2025 – PAGE 80 – ENDOCRINOLOGY

VITAMIN D & ITS EVALUATION

The liver sends 25-Vitamin D to the kidneys, where it gets hydroxylated to 1,25 Vitamin D (the active form). If looking for a nutritional deficiency, obtain a 25-Vitamin D level. SUPPLEMENT with 1,25 Vitamin D (the ACTIVE form). Typically, 25-Vit D is the first one you should check (especially if they ask for a screen). If you are given a history of renal disease, check for 1,25 Vitamin D.

MNEMONIC: Where is the Vitamin D produced that carries two numbers with it (1 and 25)? TWO organs = TWO kidneys = TWO numbers (1 and 25)!

MNEMONIC: Which one is the active form? Think of it this way: if you ingest a calcium-containing food in its natural form, it will first go to the gut, then the liver, then the blood, then finally the kidneys! So keeping the above mnemonic in mind, it’s the Vitamin D with TWO numbers!

PEARLS: Here are some ways Vitamin D deficiency could present:

• ­African-American (AA) breastfed child whose mom is not on Vitamin D supplementation
• ­African-American (AA) breastfed child whose mom is not getting enough sunlight
• ­Child with symptoms consistent with malabsorption
• ­Child with a history of epilepsy who is on anti-seizure medications

(DOUBLE TAKE) RICKETS

Rickets is a disorder with multiple possible causes that lead to defective mineralization of bones before epiphyseal closure due to a deficiency or impaired metabolism of vitamin D, phosphorus, and/or calcium. The defective mineralization can then potentially lead to fractures and deformities. Findings of Rickets may include widening of wrist and ankle physes (growth plates), bowed legs, pain, decreased growth rate, anorexia, enlarged costochondral junctions (rachitic rosary), pigeon chest, delayed suture/fontanelle closure, frontal bossing (thick skull), or bad tooth enamel. There is no singular lab pattern for Rickets. It can be due to Vitamin D deficiency secondary to one of multiple different disorders, and you MUST learn the lab patterns associated with the different disorders:

• ­NORMAL (or LOW) CALCIUM + LOW PHOSPHORUS

This pattern represents FAMILIAL HYPOPHOSPHATEMIC RICKETS (AKA “VITAMIN D RESISTANT RICKETS”). It is an X-linked DOMINANT renal disorder. The mutation causes excessive production of a growth factor that inhibits phosphate reabsorption in the proximal tubule. The treatment of choice is burosumab, a monoclonal antibody against this growth factor. Labs = Normal (or low) calcium, LOW serum phosphorus, HIGH alkaline phosphatase, normal Vitamin D 25, and NORMAL PTH since calcium is usually normal. Treat with oral phosphate supplementation and avoid hypOcalcemia by giving the active/oral form of Vitamin D (1,25).

• • PEARL: For the exam, they will probably keep it simple and avoid giving you a low calcium level.
• ­NORMAL CALCIUM + LOW PHOSPHORUS

This represents INITIAL VITAMIN D DEPLETION. Low Vitamin D results in low phosphorus reabsorption. There is a compensatory increased PTH that temporarily normalizes calcium. Treat with Vitamin D supplementation, preferably Vitamin D3 (cholecalciferol).

PEARL: For the test, they probably want you to focus on FAMILIAL Hypophosphatemic Rickets. The differentiating lab would be a low Vitamin D level (25) in early Vitamin D depletion, versus a normal level in Familial Hypophosphatemic Rickets.

• ­LOW CALCIUM + LOW PHOSPHORUS

This represents SEVERE VITAMIN D DEFICIENCY resulting in poor absorption of calcium and phosphorus from the gut. PTH should be high. Treat with Vitamin D supplementation, preferably Vitamin D3 (cholecalciferol).

• ­LOW CALCIUM + HIGH PHOSPHORUS

This represents hypoparathyroidism, pseudohypoparathyroidism (high serum PTH but PTH resistance), or phosphorus overload.

• ­NORMAL CALCIUM + HIGH PHOSPHORUS

This represents renal disease, growth hormone excess, or a high phosphorus diet.