Transcript Grand Rounds: Zebra or Duck

Grand Rounds:
Zebra or Duck
Kathryn Dao, MD
Arthritis Center
Presbyterian Hospital
June 29, 2005
Common Dx
Common S/Sx
Uncommon Dx
Common S/Sx
Common Dx
Uncommon S/Sx
Uncommon Dx
Uncommon S/Sx
Case: Unknown
CC: Joint pain, +ANA
HPI: MS is a 44 y.o. WF with hyperlipidemia who
developed ankle pain and swelling suddenly
after she finished a ballet recital. She went
to her PCP for evaluation and over the next
month she was given in series ibuprofen,
naproxen, and Vioxx. The symptoms
persisted; she returned to her PCP who drew
labs and found an abnormal ANA.
HPI (cont’d): She was given a Medrol dose pack and a
referral to rheumatology. The steroids gave her partial
relief. She stated the pain progressed to her hands,
knees, and ankles. Pain scale 4 out 10. AM stiffness
15min- 2 h. Activity and heat improve her symptoms.
She denied sick contacts, recent travel, weight loss,
fever, apthous ulcers, GI/GU complaints, and
photosensitivity.
Associated symptoms: ??Raynaud’s phenomenon,
memory difficulties, fatigue, headache, insomnia, “bone
pain”, myalgias, depressive symptoms, weight gain 5#
since on steroids
PMH: Hyperlipidemia, Acne, Allergic Rhinitis
Meds: Allegra, Lipitor, Minocin, Vioxx, Sudafed
Allergies: None
SX: Patient is married with 2 children; she is a full time
homemaker whose hobbies include the ballet and
interior design; no tobacco/EtOH/IVDU, STD risks.
FX: Mother with arthritis, Brother with UC
PE: T 98.6 BP 110/72 HR 78 RR16 weight 126 lb
G: WD female NAD
HEENT: No scalp lesions, eyes/ears normal, OP clear
Skin: no malar rash, psoriatic plaques, discoid lesions
Neck: No LAD/TM. Supple with FROM
Pulmonary, CV, Abd: normal
SkM: +synovitis LPIP2,3, right wrist, bilateral ankles
L>R. Elbows, shoulders, hips, knees normal. 2+ pedal
edema ROM good in all joints. 6 out 18 tender points
present. No nodules or deformity.
Labs: from PCP (6/29/04)5.6
_
14.1
40.9
261
138 108 12
4.1 24 0.8
102
Ca 10.6 TP 7.4 Alb 4.0 AST 18 ALT 20 ALP 100
Total chol: 190 TG 194 TSH 1.4
ANA 1:1280, RF neg, CRP 1.2 mg/dL, CK 35
From Rheum visit (7/13/04)
8.5 14.9 246
137 109 13
_
40.9
4.1 24 0.8
88
Ca 9.8 TP 7.2 Alb 3.8 AST 16 ALT 50 ALP 102
ANA 1:640, Sm/RNP neg, dsDNA Ab neg, C3, C4 nl
RF neg, CCP Ab neg, HLA-B27 neg, ACE normal
Parvo-B19 IgM neg, HBsAg neg, HCV Ab neg
ESR 1, CRP < 0.1
Hand/feet x-rays : normal
Bone scan: neg
•Possible reactive arthritis other DDx being
entertained: RA, palindromic rheumatism, SLE,
sarcoidosis, seronegative spondyloarthropathy
with peripheral arthritis, drug-induced lupus,
metabolic disorder, infectious/neoplastic not likely
•Elevated LFTs—possible from NSAID use.
Patient advised to minimize use of NSAIDs and to
stop Minocin. Repeated LFTs normal.
•Patient given prednisone 10 mg/d with followup
in 4 weeks.
Patient returned with complete resolution of joint
symptoms with the prednisone. Over the
following month, she was able to wean herself off
steroids completely. Headaches, myalgias, fatigue,
memory difficulties, insomnia, depression still
persistent.
6 months later, joint symptoms returned—pain and
stiffness in feet, ankles, knees, and hands. Now
has right thumb numbness. Recent URI illness
which resolved with antibiotics. AM stiffness 60
min. Exam: No rash; +synovitis in LPIP2-4,
RPIP2, left wrist, and right ankle
From Rheum visit (9/13/04)
5.8 12.9 310
137 109 13
_
37.9
4.1 24 0.8
88
Ca 10.4 TP 7.2 Alb 3.9 AST 18 ALT 22 ALP 102
ESR 4, CRP 0.4
Review pertinent data/abnormalities
•Acute onset inflammatory oligoarticular process with
pitting edema progressed to polyarticular process; fatigue,
memory problems, myalgias, headaches, bone pain
•+ANA
•Ca 10.6 TP 7.4 Alb 4.0 AST 18 ALT 20 ALP 100
•Ca 9.8 TP 7.2 Alb 3.8 AST 16 ALT 50 ALP 102
•Ca 10.4 TP 7.2 Alb 3.9 AST 18 ALT 22 ALP 102
PTH 98
24 hour urine calcium elevated
DEXA: Wards triangle -2.7, Hip -2.4, L-spine -2.0
24-0H vitamin D normal.
Sestimibi scan:
Primary Hyperparathyroidism


Role of PTH: regulate serum calcium and bone
metabolism
Function:
1. Stimulate renal tubular Ca reabsoption
2. Bone resorption
3. Convert calcidiol to calcitriol which
stimulates intestinal calcium absorption
NEJM 2000;343(25):1863-75.
Primary Hyperparathyroidism


Incidence: more prevalent in persons > 50 y.o.
1/1000 males
2-3/1000 females
Underlying cause in 85% of patients is a single
adenoma (less than 15% due to multiple
adenomas or glandular hypertrophy of all 4
glands; <0.5% from malignancy, MEN
syndromes, FHH)
Primary Hyperparathyroidism


NIH consensus panel classify patients as
symptomatic vs. asymptomatic
Symptomatic: (15-20%)- from hypercalcemia
Bones, stones, groans, moans, fatigue overtones
(osteitis fibrosa cystica, kidney stones, DI,
GI/CV/neuromuscular dysfunction)

Asymptomatic (75-80%)
(HTN, fatigue, PUD, normocytic anemia, weakness,
depression, anxiety, cognitive dysfunction)
NIH Consens Statement 1990 Oct 29-31;8(7):1-18.
Primary Hyperparathyroidism
Rheumatologic manifestations of PHPTH
1983 Retrospective study of 34 patients with rheumatic
symptoms:
 myalgias (41%)
 arthralgia/arthritis affecting large joints (32%)
 erosive synovitis mimicking RA (5%)
 radiologic abnormalities (24%)
1978 Prospective controlled study of PHPTH:
 8 out of 26 had chondrocalcinosis, 2 without
chondrocalcinosis had documented pseudogout
Postgrad Med J 1983;59(690):236-40
J Rheumatol 1978 Winter;5(4):460-8
Primary Hyperparathyroidism

Differential Diagnoses:
Elevated Calcium with elevated PTH
DDx: HCTZ
Lithium
FHH (Uca:cr <0.01)
3o Hyperparathyroidism (ESRD)
Normal Calcium with elevated PTH
DDx: Vitamin D deficiency (2o HyperPTH)
Primary Hyperparathyroidism
Elevated serum calcium
Recheck labs with albumin and correct or
check ionized calcium
Evaluate for secondary causes (medications)
Check intact PTH
low
Malignancy
Granulomatous Dz
Adrenal Insufficiency
Vitamin A/D Toxicity
Hyperthyroid
Milk Alkali Syndrome
Immobilization
high
low
FHH
CRI
Check 24 U CrCl, calcium,
25-OH vitamin D
high
Primary HyperPTH
Primary Hyperparathyroidism

Once Primary HyperPTH established, check:
Bone Mineral Density at all 3 sites:
distal radius, L-spine, hip
 Surgery vs. conservative management

Note: Sestimibi parathyroid scan (optional)—
sensitivity 83%, PPV 93%
Primary Hyperparathyroidism
Conservative Management:
1985 Longitudinal cohort study of 47 patients with PHPTH followed
X 5 years; 34% experienced complication from PHPTH—PUD
(8), RI (5), renal stone (1), hypercalcemic crisis (1), ventricular
conduction defect (1)
1991 Cohort study of 176 patients with sustained hypercalcemia
followed 15 years. Survival significantly lower from CV
complications
2001 Longitudinal study with matched controls in 172 patients with
PHPTH X25 years, increased mortality in patients <70y.o
(p=0.015) with CV disease representing deaths; HZ 1.72 (95%CI,
1.24-2.37); trend over time of normocalcemia in patients (NS)
Surgery 1985;98(6):1064-71. J Bone Miner Res 1991;(Suppl 2):S111-6. Surgery 2001;130(6):978-85.
Primary Hyperparathyroidism
Surgical resection:
2000 Prospective surgical cohort X 10 years- surgical cure obtained in
97.7% after initial cervical exploration; 54% recovered fully from
hypercalcemic syndrome in the 1st month, 84% patients within first
2 years. No recurrence found
2004 Prospective randomized controlled study 53 patients: 25 SGY,
28 Med Rx followed for 2 years–BMD improved at all sites with
SGY, but only in L-spine and radius with Med Rx; in SF-36 of Med
Rx decline in social functioning, physical problem, emotional
problem, energy, and health perception
2004 Controlled cohort study 3213 HPTH followed 20 years – 60%
had surgery, 40% Med Rx; SGY risk for fx (HZ 0.69), PUD (HZ
0.59), death (HZ 0.65), increased episodes of renal stones (HZ
1.87). Survival in both cohorts decreased relative to general pop. by
2.1-2.7 years; SGY not change CV event rate, psychoses, myalgias.
World J Surg 2000;24(5):564-9. J Clin End Metab. 2004;89(11):5415-22 . J Intern Med. 2004;255(1):108-14
Primary Hyperparathyroidism
Old and New Criteria for Surgery of ASx Patients
Variable
1990 NIH
2002 NIDDK
sCa concentration
24 h Urine calcium
Reduction in CrCl
BMD
Age
1.0-1.6 mg/dL above nl
>400 mg
30%
Z score <-2.0 in forearm
<50 y.o
1.0 mg/dL above nl
>400 mg
30%
T score <-2.5 any site
<50 y.o.
NIH Consens Statement 1990 Oct 29-31;8(7):1-18.
J Bone and Mineral Res 2002; 17 (Suppl 2):N2-N11.
Primary Hyperparathyroidism
Old and New Guidelines for Medical Management
Variable
1990 NIH
2002 NIDDK
sCa monitoring
24 h Urine calcium
Serum creatinine
CrCl
BMD
Abdominal radiograph
Dietary guidelines
every 6 months
every year
every year
every year
every year
every year
hydration
every 6 month
not recommended
every year
not recommended
every year all 3 sites
not recommended
intake of 1000-1200mg Ca
with 400-600IU vit D
NIH Consens Statement 1990 Oct 29-31;8(7):1-18.
J Bone and Mineral Res 2002; 17 (Suppl 2):N2-N11.
Primary Hyperparathyroidism
Medical therapy:



Bisphosphonates
Estrogens/raloxifene
Calcimimetic Drugs
Primary Hyperparathyroidism


Etidronate: 2002 Japanese study 22 patients (1 yr f/u)
Outcome
Etidronate (9)
Surgery (13)____
LS-BMD
Fracture rate
+10% (p<0.03)
Unchanged
+20% (p<0.01)
Unchanged
Alendronate vs. Placebo:
2001: Italian Study of 26 pts.: alendronate 10 mg/d after 2 years, increase
BMD of LS (+8.6%), Hip (+4.8%), T-BMD (+1.2%)
2003: Chinese Study of 40 postmenopausal patients followed 48 weeks;
alendronate increase BMD femoral neck +4.17%, LS +3.79%
2004 Canadian Study 44 patients (2 yr f/u, placebo crossover at 1 year):
BMD of LS (+6.85%, 4.1%), hip (+4.01%, 1.7%), distal radius (NS)
Gerontology.2002;48(2):103-8
J Clin Endoc Metab 2003;88(2):581-7
J Bone Min Res 2001;16(1):113-9
J Clin Endoc Metab 2004;89(7):3319-25
Primary Hyperparathyroidism

Estrogen:
1996 Australian study: 15 patients (5 ERT, 10 SGY); ERT BMD LS
(+5.3%), femoral neck (+5.5%), no sig change between ERT and SGY;
SGY patients normalized serum calcium level
2000 New Zealand study: 23 patients (4 yr f/u)- RDBPCT with 0.625 mg
conj estrogen with medroxyPG; HRT increase BMD LS (+7.5%), femoral
neck (+7.4%), forearm (+7.0%), total body (+4.6%)

Raloxifene
2003 NY study: 18 patients drug vs placebo X 8 weeks with 4 week
washout; calcium level decreased (10.8 to 10.4 mg/dL) as well as markers
of bone resorption and formation (osteocalcin 11.4 to 9.9 nm/L; sNTX
21.2 to 17.3 nm/L). No change to PTH, 1,25-OH D3 or urinary Ca
Osteoporosis Int 1996;6(4):329-33. Arch Int Med 2000;160(14)2161-6 J Clin Endo Met 2003;88(3):1174-8
Primary Hyperparathyroidism

Cinacalcet (calcimimetic)
2003 UCSF RDBPCT: 22 patients, 2 week of drug followed by 1 week
observation. Cinacalcet (30, 40 or 50 mg bid) v. placebo. Serum calcium
normalized on second dose of day 1of all treated with drug and remained
within normal range. PTH decreased by 50% with active treatment.
2004 Indiana Univ RDBPCT: 78 patients; 12 weeks therapy with 28 week
followup. Cinacalcet 73% reduction in sCa vs placebo 5%; reduction in
PTH with treatment (by 7.6%) vs. rise in PTH in placebo (by 7.7%). No
change in BMD, increase in bone resorption and formation markers
2005 Arizona RDBPCT Cinacalcet in 2o HPTH: 14 patients with ESRD,
26 week therapy. PTH decreased, BMD increased femur (p<0.05), no
effect on L-spine
J Clin End Met 2003;88(12):5644-9
J Clin End Metab 2005;90(1):135-41
Nephrol Dial Transpl 2005;20(6):1232-7
MS underwent surgical exploration or
her neck; a parathyroid adenoma was
resected from the left inferior aspect.
Biochemical confirmation was made by a
67% drop in the intact PTH within 5
minutes consistent with the removal of
autonomously functioning parathyroid
tissue.
Will her polyarticular synovitis resolve…
... or does she have an underlying CTD???