Thread by @JMTeakell

1/ 🚨#Tweetorial alert. Let’s discuss a couple cases of #Hypercalcemia 🦴🥛
@NSMCInternship #NSMC2021 #TeamTwobules #NephTwitter #MedTwitter #MedEd 🧵

2/ A patient admitted with c/o decreased appetite, abdominal pain, & constipation. Found to have severe #AKI (with hyperkalemia + acidosis) & hypercalcemia.

3/ What’s your differential for #hypercalcemia?
C - Calcium supplements
H - Hydrochlorothiazide
I - Immobilization
M - Multiple Myeloma, Milk-alkali
P - Parathyroidism
A - Alcohol
N - Neoplasm
Z - Zollinger-Ellison
E - Excessive Vit D
E - Excessive Vit A
S - Sarcoidosis

4/ Don’t forget about classic symptoms of #hypercalcemia: bones, stones, groans, & moans.
Msk: bone pain, fractures
GU: polyuria, renal colic, nephrolithiasis
CNS: confusion, irritability, depression, hallucinations, stupor, coma
GI: anorexia, nausea/vomiting, constipation

5/ First, it’s important to determine whether it’s PTH or non-PTH mediated. The vast majority of HyperCa cases are due to primary hyperparathyroidism or malignancy. A high or normal/low PTH can help distinguish.

6/ So, in this case...
✅PTH & PTHrp are low
✅SPEP & UPEP are unremarkable
✅CT Abd/Pelv showed no masses or major abnormalities.
🤔 What’s next?
👉Check Vitamin D levels 25(OH)D & 1,25(OH)D 🔍

7/ A common Q? residents (sometimes pts) ask in the CKD clinic, how much Vit-D should one take? For most, standard available OTC cholecalciferol formulations (800-2000IU) are fine. I’d even recently remarked that Vit-D overdose was rare & actually difficult to do w/o intention.

8/ Challenge accepted! This case proved me wrong. Apparently, “extra strength” cholecalciferol is available in 125 mcg (5000 IU) capsules. Unfortunately, patient had been taking multiple capsules daily… for *months* 😮#COVID19 #maddeningmisinformation

9/ Vit-D or calciferol, has two main forms ergocalciferol D2 & cholecalciferol D3. These are converted in the liver to 25(OH)D (calcidiol, half life 2-3 wk), & then metabolized further in the kidney to 1,25(OH)D (calcitriol, half life 4-6 hr).

10/ Vitamin D raises serum calcium via three main mechanisms:
✅ Increased small bowel absorption
✅ Increased kidney tubular reabsorption
✅ Increased bone resorption

11/ The daily upper limit of Vitamin D (from all sources - food, beverages, supplements) for adolescents & adults is 4000 IU (100mcg) per day. @NIH_ODS

12/ It has been difficult to define an absolute serum value of 25(OH)D at which toxicity occurs. Generally, serum total 25(OH)D level > 80 ng/mL (200 nmol/L) is associated with toxicity. Degree of hypercalcemia is influenced by dietary calcium intake.

13/ Hypercalcemia causes AKI by multiple mechanisms:
💥arteriolar vasoconstriction
💥reduction in tubular sodium reabsorption 👉volume depletion
💥acute tubular necrosis
💥nephrocalcinosis

#LiquidBiopsy urinary sediment 🔬showing calcium oxalate crystals and granular cast 👇

14/ Treatment of HyperCa secondary to hypervitaminosis D:
1 - stop the exogenous vitamin d
2 - isotonic saline, +/- furosemide, glucocorticoids (reduced gut Ca absorption)
Patients with severely decreased GFR/UOP, may also need dialysis for clearance / calcium removal.

15/ A patient presented w/ back pain after fall secondary to syncope at home. ROS positive for fatigue, unintentional weight loss, night sweats, & vague abdominal pain.
Another case of #hypercalcemia & AKI...

16/ Again the PTH & PTHrp are low, SPEP & UPEP are unremarkable. But CT Abd/Pelv showed extensive lymphadenopathy involving the supraclavicular, mediastinal, retroperitoneal, mesenteric, & inguinal regions.

17/ This raised the concern for lymphoma. Vitamin D levels were checked. The 1,25(OH)D should not be this high (nl range 18-72 pg/mL) in the setting of hyperCa with low 25(OH)D & suppressed PTH.

18/ Lymph node biopsy showed non-necrotizing granulomatous inflammation, no malignant cells. Mycobacterial/fungal infections ruled out. Leaving us with the diagnosis of #sarcoidosis.

19/ Conversion of 25(OH)D➡️1,25(OH)D occurs in sarcoid lymph nodes. 🫁 Pulm alveolar macrophages (PAM) of pts w/ sarcoidosis have 1α-hydroxylase w/ properties distinct from native kidney enzyme.
PAM 1α-hydroxylase is:
🚫NOT inhibited by Ca nor 1,25(OH)D
🚫NOT stimulated by PTH

20/ Treatment of HyperCa in sarcoidosis is similar to above. Isotonic saline +/- furosemide. Glucocorticoids suppress activity of PAM 1α-hydroxylase, reduce intestinal Ca absorption, & help w/ other systemic effects. Ketoconazole can also suppress ectopic 1α-hydroxylase activity.

21/ Also check out these excellent #HyperCa resources:
@TheSkeletonKG skeletonkey.group/calcium
@RenalFellowNtwk renalfellow.org/2010/01/10/hyp…
@CPSolvers clinicalproblemsolving.com/dx-schema-hype…
@EndoSocJournals academic.oup.com/edrv/article/3…

22/ Hope you enjoyed 😃 this #Tweetorial on Vitamin D-mediated #Hypercalcemia.
Thanks to @NSCMInternship faculty @docanjuyadav @drM_sudha @DrFlashHeart @Nephro_Sparks for review. #NephTwitter #NSMC2021

👇👇👇

https://twitter.com/aishaikh/status/1426956576498372612

Red squiggly line fail 🤦‍♀️