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History of Present Illness. 78 yo WF with ?spells" since summer 2005Described as acute onset of overwhelming fatigue, weakness, diaphoresis and ?trembling inside"2-4 episodes/weekSome flushing, occasional palpitations, some mild dyspnea, 2 pre-syncopal episodes 6 months ago no diarrhea, wheezing
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1. A 78 yo female with “spells”…why did I order a Chromogranin A? Suzanne Breckenridge, MD
Washington University
March 30, 2006
2. History of Present Illness 78 yo WF with “spells” since summer 2005
Described as acute onset of overwhelming fatigue, weakness, diaphoresis and “trembling inside”
2-4 episodes/week
Some flushing, occasional palpitations, some mild dyspnea, 2 pre-syncopal episodes 6 months ago
no diarrhea, wheezing or associated HA.
Occasional HA described as a BB hitting her face and rolling down her cheek (L)
Mild hot flashes when peri-menapausal but none for 20 years
3. History of Present Illness cont No exacerbating/relieving factors
No association with intake of certain foods, exercise or Etoh consumption
No new medications
She was seen by cardiology and pulmonolgy
4. Past Medical History Polymalgia rheumatica
“Ice pick headaches”
Pulmonary histoplasmosis
Hyperlipidemia
Mild depression
Mild GERD
No history of HTN
5. Medications: Prednisone 5mg x 10yrs, lipitor, lexapro, folic acid, vit C, asa, fish oil, PPI prn
SH: married w/ 4 children no etoh, no tob
FH: uncle and sister w/hyperparathyroism, no FH of carcinoid, gut tumors, pheo or thyroid disorders
6. Physical Exam BP 130/70, HR 80, WT 182 lbs
HEENT: EOMI,PEERL, no plethora or evidence of flushing
Neck: no goiter
CV: RRR w/o M
Lungs:CTAB
ABD Obese, no striae, no HSM
MS: Strength nl
Skin-no telangectasia, no rash
Neuro: DTR NL, no tremor
7. Laboratory evaluation 5/05 Plasma catecholamines:
dopamine <50
Epi <50 and
Norepi 821 pg/mL (<700)
11/05 Urinary catecholamines/metanephrines:
Dopamine 159 (65-400)
Epi 1.7 (0-20)
Norepi 45 (15-80)
metanepherine 63 (30-180)
Normet 363 (148-560)
8. Laboratory Cont 1/06
5HIAA level 8.8 (1-6)
Repeat 5HIAA 4.4
plasma metanephrine <0.2 (0-.49)
Plasma Normetanephrine 0.47 (0-0.89)
Cortrosyn stim test 3.3?15.7
chromogranin A 1290 (<225)
Calcitonin <5
Renal/hepatic function nl
Oct 2005 CT Abd/pelvis – no mass, pancreas
normal, adrenals nl, no liver mets
11. What is Chromogranin A? 49 kDa, 439 AA, monomeric,
hydrophilic, acidic glucoprotein
First isolated from the chromaffin cells of adrenal medulla 1965
Member of the Chromogranin/Secretogranin family
Highly conserved
Stable
12. Chromogranin A Functions Extracellular: precursor to biologically active peptides (pancreastatin, chromostatin, vasostatin, parastatin)
Intracellular: modulation of protolytic processing/packaging of peptides and directing to regulated pathways of secretion
15. Chromogranin A Location:
Anterior Pituitary
parafollicular C cells of the thyroid
chief cells of parathyroid
islet cells
chromaffin cells of adrenal medulla
wide spread neuro endocrine system including bronchial, GI tract and in Merkel cells of the skin
17. Chromogranin A Elevated levels: liver failure, renal failure, sympatheticoadrenal stimulation (up to 2 x nl), HTN?, PPI, neuroblastoma and other CNS tumors, renal cell carcinoma, hemangioblastoma
Also, Prostate CA, Colon CA, breast CA, small cell Lung CA
Can be 1000 x ULN metastatic carcinoid but nl in small neuroendocrine tumors
CGA concentration correlates with tumor burden (except gastrinomas) and can precede radiographic evidence of recurrence
Levels decline with tx with somatostatin
High levels in “non-functioning” tumors as well
19. Dx/Follow up of Carcinoid Highest levels are reported with metastatic carcinoid (up to 1000x ULN)
Advocated for the initial work-up and follow-up with 5-HIAA levels NCCN oncology guidelines
In patients with recurrent/metastatic carcinoid-CGA has better sensitivity and specificity than 5HIAA
Prognosis-Janson et al.
reported that CGA levels of
>5000ug/L in carcinoid was
an independent risk factor
for death
20. Forgut Carcinoid Midgut carcinoid Hindgut Carcinoid
Respiratory Jejunum Colon
Stomach Ileum Rectum
Pancreas Appendix
Duodenum
CGA + 80-90% CGA +70-80% CGA + 90-100%
5HIAA may be normal 5HIAA elevated 5HIAA nl
+/- carcinoid syndrome + carcinoid syndrome - carcinoid syndrome
23. Pheochromocytoma Used to help diagnose and follow-up
Can be markedly elevated
Sporatic cases: CGA 83-89% sensitivity and a 96-100% specificity
CGA levels correlate with tumor burden
Drugs used to treat Pheo/HTN do not alter level
May differentiate between malignant and benign
24. Endocrine Pancreatic Tumors CGA usually elevated and can be used to follow patients with gastrinomas, VIPoma, glucagonoma, somatostainoma
Clinically non-functioning NET
Correlate with progression/regression during treatment
Usefulness is limited as CGA can not compete with other peptide hormone markers in sensitivity or specificity
31. Other clinical implications… CGA ectopic ACTH production
Nobels et al. 30 pts w/ Cushing’s – 10 with ectopic causes, elevated CGA 7/10 (270-13,900)
Prostate CA
Immunoscintigraphy with anti-chromogranin monoclonal antibodies
32. How do I order a Chromogranin A? Immunochemiluminometric assay
Red top tube
$113.90
Send out to Mayo, 6 day turn around time
Any value >625 routinely diluted and remeasured
33. Thank you