The Endocrine System. Endocrine Glands and Hormones.
Hypothalamus
The hypothalamus is a small region of the brain near the pituitary gland that functions as a gland also. Saper and Lowell (2014) of Current Biology say that the hypothalamus is the earliest parts of the brain to form. It is also the smallest, weighing in at about 4 gm of the average 1400 gm of the adult human brain (Saper & Lowell, 2014, p. 1111). Despite its small size, the hypothalamus has several important functions including releasing hormones, regulating body temperature, maintaining biological functions, controlling appetite, managing sexual behavior and controlling emotional responses. According to Han (2018) of Healthline, the hypothalamus is divided into three regions each with its own nuclei, which is a cluster of neurons that perform the vital functions listed above (Han, 2018). Each section of the hypothalamus secretes hormones that have specific functions.
Many of the hormones that the hypothalamus produces function to stimulate the pituitary gland to produce hormones that are involved in the functioning of the body. The nuclei of the anterior or supraoptic region of the hypothalamus secretes a called corticotropin-releasing hormone (CRH). This hormone is secreted when physical and emotional stress trigger it. CRH signals the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then triggers the production of cortisol, an important stress hormone that is also credited with causing weight gain, sleep disturbances and other stress-related issues. The hypothalamus also secretes thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary gland to produce thyroid-stimulating hormone (TSH). TSH is involved with the functioning of the heart, gastrointestinal tract, and muscles (Han, 2018). Gonadotropin-releasing hormone (GnRH) is another hormone secreted by the supraoptic region of the hypothalamus. GnRH causes the pituitary gland to produce reproductive hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (Han, 2018). Other hormones associated with this region of the hypothalamus include oxytocin which controls behaviors and emotions such as sexual arousal, trust, recognition, childbirth, lactation and maternal behavior. Vasopressin, or antidiuretic hormone (ADH), regulates hydration levels in the body. It signals the kidneys to absorb water. The supraoptic region of the hypothalamus also releases Somatostatin, or Growth hormone–inhibiting hormone (GHIH), which stops the pituitary gland from releasing certain hormones, including growth hormones and thyroid-stimulating hormones (Han, 2018). The supraoptic region of the hypothalamus also helps to regulate body temperature through sweat and maintains circadian rhythms (Han, 2018).
The middle area of the hypothalamus is known as the tuberal region. The nuclei in this region help to control appetite and are involved in stimulating growth by releasing growth hormone-releasing hormone (GHRH). GHRH stimulates the pituitary gland to produce growth hormone and then GHIH from the supraoptic region of the hypothalamus stops the growth at the appropriate time. The posterior region, or the mammillary region, helps to regulate body temperature by causing shivering and blocking sweat production. While its function is not entirely clear, the mammillary portion of the hypothalamus may also be involved in memory functions (Han, 2018).
Other hormones associated with the hypothalamus include prolactin-releasing hormone (PRH), which stimulates the pituitary gland to begin milk production and prolactin-inhibiting hormone (PIH) or dopamine. PRH causes the pituitary to release prolactin and that stimulates milk production. Dopamine inhibits prolactin, and stops milk production. Prolactin also prepares the body during pregnancy to produce breast milk. Prolactin function also depends upon estrogens, progesterone, and other hormones. Dopamine also prevents milk production in non-pregnant women. Melanocyte-inhibiting hormone (MIH) functions to stimulate the pituitary gland to produce melanin which provides the bodies response to UV light exposure.
Disorders of the hypothalamus can result in appetite, temperature and sleep disorders. Hypothalamic obesity is an example of an appetite disorder caused by a major hypothalamic injury. Comorbidities include diabetes, dyslipidemia, obstructive sleep apnea and mood disorder. Wisse (2019) says that disorders of the gland are often referred to as hypothalamic syndrome. Hypothalamic syndrome can affect physical function in many areas including childbirth, emotions, behavior, memory, growth, production of breast milk, salt and water balance and sex drive (Wisse, 2019). Hypothalamic syndrome is diagnosed through blood and urine tests, hormone injections along with timed blood samples, MRI or CT scans, and possibly a visual field eye exam to see if it is a tumor causing the problem (Wisse, 2019).
The treatment for hypothalamic disorders depend upon the type of dysfunction. Tumors are usually treated with radiation or surgery. Hormonal deficiencies are treated with hormone replacements, but there are no medications that help with temperature or sleep regulation, but there are pharmacological treatments that can regulate appetite (Wisse, 2019). Melatonin is a naturally occurring chemical that can help to regulate sleep disorders and THC and CBD may also help to regulate sleep and eating disorders.
Anterior Pituitary
The pituitary gland is located at the base of the brain and is connected to the hypothalamus. It has two distinct regions, the anterior lobe or the adenohypophysis and the posterior lobe, the neurohypophysis. There is also an intermediate lobe between the anterior and posterior lobes. As discussed above, the hypothalamus regulates the hormones that the pituitary gland secretes. El Sayed, Fahmy, and Schwartz (2019) of Stat Pearls explain that the anterior pituitary is derived from embryonic ectoderm and secreted five endocrine hormones from five different types of endocrine cells (El Sayed, Fahmy, & Schwartz, 2019). The release of hormones from the pituitary gland are caused by the hypothalamus responding to stimuli and releasing hormones that go into the blood supplying vessels between the hypothalamus and the anterior pituitary gland.
The hormones released by the anterior pituitary gland include Growth hormone (GH) also known as somatotropin. GH can affect nearly every cell in the body by binding to growth hormone receptors, which then recruit and activate signaling molecules such as insulin receptors, proteins and calcium (El Sayed, Fahmy, & Schwartz, 2019). GH mainly targets bones and skeletal muscles. It also affects the metabolism of fats, proteins and carbohydrates, which then indirectly relates to skeletal growth. GH is both stimulated and suppressed by hormones from the hypothalamus, GHRH and GHIH respectively.
The anterior pituitary gland also secretes several other hormones. One of those is prolactin (PRL). PRL’s main target are mammary glands, ovaries and testes. It is secreted and transported similarly to GH and is also regulated by the hypothalamus. However, the hypothalamus mainly inhibits PRL (El Sayed, Fahmy, & Schwartz, 2019). PRL functions mainly to stimulate mammary gland growth and milk production. It can also inhibit GnRH secretions from the hypothalamus. Two other hormones that the anterior pituitary gland secretes are follicle stimulating hormone (FSH) and luteinizing hormone (LH). These hormones mainly affect the ovaries and testes. Their release is regulated by GnRH. FSH and LH regulate the functions of the gonads. FSH stimulates growth and development of ovulation and secretion of estrogens in females. In males, FSH is used to generate sperm and stimulate testosterone secretion (El Sayed, Fahmy, & Schwartz, 2019).
Another hormone that the anterior pituitary gland secretes is thyroid stimulating hormone (TSH). Like FSH and LH, TSH stimulates the release of proteins that serve the function that these hormones regulate. The function for which TSH is responsible is stimulating thyroid hormones from the follicles of the thyroid. TSH also helps to maintain the structural integrity of the thyroid gland. Adrenocorticotrophic hormone (ACTH), another anterior pituitary hormone, targets the adrenal glands. Its function is also carried out by proteins it stimulates to act. ACTH is inhibited by the hypothalamus. Its main function is to stimulate secretion of adrenal cortex hormones during stress (El Sayed, Fahmy, & Schwartz, 2019).
Melanocyte-stimulating hormone (MSH) is believed to be secreted from the intermediary lobe of the pituitary gland. Its main function is to darken the skin, but it also has other functions. Recent studies on inflammation have shown that what is also known as alpha-MSH can help to reduce inflammation. Singh and Mukhopadhyay (2014) of BioMed Research International say, [𝛼-MSH] is primarily a pigmentary hormone of the vertebrates and largely influences immune reactions in the host for controlling inflammation in the brain and peripheral organs. Both in vitro and in vivo studies have confirmed that, inside the host, 𝛼-MSH reduces the concentration of proinflammatory mediators” (Singh & Mukhopadhyay, 2014, p. 1). These recent discoveries may help to prolong life.
Disorders of the anterior pituitary gland include hypopituitarism, which is a deficiency of the gland itself and can result in dwarfism or premature aging. Other glands can be affected by deficiencies in the pituitary gland including the adrenal glands, they thyroid gland and the gonads. Kim (2015) of Endocrinology and Metabolism says, “The diagnosis of hypopituitarism is made by measuring basal hormone levels in the morning fasting status or performing stimulation tests if necessary” (Kim, 2015, p. 448). The treatment for hypopituitarism is using replacement hormones. Kim (2015) says, “Most hypopituitarism symptoms are irreversible [and] may require lifetime treatment” (Kim, 2015, p. 450). This is especially true of the damage done by tumors on the pituitary gland. They are treated with radiation, chemotherapy and surgery.
Posterior Pituitary
The posterior pituitary is also known as the neurohypophysis because it is derived from neural tissue. It is directly connected to the hypothalamus via nerves rather than blood vessels. The posterior pituitary secretes only two hormones, antidiuretic hormone (ADH) or vasopressin and oxytocin. Vasopressin targets renal distal convoluted tubules, collecting duct, and vascular smooth muscle cells (El Sayed, Fahmy, & Schwartz, 2019). It works by targeting proteins that results in higher concentrations of calcium that performs the action described above. The stimulator for vasopressin is an increase in osmolality of the blood. Osmolality refers to the concentration of dissolved particles of chemicals and minerals -- such as sodium and other electrolytes. It also responds to a decreased volume of blood circulating in the body. Vasopressin is also a vasoconstrictor (El Sayed, Fahmy, & Schwartz, 2019).
Oxytocin targets cells in the mammary glands and the uterine muscles and the myofibroblast cells in the seminiferous tubules in men. In other words, it is involved in sexual reproductive functions. One thing that stimulates oxytocin is a baby suckling and the baby’s head in the uterus during delivery. It is regulated by positive feedback from the body. Oxytocin stimulates milk production in response to sucking. It also stimulates uterine contraction during labor (El Sayed, Fahmy, & Schwartz, 2019).
Disorders of the posterior pituitary gland can result in diabetes and other disorders related to an oxytocin deficiency such as an inability to lactate, vaginal dryness, and decreased libido. The diagnosis is usually made by the complaint of symptoms and can be treated with over the counter products such as lubricants and with medications such as Viagra.
Thyroid
The thyroid gland is a butterfly-shaped gland located in the front of the trachea and just below the larynx. It has two lobes attached to one another by an isthmus. Sargis (2019) of Endocrine Web explains that the thyroid regulates metabolism with its two main hormones, triiodothyronine (T3) and thyroxine (T4). They thyroid also secretes calcitonin. Both T3 and T4 take iodine from the blood to basically produce themselves, and they control metabolism, which is the conversion of oxygen and calories to energy. A normally functioning thyroid gland produces about 80% T4 and 20% T3, as T3 is stronger. Calcitonin helps control blood calcium levels (Sargis, 2019).
Several diseases and disorders are associated with the thyroid gland. They may develop naturally with age or be the result of an injury, disease or malnutrition. Usually they are associated with too little or too much thyroid hormones (hypothyroidism and hyperthyroidism), abnormal thyroid growth, nodules or lumps on the thyroid or thyroid cancer.
Hyperthyroidism is detected by radioiodine uptake test, thyroid scan, or ultrasound. It is treated with radioactive iodine, anti-thyroid medications or beta blockers (Mayo Clinic, 2018). Hypothyroidism can be detected with a blood test. Its treatment involves daily use of the synthetic thyroid hormone levothyroxine (Levo-T, Synthroid, others) (Mayo Clinic, 2018). Goiters, are an example of an unusual growth on the thyroid. They are caused by a lack of iodine in the diet and are controlled by dietary means. They are detected by sight as they are usually quite noticeable. An abnormal growth may also be cancer. Thyroid lumps are usually aspirated and tested for cancer. Blood tests, imaging and genetic testing are also done. Thyroid cancer is treated with surgery to remove the cancer, radioactive iodine, hormone therapy, chemotherapy, and other cancer therapies (Mayo Clinic, 2019).
Parathyroid
The parathyroid gland are located in the area behind the thyroid gland but are not related to it. There are four parathyroid glands, each about the size of a grain of rice. The hormone that these glands release regulate the body’s calcium levels (Sargis R. , 2015). Calcium is important to many functions of the body including nervous and muscular system function. The parathyroid hormone (PTH) influences the cells of the bones to release calcium. PTH also regulates the amount of calcium that is absorbed, how much is excreted, and how much is stored in the bones. PTH tells the bones when to release calcium as the body needs it. PTH also increases the amount of vitamin D is formed and active in the body. Active vitamin D is important in the absorption of calcium and phosphorous in the intestines (Sargis R. , 2015).
When PTH levels are too high or too low there are some diseases which can occur such as hyperparathyroidism. This is when the parathyroid glands secrete too much PTH. Hypoparathyroidism is the opposite: the parathyroid glands do not make enough PTH. This leads to diminished levels of calcium in the blood and increased levels of phosphorous in the blood. Hypoparathyroidism is rare. Osteoporosis is another disorder that is attributed to the parathyroid glands. When hyperparathyroidism is an issue, then there is too much calcium in the blood and not enough in the bones because the bones are constantly releasing the calcium they have stored based on the stimuli from PTH (Sargis R. , 2015). With inadequate levels of calcium in the bones, they lose hardness and density. People with osteoporosis become susceptible to bone injury.
Hyperparathyroidism can be diagnosed with a blood test or bone density screening (bone densitometry), a urine test or imaging of the kidneys. Outpatient surgery to remove the malfunctioning parathyroid gland, or 3 of the 4 glands usually takes care of the issue. Medications that treat hyperparathyroidism include calcimimetics, biphosphates and hormone replacement therapy (Mayo Clinic, 2019). Postmenopausal osteoporosis can be treated with a variety of medications including alendronate (Binosto, Fosamax), ibandronate (Boniva), risedronate (Actonel) and zoledronic acid (Reclast). Hypoparathyroidism can be detected with blood or urine tests. Treatment consists of taking vitamin D, calcium tablets (like Tums), or Parathyroid hormone (Natpara) (Mayo Clinic, 2018). All of these disorders can be helped by proper nutrition.
Adrenal Cortex
The adrenal glands sit on top of the kidneys. They are triangular shaped and are about 1.5 inches high and 3 inches long. Each gland has two parts, the outer part or the cortex and the inner part or the medulla. The adrenal cortex, the outer part of the gland, produces two groups of hormones, glucocorticoids and mineralocorticoids. The reléase of the former is caused by the hypothalamus gland and the pituitary gland; the latter is caused by the kidneys. Glucocorticoids include cortisol. Cortisol regulates metabolism; specifically it regulates how the body converts fats, proteins and carbohydrates to energy. Cortisol also helps the body respond to stress by regulating blood pressure and cardiovascular function. The mindralocorticoid that the cortex also produces is aldosterone which helps to control blood pressure by maintaining the right balance of salt and wáter (Sargis R. , An Overview of the Adrenal Glands, 2015).
Adrenal Medulla
The inner part of the adrenal glands, or the medulla, produces hormones that are not essential to life. The hormones of the medulla are released when the sympathetic nervous system is stimulated. That usually occurs when a person is stressed. The hormones released by the adrenal medulla are related to the famous fight or flight response. Those hormones are epinephrine and norepineprhine. Epinephrine is also known as adrenaline. Adrenaline responds to stress by increasing the heart rate and rushing blood to the muscles and brain. Adrenaline also spikes blood sugar levels by converting glycogen to glucose in the liver. Norepinephrine also helps the body respond to stress. It causes the blood vessels to narrow though causing high blood pressure.
Several disorders and diseases of the adrenal glands exist. One common one is Addison’s disease. It occurs when the cortex fails to produce enough cortisol or aldosterone. Addison’s disease can be detected through a blood test, an ACTH stimulation test, an insulin-induced hypoglycemia test or imaging. Addison’s disease is treated with medications including Hydrocortisone (Cortef), prednisone or methylprednisolone to replace cortisol and Fludrocortisone acetate to replace aldosterone (Mayo Clinic, 2019). Adrenal cancer, while very rare, can occur and is an aggressive form of cancer. It is diagnosed through blood tests, imaging and biopsy. It is treated with radiation, chemotherapy and perhaps surgery. The National Institute of Health (NIH) (2017) says that growths on the adrenal glands are usually not cancerous and do not cause symptoms, but they may produce hormones that cause some hormone levels to be too high. This can lead to Cushing syndrome, which occurs when cortisol levels are too high in the body. Cushing syndrome is diagnosed through blood, urine or saliva tests, imaging or a petrosal sinus sampling. Cushing syndrome is treated with surgery or medications such as those that control excessive production of cortisol at the adrenal gland including ketoconazole, mitotane (Lysodren) and metyrapone (Metopirone) (Mayo Clinic, 2019). Primary hyperaldosteronism, when aldosterone levels are too high, and pheochromocytoma, which is the production of too much adrenaline, are also possible (NIH, 2017). Columbia Surgery (2019) says primary hyperaldosteronism is diagnosed with blood and urine tests, and treated with surgery or medication such as aldosterone-antagonists like spironolactone or eplerenone (Columbia Surgery, 2019). Pheochromocytoma is diagnosed through blood and urine tests. It is treated with alpha blockers, beta blockers, a high salt diet or surgery (Mayo Clinic, 2018).
Ovary
The ovaries are the female gonads and the primary female reproductive organs. They have 3 functions: to secrete hormones, protect the eggs with which a female is born, and to reléase the eggs for fertilization. They are located on either side of the Fallopian tubes and are attached to the uterus with tissue. They are the size of a large grape. The hormones produced by the ovaries include estrogen and progesterone along with some lesser hormones too. Bradford (2017) of Live Science says there are three types of estrogen: estrone, estradiol and estriol. Estrogen is used to develop female physical adult characteristics such as breasts and larger hips and to help with the reproduction cycle (Bradford, 2017). Progesterone is released after the mature egg is released from the ovary into the uterus. Progesterone makes the lining of the uterus thicker and receptive of the egg espeically if it is fertilized. Progesterone is produced by the new cells that grow where the egg was released, or the corpus luteum, which acts as a temporary gland. If the egg is not fertilized, the progesterone production stops. If the egg is fertilized then the corpus luteum stops producing progesterone and the placenta of the fetus takes over production of it (Bradford, 2017).
Ovarian cysts can cause lots of problems. Cysts are growths on the ovaries. They are quite common and most women will have them. Usually they are asympotomatic. However, polycystic ovary syndrome (PCOS) is a disorder caused by multiple cysts growing on the outer edge of the ovaries. This condition is caused by a lack of hormones that allow an egg to be released from the follicle. PCOS can lead to infertility and other serious complications such as heart disease, diabetes or stroke (Bradford, 2017). PCOS is diagnosed with a pelvic exam, blood test and/or ultrasound. It is treated with birth control pills or progestin therapy (Mayo Clinic, 2017). Cysts can become cancerous also. Approximately one in 75 women will develop ovarian cancer. Ovarian cancer is diagnosed through a pelvic exam, blood tests, imaging and surgery. It is treated with surgery to remove one or both ovaries, and/or the uterus. It may also be treated with chemotherapy or targeted therapy and palliative treatments (Mayo Clinic, 2019).
Testes
Testes are the male gonads. They are located in the groin of males beneath the penis in the scrotum. Their main function is to produce and store sperm. Biggers (2018) of Healthline explains that the testes also produce testosterone and other male hormones called androgens. Testes are oval shaped and made up of seminiferous tubules, in which sperm is created. The tubules are lined with the epithelium made of Sertoli cells that produce hormones that help in sperm production. Next to the tubules are the Leydig cells that produce testosterone and andogens (Biggers, 2018). Testosterone causes the development of adult male characteristics such as a deep voice and body hair. A condition caused by a testosterone deficiency is hypogonadism, which occurs with the body does not make enough testosterone. It is treated with hormone replacement therapy.
Pancreas
The pancreas is a gland and an organ. It is located in the abdomen and is part of the digestive system. It produces insulin, glucagon and somatostatin. The website, Hormone Health Network (2018) explains that somatostatin is a growth hormone inhibitor that can affect several areas of the body by impeding secretion of other hormones such as insulin. Several different tissues of the body produce somatostatin, but it is found primarily in the nervous and digestive systems. Somatostatin inhibits hormone production and unnatural rapid cell reproduction, such as those that cause tumors. It is also a neurotransmitter and plays a role in the gastrointestinal tract. It can regulate hormones from the hypothalamus, the pituitary and the pancreas. There somatostatin inhibits glucagon and insulin (Hormone Health Network, 2018). If somatostatin levels are too low, there will be high levels of other hormones. High levels of growth hormone can be a problem for instance. Too high of levels of somatostatin can cause a tumor that releases its own hormones. Other hormones are then suppressed and major health problems can occur (Hormone Health Network, 2018). Tumors caused by somatostatin can be detected with blood tests and imaging. They are treated by surgical removal. Low levels of somatostatin can be treated with a synthetic hormone that mimic somatostatin (Hormone Health Network, 2018).
Falck (2017) of Medical News Today says the pancreas has an endocrine function because it releases hormones directly into the bloodstream. Insulin regulates the glucose and sugar levels in the body. When insulin production is faulty, diabetes is the result (Falck, 2017). Insulin also functions to move glucose from the blood into muscles and other tissues so it can be used for energy. Insulin also helps the liver absorb glucose. When blood sugar levels decrease, pancreatic alpha cells release glucagon, which causes glycogen to be broken down into glucose in the liver. The glucose can then be released into the blood and restore energy (Falck, 2017).
Other issues with the pancreas are pancreatitis and pancreatic cancer. Pancreatitis is acute or chronic inflammation of the pancreas. It can lead to secondary diabetes. It is diagnosed with CT scan or ultrasound. It is treated by fasting for a few days, pain meds and/or IV fluids. Surgery to remove gallstones or duct blockages can also be performed to treat pancreatitis (Mayo Clinic, 2019). Cancer is another disorder of the pancreas. It is diagnosed with imaging. It is treated with chemotherapy, surgery, radiation or some combination. One other disorder of the pancreas, and the most common, is diabetes. Type 1 diabetes is an autoimmune disease. It occurs when the autoimmune system destroys the beta cells in the pancreas so it can no longer produce insulin. It is treated with insulin injections. Type 2 diabetes begins usually in mid to later life with the muscles, fat and liver cells can no longer process glucose. The pancreas reacts by producing more insulin, but cannot make enough, so the blood glucose levels are too high. It is also treated with insulin, diet, lifestyle changes or other medications that either lower glucose levels or raise insulin levels.
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