Primary hyperparathyroidism - PowerPoint PPT Presentation

1 / 51
About This Presentation

Primary hyperparathyroidism


Primary hyperparathyroidism is the third most common endocrine disorder. ... Adequate calcium intake may actually attenuate the effects of PTH on bone by ... – PowerPoint PPT presentation

Number of Views:2462
Avg rating:3.0/5.0
Slides: 52
Provided by: www2C1


Transcript and Presenter's Notes

Title: Primary hyperparathyroidism

Primary hyperparathyroidism
  • ?????
  • 2004/4/7

(No Transcript)
(No Transcript)
Treatment of primary hyperparathyroidism
  • Primary hyperparathyroidism is the third most
    common endocrine disorder.
  • behind diabetes and thyroid disorders,
  • the second most common cause of hypercalcemia.
  • Current prevalence 1200 to 11000, depending on
    the type of population surveyed
  • More common in postmenopausal women (with a ratio
    of 231)

Varieties of primary hyperparathyroidism
  • Sporadic benign adenoma 80-85
  • Primary parathyroid hyperplasia 15-20
  • Familial syndromes
  • MEN 1
  • MEN 2a
  • isolated familial
  • Jaw-tumor-PHPT syndrome
  • Parathyroid cancer lt0.1

  • Genetic mutations
  • Loss of vitamin D and calcium-sensing receptors
  • External radiation to the head and neck
  • Long-term thiazide and lithium therapy
  • Chronic vitamin D depletion

Clinical manifestations
  • Severe life-threatening hypercalcemia
  • Moderate hypercalcemia with classic bone lesions
    of osteitis fibrosa cystica
  • Mild hypercalcemia with recurrent
  • Euphemism the disease of stones, bones, groans,
    and psychic overtones.

The sweep effect Changing patterns of
presentation of primary hyperparathyroidism
Relation between parathyroid adenoma weight and
age at the time of parathyroidectomy
Diagnosis of primary hyperparathyroidism
  • Sustained hypercalcemia
  • intermittent hypercalcemia occurs over a period
    of 2 to 4 years
  • Elevated or nonsuppressed serum parathyroid
    hormone (PTH)
  • intact PTH assays measured both biologically
    active 1-84 and its N-terminally truncated 7-84
    biologically inactive fragment

Minimal laboratory evaluation in patients with
primary hyperparathyroidism
Management of contemporary primary
hyperparathyroidism the decision-making process
  • Balance the risks and benefits of
    parathyroidectomy versus medical management
  • Parathyroidectomy is the treatment of choice
  • symptomatic hypercalcemia,
  • overt bone disease or decreased bone density
  • metabolical active kidney stones
  • asymptomatic status
  • continued accelerated bone loss, increased risk
    of fractures , nephrolithiasis or renal failure
    or both , increased CV mortality

NIDDK workshop guidelines for parathyroidectomy
in asymptomatic primary hyperparathyroidism
  • Age lt 50
  • Serum calcium gt1.0 mg/dl above the reference
  • Bone density T-score gt -2.5 SD at any site
  • Creatinine clearance reduced by 30
  • Metabolically active kidney stone disease

J Bone Miner Res 2002
Management of contemporary primary
hyperparathyroidism the decision-making process
  • Medical therapy
  • Raloxifene and bisphosphonates increase bone
  • the effect on serum calcium level is not
  • Calcimimetic agents,
  • act through parathyroid cell calcium-sensing
  • inhibit PTH secretion and lower serum calcium

Oral Phosphate
  • Low the serum calcium by up to 1 mg/dl.
  • Limited G-I tolerance, possible further increase
    in parathyroid hormone levels, and the
    possibility of soft tissue calcifications, after
    long term use.
  • This agent is no longer advisable as a chronic
    treatment for primary hyperparathyroidism.

  • Reduce serum and urinary calcium levels but do
    not affect parathyroid hormone secretion
  • Risedroante lowered the serum and urinary calcium
    as well as the hydroxyproline excretion
    significantly while the parathyroid hormone
    concentration rose.

  • Reduce 0.5 to 1.0 mg/dl reduction in total serum
    calcium levels in postmenopausal women with
    primary hyperparathyroidism
  • although parathyroid hormone levels do not change
  • Raloxifene has been associated with modest
    reductions in serum calcium concentration.

  • A family of molecules that act on the parathyroid
    cell calcium sensing receptor
  • Interact at an allosteric site on the calcium
  • Mimic the effect of extracellular calcium and act
    as agonists
  • Lead to an increase in intracellular calcium and
    inhibit parathyroid cell function

  • Phenylalkylamine (R)-N-(3-methoxy-alpha-phenylethy
    l)-3-(2-chlorophenyl)-1- propylamine R-568
  • increase cytoplasmic calcium and reduce
    parathyroid hormone secretion in vitro
  • AMG 073
  • Such an agent might be effective in inducing
    sustained reductions in parathyroid hormone and
    the serum calcium without the need for

Surgical management
  • minimally invasive parathyroidectomy
  • All glands must be explored on both sides of the
    neck, along the entire length of the carotid
    sheath and para-esophageal grooves, and the
    superior mediastinum.
  • 5 to 15 of patients have more than or fewer
    than four glands, up to 35 may have
    multiglandular disease, especially in mild

Surgical management
  • A histologic distinction between adenoma and
    hyperplasia is not always possible.
  • Minimally invasive parathyroidectomy (MIP) is
    gaining popularity and accounts for approximately
    50 of the parathyroidectomies in the United
    States since its introduction in 1996.
  • Preoperative localization is not required for
    standard bilateral neck exploration, accurate
    localization of parathyroid adenoma is a
    prerequisite for successful MIP.

Surgical management
  • Combined with intraoperative rapid PTH assay,
    gamma probe, or videoscope MIP offers curative
  • The success of MIP depends heavily on
    preoperative localization of an adenoma, and
    therefore the cure rate is still less than 80,
    the sensitivity of most imaging procedures.

Surgical management
  • lt 2 for temporary or permanent recurrent
    laryngeal nerve palsy
  • lt than 2 for postoperative hypoparathyroidism,
  • 2 to 3 for reoperation because of either
    persistent or recurrent disease

conservative management
  • Adequate hydration to avoid hypercalcemic crises,
    particularly during the summer months and
    intercurrent illnesses.
  • Adequate calcium intake may actually attenuate
    the effects of PTH on bone by partially
    suppressing PTH secretion.

Secondary Hyperparathyroidism
  • A physiologic response to renal failure with the
    accompanying 1)decrease in gut absorption of Ca
    (secondary to uremia) 2) decrease in 1-25 vit D
    production, 3) elevated serum phos. secondary to
    decreased excretion.
  • The elevation in phosphate causes increased
    tissue deposition.

Secondary Hyperparathyroidism
  • The parathyroids attempt to make up for the
    decreased Ca levels and have compensatory
  • Treatment consists of management of each of the
    above three measures.
  • Calcium carbonate, bisphosphonates, avoidance of

Secondary Hyperparathyroidism
  • Only 5 of patients will develop either 1) an
    overshoot phenomenon or 2) severe symptoms
    (renal osteodystrophy, spontaneous fractures,
    intractable pruritis, headaches, malaise, soft
    tissue calcificications and psychoneurologic
    disorders) and require surgical excision of
    hyperplastic gland.
  • Most others do not benefit from surgery.

Tertiary Hyperparathyroidism
  • Tertiary hyperplasia occurs when secondary
    hyperparathyroidism goes away.
  • Basically the hyperplasia becomes monoclonal and
    adenomas will form which are resistant to normal
    feedback and require excision in patients able to
    tolerate this.

Radioguided Tumorectomy in the Management of
Parathyroid Adenomas
  • Sidiropoulos, Nikoletta MSII Vento, John MD
    Malchoff, Carl MD Whalen, Giles MD
  • Volume 138(7)   July 2003  p 716720

  • Bilateral neck exploration emerged as the gold
    standard treatment of primary hyperparathyroidism
    during a time when reliable preoperative
    localization did not exist.
  • By 1990, localize the abnormal parathyroid glands
    preoperatively were compiled and reviewed by a
    National Institutes of Health (NIH) consensus

  • The reported false-positive rates of 15 and
    true-positive rates of 60 compared with the
    general success rate of 95 demonstrated by
    experienced parathyroid surgeons who performed
    bilateral neck exploration.
  • More recent reports of high sensitivity and high
    specificity of preoperative localization with
    sestamibi suggest that the test might have
    potential value in the operative management of
    patients with primary hyperparathyroidism.

  • Experience with sestamibi scanning as a reliable
    preoperative localization tool for single
    parathyroid adenomas, in addition to the widely
    accepted prevalence rate of 80 to 85 of single
    adenomas as the cause of hyperparathyroidism, led
    surgeons to incorporate minimally invasive
  • We have selectively undertaken a minimally
    invasive, probe-directed tumorectomy in patients
    with primary hyperparathyroidism and a solitary
    adenoma found by sestamibi scanning.

  • We review our results and test the hypothesis
    that a clearly localizing sestamibi scan
    identifies individuals in whom minimally invasive
    radioguided parathyroidectomy can be performed
  • Secondary hypotheses are that radioguided
    parathyroidectomy will reduce operating room
    time, can be performed without increased
    morbidity, and will shorten hospital stay.

  • Sixty-five patients underwent parathyroidectomy
    from January 1, 1998, to June 30, 2002.
  • Fifty-five of these underwent sestamibi scanning
    at this institution and form the basis of the
    present study.
  • Forty patients had a clearly positive sestamibi
    scan result, and 31 of these underwent minimally
    invasive radioguided parathyroidectomy.
  • The remaining 24 underwent standard bilateral
    neck exploration.

  • Two patients in each group underwent redo
  • There were 9 patients with a clearly positive
    sestamibi scan result in whom a minimally
    invasive parathyroidectomy was not performed
  • in 4 patients the surgeon did not have the
    appropriate expertise,
  • in 1 patient logistic obstacles precluded the
  • in 1 patient there was a known thyroid
  • in 1 patient there was a positive family history
    that suggested multiglandular disease,
  • in 2 patients the delay between preoperative
    sestamibi injection and the operation exceeded 3

  • In these last 2 patients, the minimally invasive
    procedure had been planned but was abandoned in
    favor of a standard approach, because after 3
    hours there was no longer increased radioactivity
    in the parathyroid adenoma.

  • The criteria used in selecting patients
  • a secure biochemical diagnosis of primary
  • an elevated plasma ionized calcium concentration,
    a nonsuppressed plasma parathyroid hormone
    concentration, and urinary calcium excretion of
    more than 100 mg/24 h (2.50 mmol/d) or kidney
  • a clearly localizing sestamibi scan from our
  • unequivocally identified a solitary focus of
    technetium Tc 99m sestamibi uptake that was
    clearly distinguishable from the iodine uptake
    into the thyroid gland
  • absence of clinical suspicion of multiglandular

  • Cure of hyperparathyroidism was defined as
    normalization of ionized calcium on the follow-up
    visits to the surgeon and referring
  • Sestamibi scanning is performed via dual
    simultaneous isotope acquisition and subtraction

  • Patients ingested approximately 0.5 mCi (18.5
    MBq) of sodium iodide I 123 in the capsule form
    and then were injected intravenously with
    approximately 25 mCi (925 MBq) of technetium Tc
    99m sestamibi.
  • Four images of the iodine and sestamibi uptake
    were obtained simultaneously.
  • A pinhole collimator was used to obtain anterior,
    right anterior oblique, and left anterior oblique
  • A low-energy, high-resolution parallel hole
    collimator was used to obtain a chest view.

  • We aimed to begin the operation 1.5 to 2 hours
    after a preoperative injection with approximately
    25 mCi (925 MBq) of technetium Tc 99m sestamibi.
  • General anesthesia was used for most patients,
    although local anesthesia was used in 2 cases.
    Patients were positioned so that the neck was
    fully extended, and a collar incision was marked.
  • Counts were taken at all 4 poles before incision.
  • A small, midline, horizontal incision was made
    down the strap muscles, which were split open to
    enter the deep visceral compartment.

  • The nature of the specimen was confirmed by
    radioactive counts ex vivo and by frozen section.
  • After specimen removal, counts were taken to
    ensure that the radiation in all 4 quadrants and
    the operative bed decreased to levels below those
    recorded preoperatively.
  • Analysis of variance included, such as the size
    of the adenoma, the time since the preoperative
    sestamibi injection, the dose of sestamibi, and
    the difference in counts between the background
    and target area.

  • The average age of the patients was 62 years
    (range, 37-88 years).
  • The study group consisted of 45 women (82) and
    10 men (18).
  • Ninety-five percent of the patients had a secure
    biochemical diagnosis of primary
  • In the patients who did not have a secure
    biochemical diagnosis, we were unable in the
    retrospective review to find a documented 24-hour
    urinary calcium value.

(No Transcript)
  • Of the 31 patients undergoing radioguided
    parathyroidectomy, 30 successfully completed the
    procedure without conversion to a standard
    procedure and with cure of the hyperparathyroidism
  • One patient's operation was converted to an open
    procedure, since the parathyroid adenoma was too
    large to reach through a small incision.
  • One patient had 2 adenomas at the site of
    sestamibi uptake.

  • A clearly positive sestamibi scan result predicts
    that a minimally invasive parathyroidectomy can
    be completed in 97 of patients.
  • 6 of the patients in this group and 13 of the
    standard group experienced transient hoarseness.
  • No patients had recurrent laryngeal nerve injury.
  • There were no intraoperative complications in
    either group.

  • 3 other benefits of minimally invasive
    radioguided tumorectomy
  • did not experience any difficulties were
    discharged from the recovery room.
  • incisions were shorter, averaging 3.3 0.7 cm in
  • operative times were 41 shorter
  • Average minimally invasive, probe-directed
    operative time was converted to standard
    exploration was 75 29 minutes (range, 40-180
    minutes) vs 183 82 minutes (range, 40-390
    minutes) of standard parathyroidectomy.

  • The average time spent in the operating room for
    the minimally invasive procedures vs the standard
    procedures was 128 minutes and 224 minutes,
    respectively, which is a 57 reduction in the
    time spent in the operating room.

(No Transcript)
  • 73 of the scans were interpreted as suggesting a
    single adenoma.
  • 5 of the scans showed more than one area of
    uptake, and 22 of the scans showed no uptake.
  • In the patients with no uptake on the scan, a
    solitary adenoma was found 83 of the time.
  • Overall sensitivity and specificity were 81 and
    86, respectively.

  • In the 40 patients with a clearly positive
    sestamibi scan result, 39 (98) had a single
    parathyroid adenoma at the site predicted by the
  • One patient had a superior parathyroid adenoma
    descend behind and immediately adjacent to the
    lower pole parathyroid that was a second smaller
  • Both adenomas in this patient were at the site
    predicted by the sestamibi scan.

  • Preoperative injection of technetium Tc 99m
    sestamibi generally occurred approximately 2
    hours before the initial incision (114 32
  • At that time, preoperative counts at the 4 pole
    positions correlated with the scan findings, but
    the counts were not necessarily dramatically
    higher in the target area.
  • Surgery was delayed more than 180 minutes
    following the preoperative sestamibi injection in
    2 patients.
  • Consequently, radioguided localization of the
    adenoma, given the appropriate timing, exhibited
    increased radioactive counts did not occur.

  • Successful use of the probe requires aiming for
    the hottest spot, not the hot spot, and awareness
    that the count increase over background counts
    might be subtle compared with expectations.
  • The average bump in counts over the target area
    was only 20 over background, and this ranged
    from a low of 7 to a high of 70.
  • The size of the difference in counts between the
    target area and background did not correlate with
    the size of the adenoma, the amount of sestamibi
    injected, or the time between injection and

  • Reliable technology is available that can improve
    efficiency in localizing diseased glands,
    minimize dissection, and probably lessen patient
    discomfort associated with a collar incision.
  • A clearly localizing sestamibi scan is a highly
    reliable preoperative localization tool in
    patients with a secure biochemical diagnosis of
    primary hyperparathyroidism and no other reasons
    to suspect multiglandular disease.

  • learned 3 important lessons
  • timing is important
  • wash out the thyroid gland faster than the
    parathyroid adenoma
  • a 3-hour delay between preoperative injection and
    incision was too long
  • large adenomas in difficult locations remain
    difficult to remove through small incisions with
    prolong operative times
  • aim at the hottest spot and trust the probe
Write a Comment
User Comments (0)