Somatostatin is an important hormone that works to inhibit the release of other hormones. It also regulates the activity of your gastrointestinal tract and prevents the rapid reproduction of cells.
What is somatostatin?
Somatostatin is a hormone that regulates a variety of bodily functions by hindering the release of other hormones, the activity of your gastrointestinal tract and the rapid reproduction of cells.
Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, skin, muscles and other tissues. These signals tell your body what to do — or stop doing — and when to do it.
A somatostatinoma is a rare type of neuroendocrine tumor that grows in the pancreas and sometimes the small bowel. A neuroendocrine tumor is one that is made up of hormone-producing cells. These hormone-producing cells are called islet cells.
Many different tissues produce somatostatin, including tissues in your:
Gastrointestinal (GI) tract: The GI tract is a series of hollow organs joined in a long, twisting tube from your mouth to your anus. It includes organs in your digestive system.
Pancreas: Your pancreas is a glandular organ in your abdomen that secretes several enzymes to aid in digestion and several hormones, including glucagon and insulin. It’s surrounded by your stomach, intestines and other organs.
Hypothalamus:
The hypothalamus is a part of your brain that maintains your body’s internal balance, which is known as homeostasis. It plays a significant role in directing your pituitary gland, an endocrine gland below it, to release certain hormones.
Central nervous system (CNS): Your brain and spinal cord make up your CNS. Your brain uses your nerves to send messages to the rest of your body.
A somatostatinoma develops which is responsible for producing the hormone somatostatin. The tumor causes these cells to produce more of this hormone.
When your body produces extra somatostatin hormones, it stops producing other pancreatic hormones. When those other hormones become scarce, it eventually leads to symptoms appearing.
Symptoms of a somatostatinoma
The symptoms of a somatostatinoma usually start mild and increase in severity gradually. These symptoms are similar to those caused by other medical conditions. For this reason, it’s important that you make an appointment with your doctor to get a correct diagnosis. This should ensure proper treatment for any medical condition underlying your symptoms.
The symptoms caused by a somatostatinoma may include the following:
pain in the abdomen (most common symptom)
diabetes
unexplained weight loss
gallstones
steatorrhea, or fatty stools
bowel blockage
diarrhea
jaundice, or yellowing skin (more common when a somatostatinoma is in the small bowel)
Medical conditions other than a somatostatinoma may be causing many of these symptoms. This is often the case, as somatostatinomas are diagnosed late, not beung rare. However, your doctor is the only one who can diagnose the exact condition behind your specific symptoms.
Causes and risk factors of somatostatinomas What causes a somatostatinoma is currently unknown. However, there are some risk factors that may lead to a somatostatinoma.
Early diagnosis of somatostatinoma can be difficult as non-functional tumors often produce no symptoms, and functional tumors present with non-specific symptoms that can masquerade as other clinical conditions. Hence most non-functional tumors are discovered incidentally or during the workup of vague gastrointestinal symptoms.
Functional tumors typically have elevated fasting serum somatostatin levels (greater than 14 mmol/l).However, it is important to recognize that serum somatostatin levels may also increase in medullary thyroid cancer, lung cancer, pheochromocytoma, and paraganglioma. 24-hour urine level of 5-hydroxy indole acetic acid (5-HIAA), the breakdown product of serotonin, has been used as an alternative in some centers, but the level can be affected by a variety of dietary items and drugs.
Since somatostatinoma usually presents late, tumors are large at diagnosis and are easily visualized using imaging modalities such as CT, MRI, or MRCP. Multiphasic contrast-enhanced CT abdomen is the initial investigation of choice due to the non-invasiveness and the widespread availability.MRI is increasingly in use where pNETs have a low signal density on T1-weighted images and high signal density on T2 weighted images. MRI also has a higher sensitivity than CT to detect small liver metastases.Procedures such as esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP), or endoscopic ultrasound (EUS) can be performed to allow luminal visualization and biopsy of the tumor to confirm the diagnosis. EUS offers high sensitivity to detect lesions as small as 0.5 cm and is best indicated for lesions in the head of the pancreas and lesions of the duodenal wall.
What is the function of somatostatin?
The primary function of somatostatin is to prevent the production of other hormones in your endocrine system and certain secretions in your exocrine system. Your endocrine system consists of glands that release hormones directly into your bloodstream. Endocrine glands include your thyroid, pituitary gland and adrenal glands. Your exocrine system consists of glands that release substances through a duct. Exocrine glands include salivary glands, sweat glands and glands within the gastrointestinal tract.
Basically, somatostatin works to turn off the faucet and the flow of certain hormones and secretions when your body doesn’t need them (temporarily) anymore.
Somatostatin also stops the unnatural rapid reproduction of cells such as those that may form tumors. In addition, somatostatin acts as a neurotransmitter in your central nervous system. A neurotransmitter is a signaling molecule that a neuron releases to affect another cell.
Somatostatin affects several different areas of your body:
In your hypothalamus, somatostatin stops the release of hormones your pituitary gland makes, including growth hormone, thyroid-stimulating hormone and prolactin.
In your pancreas, somatostatin prevents (inhibits) the release of pancreatic hormones, including insulin, glucagon and gastrin, and pancreatic enzymes that aid in digestion.
In your gastrointestinal (GI) tract, somatostatin reduces gastric secretion, which is stimulated by the act of eating. It also limits the release of gastrointestinal hormones, including secretin and gastrin.
In your central nervous system (CNS), somatostatin modifies neurotransmission and memory formation.
What causes somatostatin release?
Scientists don’t yet fully understand how our bodies regulate the release of somatostatin and what causes tissues to release it. So far, they do know that several different cells and substances, such as proteins, play a role in causing somatostatin release.
One study on somatostatin revealed that glucose (sugar), the main form of energy your body uses, not only regulates somatostatin release but also plays a role in the production of somatostatin. The scientists behind the study detected insulin-stimulated somatostatin (insulin-inhibiting somatostatin) release only when there were low blood glucose levels and glucagon-stimulated somatostatin (glucagon-inhibiting somatostatin) when there were high blood glucose levels.
In other words, since insulin decreases blood glucose levels, your body releases somatostatin to stop insulin release when you have low blood glucose to prevent your levels from dropping further.
What conditions are related to somatostatin issues?
The main condition related to somatostatin issues is a very rare endocrine tumor called somatostatinoma. The tumor originates in your pancreas or gastrointestinal tract and produces excess amounts of somatostatin.
Somatostatinoma can occur randomly or in association with certain genetic syndromes, including:
Multiple endocrine neoplasia
(MEN) type 1: This is a rare genetic condition in which multiple tumors affect different aspects of your endocrine system.
Neurofibromatosis type 1 (NF1): This is an inherited condition that causes cafe-au-lait spots (flat patches of light brown or coffee-colored skin) and benign tumors.
Von Hippel-Lindau disease: This is a rare inherited condition that can cause benign or malignant tumors in your brain, spinal cord, eyes, kidneys, pancreas and adrenal glands.
Diabetes mellitus
Somatostatinomas are usually found at a later stage, which can complicate treatment options. In a late stage, cancerous tumors are more likely to have already metastasized. After metastasis, treatment is limited, because surgery usually isn’t an option.
Excess somatostatin results in an extreme reduction of the release of many other endocrine hormones. Symptoms can be similar to symptoms of many other conditions, so somatostatinoma can be difficult to diagnose.
It remains localized to the pancreas in 56 to 70% of the cases, out of which 36% occur in the head, 14% in the pancreatic body, and 32% in the tail. Other common sites include duodenum (19%), ampulla of Vater (3%), and small bowel (3%).Reports exist of rare instances of extra-gastrointestinal primaries in the lungs, kidneys, and thyroid.
There are very few reports of someone having lower-than-normal levels of somatostatin.
What tests can check my somatostatin levels?
Since somatostatin issues are rare, healthcare providers typically only use a blood test called somatostatin-like-immunoreactivity (SLI) to check somatostatin levels to diagnose somatostatinoma, a very rare tumor that produces excess somatostatin.
Issues with somatostatin levels are rare, so you likely won’t need to have your somatostatin levels checked. However, if you have a first-degree relative (parent or sibling) that has been diagnosed with multiple endocrine neoplasia type 1, neurofibromatosis type 1 or Von Hippel-Lindau disease, it’s important to tell your healthcare provider. These inherited (passed through the family) conditions can put you at risk of developing somatostatinoma.
Somatostatin is an important hormone that affects many aspects of your body. Luckily, somatostatin usually works as it should, as issues with somatostatin and somatostatinomas are rare. If a member of your family has been diagnosed with an inherited condition that puts them at risk for developing a somatostatinoma, let your healthcare provider know. They can run some tests to see if you could also have the condition.
The small cyclic peptide somatostatin (SST) is present in the human body
in two molecular forms, SS14 and SS28, consisting of 14 and 28 amino acids, respectively. SST has widespread biological actions in different organ systems. Hypothalamic SST inhibits pituitary growth hormone and thyroid-stimulating hormone (TSH) release (as a neurohormone) and in the brain SST acts as a neuro-transmitter having both stimulatory and inhibitory actions Next to these actions, locally produced SST may play a regulatory role in an autocrine and/or paracrine fashion in the
endocrine and exocrine pancreas and in the gastrointestinal tract. SST is also synthesized by lymphoid cells and may have an immunomodulatory role in these cell types.
Along with this variety of actions of SST, somatostatin receptors (SSTR)
have been detected in most of the target organs of the peptide. By auto-radiographic and membrane-homogenate binding studies, SSTR have been found in the central nervous system, the anterior pituitary gland, the endocrine and exocrine pancreas, the gastrointestinal tract and in (acti-vated) immune cells in lymphoid tissues.
The presence of SSTR in this variety of organ systems suggested that
SST could have a role in the treatment of disease due to hyperfunction of
these systems. However, several disadvantages of the native peptide ham-
pered its practical use. Due to its very
short half-life in the circulation (less than 3 minutes) the peptide has a short
duration of action and must therefore be infused intravenously. Moreover,
the post-infusion rebound hypersecretion of hormones by normal tissues is
a major disadvantage . The search for analogues of SST not having these disadvantages has led to the development of a class of octapeptide SST-analogues with a prolonged biological half-life.
Octreotide is currently the most widely used SST-analogue. It has a half-life in the circulation of approximately 2 hours, can be given subcutaneously Octreotide has proven to be a potent therapeutical agent for the
treatment of acromegaly, and for certain tumours with amine precursor
uptake and decarboxylation (APUD) characteristics (i.e. carcinoids and
glucagonomas) (Lamberts, 1988; Schally, 1988; Lamberts et al, 1991). Two
other octapeptide SST-analogues that have been developed for clinical use
are BIM-23014 (somatuline; Heiman et al, 1987; Parmar et al, 1989) and
RC-160 (octastatin; Cai et al, 1986, 1987). Both analogues are currently
being tested in clinical trials.
SOMATOSTATIN RECEPTOR SUBTYPES
A variety of human neuroendocrine tumours express SSTR. The five
recently cloned human SSTR subtypes have a distinct chromosomal localization and pharmacological profile, and a tissue-specific expression pattern which suggests a differential function of SSTR subtypes in different organ systems. Most tumours carrying SSTR may express multiple SSTR sub-types, while the SSTR2 subtype is most predominantly expressed. The somatostatin analogue, octreotide, binds with high affinity to the SSTR2 and SSTR5 subtype and with a low affinity to the SSTR3 subtype. This
analogue does not bind to the SSTR1 and SSTR4 subtypes. No major differences in the binding characteristics have been found between octreotide and two other clinically used octapeptide SST-analogues. The expression of the SSTR2 subtype in human
tumours is proposed to be related to a clinical beneficial effect of octreotide
treatment, while the functional significance of the other SSTR subtypes is not clear at present. In addition it is unclear which subtype(s) is involved in the antimitotic actions of SST(-analogues). Further developments with regard to the oncological application of SST analogues await the identifi-cation of the SSTR subtype(s) mediating anti-proliferative effects, as well
as the development of analogues which selectively activate this subtype(s).
A good correlation has been found between the presence of SSTR2 sub-type mRNA and binding of octreotide in human primary tumours.
Therefore, SSTR scintigraphy of human primary tumours and their metastases presumably visualizes SSTR2-expressing tumours, although it is reasonable to Somatostatin is an important hormone that works to inhibit the release of other hormones. It also regulates the activity of your gastrointestinal tract and prevents the rapid reproduction of cells.
What is somatostatin?
Somatostatin is a hormone that regulates a variety of bodily functions by hindering the release of other hormones, the activity of your gastrointestinal tract and the rapid reproduction of cells.
Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, skin, muscles and other tissues. These signals tell your body what to do — or stop doing — and when to do it.
A somatostatinoma is a rare type of neuroendocrine tumor that grows in the pancreas and sometimes the small bowel. A neuroendocrine tumor is one that is made up of hormone-producing cells. These hormone-producing cells are called islet cells.
Many different tissues produce somatostatin, including tissues in your:
Gastrointestinal (GI) tract: The GI tract is a series of hollow organs joined in a long, twisting tube from your mouth to your anus. It includes organs in your digestive system.
Pancreas: Your pancreas is a glandular organ in your abdomen that secretes several enzymes to aid in digestion and several hormones, including glucagon and insulin. It’s surrounded by your stomach, intestines and other organs.
Hypothalamus:
The hypothalamus is a part of your brain that maintains your body’s internal balance, which is known as homeostasis. It plays a significant role in directing your pituitary gland, an endocrine gland below it, to release certain hormones.
Central nervous system (CNS): Your brain and spinal cord make up your CNS. Your brain uses your nerves to send messages to the rest of your body.
A somatostatinoma develops which is responsible for producing the hormone somatostatin. The tumor causes these cells to produce more of this hormone.
When your body produces extra somatostatin hormones, it stops producing other pancreatic hormones. When those other hormones become scarce, it eventually leads to symptoms appearing.
Symptoms of a somatostatinoma
The symptoms of a somatostatinoma usually start mild and increase in severity gradually. These symptoms are similar to those caused by other medical conditions. For this reason, it’s important that you make an appointment with your doctor to get a correct diagnosis. This should ensure proper treatment for any medical condition underlying your symptoms.
The symptoms caused by a somatostatinoma may include the following:
pain in the abdomen (most common symptom)
diabetes
unexplained weight loss
gallstones
steatorrhea, or fatty stools
bowel blockage
diarrhea
jaundice, or yellowing skin (more common when a somatostatinoma is in the small bowel)
Medical conditions other than a somatostatinoma may be causing many of these symptoms. This is often the case, as somatostatinomas are diagnosed late, not beung rare. However, your doctor is the only one who can diagnose the exact condition behind your specific symptoms.
Causes and risk factors of somatostatinomas What causes a somatostatinoma is currently unknown. However, there are some risk factors that may lead to a somatostatinoma.
Early diagnosis of somatostatinoma can be difficult as non-functional tumors often produce no symptoms, and functional tumors present with non-specific symptoms that can masquerade as other clinical conditions. Hence most non-functional tumors are discovered incidentally or during the workup of vague gastrointestinal symptoms.
Functional tumors typically have elevated fasting serum somatostatin levels (greater than 14 mmol/l).However, it is important to recognize that serum somatostatin levels may also increase in medullary thyroid cancer, lung cancer, pheochromocytoma, and paraganglioma. 24-hour urine level of 5-hydroxy indole acetic acid (5-HIAA), the breakdown product of serotonin, has been used as an alternative in some centers, but the level can be affected by a variety of dietary items and drugs.
Since somatostatinoma usually presents late, tumors are large at diagnosis and are easily visualized using imaging modalities such as CT, MRI, or MRCP. Multiphasic contrast-enhanced CT abdomen is the initial investigation of choice due to the non-invasiveness and the widespread availability.MRI is increasingly in use where pNETs have a low signal density on T1-weighted images and high signal density on T2 weighted images. MRI also has a higher sensitivity than CT to detect small liver metastases.Procedures such as esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP), or endoscopic ultrasound (EUS) can be performed to allow luminal visualization and biopsy of the tumor to confirm the diagnosis. EUS offers high sensitivity to detect lesions as small as 0.5 cm and is best indicated for lesions in the head of the pancreas and lesions of the duodenal wall.
What is the function of somatostatin?
The primary function of somatostatin is to prevent the production of other hormones in your endocrine system and certain secretions in your exocrine system. Your endocrine system consists of glands that release hormones directly into your bloodstream. Endocrine glands include your thyroid, pituitary gland and adrenal glands. Your exocrine system consists of glands that release substances through a duct. Exocrine glands include salivary glands, sweat glands and glands within the gastrointestinal tract.
Basically, somatostatin works to turn off the faucet and the flow of certain hormones and secretions when your body doesn’t need them (temporarily) anymore.
Somatostatin also stops the unnatural rapid reproduction of cells such as those that may form tumors. In addition, somatostatin acts as a neurotransmitter in your central nervous system. A neurotransmitter is a signaling molecule that a neuron releases to affect another cell.
Somatostatin affects several different areas of your body:
In your hypothalamus, somatostatin stops the release of hormones your pituitary gland makes, including growth hormone, thyroid-stimulating hormone and prolactin.
In your pancreas, somatostatin prevents (inhibits) the release of pancreatic hormones, including insulin, glucagon and gastrin, and pancreatic enzymes that aid in digestion.
In your gastrointestinal (GI) tract, somatostatin reduces gastric secretion, which is stimulated by the act of eating. It also limits the release of gastrointestinal hormones, including secretin and gastrin.
In your central nervous system (CNS), somatostatin modifies neurotransmission and memory formation.
What causes somatostatin release?
Scientists don’t yet fully understand how our bodies regulate the release of somatostatin and what causes tissues to release it. So far, they do know that several different cells and substances, such as proteins, play a role in causing somatostatin release.
One study on somatostatin revealed that glucose (sugar), the main form of energy your body uses, not only regulates somatostatin release but also plays a role in the production of somatostatin. The scientists behind the study detected insulin-stimulated somatostatin (insulin-inhibiting somatostatin) release only when there were low blood glucose levels and glucagon-stimulated somatostatin (glucagon-inhibiting somatostatin) when there were high blood glucose levels.
In other words, since insulin decreases blood glucose levels, your body releases somatostatin to stop insulin release when you have low blood glucose to prevent your levels from dropping further.
What conditions are related to somatostatin issues?
The main condition related to somatostatin issues is a very rare endocrine tumor called somatostatinoma. The tumor originates in your pancreas or gastrointestinal tract and produces excess amounts of somatostatin.
Somatostatinoma can occur randomly or in association with certain genetic syndromes, including:
Multiple endocrine neoplasia
(MEN) type 1: This is a rare genetic condition in which multiple tumors affect different aspects of your endocrine system.
Neurofibromatosis type 1 (NF1): This is an inherited condition that causes cafe-au-lait spots (flat patches of light brown or coffee-colored skin) and benign tumors.
Von Hippel-Lindau disease: This is a rare inherited condition that can cause benign or malignant tumors in your brain, spinal cord, eyes, kidneys, pancreas and adrenal glands.
Diabetes mellitus
Somatostatinomas are usually found at a later stage, which can complicate treatment options. In a late stage, cancerous tumors are more likely to have already metastasized. After metastasis, treatment is limited, because surgery usually isn’t an option.
Excess somatostatin results in an extreme reduction of the release of many other endocrine hormones. Symptoms can be similar to symptoms of many other conditions, so somatostatinoma can be difficult to diagnose.
It remains localized to the pancreas in 56 to 70% of the cases, out of which 36% occur in the head, 14% in the pancreatic body, and 32% in the tail.[4] Other common sites include duodenum (19%), ampulla of Vater (3%), and small bowel (3%).[5] Reports exist of rare instances of extra-gastrointestinal primaries in the lungs, kidneys, and thyroid.
There are very few reports of someone having lower-than-normal levels of somatostatin.
What tests can check my somatostatin levels?
Since somatostatin issues are rare,healthcare providers typically only use a blood test called somatostatin-like-immunoreactivity (SLI) to check somatostatin levels to diagnose somatostatinoma, a very rare tumor that produces excess somatostatin.
Issues with somatostatin levels are rare, so you likely won’t need to have your somatostatin levels checked. However, if you have a first-degree relative (parent or sibling) that has been diagnosed with multiple endocrine neoplasia type 1, neurofibromatosis type 1 or Von Hippel-Lindau disease, it’s important to tell your healthcare provider. These inherited (passed through the family) conditions can put you at risk of developing somatostatinoma.
Somatostatin is an important hormone that affects many aspects of your body. Luckily, somatostatin usually works as it should, as issues with somatostatin and somatostatinomas are rare. If a member of your family has been diagnosed with an inherited condition that puts them at risk for developing a somatostatinoma, let your healthcare provider know. They can run some tests to see if you could also have the condition.
The small cyclic peptide somatostatin (SST) is present in the human body
in two molecular forms, SS14 and SS28, consisting of 14 and 28 amino acids, respectively. SST has widespread biological actions in different organ systems. Hypothalamic SST inhibits pituitary growth hormone and thyroid-stimulating hormone (TSH) release (as a neurohormone) and in the brain SST acts as a neuro-transmitter having both stimulatory and inhibitory actions Next to these actions, locally produced SST may play a regulatory role in an autocrine and/or paracrine fashion in the
endocrine and exocrine pancreas and in the gastrointestinal tract. SST is also synthesized by lymphoid cells and may have an immunomodulatory role in these cell types.
Along with this variety of actions of SST, somatostatin receptors (SSTR)
have been detected in most of the target organs of the peptide. By auto-radiographic and membrane-homogenate binding studies, SSTR have been found in the central nervous system, the anterior pituitary gland, the endocrine and exocrine pancreas, the gastrointestinal tract and in (acti-vated) immune cells in lymphoid tissues.
The presence of SSTR in this variety of organ systems suggested that SST could have a role in the treatment of disease due to hyperfunction of these systems. However, several disadvantages of the native peptide hamered its practical use. Due to its very
short half-life in the circulation (less than 3 minutes) the peptide has a short
duration of action and must therefore be infused intravenously. Moreover,
the post-infusion rebound hypersecretion of hormones by normal tissues is
a major disadvantage . The search for analogues of SST not having these disadvantages has led to the development of a class of octapeptide SST-analogues with a prolonged biological half-life.
Octreotide is currently the most widely used SST-analogue. It has a half-life in the circulation of approximately 2 hours, can be given subcutaneously Octreotide has proven to be a potent therapeutical agent for the
treatment of acromegaly, and for certain tumours with amine precursor uptake and decarboxylation (APUD) characteristics (i.e. carcinoids and glucagonomas) (Lamberts, 1988; Schally, 1988; Lamberts et al, 1991). Two other octapeptide SST-analogues that have been developed for clinical use
are BIM-23014 (somatuline; Heiman et al, 1987; Parmar et al, 1989) and
RC-160 (octastatin; Cai et al, 1986, 1987). Both analogues are currently
being tested in clinical trials.
SOMATOSTATIN RECEPTOR SUBTYPES
A variety of human neuroendocrine tumours express SSTR. The five
recently cloned human SSTR subtypes have a distinct chromosomal localization and pharmacological profile, and a tissue-specific expression pattern which suggests a differential function of SSTR subtypes in different organ systems. Most tumours carrying SSTR may express multiple SSTR subypes, while the SSTR2 subtype is most predominantly expressed. The somatostatin analogue, octreotide, binds with high affinity to the SSTR2 and SSTR5 subtype and with a low affinity to the SSTR3 subtype. This analogue does not bind to the SSTR1 and SSTR4 subtypes. No major differences in the binding characteristics have been found between octreotide and two other clinically used octapeptide SST-analogues. The expression of the SSTR2 subtype in human
tumours is proposed to be related to a clinical beneficial effect of octreotide
treatment, while the functional significance of the other SSTR subtypes is not clear at present. In addition it is unclear which subtype(s) is involved in
the antimitotic actions of SST(-analogues). Further developments with
regard to the oncological application of SST analogues await the identifi-cation of the SSTR subtype(s) mediating anti-proliferative effects, as well
as the development of analogues which selectively activate this subtype(s).
A good correlation has been found between the presence of SSTR2 sub-
type mRNA and binding of octreotide in human primary tumours.
Therefore, SSTR scintigraphy of human primary tumours and their meta-
stases presumably visualizes SSTR2-expressing tumours, although it is reasonable to assume that SSTR5, and to a lesser extent SSTR3, when
expressed simultaneously with SSTR2, also contribute to the visualization
of tumours.assume that SSTR5, and to a lesser extent SSTR3, when
expressed simultaneously with SSTR2, also contribute to the visualization
of tumours.
