Hypothermic coma

Introduction Cryogenic coma: Some patients feel ambiguous in the winter, when exposed to cold, can induce coma, or prolong the coma that has occurred. Such dangers often occur in the winter, the onset is slow, gradually into a coma, the body temperature is very low, the temperature is not measured by the ordinary thermometer, the temperature of the anus should be measured by the thermometer used in the laboratory, and the low temperature can be as low as 30. °C. Pituitary hypofunction is caused by insufficient secretion of multiple or single pituitary hormones after damage to the pituitary gland. Occurred in the latter case known as Sheehan syndrome. If the patient has a deficiency of neurohypophyseal hormone, it is called panhypopituitarism.

Cause

(1) Causes of the disease

Pituitary hypofunction is caused by insufficient secretion of multiple or single pituitary hormones after damage to the pituitary gland. Occurred in the latter case known as Sheehan syndrome. If the patient has a deficiency of neurohypophyseal hormone, it is called panhypopituitarism.

The etiology of this disease is complex, and various diseases of the hypothalamus, pituitary and adjacent tissues, such as the pituitary gland, can cause the disease.

According to the location of the primary lesion, the disease can be divided into two categories: secondary hypopituitarism caused by hypothalamic tropism, and hypoplasia of the pituitary gland is called primary pituitary hypofunction. . According to the condition of hormone involvement, it can be divided into multi-hormone deficiency type and mono-hormone deficiency type. The former is more common. The latter includes simple GH deficiency, simple ACTH deficiency, simple LH/FSH deficiency and simple TSH deficiency, and simple GH deficiency. More common. Polyhormone-deficient hypopituitarism is also known as combined pituitary hormone deficiency (CPHD), and monohormone-deficient hypopituitarism is also known as solitary pituitary hormone deficiency.

Primary hypogland hypofunction

(1) Congenital: Some congenital malformations can cause pituitary dysplasia, resulting in a variety of pituitary hormone deficiency. These diseases include: anencephaly, holoprosence-phaly, de Morsier syndrome, Hall-Pallister syndrome, and Reiger syndrome. Forebrain non-cracking malformations include cyclopia, cebocephaly, or orbital hypotelorism. De Morsier syndrome is also known as septo-optic dysplasia. The patient's septum pellucidum is absent. In the neonatal period, there are apnea, hypotonia, convulsions, persistent jaundice. Hypoglycemia with hyperinsulinemia, small penis (male). De Morsie I syndrome is caused by a mutation in the inactivation of the Hesx-1 gene. De Motsier syndrome patients with hypothalamic dysplasia, resulting in hypopituitarism, of which GH deficiency is the most common, but there may be other pituitary hormone deficiency, some patients may also develop diabetes insipidus. Hall-Pallister syndrome also has pituitary hypoplasia and even pituitary abscess, and may be associated with hypothalamic hamartomatoma (hamartoblastoma). Hall-Pallister syndrome also often has multiple finger (toe) malformations, nail dysplasia, epiglottis dysplasia, anal atresia, and abnormalities in organs such as the heart, lungs, and kidneys.

In addition to pituitary dysplasia, Reiger syndrome also has iris defects, prone to glaucoma and may be associated with dysplasia of the kidney, gastrointestinal tract and umbilicus. This syndrome is caused by a mutation in the Ptx-2 gene. In addition, cleft lip and palate can also be combined with GH deficiency. According to foreign data, about 4% of cleft lip and splitting have GH deficiency. Mutations in the transcription factors Pit-1 and Prop-1 can also cause pituitary dysplasia, resulting in a deficiency of various pituitary hormones.

In addition, mutations in some pituitary hormone genes can cause a deficiency in the corresponding hormone. For example, mutations in the GH-1 gene can cause a deficiency in GH.

(2) pituitary tumors: pituitary tumors are the most common cause of this disease. Pituitary adenomas are the most common pituitary tumors. Various pituitary adenomas can cause hypopituitarism by compressing normal pituitary tissue and pituitary stalk. The high-secretion effect of non-functioning adenoma hormone is not obvious, and the onset is latent, which is the most likely to cause hypofunction of the pituitary gland. Other pituitary tumors and tumors adjacent to the pituitary can also cause hypopituitarism, including craniopharyngioma, Rathke cysts, dermoid cysts, ganglioneuromas, paraganglioma, nasal gliomas (esthesioneuroblastoma) ), sarcoma, lipoma, hemangiopericytoma, embryonic cell tumor, and the like.

(3) pituitary apoplexy: pituitary apoplexy refers to ischemic necrosis or hemorrhage of pituitary tissue. Pituitary tumors and postpartum hemorrhage are the most common causes of pituitary apoplexy. Arteriosclerosis, especially diabetic arteriosclerosis, is also prone to pituitary apoplexy. Others such as radiation exposure and trauma are less likely to cause pituitary apoplexy. The secretion function of the pituitary gland after pituitary apoplexy is reduced, which causes the disease.

(4) Infection: Bacterial (pituitary tuberculosis, pituitary abscess, etc.), fungal, viral (encephalitis, epidemic hemorrhagic fever, etc.) and spirochete (syphilis, etc.) infection can cause hypopituitarism.

(5) invasive lesions: some invasive lesions such as hemochromatosis, sarcoidosis, Wegener granulomatosis can affect the pituitary gland, resulting in hypopituitarism. Lymphocytic pituitary inflammation is also an invasive disease.

(6) External injury: The injury of the pituitary can damage the pituitary tissue and cause its function to decline.

(7) pituitary surgery: excessive pituitary tissue or pituitary injury during pituitary surgery can cause hypopituitarism.

(8) Radiation injury: When the pituitary tumor is treated with radiation, if the dose is large, it is easy to cause hypopituitarism, and its incidence increases with time. Radiation therapy for other intracranial or extracranial tumors can also produce hypopituitarism.

(9) Other diseases: empty saddle syndrome, internal carotid aneurysm, cavernous sinus thrombosis, etc. can also cause hypopituitarism.

(10) Idiopathic: The etiology of idiopathic hypopituitarism is unknown. Some patients have perinatal abnormalities, such as breech presentation, transverse position, forceps assisted delivery, intrapartum hemorrhage, etc., which may cause fetal pituitary damage due to these abnormal factors. MRI showed that the pituitary gland and pituitary stalk became smaller.

2. Secondary hypogonadal hypofunction

The hypothalamic or other parts of the disease, such as causing hypothalamic pituitary release hormone secretion or ineffectively acting on the pituitary gland can also produce hypopituitarism, is secondary to hypogonadal hypofunction.

(1) pituitary stalk lesions: external injury, surgery can damage the pituitary stalk; pituitary and its adjacent tumors can compress the pituitary stalk, both of which can cause dysfunction of the pituitary portal system, making the hypothalamic pituitary release hormone not effective Acts on the pituitary gland, causing hypofunction of the pituitary gland.

(2) Hypothalamus and its adjacent lesions: various lesions of the hypothalamus such as tumors, infections, invasive lesions, radiation damage, trauma, surgery, etc. can cause hypothalamic hypopituitar release hormone secretion, resulting in pituitary function Decrease.

Kallmann syndrome is also a hypothalamic pituitary hypofunction. The disease-causing gene of this disease has been cloned and located in the Xp22.3 region of the X chromosome, and its encoded product is a neuron migration protein. Deletion or mutation of this gene can cause GnRH neuron migration disorder, resulting in insufficient secretion of LH/FSH.

(3) Functionality: malnutrition, hyperkinesia and anorexia nervosa can cause hypothalamic dysfunction, resulting in insufficient secretion of GnRH in the hypothalamus, which causes LH/FSH deficiency. Mental stress can cause hypothalamic dysfunction in children, and GHRH is suppressed, thus causing insufficient secretion of GH. Various critical illnesses can reduce the production of TRH in the hypothalamus and decrease the secretion of pituitary TSH. Long-term use of glucocorticoids is inhibited by hypothalamic CRH, and ACTH secretion is reduced.

an examination

Related inspection

Body temperature measurement CT scan of the brain

Determination of hormones in the hypothalamus, pituitary gland and target gland, as well as related biochemical effects and stimulation tests, can help to understand the reserve capacity of the corresponding glands, and help to clarify the diagnosis of this disease, which can be appropriately selected according to the specific circumstances.

1. Determination of growth hormone (GH): In normal people (fasting in the morning, before getting up), the serum GH concentration is higher within 2 years, with an average of 8 ng/ml (RIA method), 4 to 4 years old 4 ng /ml, 4 to 6 years old, 1 to 3 ng/ml, similar to adults. The normal value of GH fasting in adults is 1 to 5 ng/ml. The GH basic value of pituitary dwarf can not be measured, but GH fluctuates greatly after being affected by hunger, exercise, etc., and the difference is also large in one day. It is better to conduct further excitation test.

2. Growth hormone stimulation test: At present, the following are more reliable:

(1) Exercise test: Do 10 minutes of exercise such as rolling, climbing stairs or boarding, and the normal person will reach the peak at about 30 minutes or 60 minutes.

(2) Insulin (0.050.1U/kg) hypoglycemia test and arginine (0.5g/kg) stimulation test (intravenous injection): thyroid function should be measured before the test, if there is a decrease, the result may be affected. Treatment, correct it and then do it. The results were judged by the same exercise test.

(3) L-dopa test: body weight was given diethylstilbestrol (B-phenol) and propranolol (propranolol) for 2 days to reduce false positives. The results were judged by the same exercise test.

(4) Human growth hormone releasing hormone (GHRH) test: dose 1 ~ 10mg / kg, 1 intravenous injection, GH increased to at least 10ng / ml.

(5) Growth medium (IGF-1) radioimmunoassay for males with IGF-1 (435±37) ng/ml and women (570±25) ng/ml, such as IGF-1, significantly lower than the above data People, puberty will not appear to accelerate linear growth, forming a dwarf, can be seen in Laron and Pygmy dwarfism. Due to the long half-life of IGF-1, this hormone can be accurately measured throughout the day to accurately reflect its mean plasma concentration. It is reasonable to screen for GH deficiency by measuring IGF-1 if attention is paid to age-related criteria. A lower assessment of the concentration of IGF-1 should be performed. The age-related normal values of IGF-1 radioimmunoassay may vary from method to method:

3. Prolactin determination

Prolactin in normal women is slightly higher than men, and the base value is female.

4. Functional measurement of the pituitary-gonadal system.

(1) Gonadal function test: It is generally believed that the first damage to the function of the pituitary gland is the reduction of gonadotropin secretion. Therefore, directly measuring the content of sex hormones in blood and urine can understand the function of the gonads and help early diagnosis. In women, estradiol and progesterone can be measured, and testosterone in plasma can be measured in men. Others such as endometrial atrophy and vaginal epithelial atrophy provide indirect evidence.

Testosterone levels in male serum [normal value (570 ± 156) ng / dl, Shanghai Ruijin Hospital], female serum estradiol decreased (normal women in the follicular phase of 27 ~ 177pg / ml, ovulation period 239 ~ 455pg / Ml, luteal phase 44 ~ 208pg / ml, Shanghai Nanyang Hospital Radioimmunoassay Center), plasma 17-hydroxyprogesterone also decreased [normal female follicular phase (0.053 ± 0.054) g / dl, luteal phase (0.469 ± 0.289) ) g / dl, Beijing Capital Hospital]. Smear examination of vaginal exfoliated cells showed a decrease in keratinized eosinophils, mostly blue basal cells, with reduced glycogen content in the cytoplasm, accompanied by a large number of white blood cells and bacteria, suggesting that estrogen levels are low. The basal body temperature is usually single phase. Cervical mucus examination also suggests low levels of estrogen and ovarian insufficiency.

(2) Determination of gonadotropin (FSH, LH): Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) are decreased in patients with this disease.

(3) Luteinizing hormone releasing hormone (LH-RH) stimulation test: intravenous injection of 50g / time, 15min after normal people, blood LH (or chorionic gonadotropin) increased significantly, the average increased to 3 times the base value Above, the absolute value is increased by about 7.5 ng/ml or more. If there is no response, it means that the storage capacity of the pituitary is poor. Secondary to hypothalamic lesions, this trial showed a delayed response, requiring intravenous or intramuscular injection of LH-RH 50 ~ 100g / time, once every other day, a total of 3 times, the initial rise in LH. In general, due to the hypofunction of the pituitary gland, the pituitary is mostly weakly reactive even under the stimulation of LH-RH. However, a small number of atypical patients with this disease may also have a normal reaction, which may be due to the existence of some normal cells in the pituitary gland. Therefore, the LH-RH excitation is weak and helpful for diagnosis, but it can not rule out the disease when it is normal. may.

(4) Clomifen (clomifene, clopidogamine, clomiphene) test: oral 50 ~ 100mg / d, 5 days; normal people can see a significant increase in LH (men can test testosterone) after taking the drug, the increase can exceed 2 to 4 times the base value. The mechanism may be that the drug competes with estrogen for receptors in the hypothalamus, thereby relieving the negative feedback inhibition of estrogen on the hypothalamus, so that the secretion of hypothalamic gonadotropin-releasing hormone is increased, and the pituitary gland is produced more. LH.

(5) Functional measurement of the pituitary-thyroid system:

1 Thyroid function test: The concentration of total thyroid hormone (T3, T4) and free T3 and T4 in peripheral blood were directly measured by RIA method. Patients with this disease may have a decrease in thyroid hormone levels (normal human T3 80 ~ 230ng / dl, T4 3.6 ~ 14g / dl, FT3 2.5 ~ 4.7pg / ml, FT4 9 ~ 14pg / ml, Shanghai Ruijin Hospital); The thyroid 131I uptake rate or the 125I-T3/denatured albumin particle uptake ratio, the 125I-T3 resin uptake rate, and the like were measured.

2 Plasma thyroid stimulating hormone (TSH) determination and thyrotropin releasing hormone (TRH) stimulation test: the base value of TSH in serum of patients with this disease decreased (normal value TSH 0 ~ 15U / ml, S-TSH 0.3 ~ 5U / ml, Shanghai Ruijin Hospital); Because the TSH base value of some normal people (about 20%) can also be measured, it is advisable to use the TRH stimulation test to detect the reserve capacity of the pituitary. The TRH stimulation test in this patient showed a weak or no response, and the lesion was delayed in the hypothalamus.

5. Functional measurement of the pituitary-adrenal system

(1) Adrenal function test: severe cases involving the pituitary-adrenal system can cause insufficient production of adrenocortical hormone, lower 17-hydroxysteroids and free cortisol in the urine, and the water diuretic effect of corticosteroids disappears or weakens, ie The highest amount of urine per minute during the test.

(2) Pituitary adrenocorticotropic hormone test: Determination of blood adrenocorticotropic hormone (ACTH), suggesting that ACTH secretion is reduced.

(3) ACTH stimulation test: normal human intravenous infusion of ACTH 25U / d, 2 days later, the production of 17-hydroxysteroids in urine increased by 10mg or more than before administration, the absolute count of eosinophils in blood after instillation Reduced by 80% to 90% before treatment; this disease is delayed response, primary chronic adrenal insufficiency has always been an adverse reaction, but ACTH infusion has an allergic reaction and the risk of water poisoning, should be used with caution.

(4) Metopabone (metyrapone, metyrapone, metopirone, Su4885) test: This drug can inhibit 11-hydroxylase in the adrenal cortex, reducing cortisol synthesis and staying in the 11-deoxycortisol phase. The negative feedback on the secretion of ACTH in the pituitary is weakened, so the 17-hydroxycorticosteroid in the urine of normal people is significantly increased, which can be more than twice that before the administration. If there is no significant increase, it indicates that the reserve capacity for secretion of ACTH is insufficient.

Differential diagnosis

Differential diagnosis of hypothermia coma:

(1) hypoglycemic coma: the cause may be spontaneous, that is, due to eating too little or not eating, especially when there is infection, or induced by insulin (for islet tolerance test or insulin treatment appetite) Insufficient), or due to high-sugar diet or injection of a large amount of glucose, causing endogenous insulin secretion and causing hypoglycemia. In patients with this disease, due to insufficient cortisol, reduced glycogen storage, decreased growth hormone, increased sensitivity to insulin, and decreased thyroid function, the absorption of glucose in the intestine is reduced, so the fasting blood glucose is lower in normal times. In the above situation, it is easy to cause hypoglycemia and coma. This type of coma is most common. When hypoglycemia occurs, the patient is weak, dizzy, dizzy, sweating, palpitation, pale, and may have headache, vomiting, and nausea. Blood pressure is generally low, and severe cases cannot be measured. It can be irritated or unresponsive, the pupils are reflected by light, and the sputum reflexes disappear after the initial sputum. The sputum test can be positive, and the muscle tension can be increased or convulsions, convulsions, and stuns in severe cases.

(2) infection-induced coma: patients with this disease due to the lack of a variety of hormones, mainly lack of adrenocorticotropic hormone and cortisol, so the body's resistance is low, prone to infection. After concurrent infection and high fever, it is prone to unconsciousness, resulting in coma, hypotension and shock. The loss of consciousness caused by infection is mostly gradual. The body temperature can be as high as 39 to 40 ° C, and the pulse often does not increase correspondingly. The blood pressure is lowered, and the systolic blood pressure is usually below 80 to 90 mmHg. In severe cases, shock occurs.

(3) sedation, anaesthetic-induced coma: patients with this disease are very sensitive to sedation, anesthesia, the usual dose can make patients fall into a long period of slumber and even coma. Sodium pentobarbital or thiopental, morphine, phenobarbital and meperidine can cause coma. Long-term lethargy can also occur after receiving a general therapeutic dose of chlorpromazine (oral or intramuscular).

(4) sodium loss coma: sodium loss caused by gastrointestinal disorders, surgery, infection, etc., can promote a crisis like primary adrenal insufficiency. The peripheral circulatory failure of this type of crisis is particularly remarkable. It is worth noting that patients with this disease may have increased excretion of sodium during the first few days of starting corticosteroid use, possibly because the glomerular filtration rate is very low and is improved after treatment. Less than a week after treatment with cortisol, the patient entered a coma with a significant negative sodium balance. In addition, when thyroid preparations are used alone, especially when the dosage is too large, the body's need for adrenocortical hormone is increased due to an increase in metabolic rate, and the deficiency of adrenocortical hormone is more serious. On the other hand, thyroid preparations have a hypothyroidism. Promote solute excretion, causing loss of water and loss of sodium.

(5) Toxic coma in water: The patient has drainage disorder. When the water is too much, water retention can occur, and the extracellular fluid is diluted to cause hypotonic state. Then the water enters the cell, and the introduced water contains too much water and the cells are swollen. Cell metabolism and dysfunction. Excessive water in nerve cells can cause a series of neurological symptoms. The occurrence of this condition can be spontaneous or caused by water diuretic test, especially when the blood sodium concentration of the patient is very low. Therefore, blood sodium should be measured before the water test, and low blood sodium should not be suitable. Do this test. The clinical manifestations of water poisoning are weakness, lethargy, loss of appetite, vomiting, mental disorder, convulsions, and finally into a coma. This type of coma is different from the crisis caused by salt loss. The patient has no signs of dehydration, but may have edema and weight gain. If there is no obvious loss of sodium, the blood circulation remains normal. The blood cell volume is reduced, the serum sodium concentration is lowered, the blood potassium is normal or decreased, and generally no acidosis or azotemia.

(6) hypothermia coma: Some patients feel ambiguous in the winter, when exposed to cold, can induce coma, or make the coma that has occurred more prolonged. Such dangers often occur in the winter, the onset is slow, gradually into a coma, the body temperature is very low, the temperature is not measured by the ordinary thermometer, the temperature of the anus should be measured by the thermometer used in the laboratory, and the low temperature can be as low as 30. °C.

(7) coma after pituitary resection: after pituitary resection for pituitary tumors or metastatic breast cancer, severe diabetic retinopathy, etc., patients may develop coma. Those with pituitary dysfunction before surgery are more likely to occur. Coma after uterine resection can cause disturbance of consciousness due to local injury, or due to hypofunction of endocrine glands, especially preoperative adrenal insufficiency, can not tolerate severe irritation caused by surgery, or due to water before and after surgery Electrolyte metabolism disorder. The patient can't recover after surgery, and is in a state of lethargy or coma. It can last for several days or even months, incontinence, and it can still respond to pain stimulation, sometimes temporarily awakening. The grip reflection and the sucking reflex disappear, the pulse rate and blood pressure can be normal or slightly lower, and the body temperature can be high or low, or normal. Blood sugar and blood sodium can also be normal or slightly lower.

(8) pituitary apoplexy: rapid onset, headache, dizziness, vomiting, and then into coma, due to acute bleeding within the pituitary tumor, hypothalamic and other life centers were oppressed. The main cause of hypopituitarism is the metabolic disorder caused by a variety of hormone deficiency, and the body's ability to resist various stimuli is weak. The maintenance of consciousness depends on the integrity of some of the central functions of the cerebral cortex, thalamus, hypothalamus and midbrain reticular formation. If the neuronal metabolism of these conscious centers is impaired, confusion or loss of consciousness occurs. The maintenance of normal neuronal metabolism depends mainly on the oxidation of glucose and glutamate under the catalysis of some specific enzymes. Patients with hypopituitarism have biochemical changes, such as hypoglycemia, hyponatremia, and sometimes due to trauma, compression or edema, which impede the delivery of oxygen and nutrients to the above-mentioned nerve centers. Adrenal cortex hormones and thyroxine deficiency can cause neuron metabolism disorders. Coma is more common in patients with severe peripheral endocrine gland dysfunction, especially adrenal insufficiency. Adrenal cortical function can only barely cope with the patient's need for a very low metabolic condition. Once severe stimulation occurs, adrenal insufficiency occurs. Adrenal cortex hormones have a good effect on coma in patients with this disease. After the patient was treated with adrenal cortical hormone replacement therapy, the incidence of coma was significantly reduced.

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