Hypothalamus JAAKE
Gland structure
The hypothalamus is located below the thalamus, above the brainstem. It is part of the limbic system. It is separated into three regions; anterior, tuberal, and posterior. However, the hypothalamus is sexually dimorphic, so structure varies for each gender.
Gland function
The main function of the hypothalamus is to maintain homeostasis. It does this through regulating hormone secretion and production, processing fear, controlling food intake, and responding to external stimulation, to name a few. The role of hormone regulation is very expansive, because these hormones control a wide variety of processes in the body, from milk let down (Oxytocin) to reward motivation (Dopamine.) Scientists also believe the hypothalamus has an affect on sexual orientation. This claim is not completely supported as of right now, but more research is being done.
Causes and risk factors of hypothalamic dysfunction
Common causes
- Surgery
- Head trauma (injury)
- Tumors such as craniopharyngiomas, optic never gliomas, histiocytosis and sarciodosis
- Radiation
Other causes and risk factors:
- Anorexia nervosa or bulimia
- Bleeding
- Genetic disorders that cause iron buildup within the body
- Infections and swelling (inflammation)
- Malnutrition
Genetic Risk Factors:
- Hereditary Hemochromatosis is disorder that causes the body to absorb excessive iron from diet. It is caused by mutations in the HAMP, HFH, HFH2, SCL40A1, and TFR2 genes. The excess iron can build up in the hypothalamus and damage these cells.
- Anorexia Nervosa can be linked to a mutation on chromosoI'm me 1, which deals with complex psychiatric disorder. This eating disorder disrupts the endocrine response and damage the hypothalamic centers that regulating eating and reproduction.
- Prader-Willis Syndrome is a genetic disorder that results from an abnormality of chromosome 15. It is still not clear how the genetic abnormality causes hypothalamic dysfunction.
Environmental Risk Factors:
- Excess Stress can cause the hypothalamus to shut down the body to prevent damage
- Malnutrition/ Eating disorders
- Sleep deprivation
- Prenatal exposure to alcohol
The dysfunction of the hypothalamus causes the receptor to not detect changes
Hypothalamus Dysfunction can cause:
- Chronic Fatigue Syndrome: when the system is over-stressed, the hypothalamus can shut down the body to protect the mind from further damage
- Kallmann Syndrome
- Ovulation disorders: The hypothalamus is responsible for stimulating the secretion of FSH and LH from the pituitary gland. Hypothalamic dysfunction can disrupt the specific pattern in the menstrual cycle and affect ovulation.
- Type 2 Diabetes Mellitus
- Metabolic Syndrome
- Narcolepsy: New proteins with mutations within genes that aid in orexin and hypocretin function found in the hypothalamus. These mutations lead to narcolepsy.
- Obesity: Damage to the hypothalamus promotes excessive eating and weight gain
Hypothalamic obesity is a complication in some survivors of brain tumors. The hypothalamus controls energy balance. When the hypothalamus is damaged, an individual's metabolism is geared toward energy storage, which leads to excessive eating and obesity.
The following is a link for a 4 minute video that describes Rohhadnet syndrome (Rapid-onset obesity with hypothalamic dysfunction, hypo ventilation, and autonomic dysregulation) which could be a result of hypothalamic dysfunction.
Hypo- and hyperactivity of the Hypothalamus
The hypothalamus regulates the secretions of hormones from the pituitary gland, throughout the body. Any dysfunction within the hypothalamus would therefore disrupt multiple functions.
A hyperactive hypothalamus would be sending an increased amount of hypothalamic tropic factors (HTF) to the pituitary gland to stimulate the release of pituitary hormones, which are either stimulating or inhibiting hormones. Depression has been linked to hyperactivity of the hypothalamus. Multiple studies have shown that depressed individuals have increased levels of cortisol within their systems. Cortisol release is done in the adrenal glands which is stimulated by the pituitary gland which is controlled by the release of corticotropin-releasing hormone from the hypothalamus. Polycystic Ovarian Syndrome (PCOS) is also caused by a hyperactive hypothalamus. The hypothalamus regulates the menstrual cycle by releasing gonadotropin-releasing hormone (GnRH). GnRH is responsible for signaling the pituitary gland to release both luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH trigger an ovary to start producing estrogen, which stimulates the release of an egg. When the egg changes into the corpus luteum, which causes the levels of progesterone to rise drastically. If an egg isn’t fertilized both estrogen level and progesterone levels drop dramatically. This drop is responsible for menses. The drop in progesterone and estrogen is detected by the hypothalamus and this process repeats. If the egg does not change and a cyst occurs instead, the hypothalamus increases it’s production of GnRH. The GnRH, as discussed earlier triggers FSH and LH which increases estrogen leaving the menstrual cycle to be controlled by high levels of estrogen and no production of progesterone. This results in PCOS.
A hypoactive hypothalamus would send a decreased amount of hypothalamic tropic factors to the pituitary gland, which would not be as stimulating to the pituitary gland. This would result in a decrease of stimulating and inhibiting hormones being released from the pituitary gland. Hypothryroidism could occur due to hypoactivity of the hypothalamus. With the hypothalamus not releasing and adequate amount of HTF, the pituitary is not as simulated, therefore, it is releasing less thyroid stimulating hormone (TSH) resulting in hypothyroidism. This disease can result in cold intolerance, constipation, depressed mood, hoarseness, mental slowing, menstrual cycle changes, and weight gain.
Hypothalamic dysfunction can cause children and adolescents have growth failure and disorders of puberty, which can both be delayed and precious. Adults can be present with dementia, disturbances in appetite and sleep, and hormonal deficiencies.
Diagnostics
Symptoms:
- Headaches
- Loss of vision
- Constipation
- Fatigue
- Weight gain
- Dizziness
Hypothalamus dysfunction affects the controlling of the pituitary gland which controls many hormones. In order to diagnose these complications, specific tests are done including blood and urine tests, MRI's or CT scans of the brain, and visual eye exams.
- Blood and urine tests help determine the levels of cortisol, estrogen, growth hormone, pituitary hormones, prolactin, tester one, and thyroid. An increase or decrease in production of these hormones may reveal the patient has hypothalamic dysfunction.
- ADH is a test that measures the amount of antidiuretic hormone in the blood. ADH is produced in the hypothalamus and controls the amount of water excreted in urine. High or low levels of ADH may reveal problems within the hypothalamus. Normal values may range from 1-5 pg/ mL.
- Corticosteroid releasing hormone (CRH) is secreted by the hypothalamus in response to stress. Normal blood levels of CRH are low, but can be high in the second and third trimesters of pregnancy. High levels may reveal problems with the hypothalamus. Normal levels is less than or equal to 34 pg/mL.
- Thyrotropin-releasing hormone (TRH) is released by the hypothalamus, which tells the pituitary gland to produce thyroid-stimulating hormone (TSH). TRH test is used to detect early hyperthyroidism, which can be a result of hypothalamic dysfunction. Normal values of TSH is .3-5mU/mL. Patients are injected TRH and the baseline of TSH will rise to 10-20mU/mL. Those with too much thyroid hormone will not show a rise. Low or high values of TSH can indicate failure of the hypothalamus.
- MRI's or CT scans create a detailed picture of the hypothalamus to assess the size of the gland and identify masses or tumors.
- Visual eye exams Can check for vision loss and determine whether the condition is improving or worsening. They can also help detect the presence of a tumor.
Thyroid-stimulating hormone (TSH) screening of newborns will not detect the dysfunction. Hypothalamic dysfunction could be suspected in infants with cholestasis, poor growth, hypoglycemia, problems with the nervous system, or pituitary insufficiency. A central nervous system imaging may also be performed to look for malformations or hypothalamic lesions.
This is a CT scan of a craniopharyngioma, a brain tumor found near the pituitary gland. The presence of this tumor is a common cause for hypothalamic dysfunction.
CT scan of craniopharyngioma
Treatments
When hypothalamic hormones are over or under secreted, it is usually a result of either a tumor or a disconnection of some kind between the pituitary and the hypothalamus. Since most of the hormones secreted from the hypothalamus act on the pituitary gland to secrete something else, the treatments for alterations in hypothalamic function usually act as a hormone replacement or adjustment for that the pituitary gland would have secreted, had the hypothalamus given it the direction to secrete it. If the reason for the hypothalamic dysfunction is due to a tumor, radiation or surgery would be implemented to attempt correcting the problem.
Specific hormone dysfunctions related to the hypothalamus:
- If the hypothalamus sends the signal to the pituitary to release more ADH than required on a regular basis, more water gets retained than necessary resulting in an excess retention of water and hyponatremia. Treatment for this chronically includes a fluid restrictive diet, vasopressin-2 receptor antagonists, or, if those do not work, increasing the intake of solutes. Inhibition of this hormone’s release is usually caused by an intake of alcohol or caffeine and will correct itself with time and a higher intake of water.
- If CRH gets released in excess from the hypothalamus, ACTH will also get over released, causing an increase in cortisol levels. In the vast majority of cases, though, an increase in cortisol levels is due to a disruption in the negative feedback loop of CRH, ACTH, and cortisol, so a dysfunction in any of those could result in an over or under secretion of CRH, exacerbating the problem. To correct the over secretion of cortisol, drugs are under investigation to either decrease CRH or ACTH levels, but they are reported to not be the most effective. The most common reason for elevated cortisol levels (Cushing’s syndrome) are pituitary tumors, so removal of those will correct the CRH-ACTH-cortisol mechanism.
- Alterations in GHRH levels can either lead to an under or oversecretion of growth hormone from the pituitary gland. If not enough GHRH gets created, then not enough growth hormone will get released. Thus, the treatment for that would be growth hormone therapy. If too much GHRH or growth hormone gets released (usually due to a tumor), either surgery to remove a tumor occurs or Sandostatin/Somatuline Depot can be given as synthetic somatostatin, which is growth hormone inhibiting hormone from the hypothalamus.
- An underproduction of oxytocin can be treated with synthetic oxytocin medications such as carbetocin, syntocinon and pitocin. An overproduction of oxytocin is more linked to prostatic issues in men, and a way to treat this is to manipulate the levels of oxytocin.
- An underproduction of TRH is due to a tumor or an injury in the brain, so removing or shrinking the tumor would be the priority treatment for this patient. Additionally, treating with thyroid stimulating medications like levothyroxine can help simulate thyroid hormone in the body. A case of an overproduction of TRH is not known.
Importance
THE HYPOTHALAMUS IS THE MASTER GLAND. Many may argue that the pituitary gland is very important. Although that is true, there's a higher control, which is the hypothalamus. The hypothalamus controls the pituitary gland, which then regulates the activity of the endocrine glands. The hypothalamus contains many small nuclei that controls a variety of functions. This gland plays an vital role in the endocrine, as well as the nervous system. The hypothalamus controls body temperature, release of eight major hormones, food and water intake, sexual behavior, reproduction, circadian rhythm, and mediation of emotional responses.
References
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