Asymptomatic Hyperparathyroidism:

Operative Cure vs. Observation

Jim Wood25 February 2008

Primary Hyperparathryroidism

• Innapropriate or excessive secretion of PTH by one or more parathyroid glands, leading to hypercalcemia.

• Etiology– 85% from single adenoma– 15% from multiple gland hyperplasia– <1% from CA

Current Surgical Therapy. John Cameron, ed. 9th Ed. 2007

Primary Hyperparathyroidism

Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed.

Parisien M, Silverberg SJ, Shane E, et al. The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure. J Clin Endocrinol Metab 1990;70:930-938.)

Historical Perspective1

• 1852 Sir Richard Owen discovers parathyroid glands in an Indian rhinoceros

• 1887 Ivar Sandström, a 25-year-old medical student, publishes, “On a New Gland in Man and Fellow Animals.”

• 1903 William J MacCallum (Johns Hopkins) suggests parathyroids have a role in calcium metabolism

• 1925 First parathyroidectomy (Felix Mandl, Vienna).

• 1928 First successful parathyroidectomy in the U.S. (Issac Y. Olch, Barnes Hospital)

1 Organ CH JACS 2000(3); 191:284-299

Historical Perspective1

• 1963 Berson and Yalow win nobel prize for the development of an immunoassay for the measurement of parathyroid hormone and other peptides.

• 1969 Introduction of the serum chemical autoanalyzer with routine calcium determinations

• 1970’s: Four to fivefold increase in incidence of primary hyperparathyroidism 2

1 Organ CH JACS 2000(3); 191:284-299

2 Heath H III, Hodgson SF, Kennedy MA. Primary hyperparathyroidism: incidence, morbidity, and potential economic impact in a community. N Engl J Med 1980;302:189.

NIH Guidelines for Operation• Overt clinical manifestations of disease

– Kidney stones or nephrocalcinosis – Fractures or classic radiographic findings of osteitis

fibrosa – Classic neuromuscular disease – Symptomatic or life-threatening hypercalcemia

• Serum calcium >1 mg/dL above the upper limit of normal

• Urinary calcium excretion >400 mg/day • Creatinine clearance <70% of predicted • Bone mineral density low (T score <2.5) at any site • Young age (<50 years) • Uncertain prospects for adequate medical monitoring Bilezikian JP, Potts JT Jr, Fuleihan Gel H, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism:

a perspective for the 21st century. J Clin Endocrinol Metab 2002;87(12):5353-5361.

‘Asymptomatic Hyperparathyroidism’

• The Hypercalcemic Incidentaloma– Most pts present asymptomatic disease (~80%) 1

– Many have nonspecific complaints: primarily neuropsychological and quality of life2

– Some have no complaints but family members notice nonspecific changes. 2

• 80% do not meet current NIH recommendations for PTX 4

1 Silverberg SJ, Bilezikian JP. Clinical presentation of primary hyperparthyroidism in the United States. In: Bilezikian JP, Marcus R, Levine MA, editors. The parathyroids. 2nd edition. New York: Academic Press; 2001. p. 349–60.

2 Bilezikian, John P (04/22/2004). "Clinical practice. Asymptomatic primary hyperparathyroidism.". The New England journal of medicine (0028-4793), 350 (17), p. 1746.

3 Mihai R, et al. Asymptomatic Hyperparathyroidism – need for multicentre studies. Clinical Endocrinology 2008 (68): 155-164

The Debate

• How to manage asymptomatic patients (i.e. those that meet the guidelines)

• How to manage ‘asignomatic’patients (i.e. those who do NOT meet the guidelines)

Practice Patterns• 75% of endocrinologist would not refer a patient who met

criteria by hypercalcemia1 (cf. Keith J)• Estimated incidence of 1.5% in pts 65 yrs or older , but

approximately 12,000 parathyroidectomies per year 2

• 80% of endocrine surgeons would operate on patients who do not meet guidelines 3

• Almost 75% of patients undergoing PTX are asymptomatic 4

1 Mahadevia, P.J., Sosa, J.A., Levine, M.A., Zeiger, M.A. & Powe, N.R. (2003) Clinical management of primary hyperparathyroidism and thresholds for surgical referral: a national study examining concordance between practice patterns and consensus panel recommendations. Endocrine Practice, 9, 494–503.

2 Radu Mihai, John A. H. Wass, Gregory P. Sadler (2008) Asymptomatic hyperparathyroidism - need for multicentre studies Clinical Endocrinology 68 (2) , 155–164

3 Kouvaraki MA et al. (2006) Indications for operative intervention in patients with asymptomatic hyperparathyroidism: practice patterns of endocrine surgeons.” Surgery, 139, 527-534.

4 Sosa, J.A., Powe, N.R., Levine, M.A., Udelsman, R. & Zeiger, M.A. (1998) Profile of a clinical practice: thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons. Journal of Clinical Endocrinology and Metabolism, 83, 2658–2665.

Medical Therapy• Bisphosphonates:

– No study has included more than 45 patients– None have shown decreased Ca or PTH at 2 years– Rossini, et al (2001) RCT with 26 pts (bisphosphonate v.

control):• Decreased calcium at 2-6 months• Return to baseline at one year• Increased PTH during first year

– Horiuchi, et al (2002) RCT of PTX v. Etidronate for one year:• 10% increase BMD with etidronate• 20% increase BMD with PTX

1 Rossini, M., Gatti, D., Isaia, G., Sartori, L., Braga, V. & Adami, S. (2001) Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. Journal of Bone and Mineral Research, 16, 113–119.

2 Horiuchi, T., Onouchi, T., Inoue, J., Shionoiri, A., Hosoi, T. & Orimo, H. (2002) A strategy for the management of elderly women with primary hyperparathyroidism: a comparison of etidronate therapy with parathyroidectomy. Gerontology, 48, 103–108.

Medical Therapy• Calcimimetics:

– Peacock, et al (2005) RCT of Cinacalcet (Sensipar) for one year• Rapid and sustained normalization of PTH and Ca • No clinically significant change in BMD

– No trials to evaluate long-term PTH suppression, evaluation of influence on QOL and cardiovascular risk

– Cost for one year of treatment (wholesale): $7000.00 2

– Common short-term side effects include: diarrhea , muscle pain, dizziness, HTN, weakness and fatigue, loss of appetite. i.e. Abdominal groans and psychiatric overtones. (Bones and stones yet to be determined.)

1 Peacock, M., Bilezikian, J.P., Klassen, P.S., Guo, M.D., Turner, S.A. & Shoback, D. (2005) Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism, 90, 135–141.

2 Zanocco, K., Angelos, P. & Sturgeon, C. (2006) Cost-effectiveness analysis of parathyroidectomy for asymptomatic primary hyperparathyroidism. Surgery, 140, 874–882.

Medical Therapy

• Estrogen:– Women with mild asymptomatic hyperparathyroidism on ERT

have greater mean bone mass values greater than controls 1,2

– Does not decrease parathyroid hormone levels; Presumably acts at level of the bone

– Must be weighed against risks of estrogen therapy and likely should not be used outside the setting of post-menopausal women

1 McDermott, M T (1994). "Effects of mild asymptomatic primary hyperparathyroidism on bone mass in women with and without estrogen replacement therapy.". Journal of bone and mineral research (0884-0431), 9 (4), p. 5091

2 Marcus, R. (2002) The role of estrogens and related compounds in the management of primary hyperparathyroidism. Journal of Bone and Mineral Research, 17 (Suppl. 2), N146–N149.

• “No convincing data support the long-term efficacy of medical therapy or simply observation in the management of PHPT”

AACE/AAES Task Force on Primary Hyperparathyroidism, American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism, Endocr Pract 11 (2005), pp. 49–54

“.

Surgery for Hyperparathyroidism

• “It seems hardly credible that the loss of bodies so tiny as the parathyroids should be followed by a result so disastrous.”

-- W. Halsted

Standard Parathyroidectomy

• Bilateral Neck Exploration– No pre-op localization– Intraoperative frozen section– 95-98% cure rate at initial exploration– 1-2% complication rate– General anaesthesia– 1-2 day hospital stay

Townsend: Sabiston Textbook of Surgery, 18th ed.

• MIP – Preoperative localization with intraoperative PTH

– Vast majority are discharged on the day of surgery.

– 96-100% cure rate.

– Theoretical lower complication rate

• Has lowered the threshold for surgical referral

Minimally Invasive Parathyroidectomy

Parathyroidectomy

• Complications– Recurrent laryngeal nerve injury

• Reported 1-10%

– Persistent Hyperparathyroidism• Lowest in high volume centers• Remedial parathyroidectomy 85-95% cure rate

– Hypocalcemia• Seldom requires long term replacement

Townsend: Sabiston Textbook of Surgery, 18th ed.

Benefits of Parathyroidectomy• Osteoporosis:

– Normalized bone remodeling at 6 months1

– Increased BMD at sites rich in cancellous bone2

– Up to 6% increase in lumbar spine, hip, and whole body BMD at 12 months and sustained for more than 6 yrs.3

1 Christiansen, P., Steiniche, T., Brixen, K., Hessov, I., Melsen, F., Heickendorff, L. & Mosekilde, L. (1999) Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy. Bone, 25, 237–244.

2 Fuliehan, G.E., Moore, F. Jr, LeBoff, M.S., Hurwitz, S., Gundberg, C.M., Angell, J. & Scott, J. (1999) Longitudinal changes in bone density in hyperparathyroidism. Journal of Clinical Densitometry, 2, 153–162.

3 Nomura, R., Sugimoto, T., Tsukamoto, T., Yamauchi, M., Sowa, H., Chen, Q., Yamaguchi, T., Kobayashi, A. & Chihara, K. (2004) Marked and sustained increase in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism; a six-year longitudinal study with or without parathyroidectomy in a Japanese population. Clinical Endocrinology, 60, 335–342.

Benefits of Parathyroidectomy– Risk of fracture:

• 9-14% of pts have fx at time of diagnosis 1

• Risk of further fracture decreased with PTX 1

• 10 yr fx free survival increased with PTX: 73% v. 59% 2

• Decreased fracture risk at 10 yrs: 8% hip, 3% extremity 2

– Hip fracture: 3• One-year mortality 20% • 40% of survivors can perform all routine activities of daily

living• 54% of survivors can walk without an aid.

1 Vestergaard, P. & Mosekilde, L. (2004) Parathyroid surgery is associated with a decreased risk of hip and upper arm fractures in primary hyperparathyroidism: a controlled cohort study. Journal of Internal Medicine, 255, 108–114.

2 VanderWalde, L.H., Liu, I.L., O’Connell, T.X. & Haigh, P.I. (2006) The effect of parathyroidectomy on bone fracture risk in patients with primary hyperparathyroidism. Archives of Surgery, 141, 885–891

3 Wolinsky FD, Fitzgerald JF, Stump TE. The effect of hip fracture on mortality, hospitalization and functional status: a prospective study. Am J Public Health 1997;87:398–403

Benefits of Parathyroidectomy

• Neuropsychological abnormalities:– Increased cognitive skills, concentration,

memory, and ability to perform tests accurately increased with PTX 1,2

– Improved psychopathological symptoms with PTX3

– Review of published data (2002): Improved attention, memory, and

reasoning. 21 Roman, S.A., Sosa, J.A., Mayes, L., Desmond, E., Boudourakis, L., Lin, R., Snyder, P.J., Holt, E. & Udelsman, R. (2005) Parathyroidectomy improves neurocognitive deficits in patients with primary hyperparathyroidism. Surgery, 138, 1121–1128.

2 Prager, G., Kalaschek, A., Kaczirek, K., Passler, C., Scheuba, C., Sonneck, G. & Niederle, B. (2002) Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism. Surgery, 132, 930–935.

3 Dotzenrath, C.M., Kaetsch, A.K., Pfingsten, H., Cupisti, K., Weyerbrock, N., Vossough, A., Verde, P.E. & Ohmann, C. (2006) Neuropsychiatric and cognitive changes after surgery for primary hyperparathyroidism. World Journal of Surgery, 30, 680–685.

Benefits of Parathyroidectomy• Quality of Life:

– Studies consistently show decreased QOL 1

– PTX significantly improves patient-reported QOL2,3

– Greatest improvement in first 3 months. 2,3

– Improvement regardless of calcium levels. 1

1 Sheldon, D.G., Lee, F.T., Neil, N.J. & Ryan, J.A. Jr (2002) Surgical treatment of hyperparathyroidism improves health-related quality of life. Archives of Surgery, 137, 1022–1026.

2 Burney, R.E., Jones, K.R., Peterson, M., Christy, B. & Thompson, N.W. (1998) Surgical correction of primary hyperparathyroidism improves quality of life. Surgery, 124, 987–991.

3 Quiros, R.M., Alef, M.J., Wilhelm, S.M., Djuricin, G., Loviscek, K. & Prinz, R.A. (2003) Health-related quality of life in hyperparathyroidism measurably improves after parathyroidectomy. Surgery, 134, 675

Benefits of Parathyroidectomy

• Quality of Life: – Eigelberger, et al. (2004) Prospective trial

compared pts who do and do not meet guidelines v. Controls

• Equivalent pre-operative somatic and neuropsychological symptoms and increased compared to controls (thyroidectomy)

• Improvement of symptoms was dramatic and equal in the two groups

Eigelberger, M.S., Cheah, W.K., Ituarte, P.H., Streja, L., Duh, Q.Y. & Clark, O.H. (2004) NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism: are they too limited? Annals of Surgery, 239, 528–535

Quality of Life

Changes in the frequency of symptoms after surgery in the combined hyperparathyroid group versus the thyroid group.

Quality of Life

Postoperative symptomatic improvement in the NIH HPT group versus the non-NIH HPT group.

Benefits of Parathyroidectomy• Lipid metabolism:

– Increased dyslipidemia and body mass index with PHPT1

• Cardiac Morbidity:– Improved LV hypertrophy2 and dysfunction4, decreased HTN and

PVC’s (during excercise) 3, and decreased cardiac death with PTX.2

• Glucose Tolerance:– Improved in 37% of patients with PHPT and DM after PTX5

• Overall Mortality: – 33,000 men <50yrs old followed 10 yrs.: Pts with serum Ca>2.6

had doubled mortality compared to pts with Ca<2.451 Hagstrom, E., et al (2002) Clinical Endocrinology, 56, 253–2602 Garcia de la Torre, N., et al (2003). Endocrine-Related Cancer, 10, 309–3223 Almqvist, E.G., et al. (2002) Surgery, 132, 1126–11324 Nilsson, I.L., et al. (2005). Surgery, 137, 6325 Richards, M.L. & Thompson, N.W. (1999) Surgery, 126, 1160–1166.6 From Radu Mihai, John A. H. Wass, Gregory P. Sadler (2008) Clinical Endocrinology 68 (2) , 155–164

Benefits of Parathyroidectomy

• Cost Effectiveness: 1

– Operation remained cost-effective until the average cost of parathyroidectomy increased from the estimated value of US$4778 to US$14 650.

– Pharmacological therapy was not cost-effective unless the annual cost of therapy decreased from an estimated US$7406 (for cinacalcet) to US$221.

1 Zanocco, K., Angelos, P. & Sturgeon, C. (2006) Cost-effectiveness analysis of parathyroidectomy for asymptomatic primary hyperparathyroidism. Surgery, 140, 874–882.

2 Sejean, K., Calmus, S., Durand-Zaleski, I., Bonnichon, P., Thomopoulos, P., Cormier, C., Legmann, P., Richard, B., Bertagna, X.Y. & Vidal-Trecan, G.M. (2005) Surgery versus medical follow-up in patients with asymptomatic primary hyperparathyroidism: a decision analysis. European Journal of Endocrinology, 153, 915–927.

Parathyroidectomy

• Elderly patients (>80 yrs) – Sx: fatigue, weight loss, nocturia, bone pain,

constipation, and major depression.

– Improvement in all categories noted after PTX

– 25% had 5 yr delay in referral.

Eigelberger, M.S., Cheah, W.K., Ituarte, P.H., Streja, L., Duh, Q.Y. & Clark, O.H. (2004) NIH criteria for parathyroidectomy in asymptomatic primary hyperparathyroidism: are they too limited? Annals of Surgery, 239, 528–535

High Risk PHPT Patients• 14 pts refused operation: continued bisphosphonates• 19 pts underwent miPTX under local anaesthesia • Bisphosphonates:

– Significantly increased incidence of episodes of hypercalcaemiccrisis, deteriorating renal function and weight-bearing bone fractures

• miPTX: – No operative complications, mortality or recurrent

hypercalcaemia (mean follow-up of 35.5 months) – Higher incidence of improved ASA and NYHA class– Better 3-year overall survival rate (83.1%vs. 60.8%, P = 0.032)– Lower medical costs. Fang (2007). "The management of high-risk patients with primary hyperparathyroidism - minimally invasive

parathyroidectomy vs. medical treatment.". Clinical endocrinology (Oxford)

Asymptomatic?• Prospective long-term study of 360 patients undergoing

PTX: 1– Only 6% truly asymptomatic as evaluated by pre- and post-

operative studies. – Many were unaware of symptoms (e.g. fatigue) prior to

surgery.

• Epidemiological cohort-study of 582 consecutive PTX patients: 2

– 116 patients (21%) considered asymptomatic before operation

– 4% of the entire cohort confirmed asymptomatic post-op– Postoperative improvement reported in over 80% of patients

considered ‘asymptomatic’ .

1 Walgenbach, S., Hommel, G. & Junginger, T. (2000) Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study. World Journal of Surgery, 24, 564–569.

2 Hasse, C., Sitter, H., Bachmann, S., Zielke, A., Koller, M., Nies, C., Lorenz, W. & Rothmund, M. (2000) How asymptomatic is asymptomatic primary hyperparathyroidism? Experimental and Clinical Endocrinology and Diabetes, 108, 265–274.

Benefits of Parathyroidectomy

• BMD• Risk of fracture• Neuropsychological

function• Quality of life• Overall mortality and

health

• Assymptomatic• Minimal biochemical

derangements• Advanced age• Higher operative risk

Conclusions and Recommendations:

“PHPT remains a relatively common disorder of calcium metabolism that is readily cured by a low-risk operation in 95 to 98% of patients when performed by a qualified surgeon. Operative management is the treatment of choice for all symptomatic patients and all asymptomatic patients younger than age 50 years or for patients who cannot participate in adequate medical follow-up. Operative management should also be considered for all other asymptomatic patients with suitable risk and a reasonable life expectancy.”

American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism.

More Problems• Adherence to monitoring guidelines ranged

widely– 6% obtained creatinine clearance – 78% of physicians ordered serum calcium

measurements every 6 months. 1

• Progression of disease on medical therapy:– 27% of asymptomatic pts who initially do not meet

criteria for operation develop at least one criteria for operation by 10 years 2

– Most common sequelae include ongoing bone loss, nephrolithiasis, and renal colic 31 Rao, D Sudhaker (2004). "Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic

primary hyperparathyroidism.". The journal of clinical endocrinology and metabolism (0021-972X), 89 (11), p. 5415.2 Farford, Bryan (03/2007). "Nonsurgical management of primary hyperparathyroidism.". Mayo Clinic proceedings (0025-6196), 82

(3), p. 351.3 AACE/AAES Task Force on Primary Hyperparathyroidism, American Association of Clinical Endocrinologists and the American

Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism, Endocr Pract 11 (2005), pp. 49–54

Practice Patterns• Survey of 146 Endocrinologists (2004) • Awareness of guidlelines: High-volume 75%; Low-volume 50%

• Surgical referral: – 39% of all patients were referred for surgical management– 25% of all physicians referring a 40-year-old patient with PHPT

when hypercalcemia was mild (< or = 1 mg/dL above normal), – 39% when hypercalcemia was moderate *– 31% when hypercalcemia was severe (>1.5 mg/dL above

normal)– 4% reported that hypercalcemia alone was not sufficient

justification to refer a patient for surgical intervention.

* Moderate hypercalcemia now an NIH criteriaRao, D Sudhaker (2004). "Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism.". The journal of clinical endocrinology and metabolism (0021-972X), 89 (11), p. 5415.

Practice Patterns• Survey of Endocrine Surgeons (Surgery 2006)

– 89% aware of NIH guidelines– 71% would operate on pts who did not meet criteria

• If elevated Ca, decreased BMD, or decreased crt clearance

– 85% would operate for nonspecific complaints• Especially with neurophysiologic or GI symptoms

– Most favored operation in pts with adenoma localization– Age and MEN status did not affect decision

Surgery. 2006 Apr;139(4):527-34.

Practice Patterns

Surgery. 2006 Apr;139(4):527-34.

Practice Patterns

Surgery. 2006 Apr;139(4):527-34.

Parathyroidectomy

• Benefits v. Observation: RCT’s – Silverberg, S J (10/21/1999). "A 10-year prospective study of primary

hyperparathyroidism with or without parathyroid surgery.". The New England Journal of Medicine 341 (17), p. 1249.

• 121 patients, 83% asymptomatic. 50% underwent PTX• PTX

– Normalization of serum calcium concentrations – Lumbar-spine BMD increased 8±2 % at 1 y (P=0.005), 12±3% at 10 yrs

(P=0.03). – Femoral neck 6±1 % at 1 year (P=0.002) and 14±4 % at 10 years

(P=0.002). – Radius did not change significantly.

• No PTX– No change in serum calcium, urinary calcium excretion, or bone mineral

density. – 14 of 52 (27 %) developed at least one new indication for

parathyroidectomy. – All 20 patients with symptoms had kidney stones. None of the 12 PTX pts

Parathyroidectomy

• Benefits v. Observation: RCT’s – Rao, D Sudhaker (2004) “Randomized Controlled Clinical Trial of

Surgery Versus No Surgery in Patients with Mild Asymptomatic Primary Hyperparathyroidism” The journal of clinical endocrinology and metabolism. 89 (11), p. 5415.

• PTX-– increase in BMD of the spine (1.2%/yr, P < 0.001),

femoral neck (0.4%/yr, P = 0.031), total hip (0.3%/yr, P = 0.07), and forearm (0.4%/yr, P < 0.001)

• Observation-– Decreased BMD at the femoral neck (–0.4%/yr, P =

0.117) and total hip (–0.6%/yr, P = 0.007) but gained at the spine (0.5%/yr; P = ns) and forearm (0.2%/yr, P = 0.047).

Parathyroidectomy

• Benefits v. Observation: RCT’s – Bollerslev, Jens (Feb 2007). "Medical observation, compared with

parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial.". The journal of clinical endocrinology and metabolism 92 (5), p. 1687.

• At baseline, pts had lower QoL and more psychological symptoms than controls

• Calcium and PTH normalized after surgery. • The areal bone mineral density increased in the group

randomized to operation.• Bone mineral density remained stable in the medical

observation group. • No change in kidney function (creatinine) or blood pressure

was observed longitudinally or between the groups.

Parathyroidectomy

• Benefits v. Observation: RCT’s – Ambrogini, Elena (May 2007). "Surgery or surveillance for mild

asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial.". The journal of clinical endocrinology and metabolism 92 (8), p. 3114.

• Change in BMD:– at lumbar spine (+4.16 ± 1.13 for PTx vs. –1.12 ± 0.71 for no

PTx; P = 0.0002).– Total hip (+2.61 ± 0.71 for PTx vs. –1.88 ± 0.60 for no PTx; P =

0.0001).– No difference in BMD at the one-third radius site.

• Improved QOL v. observation group in four areas:– Bodily pain (P = 0.001), general health (P = 0.008), vitality (P =

0.003), and mental health (P = 0.017)

Primary Hyperparathyroidism

• Parathyroid Adenoma– Increased number of cells Increased PTH

– Inappropriate response to serum calcium

Shaded purple= normal response

Kronenberg: Williams Textbook of Endocrinology, 11th ed

Primary Hyperparathyroidism• Epidemiology

– 1-5 patients per 1000 – 13 patients per 1000 over age 65– 4:1 Female

• Classical Symptoms– “Stones, Bones, etc.”

Current Surgical Therapy. John Cameron, ed. 9th Ed. 2007