1. Vitamin D
The Sunshine Hormone
Domenic Aiello, M.D., F.A.C.E.

2. Vitamin D Program The Basics Vitamin D Toxicity Vitamin D Deficiency
Recommendations

3. Vitamin vs. Hormone Hormone Vitamin
Any organic substance, found in minute amounts in the body, that acts as an essential co-factor or co-enzyme in an organic system. It is obtained from food sources and not produced in the body.
Hormone
A substance, peptide or steroid, that is produced by one tissue and conveyed by the bloodstream to another to affect physiologic activity, such as growth or metabolism.

4. Vitamin D
-Discovered in 1921, from the irradiation of cod liver oil and found to treat rickets.
-Produced in the skin, when exposed to ultraviolet radiation between nm.
-It is essential to calcium and bone metabolism.
-Over the last 20 years, it has been noted to be a modulator of other hormone activity
and this has led to looking at cause and effects of Vitamin D in other systems.
Unfortunately, like muddy waters, nothing is clear. Thus, concern exist about the over
the use of Vitamin D, the risk of hypercalcemia, kidney stones, ectopic calcifications and
needless expense of over testing.

6. Does anyone have any epiphanies about this list?
Sources of Vitamin D
D2 – Plants (Mushrooms)
Fortified Cereals
Irradiated Yeast
D3- Animal (ultraviolet radiation and skin)
Deep Sea Fatty Fish
Egg Yolk
Liver
Does anyone have any epiphanies about this list?

7. Toxicity = Hypercalcemia
Vitamin D Toxicity
Toxicity = Hypercalcemia
This is usually related to ingestion of Vitamin D.
The ½ life of Vitamin D is 3 weeks, as apposed to calcitriol which is about 10 hours. So depending upon what was taken this can last some time.
When not related to ingestion it is from increased 1-OH activity. Think granulomatous disease, e.g.. Sarcoidosis, TB or lymphoma.
Treatment:
Fluids
Steroids
Biphosphonates

8. Vitamin D Deficiency Decrease Synthesis Age.
Amount of pigment in the skin.
Winter (actually there are only 2 weeks in mid-August, when UV radiation is optimal for skin production of Vitamin D).
Malabsorption
Celiac Sprue
Crohn’s Disease
Pancreatic Insufficiency
Cystic Fibrosis
Cholestatic Liver Disease
Gastrectomy
Decreased 25-OH Activity
Anticonvulsants.
Biliary Cirrhosis
ETOH Cirrhosis

9. Vitamin D Deficiency Binding Protein Deficiency – Nephrotic Syndrome
Decreased 1-OH Activity
Hypoparathyroidism
Renal Failure (creatinine clearance < 35 ml/min)
1-OH deficiency (Vitamin D dependent Rickets Type 1).
End-Organ Resistance
Heredity Vitamin D Resistant Rickets Type 2.

10. Vitamin D Deficiency What to measure: 25-OH Vitamin D PTH
Calcium and Albumin
Alkaline phosphatase
Urine calcium
Special Considerations:
There is a lot of variability from lab to lab and from kit to kit in 25OH Vit D measurements.
During puberty, with adequate calcium replacement, a high normal PTH and a low normal Vitamin D level, you seem to maximize bone mass.1
You get maximal calcium absorption with a 25OH Vitamin D level of about 32 ng/ml.2
If the 25 OH Vitamin D level is < 12 ng/ml, think malabsorption.
J Am Coll Nutr. 2007, 26(5):
2. Am J Nutr. 2004, 80(6 supl) 1706S-1709S.

11. Vitamin D Deficiency
Conditions resulting from Vitamin D Deficiency: 1. Secondary Hyperparathyroidism. 2. Rickets 3. Osteomalacia

12. Secondary Hyperparathyroidism
Vitamin D Deficiency
Secondary Hyperparathyroidism
(In Endocrinology, primary refers to the organ of interest as the problem, secondary are things that cause that organ to malfunction and tertiary is the waste basket of what happens next.)
In secondary Hyperparathyroidism, you have an elevated PTH in the face of a normal
calcium. The PTH is being made appropriately, to keep the serum calcium normal. It
is either related to decreased Ca++ intake, decrease GI absorption (Vit D Deficiency),
or loss of Calcium in the urine. The overall effect, is a loss in bone mass.
The goal for normal bone health/metabolism is a level of 30 ng/ml.
This is the major form of Vitamin D Deficiency and a easily correctable contributor
to osteopenia/osteoporosis.

13. Vitamin D Deficiency Rickets Presentation Hypocalcemia.
Hypophosphatemia.
Delayed closure of the Fontonelles.
Craniotabes.
Enlargement of costochondrial junction (rachitic rosary).
Enlargement of wrist and bowing of the distal radius and ulna.
Progressive lateral bowing of the femur and tibia.

14. Vitamin D Deficiency Nutritional Rickets
The number 1 cause in the western world is prolonged breast feeding. You also need to consider all the GI causes of malabsorption, esp. sprue and cystic fibrosis.
Treatment involves a) finding the cause and treating it, b) Vitamin D replacement (400 IU/day), and c) adequate calcium replacement (1000 mg/d).

15. Vitamin D Dependant Rickets Type 1
Vitamin D Deficiency
Vitamin D Dependant Rickets Type 1
This is a deficiency of 1-OH activity. Thus 25-OH vitamin D levels are normal, but the 1,25-OH levels are low. There are the x-ray findings of rickets, and a low calcium.
Treatment is with Calcitriol. Treatment goal is to maintain a normal Calcium and phosphorous level, avoiding hypoparathyroidism or hypercalcemia. Dose is based on body weight and response. Usual dose is between 0.25 mcg to 1.0 mcg/day.

16. Very Rare (50 known Kindreds)
Vitamin D Deficiency
Hereditary Vitamin D Resistance Rickets (Type 2)
Very Rare (50 known Kindreds)
Cause – mutated vitamin D receptor causing resistance to action of the hormone.
Treatment – try vitamin D, but it usually does not work. You are left with a combination of calcium supplementation/infusions.

17. Vitamin D Deficiency Osteomalacia
A change in the character of the osteoid produced by the osteoblast during bone remodeling, resulting in a defect in calcification. As a result there is decreased bone strength and micro fractures.
Presentation
Bone pain (long bones and joints)
Proximal muscle weakness
Pseudofractures
Increased alkaline phosphatase and PTH
+/- hypocalcemia

18. Causes of Osteomalacia
Vitamin D Deficiency
Causes of Osteomalacia
Vitamin D Deficiency
Hypophosphatasia
Inhibitors of mineralization -> fluoride, aluminum, biphosphonates
Phosphate Deficiency
Antacids
Vitamin D resistant rickets
Fanconi’s Syndrome, Wilson’s Disease, Cystinosis, multiple myeloma
Primary hyperparathyroidism
Renal tubular acidosis
Seconday hyperparathyroidism
Osteogenic Osteomalacia

19. Vitamin D Deficiency Name available doses 1/2 life
Calecalciderol (Vit D3)
200, 400, 600, 800, 1000, 2000, 5000 IU
3 weeks
Ergocalciferol (Vit D2)
25,000, 50, 000 u
Calcifediol (25 OH Vit D)
20 & 50 ugm.
2 weeks
Dihydrotachysterol (DHT, 1 OH Vit D)
0.125, 0.2, 0.4 mg
4 days
Calcitriol (1,25 OH Vit D)
0.25, 0.5 ugm PO & 1, 2 ugm IV
10-14 hours

21. Vitamin D Metabolism Up regulated by PTH, Down regulated
By FGF23 (Fibroblast
Growth Factor 23)

22. My Suggestions: Vitamin D is not a screening test.
If you have clinical suspicion that there is a problem, based on the problem, you order a vitamin D level. Usually, this is a 25-OH Vitamin D. A 1,25-OH is a research tool. Clinically, it serves a purpose if you are taking 1,25-OH Vitamin D or if you are looking for a) cause of hypercalcemia or b) Type 1 Rickets.
Unlike the Institute of Medicine, I subscribe to a minimal level of 30 ng/ml for bone health.
Whatever you do, you need to follow it. (This is the biggest difference between me and the Institute of Medicine Recommendations.)
Think in a circle, in-use-out.
Try to avoid Voodoo!

24. Reading List
LeFoith, D., MD, PhD, Endo and Metab Clinics of N Am, June 2010 (39)2:
“Dietary Reference Intakes for Calcium and Vitamin D”, Institute for Medicine, 11/30/2010.
Thacher, T.D. & Clarke, B.L., Mayo Clin Proc (1):
Rosen, C.J., N Engl J Med, :