The Hypothalamus (Integrative Systems) Part 4

Dysfunctions of the Hypothalamus

Destruction of hypothalamic tissue can result in a number of different disorders related to the processes considered earlier in this topic. These include: obesity, diabetes insipidus, hyperaggressivity and violent behavior, disruption of thermal regulation, emaciation, alterations in sexual development, sleep disorders, and hypertension.

Disorders of the hypothalamus may result from specific lesions caused by vascular disturbances, inflammation of hypothalamic tissue, or by tumors that usually emanate from the floor of the third ventricle or pituitary gland.

Hyperthermia

Hyperthermia is characterized by high temperature that could be fatal. It is sometimes associated with surgery involving the region adjacent to the pituitary and is believed to involve the anterior hypothalamus that controls the heat-loss mechanism.

Genital Dystrophy and Abnormalities in Sexual Development

Genital dystrophy can occur following lesions believed to be located in or around the tuberal region of the hypotha-lamus but that may extend to the ventromedial nucleus as well. This type of dystrophy is characterized by loss of sexual activity and genital atrophy. Other forms of alterations in sexual development may also occur from lesions, tumors, encephalitis, or even hematomas of the hypothalamus. In children, the disorder may result in retardation of sexual organs and sexual function. It is also possible for the disorder to lead to an opposite effect, resulting in premature sexual development of the genitalia.

Feeding, Obesity, and Emaciation

Marked increases in appetite occur as a result of lesions of the ventromedial hypothalamus. This is associated with significant weight gain and striking changes in emotional behavior (usually characterized by expressions of rage). Lesions of the lateral hypothalamus, on the other hand, result in loss of appetite and emaciation.

Diabetes Insipidus

Lesions of the supraoptic and/or paraventricular nuclei affect the release of ADH (vasopressin) from these neurons that project to the posterior pituitary. This results in the disorder of diabetes insipidus, in which the patient drinks abnormal amounts of water (because the mechanism governing thirst is still relatively intact) because he excretes abnormally large amounts of urine.

Effects Upon the Cardiovascular System: Hypertension and Horner’s Syndrome

Excessive release of corticotropin-releasing factor causes oversecretion of adrenocorticotropins. This, in turn, results in hypertension because of several factors, such as changes in sodium and water metabolism, and a release of renin from the kidney, which leads to increased synthesis of angiotensin II.

Horner’s syndrome is typically caused by lesions of the hypothalamus or of its descending sympathetic pathways that pass to the lower brainstem and, via its synaptic connections, to the intermediolateral cell column of the tho-racolumbar spinal cord situated between T1 and L3. In particular, Horner’s syndrome seen following lesions of the dorsolateral brainstem can be most likely attributed to the disruption of these descending fibers.

Sleep Disorders

Sleep disorders may result from damage (such as from encephalitis) to the posterior region of the hypothalamus (i.e., the diencephalic-midbrain juncture). The result is prolonged periods of sleep. As noted earlier, the effects may be due to damage to ascending fibers from the reticu-lar formation to the thalamus and cortex rather than damage to neurons situated within the hypothalamus.

Aggression and Rage

Tumors located near the base of the brain but that impinge on the ventromedial hypothalamus have been known to produce marked expressions of violent behavior. The tumors likely have a stimulating effect in causing aberrant expressions of emotional behavior. Such effects may also be due to vascular disturbances and inflammatory disorders. Sometimes, such disturbances were treated 2 to 3 decades ago by placing surgical lesions in the posterome-dial region of the hypothalamus (sometimes called the "ergotropic triangle"). Surgical lesions placed in schizophrenic patients generally reduced sympathetic activity and aggressive responses. It is likely that such lesions disrupt the major descending outputs of the medial hypotha-lamus to the midbrain PAG and other regions of the teg-mentum. In more recent times, surgical approaches have generally been replaced by noninvasive methods emphasizing drug therapy.

Clinical Case

History

Iris is a 29-year-old woman who stopped taking birth control pills 6 months ago to try to become pregnant. However, her menstrual periods failed to resume. Her cycles had been normal prior to starting the pills 4 years ago, and she’d taken them steadily during that period. She also noted that she had been having dull headaches, which were worsening over the past few months, as well as some problems with her peripheral vision, but didn’t pay much attention to either symptom. She thought that she already might be pregnant, so she went to see her gynecologist.

Examination

A pregnancy test was negative at her doctor’s office, and there was no evidence of any pregnancy from her physical examination. As a result, her gynecologist sent Iris’s blood for blood hormone levels. On returning for her test results, Iris learned that her prolactin level (a hormone that mediates lactation and inhibits menstruation) was high. She was also surprised that her gynecologist referred her to a neurologist but agreed to go because of her headaches and vision problems.

The neurologist found that Iris was unable to see objects in the lateral half of each visual field (heteronymous hemianopsia), but the remainder of her examination was normal. A magnetic resonance imaging (MRI) scan of Iris’s head was ordered.

Explanation

The MRI scan revealed a mass in the pituitary gland called a "microadenoma" (a benign tumor arising from the anterior pituitary gland).Most microadenomas secrete the hormone prolactin, as this one did (as evidenced by the high serum level).The pituitary gland is in close proximity to the optic chiasm,so it is common for pituitary tumors to put pressure on it.The pituitary sits near the medial aspect of the optic chiasm where the fibers associated with the temporal visual fields run. Recall that the temporal visual fields are linked with the nasal retina and that the fibers from the nasal retina cross in the optic chiasm.Thus, the vision lost is from the lateral temporal visual fields.

Prolactin-releasing factor is manufactured in the arcuate nucleus of the hypothalamus, activating the lactotropic cells of the anterior pituitary gland. Several substances, including dopamine,areableto raise serum prolactin levels. Therefore, dopamine agonists are given to treat these tumors because, by raising serum prolactin, the tumor cells producing prolactin are inhibited, resulting in a shrinking of the tumor.

SUMMARY TABLE

Afferent and Efferent Connections of the Hypothalamus

Pathway	Origin	Distribution
	Afferent Projections
Fornix	Subicular cortex of hippocampal formation	Mammillary bodies; medial hypothalamus (also to septal area and anterior thalamic nucleus)
Stria terminalis	Medial amygdala and periamygdalar cortex	Rostral two thirds of medial hypothalamus
Ventral amygdalofugal pathway	Mainly basolateral amygdala	Lateral hypothalamus (and other fibers pass caudally to midbrain PAG)
Medial forebrain bundle	Rostral orig/n: Septal area, diagonal band of Broca; Caudal origin: Monoaminergic neurons of brainstem	Both descending and ascending neurons project to wide area of hypothalamus; monoamine neurons also supply limbic structures and cerebral cortex
Thalamohypothalamic fibers	Midline thalamic nuclei	Anterior perifornical hypothalamus
Prefrontal-hypothalamic fibers	Prefrontal cortex	Medial and lateral hypothalamus
Retinohypothalamic fibers	Retina	Branches of main optic tract terminate in suprachiasmatic nucleus
Mammillary peduncle	Ventral and dorsal tegmental nuclei	Mammillary bodies and more rostral aspects of hypothalamus

Pathway	Origin	Distribution
	Afferent Projections
PAG-hypothalamic fibers	PAG	Posterior half of medial hypothalamus
Monoaminergic pathways	Locus ceruleus (noradrenergic fibers); raphe nuclei (serotonin neurons); ventral tegmental area (dopamine neurons)	To hypothalamus and limbic structures, including cerebral cortex
	Efferent Projections
Mammillothalamic and mammillotegmental pathways	Mammillary bodies	Anterior thalamic nucleus (for mammillothalamic pathway); midbrain reticular formation (for mammillotegmental pathway)
Ascending and descending projections of medial hypothalamus	Medial hypothalamus	Rostrally,to limbic structures—amygdala, septal area, and prefrontal cortex; caudally, to midbrain PAG
Medial forebrain bundle	Lateral hypothalamus	Rostrally,to prefrontal cortex, septal area,proptic area, and diagonal band of Broca; caudally,to midbrain reticular formation and PAG
Hypothalamic-pituitary projections: Neural	Supraoptic and paraventricular nuclei	Posterior pituitary (anti-diuretic hormone (vasopressin) and oxytocin)
Hypothalamic-pituitary projections: Humoral	Mainly nuclei of medial hypothalamus, including arcuate nucleus	Releasing hormones into anterior pituitary: follicle stimulating hormone, lutenizing hormone, goadotropin-releasing hormone, prolactin,growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone

PAG = periaqueductal gray matter.

Disorders of the Hypothalamus and Their Anatomical Loci

Hypothalamic Disorder	Anatomical Locus
Hyperthermia	Anterior hypothalamus (controls heat-loss mechanism)
Hypothermia	Posterior hypothalamus (heat-conservation mechanism)
Genital dystrophy and abnormalities in sexual development	Tuberal region of hypothalamus
Feeding, obesity, and emaciation	Obesity. Lesions of region of ventromedial hypothalamus Emaciation: Area of lateral hypothalamus
Diabetes Insipidus	Supraoptic and paraventricular nuclei (from which antidiuretic hormone is synthesized)
Hypertension	Excess release of corticotropin-releasing factor in medial hypothalamus; lesions of medial hypothalamus induce Horner’s syndrome
Sleep disorders	Lesions of posterior hypothalamus-midbrain border
Aggression and rage behavior	Tumors in medial hypothalamus (which presumably have a stimulating effect by inducing rage reactions