Sandostatin®
(Octreotide)

Clinical Significance:
Octreotide (Sandostatin,® Novartis Pharmaceutical Company) is used for the control of symptoms associated with functional neuroendocrine tumors. Frequent measurement of the octreotide levels may be useful in guiding therapy in patients with poorly controlled symptoms or those patients experiencing tumor growth during LAR therapy. Octreotide levels in blood need to be in a specific range to be effective. Measuring octreotide immediately prior to the monthly LAR injection will determine trough levels of the drug in your blood.

Reference Range:
Long-acting repeatable (LAR) dose-response levels: mean octreotide level ± 2 SD for patients on octreotide LAR for 3 or more months (steady-state). The following represent trough levels measured immediately before an injection of LAR.
10 mg/month: 1153 ± 748 pg/mL
20 mg/month: 2518 ± 1020 pg/mL
30 mg/month: 5241 ± 3004 pg/mL
60 mg/month: 10,926 ± 5530 pg/mL

Procedure:
Octreotide is measured by direct radioimmunoassay. There is no cross-reactivity with native somatostatin-14 or somatostatin-28. The also is no cross-reactivity with lanreotide, and this test should not be used to measure blood levels of this drug.

Patient Preparation:
This test is useful only for those patients being treated with octreotide acetate. No special preparation is needed for this test. For optimal results, blood for this test should be drawn immediately before the patient's next injection of octreotide LAR (trough levels).

Specimen Collection:
Collect 3 mL serum or EDTA plasma and separate as soon as possible. Octreotide is stable at room temperature for 3 days. Specimens can be stored at room temperature, refrigerated, or frozen in dry ice. Minimum specimen size is 1 mL.

Special Specimens:
For tumor/tissue and various fluids (e.g., CSF, peritoneal fluid, synovial fluid) contact ISI for requirements and special handling instructions.

Shipping Instructions:
Specimens can be shipped at ambient temperature, refrigerated, or frozen in dry ice.

References:

1. Woltering EA, Mamikunian PM, Zietz S, et al. The effect of octreotide LAR dose and weight on octreotide blood levels in patients with neuroendocrine tumors. Pancreas. 31(4):392-400, 2005.

 

Secretin

Clinical Significance:
Secretin is a 27 amino acid basic peptide produced by S-Cells and released by acid delivered into the duodenum.  Secretin is released into the blood when duodenal pH drops below 4.  Secretin shares structural similarity with Glucagon, Gastric Inhibitory Polypeptide, Vasoactive Intestinal Polypeptide, PHIM, and Growth Hormone-Releasing Hormone. Secretin is a potent stimulus for bicarbonate secretion.  Secretin also stimulates secretion of bile, release of Insulin, and release of gastric Pepsin in the stomach.  Secretin inhibits Glucagon release, intestinal motility, and prevents the uptake of water and sodium ions by the intestine.  In normal patients, Secretin has little effect on Gastrin levels, but stimulates Gastrin greatly in Zollinger-Ellison patients.  Secretin may also be elevated in Zollinger-Ellison patients and in patients with duodenal ulcer.  Secretin levels are low in patients with pernicious anemia and achlorhydria.  Secretin secretion can be suppressed by Somatostatin, Cimetidine, and Methionine-Enkephalin.

Reference Range:
12 - 75 pg/ml

Procedure:
Secretin is measured by direct radioimmunoassay.

Patient Preparation:
Patient should be fasting for 10 - 12 hours prior to collection of specimen.  Antacid medications and medications that affect intestinal motility should be discontinued, if possible, for at least 48 hours prior to collection.

Specimen Collection:
10 ml EDTA plasma containing the G.I. Preservative should be collected and separated as soon as possible.  Freeze plasma immediately after separation.  Special G.I. Preservative tubes are available from Inter Science.  Minimum specimen size is 1 ml.

Important Precaution:
Secretin specimens must be collected using the G.I. Preservative.  No other specimens are acceptable.

Special Specimens:
For tumor/tissue and various fluids (i.e. CSF, peritoneal, synovial, etc.) contact the Institute for requirements and special handling.

Shipping Instructions:
Ship specimens frozen in dry ice.

References:
1. A Christ, B Werth, and P Hildebrand.  Human Secretin:  Biologic Effects and Plasma Kinetics in Humans.  Gastroenterology 94:  311, 1988.

2. N Yanaihara, M Sakagami, H Sato, K Yamamoto, T Hashimoto, C Yanaihara, Z Ito, K Yamaguchi, and K Abe.  Immunological Aspects of Secretin, Substance P and VIP.  Gastroenterology 72:  803, 1977.

 

Serotonin

Clinical Significance:
Serotonin (5-Hydroxy Tryptamine) is an Indolealkylamine released by the pineal gland along with Melatonin, N-Acetyl Serotonin, 5-Hydroxy Tryptophan, and 5-Methoxy Tryptamine.  These compounds have been shown to have various neurotransmitter and/or neuromodulator properties.  Serotonin is excreted into the urine primarily as 5-Hydroxy Indole Acetic Acid (5-HIAA).  Serotonin secretion is stimulated by Norepinephrine, Thyrotropin Releasing Hormone, Luteinizing Hormone-Releasing Hormone, and Vasoactive Intestinal Polypeptide.  It is suppressed by Clonidine and Dexamethasone.  Serotonin has a stimulatory effect on Aldosterone. Serotonin is implicated in many disease states including Carcinoid tumors, Multiple Endocrine Neoplasia Type 1, hypertension, migraine headaches, depression, cirrhosis of the liver, premenstrual syndrome, Alzheimer's disease, and Parkinson's disease.

Reference Range:
Male:                                40 - 400 ng/ml
Female:                            80 - 450 ng/ml

Procedure:
Serotonin is measured by direct radioimmunoassay on plasma or serum specimens, or following extraction of whole blood specimens.

Patient Preparation:
Patient should be fasting for 10 - 12 hours prior to collection of specimen.  Because of the diurnal variation of Serotonin secretion, morning specimens are preferred.

Specimen Collection:
5 ml serum should be collected.  Separate serum as soon as possible.  Freeze serum specimens immediately after separation.  Minimum specimen size is 1 ml.

Special Specimens:
For tumor/tissue and various fluids (i.e. CSF, peritoneal, synovial, etc.) contact the Institute for requirements and special handling.

Shipping Instructions:
Ship plasma or serum specimens frozen in dry ice.  Ship whole blood specimens refrigerated.

References:
1. J Cheaveau, V Fert, AM Morel, and MA Delaage.  Rapid and Specific Enzyme Immunoassay of Serotonin.  Clinical Chemistry 37:  1178-1184, 1991.

2. JM Kellum Jr and BM Jaffee. Validation and Application of a Radioimmunoassay for Serotonin.  Gastroenterology 70:  516, 1976.

 

Sex Steroid Binding Globulin Index
(SSBG-I)

Clinical Significance:
Sex Steroid Binding Globulin (SSBG) is a b globulin glycoprotein of about 94,000 molecular weight.  It is also known as Sex Hormone Binding Globulin, Testosterone Binding Protein, and Testosterone-Estradiol Binding Globulin.  It has a high affinity and low binding capacity for several steroids including Testosterone, Dihydrotestostrone and Estradiol.  Many other steroids including Cortisol, Progesterone, and Estrone bind to SSBG but to a much lesser extent.  SSBG is the principal transport system for these hormones, but also is strongly involved with regulating the amount of active (Free) hormone available for physiologic Activity.  SSBG reduces the metabolic clearance rate of hormones that bind to it.  It appears that the more potent the androgenic or estrogenic activity of the steroid, the more strongly it is bound to SSBG.  The concentration and binding capacity of SSBG is increased by Estrogens and decreased by Androgens.  The SSBG-Index is higher in young children and decreases sharply in males and slightly in females during puberty.  The SSBG-Index is elevated by a number of clinical conditions including pregnancy, hyperthyroidism, Estrogen therapy, chronic alcoholism, and in male hypogonadism and testicular feminization.  It is decreased in hirsute females, myxodema, acromegaly, obesity, and Cushing's syndrome.  Women with hormone dependent breast cancer exhibit elevated levels of SSBG-Index.

Reference Range:
Male:                         0.9 - 1.9 ug/dl
Female:                     1.0 - 3.0 ug/dl

Procedure:
Sex Steroid Binding Globulin Index is measured by radiodisplacement assay determining the binding capacity for Dihydrotestosterone.

Patient Prpearation:
Patient should not be on any Corticosteroid, ACTH, Estrogen, Androgen, Thyroid, or Gonadotropin medications, if possible, for at least 48 hours prior to collection of specimen.

Specimen Collection:
3 ml serum or EDTA plasma should be collected and separated as soon as possible.  Minimum specimen size is 0.5 ml.

Shipping Instructions:
Ship specimens at room temperature or frozen in dry ice.

References:
1. DT Delco, IR Lee, JD Wetherall, DJ Newman, EA Medcalf and CP Price.  Particle-Enhanced Turbidimetric Immunoassay of Sex-Hormone-Binding Globulin in Serum.  Clinical Chemistry 37: 527-531, 1991.

2. DC Anderson.  Sex-Hormone-Binding Globulin.  Clinical Endocrinology 3:  69, 1974.

 

Somatostatin (Somatotropin Release-Inhibiting Factor, SRIF)

Clinical Significance:
Somatostatin is a cyclic peptide originally isolated from sheep hypothalami and shown to inhibit the release of Growth Hormone.  Somatostatin is present primarily in three main forms: a 14 amino acid peptide, a 28 amino acid peptide ("Big" Somatostatin), and a 12,000 molecular weight ProSomatostatin.  This assay measures only the 14 amino acid form of Somatostatin. All three forms of Somatostatin have similar biological properties and overall potencies.  Somatostatin is a physiological regulator of Islet Cell and gastrointestinal functions, and is a suppressor of many pituitary hormones including Growth Hormone, Prolactin, and Thyrotropin (TSH).  Somatostatin levels are often elevated in diabetics, but the levels return to normal upon correction of the hormonal and metabolic deficiencies present.  In many cases of APUDomas including VIPoma, Insulinoma, Glucagonoma, and Gastrinoma, elevated levels of Somatostatin are found.

Reference Range:
Up to 25 pg/ml

Procedure:
Somatostatin is measured by direct radioimmunoassay.

Patient Preparation:
Patient should be fasting for 10 - 12 hours prior to collection of specimen.  Patient should not be on any medications that affect Insulin secretion or intestinal motility, if possible, for at least 48 hours prior to collection.

Specimen Collection:
10 ml EDTA plasma containing the G.I. Preservative should be collected and separated as soon as possible.  Freeze plasma immediately after separation.  Special G.I. Preservative tubes are available from Inter Science.  Minimum specimen size is 1 ml.

Important Precaution:
Somatostatin specimens must be collected using the G.I. Preservative.  No other specimens are acceptable.

Special Specimens:
For tumor/tissue and various fluids (i.e. CSF, peritoneal, synovial, etc.) contact the Institute for requirements and special handling.

Shipping Instructions:
Ship specimens frozen in dry ice.

References:
1. SWJ Lamberts.  The Role of Somatostatin in the Regulation of Anterior Pituitary Secretion and Use of Its Analogues in the Treatment of Human Pituitary Tumors.  Endocrine Reviews 9:  417, 1988.

2. SE Shoelson, KS Polonsky, and T Nakabayashi.  Circulating Forms of Somatostatin-Like Immunoreactivity in Human Plasma.  American Journal of Physiology 250:  E428, 1986.

 

Substance P

Clinical Significance:
Substance P is an 11 amino acid peptide originally detected in the brain and gut, but later detected in skin, sensory organs, respiratory tract, genitourinary tract, and exocrine glands.  It is a member of the Tachykinin family that includes Substance K, Neuromedin K, Physalaemin, and Eledoisin.  Substance P increases amylase release in the pancreas and stimulates accumulation of cGMP.  It suppresses hepatic bile.  Substance P is a potent releasing agent of Histamine and reduces sensitivity of the pancreas to secretory stimulation without affecting secretion of bicarbonate, and reduces pancreatic response to acidification without affecting Secretin levels.  Substance P is capable of causing flushing, hypotension, bronchoconstriction and diarrhea.  It has been detected in elevated levels in the blood and tissue of patients with Carcinoid Tumor of the gut and Medullary Carcinoma of the Thyroid.

Reference Range:
40 - 270 pg/ml

Procedure:
Supstance P is measured by direct radioimmunoassay.

Patient Preparation:
Patient should be fasting 10 - 12 hours prior to collection of specimen.  Antacid medication or medications that may affect intestinal motility should be discontinued, if possible, for at least 48 hours prior to collection.

Specimen Collection:
Collect 10 mL EDTA plasma in special tube containing the Z-tube (G.I. Preservative) and separate as soon as possible. Freeze plasma immediately after separation. Special Z-tube (G.I. Preservative tube) is available from Inter Science Institute (ISI). Minimum specimen size is 1 ml.

Important Precaution:
Specimens for this assay must be collected using the Z-tube (G.I. Preservative). Specimens must be shipped frozen; specimens are not stable at refrigerated or room temperatures. No other specimens are acceptable.

Special Specimens:
For tumor/tissue and various fluids (i.e. CSF, peritoneal, synovial, etc.) contact the Institute for requirements and special handling.

Shipping Instructions:
Ship specimens frozen in dry ice.

References:
1. N Aronin, SE Leeman, and RS Clements Jr.  Diminished Flare Response in Neuropathic Diabetic Patients:  Comparison of Effects of Substance P, Histamine and Capaicin.  Diabetes 36:  1139, 1987.

2. N Aronin, R Coslovsky, and K Chase.  Hypothyroidism Increases Substance P Concentrations in the Heterotropic Anterior Pituitary.  Endocrinology 122:  2911, 1988.


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