PARATHYROID, THYROID HORMONE

AND ANTITHYROID DRUGS.

VITAMIN D AND CALCIUM
METABOLISM
DR O.E ANJORIN
06-03-2024
 OUTLINE
• INTRODUCTION- THYROID HORMONES
• SYNTHESIS AND TRANSPORT OF THYROID HORMONES
• ACTIONS OF THYROID HORMONES
• INDICATIONS/USES OF THYROID HORMONES
• ANTITHYROID DRUGS
• PARATHYROID HORMONES
• CALCIUM AND VITAMIN D METABOLISM
 THYROID HORMONES:
• THE THYROID SECRETES 2 TYPES OF HORMONES:
• IODINE-CONTAINING AMINO ACIDS (THYROXINE,T4 AND
TRIIODOTHYRONINE, T3) AND A PEPTIDE (CALCITONIN).
• THYROXINE AND TRIIODOTHYRONINE HAVE BROAD
EFFECTS ON GROWTH, DEVELOPMENT, AND METABOLISM.
• CALCITONIN IS IMPORTANT IN CALCIUM METABOLISM.
 INTRODUCTION- THYROID
HORMONES,SYNTHESIS
• THYROID GLAND CONTAINS FOLLICULAR CELLS AND
PARAFOLLICULAR (C) CELLS.
• FORMER SECRETES THYROID HORMONES (T3 AND T4 )
WHEREAS THE LATTER IS RESPONSIBLE FOR THE SECRETION
OF CALCITONIN.
• THYROID HORMONES ARE SYNTHESIZED AND STORED IN
THYROID FOLLICLES THUS:
• IODINE IS FIRST TAKEN UP IN THE FOLLICULAR CELL WITH THE
HELP OF NA+: I– SYMPORTER (NIS).
• AFTER ENTRY IN THE FOLLICULAR CELLS, IODINE IS
OXIDIZED TO FORM IODINIUM (I+ ) IONS - OXIDATION.
• THESE IONS COMBINE WITH TYROSINE RESIDUES OF
THYROGLOBULIN TO FORM MONO-IODO TYROSINE (MIT) AND
DI-IODO-TYROSINE (DIT).
• THIS PROCESS IS KNOWN AS ORGANIFICATION OF IODINE.
• DIT COMBINES WITH DIT TO FORM 3, 5, 3’, 5’ TETRA-IODO-
THYRONINE (T4 ) AND WITH MIT TO FORM 3, 5, 3’ TRI-IODO-
THYRONINE (T3). THIS PROCESS IS KNOWN AS COUPLING.
 SYNTHESIS AND STORAGE OF THYROID
HORMONE
• OXIDATION, ORGANIFICATION AND COUPLING REACTIONS ARE
CATALYZED BY THYROID PEROXIDASE ENZYME.
• AFTER FORMATION, T3 AND T4 ARE TRANSPORTED TO THE
FOLLICLES WHERE THESE REMAIN STORED AS COLLOID.
• ON STIMULATION VIA TSH, THESE HORMONES ARE RELEASED
IN THE CIRCULATION.
• IN THE LIVER AND KIDNEY, T4 IS CONVERTED TO T3
(PERIPHERAL CONVERSION) WITH THE HELP OF 5’-DEIODINASE
AND TAKEN UP BY TARGET TISSUES.
 SYNTHESIS AND TRANSPORT OF THYROID
HORMONES
• THYROID FUNCTION IS CONTROLLED BY THE PITUITARY
THROUGH THE RELEASE OF THYROTROPIN (THYROID-
STIMULATING HORMONE [TSH]) AND BY THE AVAILABILITY
OF IODIDE.
• THYROTROPIN STIMULATES THE UPTAKE OF IODIDE AS
WELL AS SYNTHESIS AND RELEASE OF THYROID HORMONE.
• IT ALSO HAS A GROWTH-PROMOTING EFFECT THAT CAUSES
THYROID CELL HYPERPLASIA AND AN ENLARGED GLAND
(GOITER).
 SYNTHESIS AND TRANSPORT OF THYROID HORMONES
• HIGH LEVELS OF THYROID HORMONES INHIBIT THE RELEASE OF TSH,
PROVIDING AN EFFECTIVE NEGATIVE FEEDBACK CONTROL
MECHANISM.
• IN GRAVES’ DISEASE, AN AUTOIMMUNE DISORDER, B-LYMPHOCYTES
PRODUCE AN ANTIBODY THAT ACTIVATES THE TSH RECEPTOR AND
CAN CAUSE A SYNDROME OF HYPERTHYROIDISM CALLED
THYROTOXICOSIS.
• PATIENTS WITH GRAVES’ DISEASE CAN HAVE VERY HIGH BLOOD
CONCENTRATIONS OF THYROID HORMONE.
• IS ASSOC. WITH HLA-DR3 AND HLA-B8.
• OFTEN PRESENTS DURING STRESS E.G.PREGNANCY
IMAGE OF GRAVES DISEASE
 DIFFERENCES BETWEEN T3 AND T4
Liothyronine (T3) L-Thyroxine (T4)

More potent and more active Less potent but main

thyroid hormone circulating thyroid hormone.

Short acting, therefore Long acting, therefore

beneficial in emergency preferred for long term use
situations like myxedema in hypothyroidism due to its
coma. long half life..
 ACTIONS

• THYROID HORMONES ARE REQUIRED FOR NORMAL GROWTH

AND DEVELOPMENT.
• THESE ARE CATABOLIC HORMONES AND INCREASE THE
BREAKDOWN OF FATS (TO FFA), CARBOHYDRATES (CAUSE
HYPERGLYCEMIA) AND PROTEINS (CAUSE WEIGHT LOSS).
• THESE ARE CALORIGENIC AND INCREASE BASAL METABOLIC
RATE (BMR).
• DEFICIENCY OF THYROID HORMONES LEADS TO CRETINISM IN
CHILDREN AND MYXOEDEMA IN ADULTS.
• HEAT INTOLERANCE OCCURS IN HYPERTHYROIDISM
WHEREAS HYPOTHYROIDISM CAUSES COLD INTOLERANCE.
• THYROID HORMONES STIMULATE THE HEART (INCREASE
RATE, CONTRACTILITY AND CARDIAC OUTPUT).
• IN HYPERTHYROIDISM, ATRIAL FIBRILLATION CAN OCCUR.
• HYPOTHYROIDISM RESULTS IN MENTAL RETARDATION
WHEREAS HYPERTHYROIDISM CAN RESULT IN ANXIETY,
TREMORS, NERVOUSNESS AND EXCITABILITY.
 INDICATIONS
• MAIN INDICATION OF THYROID HORMONES IS
HYPOTHYROIDISM (CRETINISM, MYXEDEMA AND
MYXEDEMA COMA).
• LEVO-THYROXINE (T4) IS PREFERRED FOR ALL THESE
INDICATIONS DUE TO ITS LONG HALF LIFE AND
REQUIREMENT OF LESS FREQUENT DOSING.
• MYXEDEMA COMA IS AN EMERGENCY SITUATION, IN WHICH
LIOTHYRONINE (ONLY INDICATION) CAN ALSO BE USED.
• T3 SHOULD BE USED CAUTIOUSLY IN PATIENTS WITH HEART
DISEASES LIKE ATRIAL FIBRILLATION (AF).
 Irreversible mental retardation
Cretinism and dwarfism caused by
congenital hypothyroidism

Myxedema Severe hypothyroidism

Goiter Enlargement of the thyroid gland

Autoimmune disorder that results

in hyperthyroidism during the
Graves’ disease
early phase and can progress to
hypothyroidism if there is ...
 INHIBITORS OF NA+–I– SYMPORTER

• IODINE IS TRAPPED IN THE FOLLICULAR CELLS WITH NA+:I-

SYMPORTER.
• THIOCYANATE, FLUOBORATE, PERCHLORATE,
PERTECHTENATE AND NITRATES INHIBIT THIS TRANSPORTER
AND THUS THYROID HORMONE SYNTHESIS.
• THESE DRUGS ARE VERY TOXIC AND ARE OBSOLETE NOW.
• THIOCYANATE IS PRODUCED BY CABBAGE, CIGARETTE
SMOKING AND SODIUM NITROPRUSSIDE.
 THYROID PEROXIDASE INHIBITORS

• THYROID PEROXIDASE ENZYME CATALYZES THREE

REACTIONS (OXIDATION, ORGANIFICATION AND COUPLING) IN
THE PROCESS OF THYROID HORMONE SYNTHESIS.
• CARBIMAZOLE, METHIMAZOLE AND PROPYLTHIOURACIL ACT
BY INHIBITING THIS ENZYME.
• THESE DRUGS CAN RARELY CAUSE REVERSIBLE
AGRANULOCYTOSIS (MOST SERIOUS ADVERSE EFFECT), WHILE
THEIR MOST COMMON ADVERSE EFFECT IS MACULOPAPULAR
PRURITIC RASH.
• CARBIMAZOLE IS A PRODRUG AND ACTS AFTER CONVERSION
• MAJOR DIFFERENCES BETWEEN CARBIMAZOLE AND
PROPYLTHIOURACIL ARE THAT THE LATTER HAS:
-HIGH PLASMA PROTEIN BINDING.
-CAN BE USED IN PREGNANCY (BECAUSE LESS TRANSFER
ACROSS PLACENTA DUE TO HIGH PPB).
-IS LESS POTENT.
-HAS SHORTER PLASMA HALF-LIFE, SO REQUIRES MULTIPLE
DAILY DOSING.
-ALSO INHIBITS PERIPHERAL CONVERSION OF T4 TO T3.
 USES
• THYROID PEROXIDASE INHIBITORS ARE USED FOR THE CONTROL OF
THYROTOXICOSIS IN PATIENTS WITH GRAVES’ DISEASE AND TOXIC
NODULAR GOITER.
• PROPYLTHIOURACIL IS DRUG OF CHOICE FOR HYPERTHYROIDISM IN
FIRST TRIMESTER PREGNANCY AND LACTATION. FOR ALL OTHER
PATIENTS, METHIMAZOLE IS PREFERRED.
• THESE ARE ALSO USED IN YOUNG PATIENTS BEFORE PERFORMING
THYROIDECTOMY.
• ANOTHER USE OF ANTITHYROID DRUGS IS TO MAKE THE PATIENT
EUTHYROID BEFORE APPLICATION OF RADIOACTIVE IODINE.
 INHIBITORS OF THYROID HORMONE RELEASE

• SODIUM IODIDE, POTASSIUM IODIDE AND LUGOL’S SOLUTION

ACT AS ‘THYROID CONSTIPATING AGENTS’ BY INHIBITING
THE RELEASE OF T3 AND T4.
• IODIDES ARE THE FASTEST ACTING ANTI-THYROID DRUGS.
THEY MAKE THYROID GLAND TO SHRINK IN SIZE AND
DECREASE ITS VASCULARITY.
• THESE PROPERTIES ARE UTILIZED IN PREOPERATIVE
PREPARATION OF THYROID GLAND.
• THYROID STORM IS ANOTHER INDICATION OF THESE DRUGS..
• LITHIUM CAN CAUSE HYPOTHYROIDISM BY INHIBITING THE
 ADVERSE REACTION
• IN SENSITIVE INDIVIDUALS, ACUTE REACTION CONSISTS OF
SWELLING OF LIPS, ANGIOEDEMA, FEVER, JOINT PAIN AND
PETECHIAL HEMORRHAGES CAN OCCUR.
• CHRONIC OVERDOSE OF IODIDES IS CALLED IODISM.
• MAJOR SYMPTOMS ARE INFLAMED MUCUS MEMBRANES,
INCREASE IN SECRETIONS (SALIVATION, LACRIMATION AND
RHINORRHOEA), HEADACHE, RASHES AND
GASTROINTESTINAL DISTRESS.
• THESE DRUGS MAY ALSO CAUSE FLARING UP OF ACNE IN
ADOLESCENTS
 DRUGS CAUSING THE DESTRUCTION OF THYROID
GLAND
• I131 IS THE MOST COMMONLY USED RADIOACTIVE IODINE WITH A HALF-
LIFE OF 8 DAYS (STABLE ISOTOPE OF IODINE IS I127).
• WHEN ADMINISTERED (AS SODIUM SALTS, ORALLY), THESE ARE
ACTIVELY TAKEN UP BY THE THYROID GLAND AND STORED IN THE
COLLOID. HERE, IT EMITS X-RAYS AND Β-PARTICLES.
• I127 CAN PENETRATE ONLY 0.5-2MM OF TISSUE AND DESTROY THE
GLAND FROM WITHIN.
• I131 CAN BE USED FOR THE TREATMENT OF HYPERTHYROIDISM BUT
RESPONSE IS SLOW (MAXIMUM RESPONSE MAY TAKE 3 MONTHS).
• THYROID PEROXIDASE INHIBITORS ARE ADMINISTERED TO MAKE THE
PATIENT EUTHYROID.
• AFTER A GAP OF 5 DAYS (AFTER STOPPING ANTI-THYROID DRUGS),
RADIOACTIVE IODINE IS GIVEN AND THYROID PEROXIDASE INHIBITOR
TREATMENT IS RESUMED TILL THE EFFECT OF I131 STARTS.
• RADIOACTIVE IODINE THERAPY IS PRIMARILY INDICATED FOR PATIENTS
OLDER THAN 35 YEARS, THOSE WITH HEART DISEASE AND IN THE
PRESENCE OF OTHER CONTRA-INDICATIONS OF SURGERY.
• COEXISTING OPHTHALMOPATHY IS A RELATIVE CONTRA-INDICATION.
• THESE DRUGS ARE NOT SUITABLE FOR YOUNG CHILDREN AND IN THE
PREGNANCY.
• ANOTHER DISADVANTAGE OF RADIOACTIVE IODINE IS THAT IF
HYPOTHYROIDISM DEVELOPS, IT IS PERMANENT (REQUIRING LIFE
LONG T4 THERAPY).
 DRUGS INHIBITING THE PERIPHERAL CONVERSION OF T4 TO T3

• PROPANOLOL (B-BLKERS), GLUCOCORTICOIDS AND

PROPYLTHIOURACIL INHIBITS PERIPHERAL CONVERSION OF T4 TO THE
MORE ACTIVE T3 BY INHIBITING 5’-DEIODINASE.
• THESE DRUGS THEREFORE, CAN BE USED IN THE TREATMENT OF
HYPERTHYROIDISM.
• AMIODARONE ALSO INHIBIT THIS ENZYME AND THUS CAN RESULT IN
HYPOTHYROIDISM.
 ADJUVANT DRUGS

• Β-BLOCKERS (PROPANOLOL, ESMOLOL, ATENOLOL)

ANTAGONIZE THE SYMPATHETIC EFFECTS OF THYROTOXICOSIS
LIKE TREMORS, TACHYCARDIA, PALPITATIONS AND ANXIETY.
• CALCIUM CHANNEL BLOCKERS LIKE DILTIAZEM CAN ALSO BE
USED FOR THIS PURPOSE.
• STEROIDS (I.V. METHYLPREDNISOLONE) ARE USED FOR
GRAVES’S OPTHALMOPATHY.
• OPHTHALMOPATHY CAN BE AGGRAVATED BY I131 AND
THIAZOLIDINEDIONES (LIKE PIOGLITAZONE AND
ROSIGLITAZONE).
CONDITION DRUG

Hypothyroidism Levo-thyroxine

Myxedema coma Levo-thyroxine

Hyperthyroidism Carbimazole or methimazole

_In lactation Propylthiouracil

_In 1st trimester of pregnancy Prophylthiouracil

– In 2nd and 3rd trimester of pregnancy Carbimazole or methimazole

Graves' opthalmopathy Methylprednisolone

Thyroid storm Propanolol (life saving)+ Iodides

 CALCIUM
• CALCIUM IS ESSENTIAL FOR MANY IMPORTANT PHYSIOLOGIC
PROCESSES, SUCH AS NEUROTRANSMITTER RELEASE, MUSCLE
CONTRACTION, AND BLOOD COAGULATION.
• DEVIATIONS IN EXTRACELLULAR CALCIUM LEVELS CAN HAVE
SERIOUS CONSEQUENCES. THEREFORE, THE BLOOD CALCIUM
LEVEL IS TIGHTLY REGULATED.
• INORGANIC PHOSPHATE CONCENTRATIONS MUST ALSO BE
REGULATED, IN PART BECAUSE CHANGES IN PLASMA INORGANIC
PHOSPHATE CONCENTRATIONS AFFECT PLASMA CALCIUM
LEVELS.
• THREE MAIN HORMONES—PARATHYROID HORMONE
(PTH), VITAMIN D, AND FGF-23 MEDIATE CALCIUM AND
PHOSPHATE HOMEOSTASIS.
• IN ADDITION, CALCITONIN, GLUCOCORTICOIDS, THYROID
HORMONE, AND GONADAL STEROIDS HAVE LESSER
EFFECTS ON CALCIUM AND PHOSPHATE HOMEOSTASIS
 PARATHYROID HORMONE (PTH)

• THE MOST IMPORTANT ENDOCRINE REGULATOR OF CALCIUM

HOMEOSTASIS IS PARATHYROID HORMONE , A PEPTIDE HORMONE
SECRETED BY THE PARATHYROID GLANDS.
• THE SECRETION OF PTH IS FINELY REGULATED IN RESPONSE TO PLASMA
CALCIUM LEVELS.
• CALCIUM-SENSING RECEPTORS RESIDE ON THE PLASMA MEMBRANE OF
CHIEF CELLS IN THE PARATHYROID GLAND; WHEN BOUND BY
EXTRACELLULAR CALCIUM IONS, THESE G PROTEIN-COUPLED
RECEPTORS MEDIATE INCREASES IN THE LEVEL OF INTRACELLULAR FREE
CALCIUM, WHICH, IN TURN, DECREASES SECRETION OF PREFORMED PTH.
• BY THIS MECHANISM, HIGH PLASMA CALCIUM CONCENTRATION
SUPPRESSES PTH SECRETION, WHILE LOW PLASMA CALCIUM STIMULATES
• PLASMA CA2+ IS THE MAJOR FACTOR REGULATING PTH SECRETION.
• HYPOCALCEMIA STIMULATES PTH SECRETION WHEREAS
HYPERCALCEMIA INHIBITS IT. CALCIUM INHIBITS PTH SECRETION BY
STIMULATING CALCIUM SENSING RECEPTOR ON PARATHYROID CELLS.
• PTH INCREASES CIRCULATING CALCITRIOL BY TWO MECHANISMS;
DIRECTLY BY STIMULATING 1ALPHA HYDROXYLASE IN KIDNEY AND
INDIRECTLY BY DECREASING SERUM PHOSPHATE.
• THUS VITAMIN D AND CALCITONIN CAN BE USED TO TREAT
OSTEOPOROSIS WHEREAS PTH EXCESS CAN RESULT IN
OSTEOPOROSIS.
• VITAMIN D2 IS ERGOCALCIFEROL WHEREAS D3 IS CHOLECALCIFEROL.
• VITAMIN D IS CONVERTED TO 25-OHD (CALCIFEDIOL) IN THE LIVER
WITH THE HELP OF 25-Α-HYDROXYLASE AND THEN TO 1, 25-
DIHYDROXY D3 (CALCITRIOL) BY THE ACTION OF 1Α HYDROXYLASE.
• CALCITRIOL IS INACTIVATED TO 1, 24, 25 (OH)3 D WITH THE HELP OF
24-Α-HYDROXYLASE IN KIDNEY.
• DOXERCALCIFEROL AND PARICALCITOL HAVE BEEN APPROVED
FOR TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN
PATIENTS WITH CHRONIC RENAL DISEASE.
• THESE ARE LESS LIKELY TO CAUSE HYPERCALCEMIA THAN
CALCITRIOL.
• PTH ACTS ON THREE ORGANS TO RAISE THE PLASMA CALCIUM
CONCENTRATION: IT ACTS DIRECTLY ON KIDNEY AND BONE, AND
INDIRECTLY ON THE GASTROINTESTINAL (GI) TRACT.
• THE MOST RAPID PHYSIOLOGIC EFFECTS OF PTH ARE TO INCREASE
REABSORPTION OF CALCIUM AND TO DECREASE REABSORPTION OF
INORGANIC PHOSPHATE BY THE KIDNEY TUBULES.
• THESE ACTIONS DECREASE RENAL CLEARANCE OF CALCIUM WHILE
INCREASING RENAL CLEARANCE OF INORGANIC PHOSPHATE.
• IN THIS MANNER, PTH RAISES PLASMA CALCIUM LEVELS AND
DECREASES PLASMA INORGANIC PHOSPHATE CONCENTRATIONS.
• PHYSIOLOGIC LEVELS OF PTH STIMULATE CELL SURFACE PTH RECEPTORS
ON OSTEOBLASTS, CAUSING THESE CELLS TO INCREASE THEIR
EXPRESSION OF THE OSTEOCLAST DIFFERENTIATION FACTOR RANKL AND
DECREASE THEIR EXPRESSION OF ITS ANTAGONIST OSTEOPROTEGERIN.
• THE RESULTING INCREASE IN OSTEOCLASTIC ACTIVITY INCREASES BONE
RESORPTION AND THEREBY INCREASES THE RELEASE OF CALCIUM AND
INORGANIC PHOSPHATE INTO THE CIRCULATION.
• PTH ALSO INDUCES BONE MARROW STROMAL CELLS TO SECRETE
CYTOKINES SUCH AS IL-6, AND THESE CYTOKINES ULTIMATELY
STIMULATE OSTEOCLAST PROLIFERATION AND BONE RESORPTION.
• FINALLY, PTH RAISES PLASMA CALCIUM BY AN INDIRECT EFFECT ON THE
INTESTINE.
• IT INCREASES THE ENZYMATIC CONVERSION OF 25-HYDROXY VITAMIN D
TO 1,25-DIHYDROXY VITAMIN D (CALCITRIOL).
• THIS HYDROXYLATION TAKES PLACE IN CELLS OF THE PROXIMAL RENAL
TUBULES.
• CALCITRIOL, IN TURN, INCREASES SMALL INTESTINAL ABSORPTION OF
CALCIUM AND (TO A LESSER EXTENT) INORGANIC PHOSPHATE.
• ALTHOUGH THE RELEASE OF SKELETAL CALCIUM AND INORGANIC
PHOSPHATE COULD BE CONSIDERED CATABOLIC, PTH SIMULTANEOUSLY
STIMULATES NEW BONE FORMATION BY PROMOTING DIFFERENTIATION
OF OSTEOBLAST PRECURSORS TO MATURE OSTEOBLASTS
 VITAMIN D

• DESPITE ITS NAME, VITAMIN D3 IS PRODUCED IN THE SKIN

AND IS NOT REQUIRED IN THE DIET IF SUN EXPOSURE IS
GENEROUS.
• BECAUSE IT IS PRODUCED ENDOGENOUSLY AND TRAVELS IN
THE BLOOD TO EFFECT RESPONSES IN DISTANT TARGET
TISSUES, VIT D3 IS MORE CORRECTLY CONSIDERED A
HORMONE.
• THE TERM VITAMIN D APPLIES TO TWO RELATED
COMPOUNDS, CHOLECALCIFEROL AND
ERGOCALCIFEROL .
• CHOLECALCIFEROL, OR VITAMIN D3, IS GENERATED NON-
ENZYMATICALLY IN THE SKIN WHEN 7-
DEHYDROCHOLESTEROL ABSORBS A PHOTON OF SHORT
ULTRAVIOLET LIGHT (UV-B).
• ERGOCALCIFEROL, OR VITAMIN D2, IS PRODUCED WHEN
ERGOSTEROL IN PLANTS ABSORBS SUCH A PHOTON.
• VITAMINS D2 AND D3 ARE EACH ADDED TO DAIRY
PRODUCTS AND SOME OTHER FOODS; EACH IS AVAILABLE
AS A DIETARY SUPPLEMENT; AND AS A PRESCRIPTION DRUG
(IN MUCH HIGHER DOSES)
• WHETHER FROM AN ENDOGENOUS (SKIN) OR AN EXOGENOUS (DIETARY)
SOURCE, VITAMIN D TRAVELS TO THE LIVER, WHERE IT IS EITHER STORED
OR CONVERTED TO CALCIFEDIOL (25-HYDROXY VITAMIN D) BY THE FIRST
OF TWO ENZYMATIC HYDROXYLATION STEPS.
• THE SECOND ENZYMATIC HYDROXYLATION CONVERTS CALCIFEDIOL TO
THE FINAL, ACTIVE FORM OF VITAMIN D CALLED CALCITRIOL [1 ,25-
DIHYDROXY VITAMIN D].
• THIS SECOND HYDROXYLATION TAKES PLACE IN MANY TISSUES,
PARTICULARLY IN THE PROXIMAL TUBULE OF THE KIDNEY (WHERE IT IS
PTH-DEPENDENT), BUT DOES NOT TAKE PLACE IN THE INTESTINES
BECAUSE THEY LACK THE ENZYME REQUIRED FOR THE SECOND
HYDROXYLATION.
• CALCITRIOL HAS IMPORTANT EFFECTS ON OTHER TARGET ORGANS,
INCLUDING THE PARATHYROID GLAND, BONE, KIDNEYS, AND THE IMMUNE
SYSTEM.
• CALCITRIOL BINDS TO NUCLEAR RECEPTORS IN PARATHYROID CELLS, AND
THEREBY INHIBITS PTH SYNTHESIS AND RELEASE.
• IN BONE, CALCITRIOL INCREASES OSTEOCLAST NUMBER AND ACTIVITY,
RESULTING IN INCREASED BONE RESORPTION.
• HIGH BLOOD LEVELS OF CALCITRIOL, AND LOWER LEVELS OF CERTAIN
CALCITRIOL ANALOGUES, INCREASE BONE FORMATION.
• IN THE DISTAL TUBULE OF THE KIDNEY, CALCITRIOL INCREASES THE
REABSORPTION OF BOTH CALCIUM AND PHOSPHATE.
THANK YOU FOR YOUR ATTENTION