What Are Cortisol Blockers?

The adrenal cortex is an endocrine gland that forms the outer layer of the adrenal glands. It can secrete adrenocortical hormones, which are a mixture of several steroids. The cortex also contains more steroids. The adrenal cortex is composed of 3 layers, the outermost layer is the zona glomerulosa, followed by the majority of the zona fasciculata, and the inner layer is the zo-na seticularis. Its abnormal function can cause the adrenal cortex concept to increase, the adrenal cortex concept to decrease, the adrenal hyperplasia and so on.

Adrenal cortex

Basic overview of the adrenal cortex

Adrenal cortex globular bands secrete mineralocorticoid steroids, bundle bands secrete glucocorticosteroids, and reticular bands secrete adrenal hormones. Adrenocorticotropin in the anterior pituitary gland can promote the development and secretion of the adrenal cortex, but the activity of the globular band is dominated by angiotensin . The adrenal cortex is important for material metabolism through the secretion of these hormones

Adrenal cortex Relationships, especially the body's stress response to all harmful stimuli. In addition, adrenocortical hormones have a feedback effect on the brain and pituitary gland, which can adjust the secretion of corticotropin-releasing factor and adrenocorticotropic hormone. In this way, the adrenal regulation system forms a feedback loop.

Adrenal cortex tissue structure

The tissue structure of the adrenal cortex can be divided into three layers, from the outside to the inside, into a globular zone, a bundle zone and a reticular zone. Glandular glandular cells are arranged in short circles or globular shapes. This layer is thin and mainly secretes mineralocorticoids, and humans are mainly aldosterone. The bundled band is located in the middle of the cortex, and the glandular cells are arranged in a bundle shape perpendicular to the surface of the gland. This layer is thicker and makes up most of the cortex. The reticular zone is located in the innermost layer of the cortex, and the glandular cells are irregularly arranged. The fascicular zone and the reticular zone secrete glucocorticoids. Cortisol is the main type in humans. The reticular zone also secretes a small amount of sex hormones. The secretion of different hormones in each layer is mainly due to the different enzymes that promote the synthesis of hormones in the cells of each layer, which results in different enzyme-promoting reactions. Although the substrates are the same, the hormones synthesized are different. If a certain kind of enzyme deficiency is caused by congenital or acquired, it can cause insufficient synthesis and secretion of certain corticosteroids.

The adrenal glands are located on the left and right, and are located above the kidney. They are surrounded by the renal fascia and adipose tissue. The left adrenal gland is semilunar, and the right adrenal gland is triangular. Both sides weigh 10-15 grams. Viewed from the side, the renal parenchyma is divided into two parts, the cortex and the medulla.

The adrenal cortex is thick and is located in the surface layer, accounting for about 80% of the adrenal glands. It can be divided into three parts: the globular band, the bundle band, and the reticular band from the outside to the inside.

1. Spherical band: It is close to the capsule and accounts for about 15% of the thickness of the cortex. The cells are low columnar or cuboid, arranged into a spherical cell cluster, with small and round nuclei, deep staining, less cytoplasm, weak basophilism, and a small amount of lipid droplets. Under the electron microscope, the most obvious features are a large number of smooth endoplasmic reticulum, rough endoplasmic reticulum, free ribosomes, and Golgi complex. This band of cells secretes mineralocorticoids, which are mainly represented by aldosterone, which regulates electrolytes and water and salt metabolism.

2. Bundle- shaped zone: It accounts for about 78% of the thickness of the cortex and is arranged into bundles by polygonal cells. The cells are large and the nuclei are lightly stained and located in the center. The cytoplasm is filled with lipid droplets. In ordinary stained specimens, the lipid droplets are dissolved away, leaving many small vacuoles, which make the bundled cells appear foamy. Under the electron microscope, the endoplasmic reticulum on the sliding surface is much more than the globular zone, which is often arranged around lipid droplets and mitochondria, and the rough endoplasmic reticulum is also more developed. The band cells secrete glucocorticoids, mainly represented by cortisone and hydrocortisone, which regulate the metabolism of sugar, fat, and protein.

3, reticular zone: about 7% of the thickness of the cortex, close to the medulla, cells arranged in irregular cords, intertwined into a net. The cells are smaller than the bundled bands, the nucleus is also small, the staining is deep, and the cytoplasm is weakly eosinophilic. Contains a small amount of lipid droplets and more lipofuscin. Under the electron microscope, the cells in this zone contained a large number of smooth endoplasmic reticulum. Cells in this zone secrete androgens, but their secretion is small, meaning little in physiological conditions.

Adrenal cortex

The adrenal cortex is a life-related endocrine gland. The adrenal cortex of the animal is removed, and if it is not handled properly, it can die within 1 to 2 weeks. If the adrenal medulla is removed, animals can survive longer. Two major hormones related to life, glucocorticoids and mineralocorticoids, are steroid hormones. Adrenocortical hormone can promote the secretion of aldosterone.

Adrenocortical hormone is a general term for a variety of hormones secreted by the adrenal cortex. According to animal experiments and clinical observations of patients with adrenal dysfunction, it is known that the adrenal cortex secretes two major types of hormones that have an important relationship with the body's life activities, namely mineralocorticoid and glucocorticoid, and also secretes a small amount of sex hormones. Mineralocorticoids play a role in sodium, water and potassium excretion in the human body, and play an important role in maintaining normal water and salt metabolism, body fluid capacity and osmotic balance. Glucocorticoids include cortisone (cortin) and hydrocortisone (cortisol). These hormones have an effect on sugar, protein and fat metabolism, and their main role is to promote protein breakdown and liver glycogenogenesis. When the sugar supply in food is insufficient (such as starvation), increased secretion of glucocorticoids will promote the breakdown of tissue proteins such as muscle and connective tissue, and inhibit the intake of amino acids by muscles and strengthen liver gluconeogenesis, and also promote liver Glycogen breaks down into the source of glucose released into the blood to increase blood sugar levels, maintaining blood sugar levels so that the energy required for brain and heart tissue activity is not lacking. Used as medicine, large doses of glucocorticoids have anti-inflammatory, anti-allergic, anti-toxin effects, anti-shock and immune response suppression effects, so they are widely used in medicine, but also have side effects that cannot be ignored. In normal adults, the adrenal cortex also secretes a small amount of sex hormones, but the effect is not obvious. When certain cells of the adrenal cortex proliferate or form a tumor, the secretion of these sex hormones (mainly androgens) increases a lot, and male patients will grow hairy and female patients will show virilization.

Adrenal corticosteroids

Adrenal glucocorticoids are mainly cortisol, with only a small amount of corticosterone. Experimental rats and mice are mainly corticosterone. Adrenal glucocorticoids play an important role in regulating the metabolism of the three major nutrients and in participating in human stress and defense responses. It also has a pharmacological effect, is a hormone with curative effect, and is widely used in clinical practice.

Adrenal cortex medical application

Adrenocortical hormone is the earliest immunomodulatory drug used to treat chronic hepatitis. It has been used for decades with ACTH, hydrocortisone, prednisone, and dexamethasone.

I. Corticosteroids combined with adjuvant therapy: (1) Fulminant hepatitis B: oral prednisone or dexamethasone intravenous infusion may reduce symptoms and jaundice, and may even relieve acute liver failure. (2) Chronic hepatitis: prednisone alone or with other immunosuppressive drugs

kidney The combination of preparations has been a conventional therapy for chronic hepatitis in foreign countries until the 1970s. Some randomized controlled clinical trials have confirmed that it can prolong survival and reduce mortality. However, after the establishment of the HBsAg test method, it was found that the previously reported effective treatment group included most of the HBsA8 () cases, which may be autoimmune hepatitis.

2. Combined therapy with interferon: Due to immunosuppression during the treatment of prednisone, serum transaminase often decreases, and if the drug is suddenly stopped, hepatitis will often worsen within 1-2 months, which will stimulate immune clearance of the virus. During this period, serum levels of HBV DNA and DNAp decreased, and even turned negative; subsequent anti-HBe conversion and clinical remission occurred. Therefore, it is believed that large-dose short-term prednisone treatment may be effective for chronic hepatitis B; however, it may cause severe deterioration of the disease and even fulminant liver failure. Short-range corticosteroids are not suitable for long-term treatment of chronic hepatitis B. Short-range rebound therapy is only suitable in combination with antiviral drugs.

(1) Treatment plan: prednisone 40mg, 30mg and 20mg / d for 2 weeks each, IFN treatment after 2 weeks interval. Pediatric lmg / (kg · d) for 1 month, also stopped for 2 weeks, waiting for immune rebound to start the IFN course.

(2) Therapeutic effect: The clinical rebound (increased serum transaminase) rate is 40% -70%. Chronic HBV infection in China often has a certain degree of immune tolerance, so the effect rate of combined treatment is significantly higher than that of alpha interferon alone. Once a single IFN treatment of low-effect and non-effect patients, a significant proportion of patients can be treated with combination therapy to obtain therapeutic effects.

(3) Therapeutic mechanism: Prednisone / IFN combined therapy profoundly affects the distribution of cell subsets and virus replication. Among the peripheral blood T cells in healthy people, CD4 + cells are about 40%, CD8 + cells are slightly more than 20%, and the CD4 / CD8 ratio is nearly 2. CD8 + T cells in patients with chronic hepatitis B are significantly increased, which significantly reduces the CD4 / CD8 ratio. . During the treatment with prednisone, the CD8 + cells decreased significantly, resulting in a significant increase in the CD4 / CD8 ratio, accompanied by an increase in serum HBV DNA levels; during the treatment with IFN, the increase in the number of CD4 'cells increased the CD4 / CD8 ratio again, with serum HBV DNA The level decreases. Therefore, CD8 + cells rebound after the hormone is discontinued, and IFN promotes the proliferation of CD4 + cells. Combination therapy may be effective by enhancing cellular immunity.

(4) Adverse reactions: Jaundice and worsening of symptoms can occur. The incidence of liver decompensation is in patients with rebound, and some non-cirrhotic patients are more likely to have clinical rebound. However, patients with liver cirrhosis-once clinical rebound occurs, the relative risk of decompensation is 16 times that of non-cirrhotic patients. .

Adrenal cortex

1. (1) The effect on the intermediate metabolism of the three major nutrients: it is both "open source" and "throttling" on glucose metabolism: on the one hand, it promotes the breakdown of proteins and converts amino acids into glycogen in the liver; on the other hand, it has Fights the effects of insulin, inhibits the use of glucose in peripheral tissues, and raises blood sugar. Excessive glucocorticoids can cause a significant increase in blood sugar and may cause steroidal diabetes. Patients with recessive diabetes should be careful when using glucocorticoids clinically. Glucocorticoids have different effects on fat in different parts. Increased decomposition of adipose tissue in the extremities increases the synthesis of fat in the abdomen, face, shoulders and back. When the adrenal cortex is hyperactive or after taking an excessive amount of glucocorticoids, physical features such as full moon face, buffalo back, and "concentric obesity" may appear.

(2) Effects on water and salt metabolism: Glucocorticoids also have effects on water and salt metabolism. It mainly affects the drainage of water. Drainage may occur in the absence of water. It may have a permissive effect on the glomerular filtration effect.

(3) Effect on blood cell generation and destruction: It can enhance the hematopoietic function of red blood cells and platelets by bone marrow, increase the number of red blood cells and platelets, increase neutrophils, and promote the phagocytic endothelial system to engulf eosinophils , So that the amount of the latter in the blood is reduced; inhibit the proliferation of lymphoid tissues, cause atrophy of lymphoid tissues, and reduce lymphocytes in the blood.

(4) Effects on muscles: The skeletal muscles of norepinephrine are relaxed and weak, and supplementation with glucocorticoids can restore muscle strength; however, excessive glucocorticoids promote protein decomposition, which makes the protein decomposition and renewal unbalanced and decomposed. More than synthetic, muscles are weak.

(5) Effect on vascular response: on the one hand, it slows down the degradation of epinephrine and norepinephrine; on the other hand, it increases the sensitivity of vascular smooth muscle to norepinephrine, which allows it to function. It also reduces capillary permeability.

(6) Role in stress response: All harmful stimuli in the environment, such as anesthesia, infection, poisoning, trauma, cold, and fear, affect the body, causing a series of changes in the body's physiological functions to adapt to the various harmful stimuli mentioned above Called a stress response. In this response, ACTH secretion immediately increased, and glucocorticoid secretion increased accordingly. Glucocorticoids can enhance the body's stress ability, and its mechanism of action is unclear. The sympathetic-adrenal medulla system is also involved in stress responses. When adrenal insufficiency occurs, the body's stress response weakens, and it is easy to die when it encounters harmful stimuli.

(7) Pharmacological effects: High-dose glucocorticoids will cause pharmacological effects, mainly anti-inflammatory, anti-toxic, anti-shock and anti-allergic effects, which will be described in detail in pharmacology.

2.Secret regulation of glucocorticoids

Secretion regulates the secretion of glucocorticoids, whether basal or under stress, is controlled by the pituitary ACTH. After the pituitary gland is removed from the animal, the adrenal cortex's fascia and reticulum atrophy, and the secretion of glucocorticoids also stops. If ACTH is added in time, the atrophic tissue and secretory function can be restored. It is shown that ACTH promotes the development and growth of fascia and reticular belts, and stimulates them to secrete glucocorticoids. ACTH secretion is controlled by CRH in the hypothalamus. ACTH is a 39 amino acid peptide. Its natural secretion is circadian. Before waking up in the morning every morning, the secretion reaches a peak, and then gradually declines. After falling asleep at night, it decreases significantly, reaching the lowest point at midnight, and then gradually increases. It is currently believed that this rhythm may be controlled by the hypothalamic circadian clock. Some people think that CRH secretion also has this rhythm, forming the hypothalamus-adenohypophysis-adrenal axis. Glucocorticoids in the blood have negative feedback regulation on CRH and ACTH, which is a closed loop circuit. Excessive secretion of glucocorticoids in the blood can inhibit the secretion of ACTH, or weaken the response of ACTH-secreting ACTH cells to CRH, so as to reduce the secretion of glucocorticoids to maintain a relatively stable content of glucocorticoids in the blood. For the needs of the body. There may also be short loop negative feedback adjustments between ACTH and CRH. In short, the combination of the hypothalamus, pituitary gland, and adrenal cortex forms a highly efficient functional axis.

In the stress response, the central nervous system strengthens the hypothalamus-adenohypophysis-adrenal cortex functional axis activity through a variety of neural channels. Glucocorticoid secretion increases sharply, at this time the negative feedback regulation of glucocorticoid temporarily fails, this is a typical open-loop regulation, the mechanism of negative feedback failure is unknown.

It should be pointed out that long-term high-dose administration of exogenous glucocorticoids can feedbackally inhibit the activity of pituitary secretory cells, and can eventually lead to atrophy of the adrenal cortex instead of secreting hormones.

Adrenal hyperfunction

Excessive secretion of one or more adrenal corticosteroids produces different clinical syndromes. Excessive production of androgens leads to adrenal virilization; excessive secretion of glucocorticoids produces Cushing's syndrome; excessive production of aldosterone leads to hyperaldosteronism. These syndromes often have Overlapping manifestations.Adrenal hyperfunction can be compensatory, such as congenital adrenal hyperplasia, or due to acquired hyperplasia, adenoma, or adrenal cancer.

Adrenal virilization (adrenal syndrome):

Any syndrome, congenital or acquired, with excessive adrenal androgen production can cause virilization.

Symptoms and signs:

Symptoms and signs depend on the gender and age of the patient at the beginning of the disease, which is more pronounced in women than in men. In adult women, adrenal virilization can be caused by adrenal hyperplasia and adrenal tumors. Both disease symptoms and signs include hairy, hair loss, acne, low voice Bluntness, amenorrhea, uterine atrophy, clitoral hypertrophy, breast shrinkage, and increased muscle mass. Sexual desire can increase. Hirsutism can be the only sign of mild cases.

an examination

Adrenal CT and MRI are used to exclude tumors that are the cause of virilization. If tumors are found, biopsy can be obtained with a small needle aspiration by means of X-ray or ultrasound localization.

Delayed androgenic adrenal hyperplasia is a variant of congenital adrenal hyperplasia, both of which are caused by a deficiency in the hydroxylation of the cortisol precursor. DHEA and sulphate (DHEAS) in urine are increased; pregnanetriol excretion is often increased , And urinary free cortisol. Plasma DHEA, DHEAS, 17-hydroxyprogesterone, testosterone, and androstenedione increased. Dexamethasone 0.5 mg orally once every 6 hours, DHEA and pregnanetriol inhibition can be definitely diagnosed. The treatment advocates dexamethasone 0.5mg ~ 1mg, taken orally before bedtime, but even such small doses can appear in some patients.

Adrenal cortex Signs of Hin Syndrome. It can also be treated with hydrocortisone (25mg / d) or prednisone (5 ~ 10mg / d). Although most symptoms and signs of virilization disappear, the hairiness and hair loss improve slowly, and the tone remains low. , Pregnancy can be affected.

Unlike adrenal hyperplasia, androgenic adenoma or adenocarcinoma dexamethasone does not inhibit or only partially inhibit androgen excretion. The location of the tumor can be determined by CT. Adrenalectomy is required for treatment. Some tumors secrete excessive androgen and cortisol at the same time, causing Cushing Syndrome with inhibition of ACTH secretion and contralateral adrenal atrophy. If so, hydrocortisone should be given before and after surgery, as described below. Mild hairy and virilization with less menstruation or increased plasma testosterone can be seen in polycystic Ovarian (Stein-Leventhal) syndrome.

Cushing syndrome:

A group of clinical abnormalities caused by chronic exposure to excessive cortisol (mainly adrenal corticosteroids) or related corticosteroids.

Etiology:

Adrenal hyperfunction can be ACTH-dependent or independent of ACTH regulation, such as cortisol produced by adrenal cortical adenomas or cancers. Treatment with high physiological doses of exogenous cortisol or related synthetic similar drugs inhibits adrenal function, mimics non-adrenal ACTH-dependent hyperfunction. ACTH-dependent adrenal hyperfunction can be caused by: (1) excessive pituitary ACTH secretion; (2) non-pituitary ACTH-secreting tumors, such as small cell lung cancer (ectopic ACTH syndrome); or (3) Originating ACTH. The term Cushing's syndrome applies to the clinical manifestations of hypercortisol caused by whatever cause (for whatever reason). Due to excessive pituitary ACTH, hyperadrenocortical function is called Cushing's disease, which means that there is a unique Physiological abnormalities. Cushing's disease patients can be pituitary basophils or chromocytoma.

Symptoms and signs:

Clinical manifestations include full moon face, multiple blood quality. Concentric obesity, prominent supraclavicular fossa and dorsal neck fat pad (buffalo dorsal); distal limbs and fingers are often very slender, muscles are thin and weak. Skin is thin, atrophy, The wound is not easy to heal and is easy to bruise. Purple stripes are visible in the abdomen. High blood pressure, kidney stones, osteoporosis, impaired glucose tolerance, poor resistance to infection and mental disorders are common. Stopping linear growth is a characteristic of children. Women often have irregular menstrual periods Adrenal tumors, in addition to cortisol, increased androgen production can lead to hairiness, temporal hair loss, and other virilizing signs in women.

diagnosis:

In the morning (6-8 o'clock), plasma cortisol is normally between 5-25 g / dl (138-690 nmol / L), and then gradually decreases to <10 g / dl (L) at night (after 6 o'clock). In patients with syndrome, cortisol usually increases in the morning, and the lack of normal cortisol production decreases during the day, so that plasma cortisol is higher than normal at night, and total cortisol production is increased in 24 hours. A single plasma cortisol sample may be difficult to explain because of the pulse Secretion causes a wide range of normal values. Patients with congenital corticosteroid-binding globulin may have pseudo-elevation of plasma cortisol, but these patients have normal circadian rhythms. In patients with Cushing's disease, free cortisol in urine, urine excretion is the most Good test [normal value is between 20 ~ 100g / 24h (55.2 ~ 276nmol / 24h)], Cushing's disease patients increased> 120g / 24h (> 331nmol / 24h), and obesity was only a slight increase of <150g / 24h (< 414nmol / 24h).

Traditional dexamethasone test, dexamethasone 1mg, orally taken at 11-12 o'clock in the evening, and plasma cortisol measured at 7-8 o'clock in the morning, this method can be used as screening for Cushing's syndrome. This method is suitable for most normal people, In the morning, plasma cortisol is 5 g / dl (138 nmol / L), and in most patients with non-pituitary Cushing syndrome, the morning cortisol level is at least 9 g / dl (248 nmol / L), and the plasma cortisol is maintained at the initial level.

Dexamethasone 0.5mg once every 6 hours for 2 days (small dose), ACTH secretion in normal people is inhibited. As a result, free cortisol in urine decreased to 50% or lower than before administration, but some patients decreased the next day To 10g / 24h (<27.6nmol / 24h). In patients with Cushing's disease, relative to dexamethasone inhibition, urine free cortisol will not normally decrease. Local dexamethasone 2mg is given every 6 hours for 2 days (large (Dose), urine free cortisol in patients with Cushing's disease is often reduced by at least 50% from the baseline value, because the disease depends on pituitary ACTH.

In patients with adrenal tumors, cortisol produces ACTH independent, so dexamethasone has no inhibitory effect. In patients with ectopic ACTH syndrome, ACTH produced by non-pituitary tumors is almost always unaffected by dexamethasone, so urine steroids remain unchanged. The Misson test can distinguish pituitary abnormalities from other types of Cushing's syndrome.

A more accurate and improved method is continuous intravenous infusion of dexamethasone 1mg / h for 7 hours. The plasma cortisol in patients with Cushing's disease has been reduced by at least 7 g / dl, and patients with adrenal tumors or ectopic ACTH syndrome have no response. Dexamethasone inhibition test can It was blocked by rifampicin, so the test for patients taking the drug did not help diagnosis.

The midnight methylpyridone test is used to determine the etiology of Cushing's syndrome. In patients with pituitary dependence Cushing's disease, plasma 11-deoxycortisol is significantly increased, while patients with adrenal tumors or ectopic ACTH syndrome do not increase. Total steroid production ( (11-hydroxylation of 11-deoxycortisol due to metyrapone) must be measured. Therefore, the determination of cortisol and 11-deoxycortisol revealed an increase in total steroids, rather than 11-deoxycortisol replacing plasma cortisol.

The less commonly used method to evaluate Cushing's syndrome is the ACTH stimulation test. For 8 hours of intravenous infusion of ACTH50u, urinary cortisol in patients with Cushing's disease increases by 2 to 5 times. These patients show bilateral adrenal glands due to long-term endogenous ACTH excitement. Hyperplasia and hyperresponsiveness to ACTH. Approximately 50% of patients with adrenal adenomas will have a pronounced ACTH excitement, sometimes with a significant increase in plasma and urocortisol. Adrenal cancers generally do not respond to ACTH.

Pituitary microadenomas can usually be detected by CT, but MRI is better, especially with high resolution. Some microadenomas are still difficult to detect even with this technique. In some cases, despite the apparently high ACTH production, they have failed. Find histological anomalies.

Differential diagnosis:

If the dexamethasone test suggests adrenal tumors or ectopic ACTH syndrome, plasma ACTH concentration can be measured. Ectopic ACTH syndrome, plasma ACTH significantly increased (usually> 200pg / ml), adrenal adenoma-induced Cushing syndrome ACTH It is so low that it is difficult to detect, except in rare cases where ACTH secretes adrenal tumors. Cushing's disease patients usually have moderately high plasma ACTH levels (75 ~ 200pg / ml). Laboratory results can also support ectopic ACTH as Cushing's syndrome. The etiology includes: low blood K (L) and HCO3-> 30mEq / L, 9AM serum cortisol> 200g / dl (> 5520nmol / L), urine free cortisol excretion> 450g / 24h (> 1242nmol / 24h).

The CRH test (see above for Addison's disease test) can usually identify ectopic ACTH hyperadrenocortical function, excessive adrenal adenoma secretion (no response in this test), and pituitary Cushing's disease (normal or increased response). However, this test can be misleading because there is an overlap between normal and abnormal reactions. When combined with a positive dexamethasone test, it has the greatest value.

After the diagnosis of hyperadrenal function, the evaluation of Cushing's syndrome should also include CT but preferably MRI pituitary examination. If the tumor is present or the location of the pituitary tumor is not sure, the most useful method is to give the patient CRH 1 g / kg, and take it before and after the medication ACTH levels were measured at the same time on both sides of the inferior petrosal sinus blood. The normal two sides responded equally. The ACTH level from the tumor sinus blood before excitement was higher than that on the non-tumor side, which had a greater response to CRH. The ectopic ACTH patients had equal increases in ACTH on both sides. CRH does not respond. In addition, tumors produced by non-pituitary ACTH must be carefully searched for. Adrenal scans can be used to identify hyperplasia and adenomas or cancers after radioiodinated cholesterol is administered to the patient. However, if biochemical experiments indicate the presence of adrenal tumors, adrenal CT (this (MRI is not better than CT).

Children have the same diagnostic methods and standards as adults, except that pregnant women prefer MRI in order to avoid exposure.

Liver disease Hydrocortisone excess Some chronic liver diseases, especially alcoholics, have clinical manifestations similar to Cushing's syndrome. Laboratory tests show elevated plasma cortisol and limited diurnal changes. Normal cortisol secretion rate. High plasma Cortisol is partly due to reduced liver liver cortisol oxidation to inactive metabolites (cortin), but persistently high cortisol also suggests reduced sensitivity of the hypothalamic-pituitary-adrenal feedback mechanism and should reduce ACTH secretion (but Not so.) Improving liver function can correct this abnormality. Corticosteroid blockers such as ketoconazole can help.

treatment:

Treatment is directed at hyperfunction of the pituitary or adrenal cortex. The correct method depends on the underlying disease.

At the beginning, patients should generally be supported by appropriate potassium and high protein. If the clinical situation is severe, they should be treated with amphenone (250 mg orally twice daily) or ketoconazole (400 mg / d increased to a maximum dose of 1200 mg / d). Steroid secretion is more reasonable. When too much ACTH originates from the pituitary gland, the standard method is to investigate the pituitary gland, such as finding a tumor, and removing it surgically. This surgical operation has certain requirements and should be performed in an experienced center. The success rate of the operation is about 70%, preferably adenoma with a diameter of less than 1cm. About 20% of tumors recur, and smaller tumors are more likely to recur. Recurrence tumors are often successful in reoperation. Pregnancy is not an indication of surgery.

If the tumor is not found, some doctors advocate pituitary resection, but most people think that the next step should be pituitary high-pressure radiotherapy (40-50Gy). Children's pituitary irradiation can reduce GH secretion and occasionally cause prepuberty in some centers. Heavy particles in some centers Beam irradiation (producing about 100 Gy) is often successful, and the response to the irradiation may take several months. Bilateral adrenalectomy is only given to patients with pituitary adrenocortical hyperthyroidism. Pituitary exploration (with possible adrenal resection) and radiotherapy (usually pituitary function returns to normal) Non-responsive patients. Adrenalectomy requires lifelong steroid replacement

kidney Treatment as needed for primary adrenal failure.

There is also a serious risk of developing Nelson syndrome. The incidence of Cushing's disease after adrenalectomy is about 5% to 10%. If the patient undergoes pituitary radiotherapy, the risk is reduced, and the patient is> 35 years old during surgery, and the risk is very low. In Nelson syndrome, continued enlargement of the pituitary gland causes ACTH and -MSH to increase, leading to severe hyperpigmentation. Although radiation therapy can prevent these patients from continuing to grow, many patients also need pituitary resection. Resection of pituitary signs is similar to other pituitary tumors. --- Volume increases, erosion of surrounding tissues, visual field defects, compression of the hypothalamus or other complications. Conventional irradiation is often performed after pituitary resection.

Adrenal tumors can be surgically removed. Patients must be supplemented with cortisol during and after surgery because non-neoplastic adrenal cortex has atrophied and inhibited. Benign adenomas can be successfully removed with laparoscopy. Multinodular adrenal hyperplasia requires bilateral adrenalectomy. It is presumed that the total resection has recurred and still accounts for about 1/3 of patients. If possible, the treatment of ectopic ACTH syndrome should remove non-pituitary tumors that produce ACTH. However, most patients have tumors that spread and cannot be removed. Adrenal inhibitors, such as A Pyridone 250 mg 4 times a day combined with amphenidone 250 mg orally twice a day, up to 2 g / d, or bischlorobenzene dichloroethane (O, P-DDD) 0.5 orally 4 times a day, up to Increase to 8 ~ 12g / d, usually can control severe metabolic disorders due to hyperadrenal function (such as hypokalemia). When taking diclofenac, at the same time take hydrocortisone 20mg / d to prevent The patient's corticosteroid secretion completely disappeared. However, ketoconazole (400 ~ 1200mg / d) is probably the best blocker of steroid synthesis, although there is a risk of liver toxicity and like dichlorobenzene dichloroethane, it can cause Eddie Symptoms of illness. In addition, corticosteroid receptors can be affected by mifepristone (RU486) block. This increases plasma cortisol levels but blocks steroid effects. Sometimes ectopic ACTH syndrome tumors respond to long-acting somatostatin analogs, such as Octreotide 100-125 g per Subcutaneous injection 3 times a day. Octreotide treatment over 2 years requires close follow-up because there can be mild gastritis, gallstones, cholangitis, jaundice and vitamin B12 malabsorption.

Adrenocortical hyperaldosteronism

Clinical syndrome due to excessive aldosterone secretion.

Aldosterone is the most potent mineralocorticoid produced by the adrenal glands, which can cause potassium excretion of osmium sodium. In the kidney, aldosterone causes distal renal tubular sodium to enter tubule cells and exchange potassium with potassium, hydrogen, and the same effect is found in salivary glands, sweat glands, and intestinal mucosal cells. The liquid inside and outside the cell is exchanged.

Aldosterone secretion is regulated by renin-angiotensin and is less regulated by ACTH. Renin (a proteolytic enzyme) is stored in the mesangial cells of the kidney. Reducing blood volume and arteriolar flow can induce renin secretion. Converts intrahepatic angiotensinogen (2 globulin) into angiotensin (10 amino acid peptide), which is converted into angiotensin (8 amino acid peptide). Angiotensin causes aldosterone secretion and a minimum degree Cortisol and deoxycorticosterone secretion. Increasing aldosterone secretion causes water, sodium retention, increased blood volume, and reduced renin secretion. Aldosterone is measured by radioimmunoassay.

Primary aldosteronism:

(Conn syndrome)

Primary aldosteronism is due to adrenal cortical spheroid adenomas, which are usually unilateral and relatively rare with adrenal cancer or hyperplasia. Adenomas are extremely rare in children, but the syndrome is sometimes a type of adrenal cancer or adrenal hyperplasia in children. Due to the lack of 11-hydroxylase, the clinical features of congenital adrenal hyperplasia are also mimicked. The difference between high aldosterone and hypokalemia in Bartter syndrome in children and hyperaldosteronism is the absence of hypertension.

Symptoms and signs:

Excessive secretion of aldosterone can cause hypernatremia, high chloride, high blood volume, and hypokalemia, with clinical manifestations of paroxysmal weakness, paresthesia, transient paralysis, and convulsions. High diastolic blood pressure and hypokalemia nephropathy Polyuria, and thirst are common. Such as tumors, high sodium intake (> 10g / d), aldosterone excretion is usually> 200 g / d. Avoid sodium can cause potassium retention. Personality changes, hyperglycemia, and occasionally visible urine glucose. Many cases are unique The manifestation is mild to moderate hypertension.

diagnosis:

The ampoulesone test is helpful for diagnosis. Administration of ampoulesone 200-400mg / d and oral administration for 5-8 weeks can reverse the clinical manifestations of the disease, including hypertension (rarely reversible with non-aldosterone hypertension). Plasma kidney The serum renin measurement is helpful for diagnosis. The plasma renin level is measured in the morning when the patient is supine, and the fasting urine is 80 mg orally, and then the patient is erected for 3 hours, and then the plasma renin is measured. After normal people, the plasma renin is significantly increased, and the patients with aldosteronism No increase. About 20% of patients with essential hypertension do not necessarily have high aldosterone and low renin, and do not respond to the upright position. Measurement of plasma aldosterone (peripheral vein or adrenal vein intubation) can be helpful. Therefore the diagnosis depends on confirmation High aldosterone secretion in the blood and urine, and an increase in plasma renin in the upright position are evidenced by extracellular fluid volume expansion and potassium abnormalities. CT often shows small adrenal adenomas in these diseases. MRI does not improve diagnostic ability.

treatment:

Once the diagnosis of primary aldosterone is confirmed, bilateral adrenal glands should be explored because multiple adenomas may be possible. It may be necessary to open the glands to look for adenomas. Obviously, aldosteronism, when a single adenoma is positive, the prognosis is good. These cases may be Laparoscopy is needed to remove adenomas. After the removal of aldosterone adenomas, the patient's blood pressure is reduced, and about 50% to 70% is completely relieved. Adrenal hyperplasia, although most patients have reduced blood pressure, about 70% are still hypertension In these patients, primary aldosteronism can usually be controlled by spironolactone, with a starting dose of 300mg / d, which gradually decreases to a maintenance amount within 1 month, usually 100mg / d, or with potassium cannate, starting dose 200mg / d, gradually reduced to about 100mg / d in 3 months. In addition, about half of patients need antihypertensive treatment (see section 119). Bilateral adrenalectomy is rarely needed. Normal serum potassium aldosterone, diagnosis And definition is difficult, surgical exploration can be futile.

Secondary aldosteronism:

Secondary aldosteronism, increased adrenocortical aldosterone production by extra-adrenal stimulation, pseudo-primary onset, and related to hypertension and edema (such as heart failure, liver cirrhosis, ascites, nephrotic syndrome), secondary to the acute phase of hypertension Hyperaldosteronism is thought to be due to the excessive secretion of renin secondary to renal vasoconstriction. Hyperaldosteronism is also seen in obstructive renal arterial hypertension (such as atherosclerosis and stenosis). This is due to the reduction of renal blood in the affected side Caused by flow. Hypovolemia, which is common in edema, especially during diuretic therapy, excites the renin-angiotensin system with excessive secretion of aldosterone. The secretion rate can be normal during heart failure, but liver blood flow and aldosterone metabolism are reduced, causing Increased blood circulation hormone levels.

Adrenal insufficiency

Overview:

When most of the adrenal glands on both sides are destroyed, there are various manifestations of corticosteroid deficiency, which is called adrenal insufficiency. Can be divided into primary and secondary. Primary chronic adrenal insufficiency, also known as Addison's disease, is relatively rare; secondary hypothalamic-pituitary insufficiency can be seen, due to insufficient secretion of CRF or ACTH, resulting in atrophy of the adrenal cortex.

Cause:

I. Adrenal tuberculosis: Only bilateral adrenal tuberculosis, most of the adrenal gland tissue is destroyed, clinical symptoms appear. It is often accompanied by tuberculosis of lung, bone or other parts. It accounted for about half of chronic adrenal insufficiency in the 1950s, and gradually decreased in recent years as tuberculosis was controlled.

2. Autoimmune disorders: Adrenal atrophy caused by idiopathic autoimmune reactions is the most common cause at present, and anti-adrenal tissue antibodies can often be detected in serum. It mainly invades mitochondrial cells, and the antigen is mainly in microsomes and mitochondria. The disease is often accompanied by other autoimmune disorders. Such as multiple endocrine gland dysfunction syndrome (Schmidt syndrome), can include

Glomerulus Such as adrenal insufficiency, hypothyroidism, hypoparathyroidism, gonadal failure, diabetes, hypopituitarism, gastric wall cell antibody positive, malignant anemia, hyperthyroidism, colon tumor, myasthenia gravis, solitary red blood cell regeneration disorder, etc. .

Third, other: adrenal metastasis of malignant tumors, which accounts for about 10% of patients with metastatic tumors, bilateral adrenal metastases, lung cancer and breast cancer are more common. Can also be seen after bilateral adrenalectomy, systemic fungal infections, adrenal amyloidosis and so on.

symptom:

First, the slow onset may not be noticed for many years. Occasionally, adrenal crisis was induced by infection, trauma, surgery, and other stress, and was only clinically detected.

2. Pigmentation The pigmentation of the skin and mucous membranes is mostly diffuse. The exposed parts, the frequently rubbed parts and the nail roots, scars, areola, external genitalia, around the anus, gums, oral mucosa, and conjunctiva are obvious. The cause of pigmentation is a decrease in feedback inhibition of melanocyte stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) secretion when glucocorticoids are reduced. Some patients may have flaky pigmented areas. Patients with secondary adrenal insufficiency had significantly lower MSH and ACTH levels, so there was no pigmentation.

Third, the degree of fatigue and fatigue are parallel to the severity of the disease. The mild person only has poor labor tolerance, and the severe person cannot lie in bed. It is caused by electrolyte disorders, dehydration, and protein and sugar metabolism disorders.

Fourth, gastrointestinal symptoms such as loss of appetite, nausea, vomiting, upper abdomen, right lower abdomen or unlocated abdominal pain, and sometimes diarrhea or constipation. More hi-sodium diet. Wasting is often accompanied. Gastrointestinal symptoms are more common in patients with a long course of illness and severe illness.

5. Cardiovascular symptoms Due to sodium deficiency, dehydration and insufficient corticosteroids, patients often have hypotension (both systolic and diastolic blood pressure decrease) and orthostatic hypotension. The heart is smaller, the heart rate is slower, and the heart sounds are dull.

6. Hypoglycemia: Due to the lack of insulin antagonists and gastrointestinal dysfunction in the body, patients' blood glucose is often low, but due to the slow development of the disease, they can tolerate it and their symptoms are not obvious. Only hunger, sweating, headache, weakness, and restlessness. In severe cases, tremors, blurred vision, diplopia, mental disorders, and even convulsions may occur. The disease is particularly sensitive to insulin, and even small doses can cause severe hypoglycemic reactions.

7. Mental symptoms: lack of energy, indifferent expression, memory loss, dizziness, and lethargy. Some patients have insomnia, irritability, and even delirium and mental disorders.

Eight. Adrenal crisis patients have low resistance, and any stress load such as infection, trauma, surgery, anesthesia, etc. can induce acute adrenal insufficiency crisis.

9. Others are very sensitive to narcotics and sedatives. Small doses can cause drowsiness or coma. Hypogonadism, such as impotence, menstrual disorders, etc.

X. Primary symptoms include tuberculosis, various autoimmune diseases and various symptoms of glandular failure syndrome.

an examination:

First, the general examination blood image examination has mild positive cell positive pigment anemia, lymphocytes and eosinophils are high. Blood biochemical examination, some patients have low serum sodium and high potassium. Blood sugar is low, about one-third of cases are below the normal range. The glucose tolerance test showed a low-level curve or reactive hypoglycemia. The low voltage of the electrocardiogram and the low or T-wave of the T wave can be prolonged. X-ray examination showed that the heart shadow was reduced and was vertical.

Special inspections

(1) Urine 17-hydroxycorticosteroid (17OHCS) and 17-ketocorticosteroid (17KS) excretion is lower than normal. The degree of reduction is parallel to the function of the adrenal cortex.

(B) Plasma cortisol was measured, and it was significantly reduced, and the circadian rhythm disappeared.

(3) ACTH excitation test This test is to check the functional reserve of the adrenal cortex. It can be found in patients with mild chronic adrenal insufficiency and distinguish between primary chronic adrenal insufficiency and secondary chronic adrenal insufficiency.

III. Determination of the basic value of plasma ACTH The primary adrenocortical insufficiency increased significantly, more than 55 pmol/L (250pg / ml), often between 88-440pmol / L (400-200pg / ml) (normal value 1.1 11 pmol / L (that is, 5-50 pg / ml) and those with secondary adrenal insufficiency have extremely low plasma ACTH concentrations.

Fourth, the cause of tuberculosis in the adrenal gland X-ray film may look at the adrenal calcifications may also have other tissues and organs of tuberculosis lesions. Adrenocortical antibodies may be detected in the serum of patients with autoimmune adrenal damage, and patients are often accompanied by other autoimmune diseases and endocrine gland dysfunction. Patients with metastatic adrenal carcinoma may find primary cancer.

treatment:

First, basic treatment usually enter a high-sodium diet, alternative therapy can take hydrocortisone 20 to 30mg per day, or prednisone 5 to 7.5mg, should be taken 2/3 of the total dose in the morning and 1/3 in the afternoon if it cannot be corrected For fatigue, fatigue, and hyponatremia, you can add a small dose of mineralocorticoids, such as 9-fluhydrocortisone 0.2 mg daily or 125 mg of trimethylcortisol acetate.

Second, in the treatment of acute cortical functional crisis, under mild stress, increase hydrocortisone by about 50mg per day, and those who cannot take it can be administered intravenously. Severe acute adrenal crisis, which is life-threatening, must be rescued in time. Replenish the saline. The saline should be replenished quickly in the first two days, 2 ~ 3L per day. Glucocorticoids. Intravenous injection of 100 mg of hydrocortisone phosphate or succinyl hydrocortisone immediately makes the plasma cortisol concentration reach the level of normal people when severe stress occurs. After that, 100 mg was intravenously infused every 6 hours, and the dose was gradually reduced on the third day. After the vomiting stopped, it could be changed to oral hydrocortisone 50-60 mg / d. 9-fluorohydrocortisone can be added.

Third, the cause of treatment such as immunosuppressive agents, anti-TB treatment.

Adrenal hyperplasia

This disease is due to pituitary or ectopic adrenocorticotrophic adenomas secreting too much adrenocorticotropic hormone and causing adrenal hyperplasia and hypertrophy.

Adrenal hyperplasia can be divided into two types:

(A) Nodular hyperplasia: multiple hyperplastic small nodules can be seen inside, outside or fat of the adrenal glands on both sides, with a diameter of several millimeters to 2.5 cm. The arrangement and morphology of the cells in the nodules are similar to the globular or bundled bands of the normal cortex. A large amount of lipofuscin is common, causing the nodules to be brown.

(2) Diffuse hyperplasia: It usually occurs on both sides. The weight of a single adrenal gland exceeds 5 grams, can reach 8 grams or more, the thickness of the cortex can reach 2 mm, and the edges are obtuse. The diffuse hyperplasia of cortical globular bands is not obvious, or only increases in levels; bundle band hyperplasia is more pronounced, cells can be seen to increase, cytoplasmic lipids increase, and common vacuole-like band cells extend into the network in a tongue shape. Ribbon. Clinical majority

Related books The patient developed hyperadrenocortical function, protein dissimilation due to excessive cortisol secretion, and secondary fatosis. Presentation of Cushing syndrome, concentric obesity, full moon face, shoulder and back hypertrophy, muscle atrophy, osteoporosis, thinning of the skin with purple lines, hairy, acne, high blood pressure, impaired glucose tolerance, menstrual disorders, and decreased sexual function .

Characteristics and treatment of various types of congenital adrenal hyperplasia:

Adrenocortical hyperplasia caused by different types of enzyme defects will affect the hormone synthesis process after the action of this enzyme (see Figure 10), block the synthesis of this hormone, and produce too much intermediate products before blocking the level , Cause corresponding clinical signs.

The most severe case of congenital adrenal hyperplasia is mineralocorticoid deficiency. Neonatal deaths can occur days after birth due to dehydration, hypovolemia, hypotension, and circulatory failure. If it can be found in time, intramuscular injection of ll-dehydrocorticosterone (2.5-5. 0 mg / day) and intravenous drip of normal saline may be able to maintain survival. After the symptoms are relieved, oral 9-fluhydrocortisone ( 0.05 mg / m2 body surface area) as maintenance treatment.

21-hydroxylase deficiency is the most common type, mainly due to glucocorticoid and mineralocorticoid deficiency and excessive androgen. The treatment is to give physiologically necessary amounts of glucocorticoids and mineralocorticoids. Children can take hydrocortisone 20-25 mg / day by the age of 5 and maintain urine 17-ketosteroid levels at 6.94-10.41 micromoles / day. In children 6-12 years old, the amount of hydrocortisone can be increased to 25-50 mg / day to maintain the urine 17-ketool at 13.88-27.76 micromoles / day. Or take the corresponding effect of prednisone or prednisone. Be careful not to overdo it, causing iatrogenic Cushing syndrome. If the hypertensive type does not respond well to glucocorticoids, careful consideration should be given to whether to perform bilateral adrenalectomy.

Patients who have developed pseudohermaphroditism should be surgically orthopedic based on the degree of malformation of their sexual organs and gender, and supplemented with estrogen or androgens, respectively.

Recipe for prescription:

Prescription: Raw cut pupae, dung beetle, pupae, stiff silkworm, shanci mushroom, artillery piece, whole scorpion, sacred house, realgar 10-15g each, raw oyster, kumbu, seaweed 30g each, tofu sulfur yellow ( Add 10g of licorice and tofu after making. After researching the details, the water pan is the size of a pill, such as mung bean, and is stored for future use. Each serving is 1.5g, twice a day. Decoction or warm water is given. 3 months is a course of treatment, which can be taken for 3 to 4 courses.

Efficacy: This formula treats 140 cases of various advanced malignant tumors. Among them, 34 cases survived 1-3 years; 42 cases were 3-5 years; 40 cases were 5-10 years; 24 cases were more than 10 years; and the longest survival time was 16 years.

Fang Yuan: Ni Yusheng: Clinical observation of 140 cases of advanced malignant tumor treated by traditional Chinese medicine. Chinese Journal of Medical Science (1): 17, 1987.

Recipes: 15g of Scutellaria barbata, 10g of Sophora flavescens, 15g of Poria cocos, 15g of golden sand, 10g of Caoheche. Shuijianbi 2 times a day.