43-year-old (male) with hypercalcemia

00:02 A 43 year old male is brought to the office by his wife due to decreased concentration and weakness for the past month.

00:10 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.

00:21 She also tells the physician that her husband has been taking vitamin D supplements for the past year.

00:28 The patient's vital signs are heart rate 60 , respiratory rate 19, temperature 36.6 degrees celsius, and blood pressure 145/90 mmHg.

00:38 On physical examination, the patient appears confused and fatigued, and there is pain to palpation of both the arms and legs.

00:47 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) - hyperparathyroidism Answer choice (C) - hypervitaminosis D Answer choice (D) - malignancy and Answer choice (E) - thyrotoxicosis Now take a moment to go through the answer choices before we go through them together.

01:40 Okay, let's tackle this question together.

01:42 The first thing we need to do is determine what type of subject we are dealing with for this question.

01:47 And this patient is having some type of endocrine abnormality - we have endocrine labs, and this is a pathology, so this is a classical pathological-endocrine Now this is a 2-step question.

01:58 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.

02:07 And the stem is absolutely required to understand both the history and the laboratory findings.

02:12 So first let's walk through this question.

02:14 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.

02:27 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).

02:36 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).

02:46 The rest of the labs are normal.

02:47 So now we've identified high calcium, low phosphate and high parathyroid hormone related protein.

02:56 Now we need to determine what's the likely cause of these abnormal lab findings.

03:02 Now the differential diagnosis for hypercalcemia is generally focused on primary hyperparathyroidism and hypercalcemia of malignancy.

03:13 Now we know that low to normal parathyroid hormone levels in the setting of hypercalcemia is actually suggestive of malignancy.

03:23 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.

03:36 And in this case, it is elevated in this patient.

03:39 Now so that's we're thinking okay, the patient's hypercalcemia, maybe thus then likely due to malignancy.

03:46 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.

04:05 Thus in this case, the correct answer is answer choice (D) - malignancy.

04:10 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.

04:24 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.

05:03 Now let's review some high-yield facts regarding hypercalcemia of malignancy and paratyroid hormone-related protein.

05:11 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.

05:32 And the most common cancers associated with hypercalcemia - and this is very important to know, include breast, lung and multiple myeloma.

05:40 Now parathyroid hormone-related protein is a biomarker of hypercalcemia of malignancy but this also has physiological function of regulating bone development.

05:53 High levels of parathyroid hormone-related protein will induce abnormal bone reabsorption which leads to hypercalcemia.