Jun 30, 2022

Hypothalamus: definition, role and associated diseases

 The hypothalamus, also called the infundibulo-tuberian region, is an organ of the central nervous system located above the pituitary gland and in contact with the cerebellum. 

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The hypothalamus is part of the brain. The brain includes the cerebral hemispheres, the diencephalon, the brain stem and the cerebellum. The diencephalon is covered by the cerebral hemispheres and includes three gray matter regions: the thalamus, the hypothalamus and the pineal gland. The hypothalamus is a small structure of 4 to 5 g and 4 cm3 in volume, located at the base of the brain. It can be arbitrarily divided into a medial and a lateral part. The medial part has three regions, anterior, middle and posterior. It is connected to the pituitary gland below by the pituitary stalk. The hypothalamus is made up of several nuclei containing nerve cells: supraoptic nuclei, paraventricular nucleus, infundibular nucleus, accessory nuclei... These nuclei are the places where hypothalamic hormones are produced. These hormones are produced by the hypothalamus but stored and then released by the posthypophysis. These two hormones are the antidiuretic hormone ADH and oxytocin.


The hypothalamus is under the control of the higher brain centers. In connection with the pituitary gland, it secretes neurohormones and is involved in endocrine and autonomic nervous system regulation. The term hypothalamus-pituitary axis is used to designate all the relationships established between the hypothalamus and the pituitary gland. The hypothalamus is the main integrating organ for the regulation of the internal environment, the sleep-wake rhythm, as well as the growth, body and mental development and reproduction of the species.


1. What is the purpose of the hypothalamus?

The hypothalamus is a very important integrating nerve center with an endocrine function. The hypothalamus is the center of all homeostatic controls. It is the regulator of physiological functions. It is directly involved in the regulation of the autonomic nervous system, itself involved in the functioning of the heart and vessels, respiration, mobility of the digestive tract, glandular secretions... in the regulation of thirst and water balance, through the stimulation of osmoreceptors, specific receptors sensitive to variations in the concentration of solutes, mainly sodium ions Na, in body fluids; in the regulation of appetite and satiety, through receptors sensitive to variations in blood concentrations of nutrients (glucose, amino acids...); in the regulation of temperature and body temperature, through the stimulation of osmoreceptors. ); in the regulation of body temperature, thanks to the existence of thermoreceptors sensitive to blood temperature and playing the role of thermostat; in the regulation of the sleep/wake cycle, but also in the regulation of biological impulses, in particular sexual impulses, hormonal secretions.

The hypothalamus is the endocrine brain of the body since it controls the secretion of all the endocrine glands of the body: TRH (thyreo releasing hormone) which stimulates the secretion and release of pituitary TSH (which stimulates the thyroid gland); GnRH ( gonadotrophin releasing hormone) which causes both FSH and LH release ( which regulate the secretion of the sex glands) ; CRF (cortico releasing factor) which promotes the release of ACTH from the pituitary gland and its synthesis (action on the adrenal gland which secretes cortisol). The other hypothalamic hormones are antidiuretic hormone, which regulates water balance, and oxytocin, which regulates uterine contractions during childbirth and the secretion of breast milk during lactation.) These 2 hormones are secreted in the hypothalamus and then transported by the pituitary stem to the posterior pituitary gland or post pituitary gland where they are stored.


2. What are the diseases of the hypothalamus?

The majority of hypothalamic dysfunction syndromes affect the hypothalamic-pituitary-adrenal axis. Because it is difficult for physicians to diagnose a specific gland that is not functioning properly, the disorders are often called hypothalamic-pituitary disorders.

Hypothalamic syndromes are a collection of endocrine, metabolic, neurological and other systemic signs and symptoms that can be caused by a wide range of disease processes. This malfunction of the hypothalamus which leads to the appearance of certain symptoms such as thirst and hunger disturbances, poor regulation of body temperature, diabetes insipidus (which is characterized by a difficulty for the organism and more precisely the kidneys to concentrate urine resulting in a significant urine leakage and intense thirst), adipsia (a tendency not to feel the need to drink for a long period of time), poor assimilation of sugars and fats leading to the appearance of obesity or, on the contrary, thinness, sleep and character disorders. The clinical syndrome depends on the location and extent of the underlying lesion. The lesion may be very small and affect only specific hypothalamic nuclei, resulting in discrete symptoms; on the other hand, larger lesions manifest with a variety of problems. There are many causes of hypothalamic dysfunction. The most common are surgery, brain injury, brain tumors (craniopharyngiomas, optic nerve gliomas), and radiation therapy to the brain. Other causes of hypothalamic syndrome are eating disorders (anorexia), extreme weight loss, blood vessel problems in the brain (aneurysm, pituitary apoplexy, subarachnoid hemorrhage...), genetic disorders, such as anorexia, anorexia, or anemia. ), genetic disorders such as Prader-Willi syndrome, familial diabetes insipidus, Kallmann syndrome, infections and inflammations (histiocytosis and sarcoidosis) due to certain immune system diseases, Frohlich syndrome.

Cocaine addiction has recently been associated with hypothalamic dysfunction. Diets high in saturated fatty acids cause mitochondrial dysfunction and an inflammatory response in the hypothalamus, which produces hypothalamic dysfunction, which promotes obesity.

The hypothalamus may be the site of a tumor resulting in various disorders of hormonal function. The cessation of hormone secretion from the hypothalamus is directly related to the size of the tumor. The tumor is characterized by various symptoms: headaches, neurological disorders, visual field impairment, pallor, asthenia (fatigue), absence of menstruation, hair loss, diabetes insipidus, etc. Craniopharyngiomas are rare tumors. Hypothalamic hamartomas (HH) are rare benign neural tumors that cause epilepsy, behavioral disorders and precocious puberty. Germinomas are rare malignant tumors, representing 0.5 to 2% of primary intracranial tumors but 50 to 60% of germinal tumors of the central nervous system. The age at diagnosis varies from 3 to 21 years.


3. How is the hypothalamus treated?

Treatment depends on the cause of the hypothalamic dysfunction and the signs and symptoms presented by the patient. For tumors, surgery or radiation therapy may be necessary. If hypothalamic hamartomas are symptomatic with uncontrolled seizures, surgery is recommended. Thermoablation and radiosurgery may also be used. In some cases, especially when the tumor is not progressing or is not an immediate risk, no treatment for the tumor is initiated. Instead, treatments are offered to relieve any symptoms caused by the tumor (headaches, seizures). For hormonal deficiencies, therapeutic hormone replacement is used. Nutritional counseling and certain medications may be used to regulate the patient's appetite. Delayed puberty in Frohlich's syndrome is treated in males with human chorionic gonadotropin and later with estrogen and later with estrogen-progestin. Kallmann's syndrome requires lifelong sex hormone replacement.


4. Which doctors specialize in the hypothalamus?

Doctors who specialize in the hypothalamus are endocrinologists. Endocrinologists detect and treat diseases of the endocrine glands: hypothalamus (diabetes insipidus, etc.) pituitary gland (acromegaly, prolactin adenoma, cushing's disease, adenomas, etc.) thyroid gland (goiter, nodules, hyper- and hypo-thyroidism, thyroid cancer, etc.) adrenal gland (Addison's disease, etc.) ovaries and testicles (gonadal insufficiency, hair problems, etc.). Neurologists, neurosurgeons and neuroradiologists are involved in the management of hypothalamic-pituitary pathologies.


5. What are the medical examinations of the hypothalamus?

The diagnostic work-up of hypothalamic dysfunction depends on the clinical condition, signs and symptoms of the patient. The classic workup includes hormone assays (serum cortisol, serum estrogen, pituitary hormones such as adrenocorticotropic hormone, growth hormone, thyroid stimulating hormone, luteinizing hormone, follicle stimulating hormone, prolactin), testosterone, thyroid hormones, sodium levels and blood and urine osmolality. Other diagnostic tests include pituitary MRI or CT scan (for urgent cases), visual field test, genetic analysis, autoimmune markers...


Sources :

Université Médicale Virtuelle Francophone - Dr. Chantal KOHLER, Les glandes endocrines, Collège universitaire et hospitalier des histologistes, embryologistes, cytologistes et cytogénéticiens (CHEC), support de cours 2010-2011

Encyclopédie médicale weebly - Axe hypthotalamo-hypophysaire

Science direct - Giustina A, Braunstein GD. Hypothalamic syndromes. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric. 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 10.

Science direct - Marshall JC,Eagleson CA,McCartney CR, Hypothalamic dysfunction. Molecular and cellular endocrinology. 2001 Oct 25

Semantic Scholar - Zhang S,Zhornitsky S,Le TM,Li CR, Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence. The international journal of neuropsychopharmacology. 2019 Dec 1

Europe PMC - Samodien E,Johnson R,Pheiffer C,Mabasa L,Erasmus M,Louw J,Chellan N, Diet-induced hypothalamic dysfunction and metabolic disease, and the therapeutic potential of polyphenols. Molecular metabolism. 2019 Sep

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