively common things (adenomas) do occur ‘by chance’ in very common illnesses (like CKD).
Your specialist is right on the money with tests and advice, but an ultrasound to seek any one obviously enlarged gland, or even a sestimibe scan, might be worthwhile. You are clearly tracking towards starting calcitriol as a means to suppress PTH = in my view and at your levels of PTH = the right thing to do. Assuming your calcium levels allow this and do not rise too far under the influence of calcitriol and the increased gu absorption of calcium it will induce, that is the direction I would be going too.
So … my reading of your question suggests the right answers are being sought … and actioned.
In addition, your precautionary use of sodium bicarbonate (esp. if your BP is not difficult to control, and the sodium component is not promoting volume overload) + the use of an ACEi … all reflect excellent management
BUT: understanding this complex area is a minefield for us all … whether patient, or doctor.
As such - and beyond your question - I offer the following explanation(s) of the complexity of PTH, if only for your interest!
…
Hyperparathyroidism is the term used for the over-activity of one or more of the (usually) 4 little glands called parathyroid glands that hide in behind the thyroid gland in the neck.
There is often confusion between the thyroid, and the parathyroids … but, they bear NO functional relationship at all … none! The parathyroids are simply near (the Greek ‘para’ means ‘adjacent’ … like parallel lines … and nothing more) … but, their role in the body is quite different to that of the thyroid gland!
The role of the parathyroid glands is to control the blood levels of calcium and phosphate in the body. It the case of calcium, the parathyroid glands directly influence the calcium levels in bone (and, thereby, the strength of our bones) via the hormone the glands produce, parathyroid hormone (or PTH).
The 5-way inter-action between PTH/kidney/bone/gut/blood is one of the most complex areas in medicine … as it involves the interplay between FIVE seemingly unrelated bits of the body: the blood, the gut, the parathyroid glands, the bones, and the kidneys … and … the problem = where to start?
Keep in mind that we absorb calcium (from the gut), we store calcium (in the bone), we excrete calcium (via the kidneys), and we control calcium (jointly by the parathyroids and by the kidneys) … with the blood serving as the lynch-pin that links all these areas.
Two main mechanisms influence calcium control: (1) parathyroid hormone, and (2) vitamin D.
BUT: … again … how and where to start?
For want of better, let’s start with the storehouse (bone) … then see how that store is supplied and used.
Bone is much more a living, ‘happening’ place than we can ever imagine. Bone is one of the most industrious tissues in the body and is a hive of activity. Not only does the soft ‘marrow’ of bone make all our blood cells - including our red cells under the influence of erythropoietin - but the hard outer ‘shell’ of bone is in a state of constant turn-over, with new bone being built by cells called osteoblasts and old bone being broken down by an opposing set of cells called osteoclasts.
Bone is our storehouse for calcium. As any good business will know, it is important to keep the right balance between supply, storage, and removal (or use), and while bone is the storehouse, PTH is directs the traffic between ‘product supply’ and ‘product demand’ … it provides the software that balances the whole chain of supply and demand. And, off to the left of centre, the kidneys provide the equivalent of quality control!
The parathyroid glands are, primarily, all about controlling the calcium and phosphate levels of the blood … and the balance between storage and release at bone level.
U The level of calcium in the blood is controlled in two main ways:[/U]
B The parathyroid glands.[/B]
As parathyroid hormone (PTH) has a controlling influence over the osteoclast activity of bone, and if small sensors (receptors) in the parathyroid gland tissue ‘sense’ the the blood calcium level is falling, the parathyroid glands make more PTH in response to their sensor messages … and that extra PTH then stimulates the osteoclasts to chomp up a bit more hard bone and release the calcium it contains into the bloodstream. This thus restores the blood calcium level.
B The kidneys and the gut[/B]
In the first instance, calcium must be absorbed into the body from food in the gut … and this absorption is dependant on a vitamin called vitamin D. Vitamin D is where the kidneys come into the ‘calcium’ act … the kidneys provide the final step in the processing of vitamin D in the body. The kidneys convert the inactive form of vitamin D that we ingest from our food into an ‘activated’ or biologically effective form that ‘does stuff’ … and that ‘stuff’ is to assist the gut to absorb calcium. In kidney failure, this final step in vitamin D processing begins to fail. As a result, less activated vitamin D is made, and - in turn - less calcium is able to be absorbed from food.
U The level of phosphate in the blood is also controlled, in part, by PTH.[/U]
PTH also effects the function of the tubule segment of each nephron. I won’t expand on this here, except to note that PTH directly increases capacity for each nephron to excrete (remove) phosphate from the body and thus helps to maintain a normal phosphate level in the blood. As the number of functioning nephrons diminishes in the situation of progressive chronic kidney disease, eventually there will be insufficient tubules left to excrete enough phosphate - even though they are being coerced by PTH to do so, and phosphate levels then begin to inexorably rise.
Ok … back to the issues raised in your question … in chronic kidney disease (CKD), as kidney function declines, two changes begin to emerge: one affecting the blood calcium (a tendency for it to fall) and the other affecting the blood phosphate (a tendency for it to rise).
Let’s now concentrate on calcium, and leave phosphate aside … though in CKD, it really is just as important …
A fall in calcium, due (a) to less absorption and (b) to the effect that a rising phosphate has on pushing down the blood calcium level, stimulates PTH production. This turns the osteoclasts into little bone-surface Pac-men to release calcium. A bone weakening process is thus set in motion.
As the progressive decline in kidney function that IS what we call CKD continues, the stimulus to (a) and (b) continues, and the parathyroid glands continue to be stimulated to make PTH. Sooner or later, the glands permanently enlarge and grow to a point where they become big, juicy, PTH-making factories … and at this stage, secondary hyperparathyroidism become ‘self-fulfilling’ and a third (or tertiary) state is reached.
To try to prevent this, active vitamin D therapy with calcitriol is used to increase gut uptake of calcium and to raise the blood calcium level so that the parathyroid receptors (the sensors of blood calcium levels) are switched off, PTH production is reduced, and the bone-destructive effect that PTH exerts on bone through osteoclast activity is turned down.
So … step one in treatment is calcitriol.
Step two is cinacalcet = a drug that to the parathyroid calcium sensors “looks like” calcium … it ‘mimes’ calcium … and is thus called a ‘calcium-mimimg-agent’ or a ‘calcimimetic’. This drug actually ‘hoodwinks’ the parathyroid gland receptors into ‘thinking’ that they seeing calcium and that the blood calcium level is higher than it really is … and PTH production is turned down.
But, it is an expensive drug and, as there remains some disagreement over its usefulness and the circumstances in which it should be used, some countries - including Australia - have tight regulations guiding its prescription.
Step three is to move to gland removal by parathyroidectomy = usually a sub-total (or three and a half out of four gland removal).
Some might think this a radical step, but usually a sub-total parathyroidectomy is relatively easy surgery and doesn’t mean more than 3-4 days hospitalisation. In addition, it is one of the more effective ‘surgeries’ in CKD and despite a sometimes ‘avid’ sucking-up of calcium after surgery - the ‘hungry bone syndrome’ … [google it] … it can be a very useful bit of surgery. However, to this point in time, it is still regarded as a ‘last resort’.
This explanation has been provided as background information to the initial question from AchillesHeel.
But … and back to AchillesHeel … in simple terms, her problem would seem most likely to be secondary hyperparathyroidism, and her next step is thus calcitriol … with the caveat that exclusion of an adenoma - in her case - might be sensible, just to be sure there isn’t a reversible issue here.
The only reason I throw an adenoma into the ring in her case is that if she has an eGFR up towards the upper end of the CKD3 eGFR spectrum (say >45-50), then it is a little too early to suspect significant secondary hyperparathyroidism. Thus a possible adenoma in this circumstance might need consideration.
But … if her eGFR is further down … say, in the low 30’s … then secondary hyperparathyroidism will almost certainly be present and may be sufficiently ‘up and about’ to generate a biochemically abnormal PTH level, as a rising PTH from CKD-related (secondary) hyperparathyroidism becomes increasingly common as eGFR falls.
Her specialist is clearly on top of all this, and there is nothing for me to say other than to agree with the line being taken.
Her worry about cardiovascular disease and/or bone disease is a fair concern … but the early management that is being considered by her nephrologist will certainly help minimise this anxiety, and it seems like she is already on the right course to maximally achieve benefit from her therapy.
[B]OK … I know that was long … SORRY!
I know that it seemed complex … also SORRY
But - this IS one of the most complex issues in ALL of medicine …
So … give me a break …
Re-read it … mull it over … try to get your head around it … 'cos there is little else I can do to make it more simple!
JA
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