Hypothalamic dysfunction is a general term referring to any condition implying anomalies in the operation of the hypothalamus, one of the phylogenetically oldest parts of the brain. The hypothalamus plays a key role in regulating the body's metabolic state, is involved in the control of autonomous and endocrine processes as different as respiration, circulation, body temperature, sexual behavior, and water and electrolyte balance. Accordingly, the presentation of hypothalamic dysfunction is highly heterogeneous and often complex.
The hypothalamus is small, and lesions that come to clinical attention often achieve a considerable size before their recognition, so they are rarely limited to a specific population of neurons or a single hormone axis . Quite the contrary, the complexity of hypothalamic function generally implies a highly heterogeneous and multifaceted presentation of hypothalamic disorders. It should also be noted that the clinical picture varies depending on the patient's developmental stage at the onset of hypothalamic dysfunction.
Besides the aforementioned symptoms, patients with hypothalamic dysfunction frequently suffer from disorders of body temperature, namely with hypothermia, hyperthermia, or poikilothermia . They may also present with sleep disorders, eating disorders, and mood swings and are more likely to develop depression .
Depending on the underlying condition, additional symptoms may be present, such as headaches, vomiting, and ophthalmological abnormalities.
Both direct, non-stimulated measurements of hormone levels and provocation tests are carried out to identify and localize abnormalities in the function of the hypothalamus, pituitary, and peripheral glands. Dynamic testing is recommended to determine if low levels can be raised by the stimulation of hormone synthesis or release, and if elevated levels are suppressible . In this context, it should be noted that levels of hypothalamic hormones as determined in common serum samples don't necessarily correlate with concentrations in hypothalamic-hypophysial portal serum. In order to increase the reliability of results, such analyses should be interpreted with simultaneous measurements of downstream hormones like pituitary tropic and non-tropic hormones as well as peripheral effector hormones. Furthermore, circadian rhythms should be considered when choosing the ideal time of the day to obtain blood samples.
In any case, the diagnosis of hypothalamic dysfunction should be complemented by a thorough workup aiming at the identification of the causes of this condition. The patient's medical history may play a crucial role in this context, as do the results of neuroimaging and the analysis of cerebrospinal fluid . Hereditary conditions associated with hypothalamic dysfunction may be suspected in case of a positive family history, which should prompt the screening for gene defects known to predispose for the respective disorder.
Treatment largely depends on the underlying condition and may comprise pharmacotherapy, surgical interventions, and radiation:
If the cause of hypothalamic dysfunction cannot be removed, therapy must be continued throughout life. Patients should be informed about the possible consequences of any lack of compliance and be encouraged to partake in monitoring programs.
The extent and cause of hypothalamic dysfunction, the severity of the disease, and the presence of comorbidities all affect the patient's prognosis. Notwithstanding, irreversible hypothalamic dysfunction may partially be compensated by pharmacotherapy: Appropriate hormone replacement or antihormone therapy can improve the quality of life and prevent complications. It should generally be kept in mind that the time course of the development of hormonal disorders varies, and predictors of hypothalamic-pituitary dysfunction are unreliable .
Hypothalamic dysfunction may be provoked by very different conditions. Numerous benign and malignant diseases may interfere with the physical integrity of the hypothalamus, with blood supply and drainage. Limited blood supply would result in hypoxia and nutrient deficiencies, but the latter may also be caused by metabolic disorders. Additionally, infectious diseases as well as autoimmune disorders may trigger hypothalamic inflammation, which is likely to alter the function of hypothalamic neurons. Any of the aforementioned conditions leading to hypothalamic function may affect the hypothalamus only, involve adjacent brain regions, additional parts of the central nervous system or even the entire body. Moreover, different lesions may produce identical signs and symptoms, and similar pathologies may result in distinct clinical pictures.
Hypothalamic dysfunction is usually acquired, but certain hereditary conditions may interfere with the operation of the hypothalamus and result in congenital hypothalamic disorders. Hereditary diseases with hypothalamic dysfunction comprise, but are not limited to, Prader-Willi syndrome, de Morsier syndrome, Kallmann syndrome, the syndrome of inappropriate antidiuretic hormone secretion, Kleine-Levin syndrome, Bardet-Biedl syndrome, Wolfram syndrome, familial diabetes insipidus, Pallister-Hall syndrome, rapid-onset obesity with hypothalamic dysfunction, and Shapiro syndrome.
A more detailed list of possible etiologies of hypothalamic dysfunction has been compiled by Braunstein .
Due to the heterogeneity of causes, precise data regarding the incidence and prevalence of hypothalamic dysfunction cannot be provided. Patients of any age may be affected: Although most conditions involving hypothalamic dysfunction are acquired, it may be present at birth. Developmental malformations and hereditary disorders as enumerated in the previous paragraph may be accompanied by congenital hypothalamic dysfunction . While gender preference or ethnic predisposition may be described for certain etiologies, hypothalamic dysfunction may essentially affect everyone.
The hypothalamus is the "command center" of the endocrine and autonomous nervous system. In order to understand the possible implications of hypothalamic dysfunction, the multiple tasks of this organ should be considered.
As for the majority of disorders resulting in hypothalamic dysfunction, no recommendations can be given to prevent this condition. In general, safety measures to protect the integrity of the brain may help to reduce the incidence of traumatic brain injury with hypothalamic dysfunction. The avoidance of consanguineous marriage as well as the education of the population regarding the possible consequences of this practice may contribute to decreasing the incidence of hereditary disorders associated with hypothalamic lesions. Furthermore, the early diagnosis of any cerebral pathology may allow for the initiation of treatment before the hypothalamus becomes involved.
Hypothalamic dysfunction is no entity but a pathological condition that may arise in the scope of diverse disorders such as cerebrovascular accidents, infectious diseases affecting the central nervous system, autoimmune conditions, metabolic disturbances, traumatic brain injury, neoplasms, and neurodegeneration, among others. Furthermore, hypothalamic dysfunction is part of syndromes like syndrome of inappropriate antidiuretic hormone secretion, Kallmann syndrome, and Kleine-Levin syndrome, among others.
The hypothalamus is a rather small but vital part of the brain. It may be considered the upper control center of the endocrine and autonomous nervous system. The hypothalamus is involved in the regulation of numerous processes, such as growth, respiration, circulation, body temperature, sexual behavior, hunger and thirst, energy management and water and electrolyte balance. Accordingly, hypothalamic dysfunction may manifest in many different, often contrasting ways:
The diversity of signs and symptoms associated with hypothalamic dysfunction may be explained by the fact that hypothalamic hormones act on the pituitary and distinct peripheral glands, such as the thyroid and adrenal glands, gonads, and kidneys.
Hypothalamic dysfunction may be caused by any condition affecting the physical integrity or functionality of the hypothalamus. Developmental malformations, genetic disorders, traumatic brain injury and tumors, infectious diseases, immunological and metabolic diseases, cerebrovascular accidents, and neurodegenerative disorders may all produce hypothalamic lesions. The diagnosis of the underlying condition may thus pose a major challenge but is essential to design the optimum treatment regimen.