Q:

2/19/2013
Isolated elevated Chromogranin A

69 F presenting to allergy clinic with "allergy-like" symptoms

She states, "I have allergy to shellfish [nose-runs eyes-puffy face-red completely-congested"

Also to chocolate "if I eat >1 oz for more than several days, my face is red"

Also to bee stings-last sting 30 yrs ago- "complete swelling and trouble breathing"

And also chronic intermittent-dizziness nausea balance-loss middle-ear block nasal-congestion rhinorrhea[saw ENT]

She discovered that 3-4 allegra a day needed to control her chronic symptoms

Blood Allergy tests [unable to stop allegra] to shellfish chocolate hymenoptera airborne-allergens NEGATIVE [except for minor elevation to cat- she doesnt own a cat]

Also has idiopathic VTE [on warfarin] - seen by local oncolology for screen for malignancy

WNL tryptase[2] SPEP/immunofixation blood-serotonin 24-hour-urine-5HIAA [3.3mg/24 hr] AST ALT

ABNORMAL: serial chronogranin A (ECL Quest) [104 ng/mL 11/26/2012 | 142 ng/mL 2/12/13]

She has had multiple CT scans for her VTE diagnosis and malignancy scan and would like to minimize radiation exposure [after we proposed a CT of abdomen]

I located a local carcinoid expert and have suggested she meet with that expert. She has researched the condition online and she feels that her likelihood is low. What are your thoughts on the pretest probability for carcinoid?

References
Aranguren et al Letter in Thromb Haemost 2001; 86: 1134–6
"The reported case illustrates for the first time an association of carcinoid tumor diagnosed long after portal thrombosis in a patient with APS, emphasizing the need to look for a hidden carcinoid tumor in patients diagnosed of idiopathic acquired venous thrombosis"

Chromogranin A from medscape

Although it varies widely with the techniques used, the reference ranges for serum chromogranin A are as follows:
Less than 36.4 ng/mL (conventional unit)

CgA can also be elevated in prostate adenocarcinoma. Serum chromogranin A can be elevated in other situations and conditions, including chronic proton-pump inhibitors use, renal failure, liver failure, heart failure, rheumatoid arthritis, inflammatory bowel disease, and hypertension.

A:

Thank you for your inquiry.

I assume you are most concerned about carcinoid syndrome based on the elevation of chromogranin A. Therefore, I think it is important to understand the role of chromogranin A in the diagnosis of carcinoid tumors.

First, and most importantly, is that chromogranin A is not a specific marker for carcinoid tumors. It can be found elevated in other neuroendocrine tumors including pheochromocytomas, parathyroid adenomas, thyroid carcinoma, oat-cell carcinoma of the lung, pancreatic islet-cell tumor, aortic-body tumor, carcinoma of the prostate, neuroblastoma, and others. In addition, it can be elevated for a number of other reasons unrelated to tumors such as liver disease, renal insufficiency, inflammatory bowel disease, and stress. It is in general considered more sensitive than a urinary 5-HIAA in the detection of carcinoid (however, this is debatable - see abstract by Anthony, et al., copied below), but is therefore far less specific.

In direct response to your question, the fact that your patient has a normal urinary 5-HIAA and plasma serotonin level mitigates against a diagnosis of carcinoid as the cause of her elevated chromogranin A.

Thus, I think the chances of her having carcinoid are slim.

Thank you again for your inquiry and we hope this response is helpful to you.

Proc Am Soc Clin Oncol 21: 2002 (abstr 664)
Author(s):
Lowell B Anthony, David Vance, Joseph Rubin, Jaffer A Ajani, Mats Stridsberg, LSU New Orleans, New Orleans, LA; Mayo Clinic, Rochester, MN; M.D. Anderson Cancer Center, Houston, TX; University Hospital, Uppsala, Sweden.
Abstract:
Biochemical markers assist the clinician in managing hormonally active tumors such as carcinoid and pancreatic islet cell neoplasms. 5-HIAA, the end-product of serotonin metabolism, requires the subject to collect urine and maintain a serotonin-free diet immediately prior to and during the urine collection. Chromogranin A measurements may vary with meal consumption and should be drawn fasting. To determine whether 24-hr urinary 5-HIAA or plasma chromogranin A (CGA) can be used interchangeably, these markers were simultaneously measured in patients enrolled in a randomized multi-center octreotide acetate (Sandostatin) LAR clinical trial evaluating 3 octreotide acetate LAR doses (10, 20 and 30 mg IM every 30 days) in carcinoid syndrome. Of the 93 subjects in the intent-to-treat group, 65 subjects were evaluable for 24-hr urinary 5-HIAA and 56 subjects were evaluable for CGA responses measured on days 29, 57, 85, 113, 141 and 169 days post octreotide LAR treatment. All samples were batched and performed blinded by either a commercial laboratory (5-HIAA) or a university laboratory (CGA). Maximal responses were classified according to percent change from baseline as follows: complete response (marker normalization), partial response (> 50% decrease), minor response (<50% but > 25% decrease), stable response (<25% decrease to< 25% increase), progressive disease (> 25% increase). In addition, plasma octreotide levels were drawn on the same days. The results are indicated in the following table. The degree of either marker suppression was not correlated to octreotide acetate plasma concentration. These results suggest that 24-hr 5-HIAA and plasma CGA can be used interchangeably since classification of response is similar for each marker.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology