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The hypothalamus lies on either side of the third ventricle, below the thalamus and between the optic chiasm and the midbrain. It receives a significant input from limbic system structures (see Chapter 45) as well as from the retina. It contains a large number of neurones that are sensitive to changes in hormone levels, electrolytes and temperature.

It has an efferent output to the autonomic nervous system (ANS), as well as a critical role in the control of pituitary endocrine function (a detailed discussion on the endocrinology of the hypothalamic–pituitary system is beyond the scope of this book). Thus, the hypothalamus, while being important in the control of the ANS, has a much greater role in the homoeostasis of many physiological systems (e.g. thirst, hunger, sodium and water balance, temperature regulation), the control of circadian and endocrine functions, the ability to form anterograde memories (in conjunction with the limbic system; see Chapters 45 and 46) and the translation of the response to emotional stimuli into endocrinological and autonomic responses.

The hypothalamus performs a number of other functions, all of which can be lost or deranged in the disease state. The most common cause is as a side-effect of surgical removal of pituitary tumours.

Functions of the hypothalamus
   The hypothalamus controls the ANS and damage to it can cause autonomic instability. The ventromedial part of the hypothalamus has a major role in controlling the sympathetic nervous system while the lateral hypothalamic area controls the parasympathetic nervous system (see Chapter 3).
   It controls the endocrine functions of the pituitary by the production of releasing and inhibiting hormones as well as producing antidiuretic hormone (ADH, also known as vasopressin) and oxytocin. Hypothalamic damage can have profound systemic effects because of the endocrinological disturbances associated with it, of which perhaps the most common example is neurogenic diabetes insipidus, in which there is a loss of the production of ADH from the hypothalamus. In this condition the patient passes many litres of urine each day, which needs to be compensated for by increased fluid intake. This is to be distinguished from nephrogenic diabetes insipidus, where the problem lies within the ADH receptor in the kidney.
   It has a major role in coordinating autonomic and endocrinological responses, both under physiological conditions, and in the expression of emotional states as coded for by the limbic system. In cases of hypovolaemia or extreme anxiety, for example, the hypothalamus mediates not only increased sympathetic activity, but also enhanced cortisol production via the stimulated release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. This is termed the stress response, which is defined by the rise in cortisol.
   It has an important role in thermoregulation. Lesions to the anterior hypothalamic area cause hyperthermia, while stimulation of this same area lowers body temperature via the ANS, in contrast to the posterior hypothalamic area, which behaves in an opposite fashion. It may also mediate some of the more long-term responses seen with prolonged changes in ambient temperature, such as increased thyrotrophin-releasing hormone (TRH) production in patients exposed to a chronically cold environment. Damage to the hypothalamus can lead to profound changes in the central control of temperature. In septic states, the production of some cytokines (e.g. interleukin-1) may reset the thermostat in the hypothalamus to a higher than normal temperature, accounting for the paradoxical situation of a fever with physiological evidence of mechanisms designed to conserve or generate heat (e.g. shivering).
   It has a role in the control of feeding. In simple terms, the ventromedial hypothalamus is often called the satiety centre, in that damage to it causes excessive eating (hyperphagia) and weight gain, while damage to the lateral hypothalamic (or hunger) area produces aphagia (no eating at all). The control of these centres involves a number of hormones, including insulin and the more recently described leptins.
   It has a role in the control of thirst and water balance by virtue of its osmoreceptors; the afferent input from a host of peripheral sensory receptors (e.g. atrial stretch receptors in the heart, arterial baroreceptors); the activation of hypothalamic hormone receptors (e.g. angiotensin II receptors); and its efferent output via the ANS to the heart and kidney as well as the production of ADH.
   It has a role in the control of circadian rhythms via the retinal input to the suprachiasmatic nucleus. This nucleus appears to be critical in setting the circadian rhythm as lesion and transplant experiments have shown. Although the exact mechanism by which these rhythms are mediated is not known, it may involve the production of melatonin by the pineal gland.
   It has a role with the limbic system in memory. Damage to the mammillary bodies, which receive a significant input from the hippocampal complex as occurs in chronic alcoholism with thiamine deficiency, produces a profound amnesia (Korsakoff’s syndrome) of both an anterograde (inability to lay down new memories) and retrograde (inability to recover old memories) nature. The latter feature distinguishes these patients from those who have hippoc- ampal damage (see Chapters 45 and 46) and may explain why patients with Korsakoff’s syndrome tend to invent missing information  (confabulation).
   The hypothalamus may also have a role in sexual and emotional behaviour independent of its endocrinological influences.