By: Catherine Joachin

What is the hypothalamus?
The hypothalamus is the brain structure that connects the central nervous system to the endocrine system. It acts as the body’s central coordinating center, regulating metabolic functions by stimulating autonomic nervous system activity and hormone release (Cleveland Clinic, n.d.)
Functions of the hypothalamus
The hypothalamus primarily works to maintain homeostasis, a state of internal equilibrium. It achieves this through self-regulating physiological processes that stabilize body functions (Cleveland Clinic, n.d.). The pituitary gland, which secretes and releases the hormones that regulate these bodily functions, is controlled by signals from the hypothalamus (Shahid, Asuka & Singh, 2023). By sending out these signals, the hypothalamus can manage mood, sex drive, sleep-wake cycle, appetite, breast milk production, blood pressure, body temperature, and growth (Cleveland Clinic, n.d.; Sanchez Jimenez et De Jesus, 2023).
Through communications with the anterior and posterior pituitary, the hypothalamus is involved in the production and secretion of the following chemical messengers:
- Antidiuretic hormone (ADH), which helps maintain blood pressure and water volume. • Corticotropin-releasing hormone (CRH), which regulates metabolism and immune response. It is particularly responsive to stress.
- Gonadotropin-releasing hormone (GnRH), which influences the release of sex-related hormones
- Oxytocin. This hormone aids in childbirth and breast milk production
- Prolactin-controlling hormones, including dopamine and estrogen, are also involved in breast milk production
- Thyrotropin-releasing hormone (TRH), which regulates thyroid gland activity.
(Cleveland Clinic, n.d.; Sanchez Jimenez et De Jesus, 2023).
Hypothalamic dysfunction
Damage to the hypothalamus can impair the functioning of several physiological processes such as lactation and body temperature regulation (Sanchez Jimenez et De Jesus, 2023). Hypothalamic dysfunction can be caused by traumatic brain injury, tumors, infections, brain defects, swelling, or surgery (Cleveland Clinic, n.d.). Nutritional problems, radiation treatment (e.g., chemotherapy), genetic disorders, and inflammatory diseases may also lead to hypothalamus-related issues (Mount Sinai, n.d.).
Symptoms associated with hypothalamic dysfunction include:
• Irregular blood pressure (low or high)
• Infertility
• Poor bone health
• Water retention or dehydration
• Delayed puberty
• Poor muscle tone
• Body temperature fluctuations
• Insomnia
• Malnutrition
(Cleveland Clinic, n.d.)
While hypothalamic dysfunction plays a significant role in several hereditary conditions, including Prader-Willi syndrome, diabetes insipidus, and Kallmann syndrome, it is also a prominent characteristic of:
• Functional hypothalamic amenorrhea: a condition marked by a prolonged absence of menstruation
• Hypopituitarism: pituitary gland hormone deficiency
• A range of hypothalamic-pituitary disorders
(Cleveland Clinic, n.d.)
Epilepsy-related complications
Hypothalamic damage can affect the lives of people with epilepsy via hamartomas. A hypothalamic hamartoma (HH) is a rare, congenital tumor-like growth that can lead to precocious puberty, Gelastic epilepsy, developmental delays, and cognitive problems (Cleveland Clinic, n.d.). While it may present itself as asymptomatic for several years, the condition becomes more apparent as people start exhibiting signs of central nervous system dysfunction, hormone imbalances, behavioral disturbances, and seizures (Qasim & Mohammed, 2020). Hamartomas can cause disruptions in the bodily functions regulated by the hypothalamus as well (Cleveland Clinic, n.d.).
Gelastic seizures, which are characterized by sudden fits of laughter, are the most prevalent symptom of epileptic HH. However, other types of seizures can occur:
• Atonic seizures, which are marked by loss of muscle tone
• Dacrystic seizures, which are akin to bouts of crying fits
• Tonic-clonic seizures. These cause uncontrollable muscle contractions and a loss of consciousness
(Cleveland Clinic, n.d.)
Gelastic convulsions are quite challenging to control as they cannot be treated with anticonvulsant medication (Cleveland Clinic, n.d.). Fortunately, research has revealed that surgically removing the mass from the hypothalamus generally resolves epilepsy symptoms, suggesting that these seizures were inherently linked to the hamartomas (Qasim & Mohammed, 2020). However, a study investigating the resurgence of seizures following the ablation of a hypothalamic hamartoma suggested that while Gelastic epilepsy may be of hamartoma origin, the other types of seizures that can occur in the presence of HH may originate from other brain regions as a result of propagation or increased seizure sensibility of brain networks over time (Roodakker et al., 2021).
Research on the hypothalamus also provides insight that can guide epileptic treatment procedures. In a study focused on the effect of electrical brain stimulation on drug-resistant epilepsy (DRE) symptoms, Benedetti-Issac and colleagues (2015) found that deep brain stimulation (DBS) of the posteromedial hypothalamus had the potential to control aggressiveness associated with DRE and reduce the rate of epileptic seizures.
Evaluation
Clinical symptoms shape the diagnostic toolkit for hypothalamic dysfunction (Sanchez Jimenez et De Jesus, 2023). Blood and urine tests can help detect any hormonal abnormalities, if any, by determining patients’ levels of:
• Serum cortisol
• Serum estrogen
• Pituitary hormones
• Growth hormones
• Testosterone
• Thyroid hormones
• Sodium levels
• Blood and urine osmolality
(Mount Sinai, n.d.)
Other diagnostic tests may include:
• Brain imaging scans such as MRI or CT
• Visual field exam (for tumor detection)
• Hormone injections
• Genetic analysis
• Autoimmune markers
(Sanchez Jimenez et De Jesus, 2023)
The emergence of MRI as a diagnostic tool has proven to be particularly helpful in the detection of hamartomas of the hypothalamus (Qasim & Mohammed, 2020). Electroencephalograms (EEG) can be used to monitor electrical activity in individuals with epileptic HH, but Gelastic seizures may not be detected since this test does not record deep brain activity (Cleveland Clinic, n.d.).
There exist differential diagnoses for some of the symptoms observed in people with hypothalamic dysfunction. For instance, sleep problems could be caused by substance use, sleep-altering stimulants, psychiatric conditions (e.g., GAD or MDD) and REM-sleep behavior disorders. Other conditions that can imitate the signs of hypothalamic dysfunction include:
• Pituitary gland lesions, which mimic hormonal deficiencies
• Central or nephrogenic diabetes insipidus, which are caused by antidiuretic hormone related issues
• Hyperthyroidism, which causes an increase in appetite
(Sanchez Jimenez et De Jesus, 2023)
Treatment and management
Depending on the condition and severity of hypothalamic dysfunction, treatment options may include a variety of medications. Pharmacological interventions for hypothalamus disruptions usually target hormone replacement and nutrition (i.e., for appetite regulation and weight gain) (Mount Sinai, n.d.). Hormone replacement therapy can vary in length; for Kallman syndrome, this treatment is lifelong (Sanchez Jimenez et De Jesus, 2023).
For tumors, surgery or radiation therapy may be required (Cleveland Clinic, n.d.; Mount Sinai, n.d.). This is especially true regarding symptomatic hypothalamic hematomas with uncontrolled seizures. However, other options such as thermoablation and radiosurgery can be used instead (Cleveland Clinic, n.d.; Sanchez Jimenez et De Jesus, 2023).
Conclusion
The hypothalamus is the bridge between the hormonal glands and the central nervous system. It coordinates essential bodily functions in order to maintain homeostasis. Evidence suggests that hypothalamic damage can cause hormonal imbalances, autonomic dysfunction, cognitive disturbances, and seizures. Research into the relationship between the hypothalamus and epilepsy could uncover underlying mechanisms contributing to the generation and propagation of seizure activity and pave new therapeutic avenues.
References:
Benedetti-Isaac, J. C., Torres-Zambrano, M., Vargas-Toscano, A., Perea-Castro, E., Alcalá-Cerra, G., Furlanetti, L. L., Reithmeier, T., Tierney, T. S., Anastasopoulos, C., Fonoff, E. T., & Contreras Lopez, W. O. (2015). Seizure frequency reduction after posteromedial hypothalamus deep brain stimulation in drug-resistant epilepsy associated with intractable aggressive behavior. Epilepsia (Copenhagen), 56(7), 1152–1161. https://doi.org/10.1111/epi.13025
Cleveland Clinic. (n.d.). Hypothalamic Hamartoma. Cleveland Clinic. https:// my.clevelandclinic.org/health/diseases/17118-hypothalamic-hamartoma#overview
Cleveland Clinic. (n.d.). Hypothalamus. Cleveland Clinic. https://my.clevelandclinic.org/health/ body/22566-hypothalamus
Mount Sinai. (n.d.). Hypothalamic dysfunction. Mount Sinai Health System. https:// www.mountsinai.org/health-library/diseases-conditions/hypothalamic
dysfunction#:~:text=The%20hypothalamus%20helps%20control%20the,give%20rise%20to%20 cluster%20headaches.
Qasim, B. A., & Mohammed, A. A. (2020). Hamartoma of hypothalamus presented as precocious puberty and epilepsy in a 10-year-old girl. International Journal of Surgery Case Reports, 77, 170–173. https://doi.org/10.1016/j.ijscr.2020.10.065
Roodakker, K. R., Ezra, B., Gauffin, H., Latini, F., Zetterling, M., Berntsson, S., & Landtblom, A.-M. (2021). Ecstatic and gelastic seizures related to the hypothalamus. Epilepsy & Behavior Reports, 16, 100400–100400. https://doi.org/10.1016/j.ebr.2020.100400
Sachez Jimenez, J. G., & De Jesus, O. (2023). Hypothalamic Dysfunction. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK560743/
Shahid, Z., Asuka, E., & Singh, G. (2023). Physiology, Hypothalamus. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK535380/