A 43 year old male is brought to the office by his wife due
to decreased concentration and weakness for the past month.
His wife tells the physician that the patient
has been constipated for the last few months
and has had an unintentional weight loss
of about 3 kilograms during that time.
She also tells the physician that her husband has
been taking vitamin D supplements for the past year.
The patient's vital signs are heart
rate 60 , respiratory rate 19,
temperature 36.6 degrees celsius,
and blood pressure 145/90 mmHg.
On physical examination, the patient
appears confused and fatigued,
and there is pain to palpation
of both the arms and legs.
A laboratory examination is performed
which reveals the following:
Calcium 14.5 (mg/dL), Phosphate 2.2
(mg/dL), Parathyroid hormone 18 (pg/mL),
Parathyroid hormone-related protein 4 (pmol/L), Calcitriol
46 (pg/mL), T3 100 (ng/mL) and T4 10.2 (mcg/dL)
Taking into account the clinical and laboratory findings,
what is the likely cause of the patient's hypercalcemia?
Answer choice (A) -
chronic kidney disease
Answer choice (B) -
Answer choice (C) -
Answer choice (D) - malignancy
and Answer choice (E)
Now take a moment to go through the answer
choices before we go through them together.
Okay, let's tackle this question together.
The first thing we need to do is determine what type
of subject we are dealing with for this question.
And this patient is having some type of
endocrine abnormality - we have endocrine labs,
and this is a pathology, so this is a
Now this is a 2-step question.
We have to first figure out what is clinically
going on with the patient, to diagnose
and then use the laboratory values to then
figure out the cause of the abnormality.
And the stem is absolutely required to understand
both the history and the laboratory findings.
So first let's walk
through this question.
Step 1 - the question as it tells you, the patient
has hypercalcemia and is elevated at 14.5
but we need to be able to look at the labs and
be able to identify the other abnormal lab findings.
Now in this case, we can see at
the patient's lab findings,
that they have a low phosphate level -
it's 2.2 and the range is 3.4-4.5 (mg/dL).
And we also see the patient has elevated
parathyroid hormone-related protein level
which is 4, and normally it
should be less than 2.5 (pmol/L).
The rest of the labs are normal.
So now we've identified high calcium, low phosphate
and high parathyroid hormone related protein.
Now we need to determine what's the likely
cause of these abnormal lab findings.
Now the differential
diagnosis for hypercalcemia
is generally focused on primary hyperparathyroidism
and hypercalcemia of malignancy.
Now we know that low to normal parathyroid hormone levels in the
setting of hypercalcemia is actually suggestive of malignancy.
And in this case, parathyroid hormone related protein,
we know is to be secreted by various malignant tumors
and is actually an important biomarker
of hypercalcemia of malignancy.
And in this case, it is
elevated in this patient.
Now so that's we're thinking okay, the patient's
hypercalcemia, maybe thus then likely due to malignancy.
And actually the patient's clinical
presentation even supports malignancy more so,
to say that the patient has weight loss and pain
upon palpation, and that's due to bone pain
caused by parathyroid hormone related
protein-induced bone reabsorption.
Thus in this case, the correct answer
is answer choice (D) - malignancy.
Now let's refer to our image, which is extremely high-yield
which discusses the relationship via visual form
of looking at the blood parathyroid
hormone level and blood calcium levels,
very important to get
a few points here.
As you can see, we'll start with the high calcium
of malignancy as it's relevant to this question
in the bottom right hand corner of the graph, we can
see that in this case, a high blood calcium level
with a low to normal PTH is consistent with a high
calcium of malignancy which is what's going on here
Now if you have low both, low PTH and low
calcium - that's hypoparathyroidism,
If you have high both - high calcium and high PTH - that's primary
hyperparathyroidism, and then the variants fall in between
in which a patient has a very high PTH but low
calcium and that's due to kidney failure.
Now let's review some high-yield facts regarding hypercalcemia
of malignancy and paratyroid hormone-related protein.
Now hypercalcemia of malignancy is actually relatively common in
cancer patients and actually affects 40% of all cancer patients
Now the mechanism of this hypercalcemia depends
on the underlying condition for each patient
but parathyroid hormone-related protein induced
osteolysis actually count for the majority of causes.
And the most common cancers
associated with hypercalcemia -
and this is very important to know, include
breast, lung and multiple myeloma.
Now parathyroid hormone-related protein is
a biomarker of hypercalcemia of malignancy
but this also has physiological function
of regulating bone development.
High levels of parathyroid hormone-related protein will induce
abnormal bone reabsorption which leads to hypercalcemia.