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Secondary Hyperparathyroidism


Secondary Hyperparathyroidism. Chou Chien Wen M.D. Endocrine and ... Impaired mineralization of osteoid. Abnormalities in formation and maturation of collagen ... – PowerPoint PPT presentation

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Title: Secondary Hyperparathyroidism

Secondary Hyperparathyroidism
  • Chou Chien Wen M.D.
  • Endocrine and Metabolism Section
  • Chi-Mei Medical Center
  • 7 Nov 2003

Case Report
  • Name ??x?
  • Chart No 14117599
  • Sex female
  • Age6 Jan 1994 (49 y/o)
  • Cause of Renal failure Polycystic kidney
  • Duration of HD 5 yrs

Clinical Course
Medication History
  • Before 92-6-30
  • FA 1 qd
  • Vit BC 1 qd
  • Calcium Carbonate 1 tid
  • AH 2 tid
  • EPREX 2000 IU/0.5 cc IM stat
  • Lopid 1 tid for CH 237 TG 869
  • After then
  • D C Calcium Carbonate

Image Study
  • Parathyroid echo 92-10-16
  • Parathyroid hyperplasia, both lower pole
  • CT scan of neck 92-10-30
  • Bilateral parathyroid hyperplasia or adenoma,
    lower pole
  • RT 1 cm LT 0.6 cm

Stage of Chronic Kidney Disease
Major Features of Abnormalities in Mineral
Metabolism in Kidney Failure
  • Hypoclacemia
  • Secondary hyperparathyroidism
  • Hyperphosphatemia
  • Defective intestinal absorption of calcium
  • Altered vitamin D metabolism
  • Bone disease
  • Soft-tissue calcification including coronary
    arteries and cardiac valves calcification
  • Altered handling of phosphate, calcium and
    magnesium by the kidney
  • Pruritus
  • Proximal myopathy
  • Skin ulceration and soft-tissue necrosis

Three factors are central to its development
  • The first, reduced renal synthesis of
    1,25-dihydroxyvitamin D (calcitriol)
  • As the disease progresses, renal phosphate
    clearance and net calcium balance become
    inadequate to maintain serum phosphorus and
    ionized calcium levels within an optimal range.
  • The synthesis and release of PTH are stimulated
    by a low serum calcium level, reduced inhibitory
    activity of calcitriol, and an elevated serum
    phosphate level.
  • progressive increase in the mass of the
    parathyroid gland and, often, a benign,
    tumor-like growth.
  • In its extreme form, severe hyperparathyroidism
    becomes unresponsive to medical treatment, and
    necessitates parathyroidectomy

Biological Consequences of Vitamin D Deficiency
and its Metabolism
  • Shift in set-point of calcium for the parathyroid
  • Secondary hyperparathyroidism
  • Skeletal resistance to the calcemic action of PTH
  • Impaired mineralization of osteoid
  • Abnormalities in formation and maturation of
  • Retarded growth in uremic children
  • Defective intestinal absorption of calcium and
  • Abnormalities in the structural integrity of the
    intestinal mucosa
  • Proximal myopathy

Ca and Vitamin D Supplement
  • The early administration of calcium supplements
    or vitamin D attenuates the development and
    progression of hyperparathyroidism
  • If not closely monitored, though, vitamin D
    administration may lead to hypercalcemia because
    of the prolonged half-life of native vitamin D.
  • More active vitamin D derivatives and analogues
    with shorter half-lives primarily calcitriol
    and alfacalcidol have been used for the past
    two decades.
  • Their administration results in a prompt
    reduction in the plasma levels of intact PTH in
    patients undergoing hemodialysis who have severe
    forms of secondary hyperparathyroidism

Recommended Supplement for Vit D Deficiency
/Insufficiency in Patients with CKD Stages 3 and 4
Serum Levels of PTH, Ca and P required for
Initiation of Oral Vitamin D sterol Therapy, and
Recommended Initial Doses in Patients with Stages
3 and 4
Recommended Initial Dosing for Vitamin D sterols
by Serum levels of Intact PTH, Ca, P and Ca-P
Frequency of measurement of PTH and Ca/P by Stage
of CKD
Target Range of Intact Plasma PTH by Stage of CKD
Side Effects of Vitamin D Derivatives
  • including hypercalcemia and hyperphosphatemia
    and, as a result, a high level of the
    calciumphosphate product.
  • soft-tissue calcification, particularly vascular
    calcification, a key factor underlying the
    accentuated risk of CVD in patients with CKD
  • prolonged administration of high doses of
    calcitriol or alfacalcidol is associated with
    adynamic bone disease, as is the administration
    of high doses of calcium-containing phosphate
  • These adverse outcomes have prompted the
    development of novel, "nonhypercalcemic" vitamin
    D analogues (Figure 1).
  • Three of these analogues have recently been
    marketed 19-nor-1,25-dihydroxyvitamin D2
    (paricalcitol), 1 -hydroxyvitamin D2
    (doxercalciferol), and 22-oxacalcitriol.

Figure 1. Chemical Structures of Calcitriol and
the Newer Vitamin D Analogues.
Differential actions of vitamin D analogues
  • The affinity of 22-oxacalcitriol for the vitamin
    Dbinding protein is less than 1 percent that of
  • In contrast, both paricalcitol and
    doxercalciferol have binding affinities
    equivalent to that of calcitriol.
  • Vitamin Dbinding protein enhances the half-life
    of vitamin D derivatives in the circulation, an
    effect that probably decreases their tissue
  • Altered binding affinity for the vitamin D
    receptor has also been reported.
  • The affinity of 22-oxacalcitriol for the receptor
    is one eighth that of calcitriol, and the
    affinities of paricalcitol and doxercalciferol
    are similar.
  • Paricalcitol down-regulates the expression of
    vitamin D receptor in the intestine, whereas
    calcitriol up-regulates it.
  • Vitamin D analogues may act differently from
    calcitriol in inducing conformational changes in
    the vitamin D receptor and modulating its binding
    to vitamin Dresponsive elements to affect the
    transcription of numerous genes.

Calcimimetic agents and secondary
hyperparathyroidism rationale for use and
results from clinical trials.
  • Calcimimetic agents are small organic molecules
    that act as allosteric activators of the calcium
    sensing receptor (CaSR).
  • In parathyroid cells, they lower the threshold
    for receptor activation by extracellular calcium
    ions and diminish parathyroid hormone (PTH)
  • Calcimimetic compounds thus represent a novel way
    of controlling excess PTH secretion in clinical
    disorders such as secondary hyperparathyroidism
    (SHPT) due to chronic renal failure.
  • Clinical trials have documented that the
    calcimimetic agent cinacalcet hydrochloride
    effectively lowers plasma PTH levels without
    increasing serum calcium or phosphorus
    concentrations in adult hemodialysis patients
    with SHPT.
  • Serum phosphorus levels and values for the
    calcium-phosphorus ion product in serum often
    decline as plasma PTH levels fall during
  • Experimental evidence suggests that calcimimetic
    agents may also impede the development of
    parathyroid gland hyperplasia, an integral
    component of SHPT due to chronic renal failure.
  • Calcimimetic agents have considerable potential,
    therefore, as part of new therapeutic strategies
    for SHPT.

Goodman WG. Pediatr Nephrol. 2003 Oct 28
Survival of Patients Undergoing Hemodialysis with
Paricalcitol or Calcitriol Therapy
  • paricalcitol was associated with a lower
    mortality rate over the 36-month follow-up period
    (18.0 percent) than calcitriol (22.3 percent).
  • This difference of 4 to 5 percentage points in
    yearly mortality rates was most evident for the
    cardiovascular end points.
  • A difference in the final calciumphosphate
    product value does not appear to explain the
    outcomes of the study.

N Engl J Med 2003 349446-456, Jul 31, 2003.
Potential medical Uses of Calcium Receptor
  • Parathyroids
  • Inherited parathyroid disorders
  • Primary hyperparathyroidism
  • Secondary hyperparathyroidism
  • Parathyroid carcinomatosis
  • Surgical parathyroidectomy failure
  • Ectopic parathyroid gland localization
  • Parathyromatosis
  • Parathyroid surgery refusal
  • Surgical contraindication
  • Cardiovascular
  • Arterial hypertension
  • Calciphylzxis
  • Renal
  • Diuretic
  • Slow progressive chronic renal failure

(No Transcript)
Factors That May Predispose to Soft-Tissue
Calcification in Stages 4 and 5 CKD
  • Hyperphosphatemia
  • An increase in serum calcium-phosphorus product
  • Secondary hyperparathyroidism
  • Local tissue injury
  • A rise in local pH of tissue
  • Removal of calcification inhibitors by dialysis
  • Excessive calcium intake

Subtotal parathyroidectomy a possible treatment
for calciphylaxis.
  • Calciphylaxis is a rare disorder in patients with
    chronic renal failure that is characterized by
    ischemic necrotic skin lesions.
  • The prognosis is grave and mortality is high
  • The precise mechanism of calciphylaxis is still
    unknown, but in addition to chronic renal
    failure, elevated parathyroid hormone levels
    appear to play a role.
  • The role of parathyroidectomy in treating
    affected patients is questionable.
  • In this article, we describe the case of a
    patient with chronic renal failure who developed
    rapidly progressive subcutaneous calcifications
    and ulcerations in the lower extremities.
  • These lesions regressed following subtotal

Bahar G Ear Nose Throat J. 2003 May82(5)390-3.
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