Hormones
Symptoms & syndromes.
Our bodies are made up of billions of cells including neuroendocrine cells. In health, neuroendocrine cells, alongside endocrine glands, help regulate our bodily functions by releasing hormones or substances that have a similar effect.
Neuroendocrine cancers occur when neuroendocrine cells stop working normally. They can start to grow uncontrollably and may produce and release abnormal levels of hormone.
Less than half of all Neuroendocrine Cancers are associated with abnormal hormone release.
What are hormones?
Hormones are necessary for many of the body’s normal activities to occur. They are vital to our growth and development, our appetite and digestion, activity and sleep – and play a role in our immune response and mental health.
If our hormone levels are abnormally increased or decreased this can result in several symptoms or syndromes occurring that can affect both our physical and psychological well-being.
According to the Society for Endocrinology:
A hormone is a chemical that is made by specialist cells*, usually within an endocrine gland, and it is released into the bloodstream to send a message to another part of the body. In the human body, hormones are used for two types of communication: The first is for communication between two endocrine glands, where one gland releases a hormone which stimulates another target gland to change the levels of hormones that it is releasing. The second is between an endocrine gland and a target organ, for example when the pancreas releases insulin which causes muscle and fat cells to take up glucose from the bloodstream.
https://www.yourhormones.info/hormones * specialist cell refers to both endocrine and neuroendocrine cells.
Neuroendocrine cells can communicate with each other in the same way as explained above. So, although hormones can circulate throughout the body, encountering many different types of cells, they can only affect cells that have specific hormone receptors.
In short – the sender is the cell or gland that makes the message (the hormone) – and the message must reach the right recipient (target cell or gland) – for ‘normal’ health / function to be maintained.
Cells may have many receptors for a specific hormone or receptors for more than one type of hormone. The number of receptors may also change over time – either increasing or decreasing the cell’s sensitivity to a particular hormone.
Types of Hormones
By structure
Amino acids are essential to life because the proteins they form are involved in virtually all cell functions. Cholesterol, despite its bad press, is essential to cell development and the production of certain hormones – including vitamin D, and substances such as fat-dissolving bile acids.
Peptide and protein hormones
Most hormones are made from amino acids – molecules known as peptides. Multiple peptides together form proteins.
Insulin is a protein hormone. Oxytocin is a peptide hormone.
Steroid hormones
Some hormones are made from fat (lipids) – mainly cholesterol.
Cortisol is a steroid hormone.
Amino or fatty-acid derivatives
– made from or utilising amino-acids or lipids
Amino-acid derivatives include thyroid hormones, catecholamines – which include Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline), Histadine – which converts to Histamine, Tryptophan – which gives us Serotonin and Melatonin.
Fatty-acid derivatives include Prostaglandins, Prostacyclins, Leukotrienes and Thromboxanes.
So, technically speaking, these bio-active substances – that have the ability to influence body functions and processes to maintain health – though mostly called hormones, may also be referred to as peptides or catecholamines.
By action
The type of hormone (or ‘bioactive’) neuroendocrine cells release can depend on what part of the body they are in, for example:
- In the digestive system they are released help to break down food in our gut and move food through the small and large bowel – helping both nutritional uptake and eliminating waste.
- In the respiratory system they help with the development of our lungs and to regulate breathing.
- In the brain they can affect social bonding, sleep and sleep-wake pattern.
- In the adrenal glands they can control our ‘fight or flight response’ – which can affect blood pressure, heart rate – which may also make us feel anxious.
or the action that is needed, for example :
- Gastrin produced by cells in the pancreas or duodenum trigger the stomach to increase acid production.
Here is a list of hormones that may be produced by the body – and their normal function.
Hormone control is usually regulated by negative feedback: so, may be due to response to changes in fluids such as blood:
- For example: When blood sugar level rises, insulin is released to reduce it and when the level has normalised, a message is received back to stop producing insulin, or triggered by the actions of another hormone. However, hormone release may also be as a result of a message from the nervous system – e.g., to prepare the body for the ‘fight or flight’ response in times of stress – where Adrenaline is released. In this instance control is not due to negative feedback – that is, a particular level in the blood – it is controlled by stimulus to ‘stress’ / ‘sudden or vigorous activity’.
- For example; when blood sugar rise, insulin is released. This sends a signal to the liver, muscles and other cells to store the excess glucose: as body fat and/or as glycogen. This reduces circulating blood sugar and when levels have normalised, a message is received back to stop producing insulin.
- Hormone release in response to changes in fluids such as blood is termed humoral stimuli.
- Hormonal stimuli refer to the release of a hormone in response to another hormone.
- Neural stimuli refer to hormone release as a result of a message from the nervous system – e.g., fight or flight. N.B. Adrenaline is not controlled by negative feedback.
Hormones and Neuroendocrine Cancer
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When neuroendocrine cells become cancerous – there is a risk of excessive or ectopic secretion of hormones. N.B. Less than half of all Neuroendocrine Cancers are associated with abnormal hormone release.
Excessive secretion – also known as hyper secretion – occurs when the normal hormone release escapes normal control
Ectopic secretion refers to the secretion of hormones by cells that do not normally produce and/or secrete the particular hormone, for example:
- ACTH release by lung neuroendocrine cancer cells
- PTHrP release by pancreatic neuroendocrine cancer cells.
See list of hormones and some of their related symptoms/syndromes below:
| Hormone |
| Health |
| Excess or Hyper-secretion symptoms and syndromes |
| Protein Hormone | regulates levels of cortisol, which released from the adrenal gland | produced by the pituitary gland to stimulate the production and release of cortisol from the cortex (outer part) of the adrenal gland | can lead to high levels of cortisol in the body, also known as Cushing syndrome. | |
| Steroid Hormone | regulation of the salt and water balance of the body | produced in the cortex (outer part) of the adrenal gland | can cause high blood pressure, low potassium levels | |
| Polypeptide | increases blood pressure and exerts an antidiuretic effect | produced in the hypothalamus and is transported to the pituitary gland for release | high levels can lead to Syndrome of Inappropriate Anti-Diuretic Hormone secretion (SIADH; a type of hyponatraemia) | |
| Polypeptide | regulates the levels of calcium (and phosphate) in the blood – by opposing the action of parathyroid hormone | produced and released by the C-cells of the thyroid gland | calcitonin levels can be altered by changes in calcium levels – raised calcitonin itself may not lead to symptoms/syndrome -though there have been reports of excess calcitonin leading to watery diarrhoea and facial flushing. Raised calcitonin is usually related to a problem with calcium control but may also be raised in Medullary Thyroid Carcinoma (MTC) : can be a marker for MTC – but is not a contributory factor to cancer development. It may be associated with hypercalcaemia | |
| Catecholamines:
Adrenaline (epinephrine)
Noradrenaline (norepinephrine) | Derivative | work together to prepare the body for ‘fight or flight’ response in times of stress, i.e. for vigorous and/or sudden action | produced in the medulla (central part) of the adrenal glands and in some neurons of the central nervous system | overproduction of adrenaline/noradrenaline may be caused by a tumour within the medulla (central part) of the adrenal gland called pheochromocytoma or a paraganglioma (nerves of sympathetic nervous system that run through the chest and abdomen) |
| Peptide hormone | slows down the emptying of food from the stomach and stimulates the production of bile in the liver as well as its release from the gall bladder. | produced by I-cells in the lining of the duodenum and is also released by some neurons in the brain. | no identified association of symptoms/syndrome with excess cholecystokinin – emerging research suggests that deficiency/levels too low may be linked with obesity. | |
| Steroid Hormone | Stress response, metabolism, blood sugar control & immune response | produced in the cortex (outer part) of the adrenal gland | High cortisol levels can lead to Cushings syndrome – also to changes in a woman’s libido and menstrual cycle, anxiiety and depression, in both sexes, may also occur | |
| (FSH)
and
(LH) | Peptide hormone | FSH & LH regulate the functions of both the ovaries and testes | both are released by the pituitary gland into the bloodstream | FSH levels can rise in the approach to the menopause – but excess FSH is associated with primary ovarian failure or testicular failure which may be seen in certain genetic/chromosomal disorders – non-neuroendocrine cancer related -conditions such as Klinefelter’s syndrome in men and Turner syndrome in women. Excess LH may also indicate / be associated with these genetic/chromosomal disorders – but can also be seen in PCOS and/or reduced fertility |
| Peptide hormone | stimulates the stomach to release gastric acid | produced by the pancreas, ’G’ cells in the lining of the stomach and upper small intestine (duodenum). | Too much gastrin hormone is associated with Zollinger-Ellison syndrome, a syndrome caused by a gastrinoma – a rare neuroendocrine tumour that can occur in the pancreas or duodenum.. However, high gastrin can also occur if the pH of the stomach is too high, – where the lining of the stomach is damaged, preventing it from releasing acid. Antacid medications – such as PPIs – taken to relieve heartburn or gastroesophageal reflux disease (GERD) can also raise gastrin levels. NB if you have been prescribed high dose PPI for the treatment of a gastrinoma – do not stop taking PPI without medical instruction/supervision. | |
| Peptide hormone | Breaks down glycogen to glucose – helps to control blood sugar (glucose) levels. | Pancreas (alpha cells within the islets of Langerhans) | excess glucagon may be due to a rare neuroendocrine tumour of the pancreas called a glucagonoma – and can cause diabetes mellitus, weight loss, venous thrombosis and a characteristic skin rash (NME – Necrotising or Necrolytic Migratory Erythema) | |
| Peptide hormone | encourages the release of insulin and holds back glucagon release It can also reduce appetite and slow stomach emptying | small intestine, pancreas and the central nervous system |
| |
| Peptide hormone | enhances the release of insulin following the intake of food | upper section of the small intestine from a specific type of cell known as the K cell | may be linked with diabetes and/or obesity | |
| Peptide hormone | Stimulates growth – helps to maintain normal body structure and metabolism | anterior pituitary gland | excessive growth hormone can produce a condition known as acromegaly | |
| Histamine | Derivative | has a number of functions within the body including acute allergic responses, secretion of gastric acid, smooth muscle contraction, acts as a neurotransmitter within the central nervous system and in regulating immune responses | is present in peripheral nerves and endocrine cells in addition to mast cells | there are 4 key Histamine receptors – each related to various parts of the body and functions – excess histamine can therefore result in a number of symptoms including headaches or migraines, nasal congestion or sinus issues, fatigue, insomnia, mood changes, hives, digestive issues, irregular menstrual cycle, nausea and/or vomiting. |
| Protein Hormone | control of blood sugar (glucose) levels | Pancreas (beta cells within the islets of Langerhans) | excess insulin leads to abnormally low blood glucose levels (called hypoglycaemia) – it may also be associated with a rare neuroendocrine tumour called an insulinoma that occurs with an incidence of 1-4 per million population. | |
| Derivative | is associated with control of the sleep–wake cycle – circadian rhythm, and also seasonal (or circannual) rhythm | produced and released from the pineal gland occurs with a clear daily (circadian) rhythm | The amount of melatonin produced by the body, whether low or high, is not usually associated with any health problems. However, some people may take it as a sleep aid – taking too much can result in drowsiness, a reduced core body temperature, headaches and fatigue – very high levels may affect sexual function and fertility. | |
|
Oestradiol
Oestriol
Oestrone | Steroid Hormone | acts to mature and maintain the female reproductive system
is in involved in pregnancy and childbirth it is thought that oestrone may act as a reservoir that can be converted into oestradiol as needed | In premenopausal women, oestradiol is mostly made by the ovaries – also by the placenta in pregnant women. is made by the placenta is primarily produced by the ovaries as well as by adipose tissue and the adrenal glands | too much oestradiol can cause acne, constipation, loss of libido, depression, female infertility, male sexual dysfunction
Obese women can produce more oestrone from their fat tissues. Increased levels may be seen in women with breast cancer and in men undergoing treatment for testicular or prostate cancer |
| Peptide hormone | In women – stimulates contraction of the womb (uterus) during childbirth and lactation. In men – it plays a role in sperm transport and production of testosterone by the testes. It is also thought to play a role in certain aspects of human behaviour – including social bonding. | produced in the hypothalamus and is secreted into the bloodstream by the posterior pituitary gland. | it is not fully understood at present if there are any implications of having too little oxytocin in the body – though abnormal levels may have an impact on milk production in breast-feeding mothers. High levels have been linked to benign prostatic hyperplasia | |
| PP (Pancreatic polypeptide) | Polypeptide | inhibits pancreatic secretion, gall bladder activity and small bowel contraction – though its full function, in humans(!), is incompletely understood. | Pancreas (PP cells) | rarely produces hormone related symptoms or syndrome, but may be secreted alongside VIP and / or Gastrin – it can be associated with a rare neuroendocrine tumour called a PPoma. |
| Steroid Hormone | progesterone prepares the body for pregnancy in the event that the released egg is fertilised. If it isn’t, the production of progesterone falls and a new menstrual cycle begins | mainly secreted by the corpus luteum in the ovary during the second half of the menstrual cycle. progesterone is also produced in smaller quantities by the ovaries themselves, the adrenal glands and, during pregnancy, the placenta from about week 8-12. | abnormally raised levels of progesterone can be associated with congenital adrenal hyperplasia (associated not causative) – but may also indicate pregnancy with one or more babies, cysts on your ovaries, molar pregnancy, a disorder affecting your adrenal glands, ovarian cancer and/or breast cancer. | |
| Polypeptide | is usually associated with lactation, but has numerous other functions within the body including reproduction, metabolism, regulation of the immune system & fluid balance and behaviour. | produced in the anterior pituitary gland and elsewhere including the uterus, immune cells, brain, breasts, prostate, skin and adipose tissue | too much prolactin circulating in the blood is called hyperprolactinaemia – common causes include pregnancy, medications that reduce dopamine action in the body, thyroid underactivity and benign pituitary tumours (known as prolactinomas) | |
| Eicosanoids (fatty-acid derivative) | control processes such as inflammation, blood flow, the formation of blood clots and the induction of labour. | prostaglandins are produced at the site where they are needed so can be made by nearly all cells | High levels of prostaglandins are usually produced in response to injury or infection and can cause inflammation. Excess, prolonged release may lead to unwanted inflammation in the body such as arthritis and/or painful menstruation with heavy bleeding. | |
| Peptide hormone | regulates calcium levels in the blood – through its actions on the kidneys, bones and intestine | parathyroid glands | too much parathyroid hormone causes raised calcium levels in the blood (hypercalcaemia) and this is referred to as primary hyperparathyroidism | |
| PTHrP (Parathyroid Hormone-Related Peptide) | Peptide hormone | as PTH – also smooth muscle relaxation and cell development | parathyroid glands | excess PTHrP is a common cause of cancer-related hypercalcaemia ( however PTHrP related hypercalcaemia tends to have suppressed/low PTH) |
| Serotonin | Derivative | affects many aspects of how the gut functions including how fast food moves through your system (motility), how much fluid, such as mucus, is secreted in your intestines and how sensitive your intestines are to sensations like pain and fullness from eating. It is derived from tryptophan – an essential amino-acid that comes from dietary intake. | approx 90% of serotonin is located in the GI tract, where it regulates intestinal function, 8% is found in platelets and 1-2% in the brain/CNS (central nervous system). Serotonin is also a precursor to melatonin | excess serotonin is associated with Carcinoid Syndrome, Carcinoid Heart Disease and / or Mesenteric Fibrosis in people with Neuroendocrine Cancer (predominantly small bowel – also lung & ovarian primaries and those with liver and/or peritoneal secondary disease {metastasies}) |
| Peptide hormone | regulates numerous bodily functions : it inhibits the secretion of other hormones, the activity of the gastrointestinal tract and the rapid reproduction of normal and tumour cells. | produced by many tissues in the body, principally in the nervous and digestive systems | excess secretion may be caused by a rare neuroendocrine tumour called a ‘somatostatinoma’ – symptoms may include diabetes, gallstones, steatorrhoea and diarrhoea.
NB Chemically altered equivalents (analogues) of somatostatin (SSAs) can be used as a medical therapy to control excess hormone secretion and/or neuroendocrine tumour (NET not NEC) growth | |
| Steroid Hormone | is responsible for many of the physical characteristics specific to adult males. It plays a key role in reproduction and the maintenance of bone and muscle strength | produced by the testes and ovaries, with small quantities being produced by the adrenal glands in both sexes | The effect excess testosterone has on the body depends on both age and sex – in children it can lead to precocious puberty and may result in infertility. In women – it has been associated with PCOS – and increased levels can cause acne, body and facial hair and deepening of the voice In men – it has been associated with mood changes, irritability, but may also have other health consequences such as lowered sperm count, sexual dysfunction, heart and liver problems, acne, insomnia, sleep apnoea. . . | |
| Peptide hormone | controls production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland | is produced and released into the bloodstream by the pituitary gland | excess TSH can lead to an underactive thyroid gland or hypothyroidism. | |
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| plays vital roles in digestion, heart and muscle function, brain development and maintenance of bones | it is secreted into the bloodstream by the thyroid gland | too much thyroxine is known as thyrotoxicosis may be caused by overactivity of the thyroid gland (hyperthyroidism), as in Graves’ disease, inflammation or a benign (non-cancerous) nodule or growth. too little thyroxine is known as hypothyroidism. | |
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| alongside thyroxine, triiodothyronine plays vital roles in digestion. heart and muscle function, brain development and bone maintenance. | Approximately 20% of triiodothyronine is secreted into the bloodstream directly by the thyroid gland. The remaining 80% is produced from conversion of thyroxine by organs such as the liver and kidneys. | too much is known as thyrotoxicosis may be caused by overactivity of the thyroid gland (hyperthyroidism), as in Graves’ disease, inflammation or a benign (non-cancerous) nodule or growth. too little is known as hypothyroidism. | |
| VIP (Vaso-active Intestinal Peptide) | Polypeptide | is a potent vasodilator, regulates smooth muscle activity, epithelial cell secretion, and blood flow in the gastrointestinal tract. It also stimulates the secretion of electrolytes and water by the intestinal mucosa. | secreted by cells throughout the intestinal tract and pancreatic islet cells. | excess VIP can be associated with a rare neuroendocrine cancer of the pancreas called a VIPoma – too much VIP can lead to WDHA syndrome : profuse watery diarrhoea, hypokalaemia, achlorhydria( reduced stomach acid), lethargy, muscular weakness, nausea, vomiting, and cramp-like abdominal pain |
| Steroid Hormone | Vitamin D is actually a hormone rather than a vitamin; it is required to absorb calcium from the gut into the bloodstream, it is important for normal growth and development of bones and teeth, and may also play a role in the body’s immune system and heart health too | Vitamin D is mostly produced in the skin in response to sunlight and is also absorbed from food eaten (about 10% of vitamin D is absorbed this way) as part of a healthy balanced diet. The liver and kidneys convert vitamin D, into the active hormone, which is called calcitriol. | Vitamin D deficiency is very common – and though excess Vitamin D is incredibly rare it can be toxic – Importantly, toxicity almost exclusively in people who take long-term, high-dose supplements without having their blood levels monitored – symptoms associated with excess vitamin D are similar to and include hypercalcaemia |