Primary Hyperparathyroidism in the Geriatric
Population
Nahid Rianon, M.D., Dr.Ph.
The University of Texas Health Science Center at
Houston (UTHealth)
Learning Objectives



Attendees will have the understanding of the changing
epidemiology of primary hyperparathyroidism in older adults.
Attendees will be able to recognize clinical presentation and
indication for surgery in older patients with primary
hyperparathyroidism.
Attendees will be able to determine fracture risk in older patients
with primary hyperparathyroidism.
Primary Hyperparathyroidism (PHPT)
Primary hyperparathyroidism is the unregulated
overproduction of parathyroid hormone (PTH)
resulting in abnormal calcium homeostasis1.
(1) http://emedicine.medscape.com/article/127351-overview#aw2aab6b4
Image from UTHealth’s Multimedia Scriptoriu (www.uth.tmc.edu/scriptorium)
Why Geriatric Population?


Risk of PHPT increases with age – often dx in 6th or 7th decade of life.
Prevalence of PHPT




General: 1-4/1000
Elderly: 1/100
By 2030, ~1/5 people ≥65 years in the USA
Presenting symptoms


May often be confusing with other age related disease presentations.
Presenting symptoms may be different in older patients.
4
Adami et al., JBMR 2002; Siilin et al., World J Surg 2011; Shin et al., J Am Coll Surg, 2009
Epidemiology


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Very few studies with somewhat varied range
Few studies in the US and most others in Europe
Most studies done in Caucasian population



Ethnic/racial variation?
Women: Men = 3-5: 1
Rising numbers in older adults

Most studies in countries with high life expectancy
5
Changing Rates of Incidence in the USA: Before and After 1974
1965 - June 1974 = 7.8/100,000 person-years
Introduction of auto-analyzer in the 70’s &
start of routine serum calcium testing
July 1974June 1975
=
51/100,000
person-yrs
1975 =
112/100,000
person-yrs
1992 =
4/100,000
person-yrs
Wermers et al., 1997, Ann
6 Int Med
Incidence of PHPT in the USA
Age & sex-adjusted
definite & possible
cases, Rochester, MN
1965-1992
1965
1970
1975
1980
1985
1990
Melton III., JBMR, 2002
7
Change in Prevalence: Asymptomatic Patients
Before June 1974 = 18%
After July 1974 = 52%
Heath et al., 1980 N Eng
8 J Med
Mortality & Hospitalization for HPT

In 1999, 83 deaths from HPT (0.3/million- crude)


No change in survival after diagnosis


Observed = expected
Reason for hospitalization as a first dx


Total death = 2.4 million (from all causes)
4.7/100,000 in 1977 & 2.9/100,000 in 1986
Diagnose & treat to improve quality of life
9
Melton III., JBMR, 2002
A Case

RW is a 70 year old AA man with PMHx of HTN, HLD, COPD (on steroid
inhaler- former smoker) recurrent abdominal pain which was diagnosed as
diverticulitis, chronic constipation for several years that he treated on his
own with OTC meds and PRN use of lactulose in the past - was being seen
in August, 2011 in the outpatient clinic for constipation with no BM for past
5 days and abdominal discomfort - he ran out of lactulose, wanted refill. He
was not taking any multivitamin, or any calcium/vitamin D supplements. He
lives alone, independent with ADL and IADL.

Mild cognitive decline; hypercalcemia in May with 11.1 mg/dl (nl range 8.510.5), in August 10.4 and in Sept 10.4; 25 Hydroxy vitamin D 17 ng/ml (was
replaced); Mg and Phos were within normal range; PTH in Aug 149 and in
Sept 147 pg/ml (nl range 11.1 – 79.5); GFR >60.

Not taking medications known to alter serum calcium, e.g., HCTZ, Lithium,
bisphosphonates (no DXA done in the past).
Clinical Presentation of PHPT
Signs and Symptoms

Fragility fracture (osteoporosis)

Pain due to kidney stones

Excessive urination

Abdominal pain

Tiring easily/weakness/fatigue
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Depression or forgetfulness

Bone and joint pain
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Frequent complaints of illness with no apparent cause

Nausea, vomiting or loss of appetite
In the geriatric population: these symptoms may be confusing in the
setting of dementia, depression, infection
Biochemical Indices in PHPT:
Data from Prospective Observational Study
In mild PHPT patients – baseline data of a 15 yr follow up study
Biochemical tests
Patient
Normal range
Calcium (mg/dl)
10.7± 0.1
8.4 -10.2
Phosphorus (mg/dl)
2.9 ± 0.1
2.5 - 4.5
Alk Phos (IU/I)
114 ± 4
<100
PTH (pg/ml)
121 ± 7
10-65
25-OH Vit D (ng/ml)
21 ± 1
9-52
Urinary calcium (mg) 248 ± 12
100-300
DPD (nmol/mmol Cr) 17 ± 6
4-21
85% of patients with PHPT usually have single adenoma.
Bilezikian, 2011
Presentation in the Elderly

50% patients present with mental disturbance


Personality change, depression, psychosis
Sudden fast decline in health/becoming frail
Presenting symptoms by age group in Swedish study
Signs/Symptoms
< 60 years (N = 74)
≥ 60 years (N = 112)
Neuromuscular
16%
31%
Renal
41%
19%
Hypercalcemic crisis
4%
4%
Gastrointestinal
1%
1%
Skeletal abnormality 2%
1%
Tibblin S et al., Ann Surg 1983
Normocalcemic PHPT

Asymptomatic PHPT
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“Consistently normal calcium with persistently abnormal PTH in the
absence of recognizable underlying cause of elevated PTH”

Vitamin D >30 ng/ml

GFR >60 ml/min/1.73m2

Observational study of 37 post-menopausal women with follow up
for a mean of 3 years


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19% became hypercalcemic
40% symptomatic with renal stones and fractures
10% marked decline in BMD
Lowe et al., 2007; Bilezikian, 2011
Risk Factors & Complications
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
Complications:

Osteoporosis

Kidney stones

Cardiovascular disease: HTN, LVH, carotid plaque thickness
Risk factors:

Post-menopausal women

Prolonged, severe calcium or vitamin D deficiency

Rare, inherited disorder, such as multiple endocrine neoplasia-type I usually affects multiple glands

Radiation exposure to head and neck regions

Medications, e.g., lithium, a drug most often used to treat bipolar
disorder
Guidelines for Surgery in PHPT

All biochemically confirmed PHPT with signs/symptoms

Asymptomatic patient with one of the following criteria



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Age < 50
Serum calcium >1 mg/dl (0.25 mmol/L) above normal range
GFR <60 ml/min/1.73m2
T score <-2.5 SD at spine, hip (total or femoral neck) or radius (distal 1/3
site) or presence of fragility fracture
17
Bilezikian et al., 2009; NIH workshop report, 2008
Surgery in the Elderly?

Improved symptoms, e.g., ↑BMD, ↓renal stones, neurocognitive
function, support PTX

Higher quality imaging

Advances in effectiveness & safety of surgical techniques

Out-patient minimally invasive PTX in the elderly

Age criteria needs to be revisited.
Bilezikian et al., 2009; Bilezikian, 2011; Shin et al., 2009
Bone Loss in PHPT


PHPT associated with “high bone turnover & accelerated
bone remodeling”
PTH catabolic to cortical & anabolic to cancellous bone
Highest



to

lowest BMD loss
In PHPT patients - highest loss in distal radius BMD & least or
no change in lumbar spine BMD
Deficit in distal radius often persists even after PTX
Bilezikian et al., 2009; Bilezikian, 2011; Silverberg et al., 1989; Vestergaard & Mosekilde 2003; Siilin et al., 2011
Differences in Hip BMD: Mr. Os Sweden Study
N in PHPT = 22 & Control = 2213; Age range for 2235 men 69-81 years;
Mean±SD age in PHPT = 74.8±3.5 & Control = 74.9±3.1 years
1600
1400
BMD mg/cm2
1200
1000
p = NS
800
600
400
200
0
PHPT
control
L total hip
PHPT
Control
L femoral neck
PHPT
Control
Lumbar Spine
Siilin et al., 2011
Fracture Risk in PHPT


Monitoring BMD - traditional way of determining
fracture risk in PHPT.
Significant ↓in BMD often leads to fracture before
diagnosing PHPT or parathyroidectomy.

Older patients are at risk of bone loss due to age.

Discussion about FRAX (future research)
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
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PHPT is not a listed 2ndary risk of osteoporosis
NIH recognizes PHPT as 2ndary risk of osteoporosis.
Bone marker monitoring (ongoing research)
Bilezikian et al., 2009; Sankaran S et al., 2010
Summary

Changing epidemiology of PHPT


Clinical presentation in older patients



May be confusing with other age related complications in older
patients.
Presentations may be different in older patients.
Indication for surgery


Routine screening for S-calcium, vitamin D & osteoporosis
Age criteria needs to be revisited.
Fracture risk in older patients

Future research with FRAX and bone markers
References

Primary hyperparathyroidism diagram. Retrieved from: http://emedicine.medscape.com/article/127351-overview#aw2aab6b4

Adami S, Marcocci C, Gatti D. Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res 2002;17 Suppl 2:N18-23.

Siilin H, Lundgren E, Mallmin H, Mellström D, Ohlsson C, Karlsson M, Orwoll E, Ljunggren O. Prevalence of primary hyperparathyroidism and
impact on bone mineral density in elderly men: MrOs Sweden. World J Surg 2011;35:1266-72.

Shin SH, Holmes H, Bao R, et al. Outpatient minimally invasive parathyroidectomy is safe in elderly patients. J Am Coll Surg 2009;208:10711076.

Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O'Fallon WM, Melton III LJ. The Rise and Fall of Primary Hyperparathyroidism: A
Population-Based Study in Rochester, Minnesota, 1965-1992. Ann Int Med 1997;126:433-440.

Melton III LJ. The epidemiology of primary hyperparathyroidism in North America. Journal of bone and mineral research. JBMR 2002;17
Supp 2:N12-N17

Heath III H, Hodgson SF, Kennedy MA. Primary Hyperparathyroidism — Incidence, Morbidity, and Potential Economic Impact in a
Community. N Engl J Med 1980;302:189-193

Bilezikian JP, Khan A, Potts JT, et al. Hypoparathyroidism in the adult: Epidemiology, diagnosis, pathophysiology, target-organ involvement,
treatment, and challenges for future research. J Bone Miner Res 2011;26:2317–2337.

Tibblin S, Pålsson N, Rydberg J. Hyperparathyroidism in the elderly. Ann Surg 1983;197:135–138.

Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, et al. Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New
Clinical Phenotype. J Clin Endocrinol Metab 2007;92:3001–3005

Bilezikian JP, Khan A, Potts JT. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from
the Third International Workshop. J Clin Endocrinol Metab 2009;94:335–339

Silverberg SJ, Shane E, de la Cruz L, Dempster DW, et al. Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 1989;4:283–291.

Vestergaard P, Mosekilde L. Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism. BMJ
2003;327:530-535

Sankaran S, Gamble G, Bolland M, et al. Skeletal Effects of Interventions in Mild Primary Hyperparathyroidism: A Meta-Analysis. J Clin
Endocrinol Metab 2009;95: 1653-1662
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Photographs used for the cover slide are allowed by the MorgueFile free photo agreement and the Royalty Free usage agreement at
Stock.xchng. They appear on the cover slide in this order:
Wallyir at morguefile.com/archive/display/221205
Mokra at www.sxc.hu/photo/572286
Clarita at morguefile.com/archive/display/33743
23
The Training Excellence in Aging Studies (TEXAS)
program promotes geriatric training from medical
school through the practicing physician level. This
project is funded by the Donald W. Reynolds
Foundation to the division of Geriatrics and Palliative Medicine
within the department of Internal Medicine at The University of
Texas Health Science Center at Houston (UTHealth).
TEXAS would also like to recognize the following for contributions:
Houston Geriatric Education Center
Harris County Hospital District
Memorial Hermann Foundation
The TEXAS Advisory Board
Othello "Bud" and Newlyn Hare
UTHealth Medical School Office of the Dean
UTHealth Medical School Office of Educational Programs
UTHealth School of Nursing
UTHealth Consortium on Aging