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5.3 Pathophysiology of Hypo- Thalamic-Hypophyseal Sys

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5.3 Pathophysiology of Hypo- Thalamic-Hypophyseal Sys 310 Chapter 5. Pathophysiology of endocrine system ( L. Zlatoˇs) in food, which inhibits synthesis of thyroid of various hormones (hypothalamic releasing hor- hormones, may be also a cause of endocrine mones, hypothalamic inhibiting hormones or factors, disorder. antidiuretic hormone, and oxytocin). Hypothala- D. Iatrogenic causes. Endocrine disorders mus, therefore, has an important role in the reg- may occur as a complication of various ulation of endocrine system as well. In the hier- kinds of therapy (e.g., surgical interven- archy of endocrine glands hypothalamus has a role tion, radiotherapy, inadequate hormone of a control centre and along with hypophysis it treatment, or therapy with some non- forms a functional unit. In the consequence of its hormone drugs). organic or functional disorder, a hypothalamic syn- drome develops. In the clinical picture of this syn- E. Primary hyperplasia of endocrine gland drome only endocrine symptomatology is present, cells. As its consequence, a hyperfunc- or its endocrine symptomatology may be combi- tional endocrine syndrome develops. nated with neurovegetative symptomatology. These F. Other acquired causes. They are rather disorders are usually distinguished as: disorders of rare. They include, e.g., destruction of hypothalamic-neurohypophyseal system and disor- endocrine cells by hormone inactive neo- ders of hypothalamic-adenohypophyseal system. plasma, various kinds of vascular disorders (mostly aneurysm or hemorrhage), cyst, trauma, degenerative process, metabolic 5.3.1 Pathophysiology of hypothala- defect, and by toxic influences. mic-neurohypophyseal system 2. Genetic causes Antidiuretic hormone (ADH, vasopressin) and Relatively frequent genetic causes of endocrine oxytocin are the hormones of hypothalamic- disorders are defects of various enzymes (enzy- neurohypophyseal system. They are produced in mopathies) taking part in a hormone biosynthe- the nuclei of the front hypothalamus, i.e., in nucleus sis. The other inherent cause can be the synthe- supraopticus and in nucleus paraventricularis. They sis of a defective prohormone or hormone or the are transported to neurohypophysis via the axons of disorder of conversion of prohormone to active the cells of these nuclei, where they are stored and hormone. The existence of genetic disorder of released into the circulation when needed. Clinical cell receptors for hormones is assumed as well. symptoms of deficiency or overproduction of ADH Inborn causes of endocrine disorders can also in- are known only in human being. Disorders of oxy- clude hypoplasia or aplasia of endocrine gland as tocin secretion are unknown at present. well as chromosome anomalies concerning X or Y chromosomes (gonosomes). 5.3.1.1 Central diabetes insipidus Central diabetes insipidus (neurogenic diabetes in- sipidus, diabetes insipidus verus) is a rare disease caused by partial deficiency or total absence of ADH. The kidneys of a patient, therefore, are not able to 5.3 Pathophysiology of hypo- produce hypertonic urine and thus to prevent exces- sive loss of water from the organism. Most often it thalamic-hypophyseal sys- develops in the consequence of the damage of front tem hypothalamus, namely of nucleus supraopticus, e.g., by severe head trauma, intracranial tumors (cran- iopharyngioma, Rathke’s pouch tumor, germinoma, pinealoma, pituitary adenoma, and metastatic tu- Hypothalamus has an important integrative in- mors), cysts, inflammatory lesions, vessel lesions fluence on the function of vegetative nervous sys- (hemorrhage or aneurysm), sarcoidosis, or by sur- tem and also it is a place of various vital cen- gical intervention in the area of hypothalamus. Di- tres. It has a key role in regulation of basic bi- abetes insipidus, which is due to any organic lesion ological rhythms and it is the place of production mentioned above, is called symptomatic (secondary) 5.3. Pathophysiology of hypothalamic-hypophyseal system 311 diabetes insipidus. However, in about 45 % of cases frequently, however, urine volume is only moderately the cause of ADH deficiency is not found out. It is increased (from 3 to 6 litres per day). idiopathic diabetes insipidus. In rare instances, cen- Polyuria is the most expressive objective symp- tral diabetes insipidus may be inherited as an iso- tom, and excessive thirst is the main subjective lated defect (autosomal dominant inheritance) or as symptom. Polydipsia provides an adequate compen- a part of an autosomal recessive syndrome (Wolfram sation for large volumes of excreted water. The slight syndrome) consisting of diabetes insipidus, diabetes rise in serum osmolality, resulting from hypotonic mellitus, optic atrophy, and deafness. polyuria, stimulates thirst. Large volumes of fluid, From the point of view of etiopathogenesis pe- therefore, are imbibed, and cold drinks are preferred. ripheral diabetes insipidus (nephrogenic diabetes in- For the patient excessive thirst is hard to control, sipidus) can be also distinguished. It originates as a and due to that he often awakes throughout night. consequence of reduced sensitivity even of insensitiv- During the sleeping hours he often drinks and mic- ity of the distal tubules and mainly of the collecting turates (nycturia). Interrupted sleep may cause the ducts to ADH. It is caused by disorder or lack of cell origin of neuroasthenic syndrome. If the patient did receptors for this hormone. Peripheral diabetes in- not take adequate quantity of fluids he would de- sipidus is hypofunctional pseudoendocrinopathy.It velop severe dehydration, hypernatremia, plasma hy- may be inborn or acquired. Hereditary nephrogenic perosmolality, fever, psychic disturbances, prostra- diabetes insipidus is the disease with X chromosome- tion, collapse, and towards the end oligemic shock linked inheritance. The abnormal gene is localized and death may occur. on the long arm of this chromosome. It is trans- mitted by heterozygous women and clinically man- 5.3.1.2 Syndrome of inappropriate ADH se- ifestedinman. Acquired nephrogenic diabetes in- cretion sipidus has heterogeneous etiology. It may develop, e.g., due to chronic hyperkalemia, chronic renal in- The syndrome of inappropriate ADH secretion sufficiency, nephrocalcinosis caused by chronic hy- (Schwartz-Bartter syndrome, primary vasopressin perparathyroidism, amyloidosis, multiple myeloma, excess) is the term applied to persistent production or due to long-lasting therapy by some drugs, such as of ADH or ADH-like peptide despite body fluid hy- demeclocycline, methoxyflurane, and lithium (drug- potonicity and an expanded effective circulating vol- induced nephrogenic diabetes insipidus). ume. These peptides are syntethized and released autonomously, i.g., independently from plasma os- Pathophysiology and clinical features.Diabetes molality. There is sustained release of ADH in the insipidus refers to the passage through the body of a absence of either osmotic or nonosmotic (volume- large quantity of dilute fluid. This state of excessive mediated) stimuli. It means that simple feedback water intake (polydipsia) and hypotonic polyuria is control mechanism between plasma osmolality and due to failure of vasopressin (ADH) release in re- ADH secretion is broken (osmoreceptors of the front sponse to normal physiologic stimuli (neurogenic di- hypothalamus lost or cannot realize their control abetes insipidus) or due to inability of renal tubules function). to respond to ADH (nephrogenic diabetes insipidus). The syndrome of inappropriate ADH secretion Polyuria, excessive thirst and polydipsia are primary originates by numerous causes. Its most fre- symptoms almost invariably present in the patients. quent cause is an ectopic ADH or ADH-like pep- Characteristically, they are sudden in onset. The tide production from neoplastic tissue (small cell patient may recall the precise day or hour when bronchogenic carcinoma, pancreatic carcinoma, lym- polyuria and thirst began. phosarcoma, Hodgkin’s disease, reticulum cell sar- Urine osmolality is below that of the serum (less coma, thymoma, and carcinoma of duodenum or than 290 mmol/kg). A urine specific gravity is from bladder), and from lung cells during inflamma- 1.001 to 1.005. Persistent hypostenuria is the hall- tory pulmonary diseases (tuberculosis, lung abscess, mark of diabetes insipidus. In severe cases, the urine pneumonias, empyema). In other cases the cause of is pale color, and the volume may be immense (up this syndrome is organic disorder of hypothalamic- to 16–24 litres per day), requiring micturition every neurohypophyseal system (skull fracture, subdural 30 to 60 minutes through the day and night. More or subarachnoid hematoma, cerebral vascular trom- 312 Chapter 5. Pathophysiology of endocrine system ( L. Zlatoˇs) bosis, encephalitis, and purulent meningitis). Such serum osmolality and dilutive hyponatremia.Hy- cases are, however, very rare. ponatremia is paradoxically connected with in- The symptoms of permanent inadequate antidi- creased excretion of natrium by urine (inadequate uresis may also result from drug therapy.Some natriuresis), so that urine osmolality is higher drugs, such as vincristine, cyclophosphamide, clofi- than plasma osmolality. In paradoxically increased brate, carbamazepine, metoclopramide, and beta- glomerular filtration rate, decreased aldosterone se- adrenergic agents, may stimulate excessive ADH re- cretion and increased production of atrial natriuretic lease from the neurohypophyseal system, and other peptide take part. These changes arise secondary to drugs, as chlorpropamide and nonsteroidal
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