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Parathyroid Disorders
Table 1: Comparison of Guideline Indications for Surgery in Asymptomatic Primary Hyperparathyroidism Patients
a,7
Measurement 1990 2002 2008
Serum calcium (>upper limit of normal) 1–1.6mg/dl (0.25–0.4mmol/l) 1.0mg/dl (0.25mmol/l) 1.0mg/dl (0.25mmol/l)
24-hour urine for calcium >400mg/day (>10mmol/day) >400mg/day (>10mmol/day) Not indicated
b
Creatinine clearance (calculated) Reduced by 30% Reduced by 30% Reduced to <60ml/min
BMD Z-score <-2.0 in forearm T-score <-2.5 at any site
c
T-score <-2.5 at any site
c
and/or
previous fracture fragility
d
Age (years) <50 <50 <50
a. Surgery is also indicated in patients for whom medical surveillance is neither desired nor possible.
b. Some physicians still regard 24-hour urinary calcium excretion >400mg as an indication for surgery.
c. Lumbar spine, total hip, femoral neck or 33% radius (1/3 site). This recommendation is made recognising that other skeletal features may contribute to fracture risk in primary HPT and the
validity of this cut-point for any site vis-à-vis fracture risk prediction has not been established in primary HPT.
d. Consistent with the position established by the International Society for Clinical Densitometry, the use of Z-scores instead of T-scores is recommended in evaluating BMD in
pre-menopausal women and men under 50 years of age.
BMD = bone mineral density; HPT = hyperparathyrodism.
Source: Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop, J Clin Endocrinol Metab, 2009;94:335–9.
© 2009, The Endocrine Society.
Figure 1: Changing Presentation of
This approach may also be beneficial for some patients with
Primary Hyperparathyroidism
asymptomatic primary HPT, particularly as data suggest positive
effects on BMD and neurocognitive symptoms following surgery.
9
The
‘Bones, stones, abdominal ‘Asymptomatic’
moans and psychic groans’
guidelines from the Third International Workshop include modified
surgical criteria for asymptomatic individuals, with changes from the
2002 guideline including exclusion of 24-hour urine calcium as an
indication for surgery (as 24-hour urine calcium is a poor predictor of
kidney stones in these patients, is highly variable and is dependent on
Prior to early 1970s: Mid 1970s to present:
kidney function, vitamin D status, race and sex),
4,7
amending the
before routine use of serum calcium test; diagnosis by biochemical profile
creatinine clearance to <60ml/min and adding previous fracture
diagnosis by symptoms and subclinical symptoms
fragility to the BMD indication. Age-based criteria and serum calcium
levels remained unchanged (see Table 1).
7
Those asymptomatic
Table 2: Management Options for Patients with
Asymptomatic Primary Hyperparathyroidism
7 patients who do not meet the criteria for surgery should be monitored
in accordance with the guidelines, or in some cases considered for
Surgery or No Surgery Recommendations 1990/2002/2008
medical management.
7,10
If no surgery Monitoring strategy
Medical options Bisphosphonates
Current Treatment Options
HRT and SERMs The primary aim of management in primary HPT is to normalise
Calcimimetics serum calcium levels and reduce excessive PTH levels, leading to
HRT = hormone replacement therapy; SERMs = selective oestrogen receptor modulators. improvements in any associated symptoms. It is treated primarily by
parathyroidectomy,
9
which is usually curative. However, there are few
Figure 2: Sustained Reductions in Serum Calcium with alternative treatment options for patients who are ineligible for, or
Cinacalcet Compared with Placebo
16
unwilling to undergo, surgery and those in whom parathyroidectomy
has failed. Current options include bisphosphonates, selective
2.8
Placebo (n=24)
oestrogen receptor modulators (SERMs) and hormone replacement
Cinacalcet (n=21)
2.7
therapy (HRT; off-label use), which inhibit bone resorption and
2.6
increase BMD without altering calcium, and the recently approved
calcimimetic cinacalcet, which reduces serum calcium levels without
2.5
major changes in BMD (see Table 2).
7,10–12
2.4
2.3
Calcimimetics – A New Approach for
Primary Hyperparathyroidism
2.2
Serum calcium (mmol/l)
The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor
2.1
Double-blind
Open-label
found on various tissues in the human body, including the parathyroidcinacalcet versus placebo
2.0
glands.
13
The CaSR plays a key role in regulating extracellular calciumB 4 816 24 36 52 64 76 90 104 118 132 146 160 174 188 202 216 230 244 258 272 286
Study week levels by controlling PTH secretion.
14
Calcimimetics, such as
B = baseline of initial double-blind study.
cinacalcet, are allosteric regulators of the CaSR, acting to sensitise
Normal range (2.1–2.575mmol/l) shaded. n represents the number of subjects at baseline; this receptor to extracellular calcium,
14
therefore representing a
30 subjects completed ≥5 years.
Reproduced from J Bone Miner Res, 2006;21:S38, with permission of the American Society
logical new approach for the management of primary HPT.
for Bone and Mineral Research.
Cinacalcet has been found to be effective in reducing or normalising
Management of Primary Hyperparathyroidism serum calcium levels in several groups of primary HPT patients,
It is generally accepted that most patients with biochemically confirmed including those with mild to moderate disease, intractable disease
symptomatic primary HPT should undergo parathyroidectomy.
9
and parathyroid carcinoma.
15–18
In a multicentre, randomised, double-
68 EUROPEAN ENDOCRINOLOGY
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