Non Surgical Managmenent of
Hyperparathyroidism
Evidence Based Medicine
David Roodhuyzen PA-S
Prevalence of Hyperparathyroidism
• Effects 28 per 100,000 people
• 4:1 Prevalence woman to men
• Seen more often in older patients especially
post menopausal women
Parathyroid
• Closely regulates serum calcium.
• If serum calcium is low parathyroid will
release PTH.
• PTH will cause calcium to be taken out of the
bone and increase serum calcium.
• If serum calcium is high parathyroid will inhibit
PTH release.
Hyperparathyroid
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Hyperparathyroid is the uncontrolled release of PTH.
80% of the time the cause is solitary adenoma
15% is caused by 4 gland hyperplasia
5% is caused by Cancer
50% of the time hyperparathyroidism is diagnosed in
the asymptomatic patient with routine lab testing.
• The cause is PHPT is unknown
• It is hypothesized that there is a genetic predisposition
Signs and Symptoms
Neurologic
Musculoskeletal or Rheumatologic
•Osteopenia
•Osteoporosis
•Gout
•Pseudogout
•Bone or joint pain
•Cystic bone lesions
•Chondrocalcinosis
Cardiovascular
•Inability to concentrate
•Confusion
•Depression
•Anxiety
•Fatigue
• Hypertension
• Left ventricular hypertrophy
• Prolonged QT interval
• Bradycardia
• Valvular calcification
• Arrhythmia
Signs and Symptoms of
Primary
Hyperparathyroidism
Renal
• Nephrolithiasis
• Renal
insufficiency
• Nephrocalcinosis
• Polydipsia
• Polyuria
Gastrointestinal
• Anorexia
• Nausea
• Constipation
• Vomiting
• Abdominal pain
• Pancreatitis
• Peptic ulcer disease
PICO Question
• P - Patient or problem: Patients 60 years or older
with hyperparathyroidism
• I – Intervention: The surgical resection of the
hyperparathyroid.
• C - Comparison Using medical management including
diet, biphosphates, calcimimetics, estrogen receptor
agonists, and estrogen therapy.
• O - Outcome(s) Can the serum calcium be controlled
and a decrease in PTH secretion? Can bone density
improve? Will adverse reaction of medical treatment
outweigh the risk and side effects of surgery?
Surgical Parathryoidectomy
• Gold Standard of care
• The procedure is curative
What makes it so good?
Advances in procedure
• In 1989 Tc 99 m sestamibi exhibited uptake
and retention in abnormal parathyroid's
glands prior to suurgey. Prior to this
enhancement there was not a better
technique than conventional imaging.
• Now adequate scans find 75% to 85% of
adenomas in patients with PHPT
Surgery
• Now surgeons can use an intra-operative
gamma probe with a smaller incision to locate
the abnormal gland.
• The introduction of the rapid intra-operative
parathyroid assay has improved success rate.
• Half life of intact PTH is 3-5 minutes.
Surgery
• With successful removal of abnormal gland
PTH levels should fall greater then 50% within
5-10 minutes.
• So why the medical management?
Medical Management?
• 1. Patients who elect not to have the surgery.
• 2. Surgical resection is only indicated for
moderate to severe disease by the National
Institute’s Health summary statement.
• Moderate to severe disease is defined as
National Institutes of Health Guidelines for
Parathyroidectomy in Asymptomatic Patients With Primary
Hyperparathyroidism
*Serum calcium 1.0mg/dL above the upper limit
of normal
*24h urinary calcium >400 mg
*Creatinine clearance reduced by 30%
*Bone mineral density T score less than -2.5 SD
at any site
*Age <50 years
Non Surgical Management
• Diet
• Maintain consistent levels of dietary Calcium
and Vitamin D.
• To little dietary calcium = increase in PTH
secretion.
• Too much = hypercalcemia
• 800-1000g is indicated daily
Vitamin D
• The active agent in Vitamin D is 1,25(OH)D which
increases transport of Calcium from gut
• Vitamin D deficiency will increase PTH secretions
• Will also increase bone resportion as well
• Bone resorption is a process where the osteoclasts
break down bone. This releases minerals which allows
for the transfer of calcium from bone to the blood.
• Dosage differs for men and women
• Women older then 50 should take 400 IU/d and older
then 75 should take 600 IU/d.
Bisphoshonates
• Bisphoshonates are analogues of inorganic
pyrophosphate that inhibit osteoclast
mediated bone resorption.
• This causes significant osteoporosis.
• One of the side effects of HPT is the decrease
in cortical bone density with relative
preservation of trabecular bone density.
Osteoporosis
Alendronate
• Also called Fosamax. Is the most studied
bisphosphanate.
• A randomized, double blind clinical study of 228
postmenopausal women was conducted on
asymptomatic PHPT patients taking Alendronate.
• The study showed a 6.9% increase of bone mineral
density of the spine and a 3.7% increase in the hip.
• A second 2 year study including 32 women with PHPT
showed a 4% increase in the spine. There was no other
increased noted in other bones tested.
Risedronate
• In a study of 19 patients with PHPT Risedronate
showed to reduce serum calcium levels and bone
markers of bone turnover.
• They found in the study that after the patients
were given a oral calcium load the serum levels
increased again.
• The results from these studies show significant
increase in bone density. These should be
considered first line agents for the medical
management of PHPT.
Hyperparathyroid Problem
• Patients with hyperparathyroidism do not
react as well to increases in serum calcium as
well as healthy individuals.
• This causes fluctuations in the secretions of
PTH.
Calcimimetics
• Calcimimetics work on the parathyroid chief
cells by increasing there sensitivity of the
calcium-sensing receptors
• The most studies calcimetic is Cinacalcet.
Cinacalcet
• Cinacalcet was studied in a randomized, double-blind,
dose-finding study in 22 patients with PHPT. It was also
studied in 76 patient with PHPT with a multicentre,
randomized, double blind, placebo-controlled study for one
year.
• In both studies the patients remained within normal range
throughout the entire duration of the study.
• PTH hormone levels decreased 50% 2-4 hours after dosing.
• Currently approved for secondary hyperparathyroidism due
to kidney failure or dialysis.
• No effect on bone mineral density, however, studies are
currently being done.
• Should be considered as initial treatment for PHPT.
Raloxifene
• Also called Evista
• It is a selective estrogen receptor modulator.
• Has estrogenic action on the bone by being a
partial agonist on alpha and beta receptors in the
bone and lipid metabolism.
• At same time is has anti-estrogenic activities on
the breast and uterus by partial antagonists on
alpha and beta receptors.
• 18 post menapausal patients with asymptomatic
PHPT were randomized and were given
Raloxifene or placebo.
Raloxifene
• THE EFFECTS
• Lower serum calcium
• Decrease specific makers on bone turnover
and urinary calcium below baseline after 12
months
• Decrease in PTH after 6 months returned to
baseline after 12
• More data needs to be collected on Raloxifene
and its effect of decreasing PTH.
Warning with Raloxifene
• Women treated with Raloxifene have been
showed to have an increased risk of DVT, PE,
and stroke.
• Risk/rewards of starting therapy should be
evaluated on an individual basis.
Estrogen Therapy
• Improved bone mineral density
• Decline in bone turnover
• Decrease levels of serum calcium has also
been observed.
• There was no effect on the PTH levels
• Risk/reward needs to be addressed due to
same risks as Raloxifene.
Clinical Application
• For non-surgical patients there are no current
guidelines for the medical management.
phonates
Bone Mineral Density Decreased Cerum Calcium Lower Secrehun of PTH Bone Resorphun & Bone T
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metics
e Estrogen Receptor
n Therapy
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X
Work Cited
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DeLellis, R.A., Mazzaglia, P., & Mangray, S., (2008). Primary hyperparathyroidsim. Archives of Pathology & Laboratory Medicine, 137,
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Farford, B., Presutti, R.J., & Moraghan, T.J., (2007). Nonsurgical management of primary hyperparathyroidism . Mayo Clinic
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Legrand, S.B., Leskuski, D., & Zama, R., (2008). Narrative review: furosemide for hypercalcemia: an unproven yet common practice .
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Reasner, Charles, A, Stone, Michael, D, Hosking, David, J, Ballah, Ahmed, & Mundy, Gregory, R (1993). Acute Changes in Calcium
Homeostasis during Treatment of Primary Hyperparaythroidism with Risedronate. Journal of Clinical Endocrinology and Metabolism,
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Rubin, Mishaela, R, Lee, Kristen, H, McMahon, Donald, J, & Silverberg, Shonni, J (2003). Raloxifene Lowers Serum Calcium and Markers
of Bone Turnover in Postmenopausal Women with Primary Hyperparathryoidism. The Journal of Clinical Endrocrinology & Metabolism,
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