Hypothalamus disorders

Secondary adrenal insufficiency occurs as a result of a pituitary gland dysfunction whereby decreased production and secretion of ACTH leads to a decrease in cortisol synthesis. Tertiary adrenal insufficiency is a disorder of the hypothalamus that results in decreased production and release of CRH, which, in turn, decreases pituitary ACTH production and release. In contrast to Addison s disease (i.e., primary adrenal insufficiency), aldosterone production is unaffected in the secondary and tertiary forms of the disease. Chronic adrenal insufficiency often has a good prognosis if diagnosed early and treated appropriately. 

O Unrecognized pregnancy remains the most common cause of amenorrhea, and a urine pregnancy test should be one of the first steps in the evaluation of this disorder. To help organize an approach to diagnosis and treatment, it is helpful to consider the organs involved in the menstrual cycle, which include the uterus, ovaries, anterior pituitary, and hypothalamus. 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Guan, J. L., Uehara, K., Lu, S. et at (2002). Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus a novel circuit implicated in feeding regulation. Int. J. Obes. Relat. Metab. Disord. 26, 1523-32. 

Mignot E., Taheri S., Nishino S. (2002). Sleeping with the hypothalamus emerging therapeutic targets for sleep disorders. Nat. Neurosci. 5 (Suppl), 1071-5. 

Cannabinoid receptors are expressed throughout the cerebral cortex and the hippocampus, and a subpopulation of these cells appear to show an unusually high level of activity. It is possible that cells in these areas modulate the sensory effects of cannabis, particularly the effects on perception, task performance and memory. In addition, the anticonvulsant properties of cannabis are believed to be mediated here. Parts of the hypothalamus show high levels of receptor sites for cannabinoids this may be related to hypothermia effects. High levels in the cerebellum may be related to mediating the property of cannabinoids that produces the reduction in ataxic (muscle co-ordination) symptoms in certain disorders (Herkenham et al., 1991). 

Figure 13.32 The female triad disordered eating, osteoporosis and menstrual cycle disturbance. A low energy intake and high energy expenditure can Lead to endocrine changes that result in osteoporosis and disturbance in the menstrual cycle. A low energy intake in female runners, rowers or gymnasts in order to maintain a low body weight can lead to other disturbances in eating such as bulimia or anorexia nervosa. Stress may contribute to energy imbalance and may have additional effects on the hypothalamus.

Sensitization Dopaminergic, noradrenergic NMDA receptors Nucleus accumbens, amygdala, striatum, hypothalamus May explain the adverse effects of early life trauma on subsequent responses to stressful like events. May play a role in the chronic course of many anxiety disorders and, in some cases, the worsening of the illness over time Suggests the efficacy of treatment may vary according to the state of evolution of the disease process. Emphasizes the importance of early treatment intervention... 

Tertiary hypothyroidism, or hypothalamic hypothyroidism, results from impaired TRH stimulation of pituitary TSH. This may be due to a disorder that damages the hypothalamus or interferes with hypothalamic-pituitary portal blood flow, thereby preventing delivery of TRH to the pituitary. Tumors, trauma, radiation therapy, or infiltrative disease of the hypothalamus can cause such damage. This relatively rare form of hypothyroidism is also characterized by inappropriately low levels of serum TSH. 

Within the brain, panic disorder has been associated with multiple neurotransmitters, including GABA, serotonin, norepinephrine, and corticotropin-releasing hormone, which is a stress hormone. Several brain areas have also been implicated in the development of panic attacks, because different manipulations in those areas produce or reduce panic-like behaviors in laboratory animals. For example, activating an area of the brain called the dorsomedial hypothalamus produces what looks like a panic attack in rats. Moreover, injecting the stress-associated corticotropin-releasing hormone into the amygdala can increase the sensitivity of rats to other manipulations that produce panic attacks, like lactate injection. 

Another approach considers the effects of various ligands on their receptors located in the diencephalic and mesiotemporal areas. Cell clusters in the hypothalamus coordinate the normal regulation of the vegetative functions of sleep, appetite, and sexual drive, which are typically disrupted in severe depression. In addition, the limbic area modulates many aspects of behavior and mood that are characteristically disturbed in affective disorders. 

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