adrenal insufficiency
Introduction
Introduction to adrenal insufficiency Adrenal insufficiency can be divided into primary and secondary according to the cause, and can be divided into acute and chronic according to the course of the disease. The most common type of primary adrenal insufficiency is Addison disease, a common cause of adrenal tuberculosis or autoimmune adrenalitis; rare causes include deep fungal infections, immunodeficiency, viral infections, malignant tumors, Extensive adrenal hemorrhage, surgical resection, adrenal white matter malnutrition and POEMS disease, secondary adrenal insufficiency, most commonly used in long-term application of super-physiological doses of glucocorticoids, can also be secondary to hypothalamic-pituitary disease, Such as saddle area tumors, autoimmune pituitary inflammation, trauma, surgical resection, postpartum hemorrhage caused by large infarcts and necrosis of the pituitary, namely Sheehan syndrome. basic knowledge The proportion of illness: 0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: constipation amenorrhea impotence headache headache diabetes insipidus
Cause
Cause of adrenal insufficiency
(1) Causes of the disease
1. Primary adrenal insufficiency, Addison disease, was named in 1856 and is a long-established endocrine disease with a low prevalence of 39/1 million in the United States. In the United Kingdom and Denmark, 60/1 million people, due to the prevalence of acquired immunodeficiency syndrome and the prolongation of survival of patients with malignant tumors, the incidence of Edison's disease has a rising trend, there is no exact epidemiological data in China, male Slightly less than women.
Adrenal tuberculosis (35%):
In developed countries, adrenal tuberculosis accounted for 80% of Edison's disease before the 1960s, and only 20% after the 1960s, but in countries and regions with high rates of tuberculosis, adrenal tuberculosis remains primary adrenal function. The primary cause of the decline, the proportion of adrenal tuberculosis in China is still relatively high, adrenal tuberculosis is caused by blood line dissemination, can be accompanied by other systems of tuberculosis, bilateral adrenal gland tissue including cortical and medulla damage, often more than 90%, The 3-layer structure of the adrenal cortex disappeared, replacing with large pieces of caseous necrosis, tuberculous granuloma and nodules, and residual adrenocortical cells distributed in clusters. About 50% of patients had adrenal calcification, and the adrenal gland volume was significantly larger than normal.
Autoimmune adrenal inflammation (30%):
Since the 1960s, with the control of tuberculosis in developed countries, the overall incidence of Edison's disease has decreased, the proportion of adrenal tuberculosis in the cause of Addison's disease has also decreased, and autoimmune adrenalitis has been promoted to Edison's disease. The cause of the disease, accounting for about 80%, autoimmune adrenalitis used to be called idiopathic adrenal cortical atrophy, "idiopathic" means the cause is unknown, and the cause is now clear, considered to be the main evidence of autoimmune adrenalitis 1 Adrenal cortex atrophy, extensive hyaline degeneration, often accompanied by a large number of lymphocytes, plasma cells and monocytes infiltration; 2 more than half of the patients in the serum anti-adrenal cells antibody; 3 often accompanied by other organs and In other autocrine diseases of endocrine glands, autoimmune adrenal inflammation generally does not affect the medulla.
Autoimmune adrenalitis can exist independently or in combination with other autoimmune diseases including endocrine or non-endocrine diseases. Two or more endocrine glands are involved in autoimmune diseases called autoimmune polygland synthesis. Polyglandular autoimmune syndrome (PGA), divided into type I and type II, type I has significant familial features, often accompanied by mucocutaneous candidiasis (75%), adrenal insufficiency (60%) and primary Low parathyroid function (89%), may also have premature ovarian failure (45%), pernicious anemia, chronic active hepatitis, malabsorption syndrome and alopecia, etc., which is an autosomal recessive hereditary disease. Not associated with HLA, there may be multiple involvement in siblings, mostly in childhood, the average age of onset is 12 years old, type II, also known as Schmidt syndrome, often in adulthood, the average age of onset is 24 years old, including adrenal insufficiency, chronic lymphocytic thyroiditis and insulin-dependent diabetes mellitus (IDDM); others may have premature ovarian failure, pernicious anemia, vitiligo, hair loss, heat Banded stomatitis diarrhea and myasthenia gravis, type II and chromosome 6 gene mutations; associated with HLA B8 and DR3/DR4.
Deep fungal infections (26%):
Deep fungal infection causes adrenal insufficiency: its incidence is not low, autopsy found that one third of patients who died of histoplasmosis had adrenal fungal infection, and other fungal diseases such as coccidioidomycosis , blastomycosis, cryptococcosis and yeast disease can also cause pathological changes in the adrenal cortex similar to tuberculosis and cause dysfunction.
1 Acquired immunodeficiency syndrome: The adrenal gland is the most serious endocrine gland affected by acquired immunodeficiency syndrome, but in most cases adrenal cortical function compensation, only about 5% of patients with advanced acquired immunodeficiency syndrome due to opportunistic Infection leads to hypocortical dysfunction, such as cytomegalovirus (CMV)-induced necrotic adrenal inflammation, mycobacteria or cryptococcal adrenalitis, and sometimes Kaposi sarcoma also invades the adrenal gland.
2 metastatic cancer: Adrenal metastatic cancer is not uncommon, but only a few patients in the clinic have symptoms and signs of adrenal insufficiency. The primary tumors are mainly breast cancer, lung cancer, stomach cancer, colon cancer, melanoma and lymphoma. About 80% of metastatic breast cancer and lung cancer develop adrenal metastases.
3 demyelinating diseases: 2 kinds of demyelinating diseases, adrenal leucod-ystrophy (ALD, also known as brown Schilder disease) and adrenal myelon-europathy (AMN) may have low adrenal function Less, both are sexually linked recessive hereditary diseases, the gene is located on the short arm of the X chromosome (Xq28), which is a single gene mutation caused by peroxidase (24 alkanoic acid-CoA ligase, lignceroyl- CoA ligase) causes extremely long-chain fatty acids (C24 or higher) to oxidize and accumulate in cells, adrenal glands and gonadal cells swell and die, and extremely long-chain fatty acid levels in the blood rise. The former occurs in childhood, with a serious central Demyelinating lesions are characterized by cortical blindness, epileptic seizures, dementia and coma, which usually die in the first 10 years of age, the latter usually starting in adolescence, with slow progression of peripheral sensory and motor neuropathy The upper motor neuron lesions are mainly characterized by spastic paralysis, with progressive failure of adrenal gland and gonad function, and the life span can reach 30-40 years or longer.
4 simple glucocorticoid deficiency: rare, is caused by point mutation of ACTH receptor gene, adrenal gland does not respond to ACTH, but respond to Ag-II, aldosterone levels are normal, mostly family history, is autosomal recessive inheritance.
5 other: congenital adrenal hyperplasia (CAH), amyloidosis, hemochromatosis, adrenal radiotherapy and surgery, as well as drugs (such as rifampicin, ketoconazole, aminoglutethimide, mitoxant, etc.) Causes adrenal insufficiency.
6 acute adrenal hemorrhage, necrosis or embolism: can cause acute adrenal insufficiency, War-House (Farritor and Friderichsen) syndrome, acute adrenocortical dysfunction caused by adrenal hemorrhagic necrosis in patients with fulminant meningococcal meningitis, currently Rarely, antiphospholipid syndrome, anticoagulant therapy, disseminated intravascular coagulation (DIC), acute adrenal hemorrhage in patients with low back trauma and postoperative surgery, necrosis and adrenal venous thrombosis can cause acute adrenal insufficiency.
2. Secondary adrenal insufficiency is caused by insufficient secretion of ACTH or hypothalamic disease caused by pituitary disease, followed by insufficient secretion of CRH, followed by insufficient secretion of ACTH in the pituitary, the result can cause adrenal cortisol and dehydrogenation The secretion of epiandrosterone and androstenedione is insufficient for the following reasons:
(1) Long-term large-scale intake of exogenous glucocorticoids: long-term large-scale intake of exogenous glucocorticoids is the most common cause of secondary adrenal insufficiency, and the hypothalamic-pituitary-adrenal axis is severely inhibited. The symptoms of hypofunction of the adrenal cortex often appear within 48 hours of withdrawal, and this low can last for more than 1 year after stopping the drug.
(2) Shehan disease, pituitary apoplexy and craniocerebral trauma: Xihahan disease caused by postpartum pituitary hemorrhagic necrosis, pituitary stalk injury caused by pituitary apoplexy and craniocerebral trauma can cause acute anterior pituitary and even full Pituitary dysfunction, including secondary adrenal insufficiency, pituitary ACTH tumors and adrenal cortisol secretory tumors, hypothalamic pituitary adrenal axis is still in a state of inhibition, adrenal function usually takes six months to one year to recover.
(3) Hypothalamic pituitary occupying, infiltration and infection diseases: can cause low hormonal expression of the anterior pituitary, and adrenal insufficiency is one of the manifestations.
(4) Lack of isolated ACTH: rare, and the cause is unknown.
(two) pathogenesis
1. Primary adrenal insufficiency includes two aspects of pathophysiological factors: 1 is insufficient secretion of adrenal cortex hormone; 2 is adrenocorticotropic hormone (ACTH) and its related peptides such as melanin secretion increased, typical Edison disease Adrenal destruction is generally more than 90%, and not only affects the fascicular zone and reticular zone, but also affects the globular zone. Adrenal tuberculosis also affects the medulla. Therefore, glucocorticoids, adrenal hormones and mineralocorticoids are simultaneously deficient, and glucocorticoids That is, cortisol deficiency can cause fatigue, burnout, loss of appetite, nausea and weight loss; can cause weakened gluconeogenesis, hepatic glycogen depletion and increased sensitivity to insulin, hunger is prone to hypoglycemia; stress ability declines Susceptible to colds and other infections, mineralocorticoid deficiency can cause increased sodium loss in the body, loss of body fluids, decreased blood volume, orthostatic hypotension, hyponatremia, hyperkalemia and mild metabolic acidosis; plus glucocorticoids The "allowing" effect of catecholamines is weakened, the stroke volume and peripheral resistance are decreased, and the orthostatic hypotension is further aggravated; the kidneys are free water. Elimination of diminished capacity, prone to water intoxication, adrenal hormones mainly weak androgen deficiency in women showed more obvious decline for the pubic and armpit hair shedding and sexual desire, the secretion of ACTH and melanocyte increase may cause mucocutaneous pigmentation.
2. Secondary adrenal insufficiency is different from primary disease changes, because aldosterone is mainly regulated by renin-angiotensin in physiological conditions, and in the absence of ACTH in secondary adrenal insufficiency Mainly leading to glucocorticoid deficiency, aldosterone secretion is less affected, therefore, in secondary adrenal insufficiency, although cortisol is "allowed" to the role of catecholamines, blood pressure decreased, vasopressin (AVP) secretion increased Can cause dilute hyponatremia, but water and salt metabolism disorders and hypotension are lighter than the primary; while the presence of growth hormone and thyroid hormone deficiency, the tendency of severe fatigue and hypoglycemia is more obvious; due to the lack of ACTH And melanocyte stimulating hormone (MSH), the patient has no skin mucosal pigmentation.
3. Adrenal insufficiency is not properly treated, or does not increase the dose of glucocorticoids in a timely manner under stress, or acute extensive destruction of the adrenal gland or pituitary apoplexy, leading to acute failure of adrenal function, causing adrenal crisis .
Prevention
Adrenal insufficiency prevention
Educate patients to understand the nature of the disease, adhere to lifelong hormone replacement therapy, including long-term physiological dose replacement and short-term stress replacement therapy, usually use appropriate physiological doses to supplement the basic amount; such as complications or surgery In order to prevent the crisis, it is necessary to increase the dose by 3 to 5 times or more, and educate the patient to carry the disease card with the contact person and address to facilitate timely treatment.
Complication
Adrenal insufficiency complications Complications constipation amenorrhea impotence headache diabetes insipidus
If the disease is due to adrenal tuberculosis activity or other organs active tuberculosis, it may present low fever, night sweats, and other symptoms of tuberculosis poisoning. If accompanied by other autoimmune endocrine diseases, it may present autoimmune multi-function failure syndrome. In combination with hypoglycemic dysfunction, there may be thyroid and hypogonadal dysfunction, such as cold, constipation, amenorrhea, mane, pubic hair, decreased libido, impotence, etc., adolescent patients often show growth delay and puberty delay, hypothalamus or pituitary The lesion may have headache, diabetes insipidus, vision loss and visual field defect.
Symptom
Adrenal insufficiency symptoms Common symptoms Back pain, fatigue, nausea, irritability, restlessness, abdominal pain, pubic hair, pubic hair, coma, convulsion
1. Chronic adrenal insufficiency: Chronic adrenal insufficiency is insidious, the condition is gradually worsening, various clinical manifestations are seen in many chronic diseases, so the diagnosis is difficult, primary and secondary adrenal insufficiency have a common Clinical manifestations, such as progressive increase in general malaise, listlessness, fatigue, fatigue, loss of appetite, nausea, weight loss, dizziness and orthostatic hypotension.
Skin mucosal pigmentation is a characteristic manifestation of chronic primary adrenal insufficiency. The pigment is tan, shiny, not higher than the leather surface. The pigmentation distribution is systemic, but it is more exposed and easy to rub. Obviously, such as the face, hands, palm prints, areola, nail bed, back, scars and belts; white spots often appear on pigmented skin, gums, tongue surface and buccal mucosa often have obvious pigments Sinking, sometimes combined with other autoimmune endocrine and non-endocrine diseases, patients with adrenal leukodystrophy may have central nervous system symptoms.
Patients with secondary adrenal insufficiency have pale skin color, and other anterior pituitary dysfunction may have clinical manifestations of thyroid and hypogonadism, manifested as cold, constipation, amenorrhea, spasm and pubic hair sparse, decreased sexual desire, impotence; In adolescent patients, growth retardation and puberty are often delayed. Hypothalamus or pituitary space may have headaches, diabetes insipidus, decreased vision and visual field defects.
2. Acute adrenal cortical crisis: When the primary adrenal insufficiency is in crisis, the condition is critical: most patients have fever, some body temperature can reach above 40 °C, it is likely to have infection, and the adrenal crisis itself can also Fever; severe hypotension, even hypovolemic shock, accompanied by tachycardia, cold limbs, cyanosis and collapse; patients with extreme weakness, weakness, apathy and lethargy; can also express irritability and convulsions, and even coma Gastrointestinal symptoms are often prominent, manifested as nausea and vomiting and abdominal pain, diarrhea, abdominal pain often accompanied by deep tenderness and rebound tenderness and misdiagnosed as acute abdomen, but often lack specific specific signs, adrenal hemorrhage patients may also have flank Pain in the ribs and chest and back, a rapid decline in hemoglobin.
Secondary adrenal insufficiency causes less crisis, hypoglycemic coma is more common in the crisis than in the primary, may have hyponatremia, but no significant hyperkalemia, pituitary tumors often have severe Headache, sudden drop in vision, sudden reduction in visual field, and other brain damage, sudden loss of ACTH secretion can also cause shock.
Examine
Examination of adrenal insufficiency
1. General inspection:
There may be hyponatremia, hyperkalemia, severe dehydration, low blood sodium may not be obvious, hyperkalemia is generally not serious, such as obvious need to consider, renal dysfunction or other reasons, a small number of patients may have mild or moderate high blood Calcium (glucocorticoids promote, kidney, intestinal calcium), such as hypocalcemia and hypophosphatemia suggest a combination of hypoparathyroidism, often positive cell, orthochromatic anemia, a small number of patients with Pernicious anemia, white blood cell classification showed neutropenia, lymphocytes increased, and eosinophils increased significantly.
2. Blood sugar and glucose tolerance test:
There may be fasting hypoglycemia, and the oral glucose tolerance test shows a low level curve.
3. Hormone determination:
(1) plasma cortisol: It is generally believed that the plasma total cortisol baseline value 3g / dl can be diagnosed as adrenal insufficiency, 20 / dl can rule out the disease, but for acute critically ill patients, the basic plasma total cortisol is in the normal range Adrenal insufficiency can not be ruled out. Some scholars have suggested that adrenal insufficiency can be ruled out in patients with sepsis and traumatic basal plasma total cortisol 25g/dl.
(2) Plasma ACTH: plasma ACTH is often elevated in primary adrenal insufficiency. Plasma total cortisol is in the normal range, plasma ACTH is also often 100pg/ml, and plasma ACTH is normal to exclude chronic primary adrenal insufficiency. Symptomatic, but can not rule out mild secondary adrenal insufficiency, because the current measurement method can not distinguish between lower and lower normal ACTH levels.
(3) Blood or urine aldosterone: blood or urine aldosterone levels may be low or normal low in primary adrenal insufficiency, while plasma renin activity (PRA) activity or concentration is elevated; Adrenal insufficiency is normal blood or urine aldosterone levels, the level of which varies according to the location and extent of lesion destruction. If the adrenal globular band is severely damaged, its content may be lower than normal, such as the damage of the bundle. , its content can be normal or close to normal.
(4) Urinary free cortisol: usually lower than normal.
(5) urinary 17-OHCS and 17-KS: generally lower than normal, a small number of patients can be in the normal range, should consider the possibility of partial Addison disease, and some pathological adrenal cortex under ACTH stimulation, can still be close to secretion Normal or slightly more than normal steroid hormones.
4. ACTH Excitatory Test:
(1) ACTH stimulation test: primary adrenal insufficiency due to endogenous ACTH has been maximally excited to secrete cortisol from the adrenal gland, so exogenous ACTH can not further stimulate cortisol secretion, the plasma total cortisol baseline value is lower than Normal or at a lower limit of normal, plasma total cortisol rarely rises or does not rise after stimulation; secondary adrenal insufficiency in patients with secondary adrenal insufficiency, plasma total cortisol rarely rises Or not, but mild or initial patients, such as asthmatic patients who inhaled glucocorticoids and Cushing syndrome, in patients with pituitary or adrenal adenoma, even if there is already metyrapone (methipone) or Insulin hypoglycemia stimulation test is abnormal, but the ACTH stimulation test can be normal, because in normal people, 5 ~ 10g ACTH can stimulate the adrenal cortex to approach the maximum secretion, so the test used 250g ACTH far exceeds this amount, thus, some scholars It is proposed that a small dose of ACTH stimulation test can detect mild or initial secondary adrenal insufficiency (such as inhaled corticosteroids) Asthma treatment).
(2) Low-dose rapid ACTH stimulation test: plasma cortisol 18g/dl (496.8nmol/L) after normal or excitatory; plasma cortisol does not rise in patients with secondary adrenal insufficiency, it should be noted that when When the plasma cortisol basal value is 16 g/dl, a further test for methotrexate or insulin hypoglycemia is required.
(3) Continuous ACTH stimulation test: ACTH intravenous injection method, that is, intravenously, 25 g of ACTH, 500 ml of 5% glucose solution, and evenly maintained for 8 hours for 3 to 5 days; or continuous intravenous infusion of ACTH for 48 hours. And 24h urinary free cortisol or 17-OHCS on the stimulation day, if the urinary free cortisol or 17-OIHCS reaction is low after 3 to 5 days of continuous stimulation, respectively <200g/24h (0.55mod/24h) or <10mg/24h (27.6 mod/24h) supports primary chronic adrenal insufficiency; secondary adrenal insufficiency has a low or delayed response to urinary free cortisol or 17-OHCS.
(4) ACTH diagnosis and treatment test: This test is used for patients with severe disease and high suspicion of the disease. At the same time, dexamethasone (intravenous or intravenous) and ACTH are administered. Plasma cortisol is measured before and after administration. Therapeutic effect can be used as a diagnostic tool.
(5) Insulin hypoglycemia test: At 10 o'clock in the morning, after intravenous injection of insulin 0.1/kg; blood samples were taken at 0, 15, 30, 45, 60, 90 and 120 min, and ACTH and cortisol were measured simultaneously. At 40 mg/dl, the normal reaction was post-excitation with cortisol 20 g/dl (55 mmol/L), and those with secondary adrenal insufficiency did not increase blood ACTH and cortisol.
(6) Simplified melilone (methione) test: oral metoprolone (methione) 30 mg/kg at midnight, and plasma 11-deoxycortisol, cortisol and ACTH were measured at 8 am the next day, normal Human plasma 11-deoxycortisol should be 8g/dl to determine whether adrenal cortical hormone synthesis is inhibited. The normal response is excitatory blood 11-deoxycortisol rise 7g/dl, ACTH is generally greater than 150pg/ml; Secondary adrenal insufficiency blood 11-deoxycortisol and ACTH do not rise.
(7) oCRH141 excitatory test: After intravenous injection of 1U/kg or 100g CRH141, blood samples were taken at 0, 15, 30, 45, 60, 90 and 120 min, and ACTH and cortisol were measured simultaneously. After stimulation, the peak of ACTH and cortisol 100% of the original basal value, and the increase of ACTH and cortisol after the stimulation of secondary adrenal insufficiency.
(8) Adrenal autoantibody assay: The most classical method for determining autoantibodies is to use indirect immunofluorescence staining with bovine or human adrenal gland sections. It has been reported that radiolabeled recombinant human 21-hydroxylase simple binding assay for the determination of adrenal autoantibodies Sensitivity and specificity are higher than indirect immunofluorescence methods.
5. Electrocardiogram: It can show low voltage, T wave is low or inverted, and PR interval and QT time can be extended.
6. Imaging examination: chest X-ray examination can show the heart is reduced (vertical), adrenal gland and CT examination in patients with tuberculosis can show adrenal enlargement and calcification shadow, other infections, hemorrhage, metastatic disease also showed in CT scan Adrenal gland enlargement (adrenal gland enlargement, the general course of disease is less than 2 years), the adrenal gland does not increase due to autoimmune etiology, for the hypothalamic and pituitary lesions, can be done with sella CT and MRI, B-ultrasound or CT guidance A fine needle aspiration biopsy of the lower adrenal gland contributes to the diagnosis of the adrenal gland.
Diagnosis
Diagnosis and diagnosis of adrenal insufficiency
diagnosis
Typical clinical manifestations as well as routine hematuria and biochemical tests can provide clues to the diagnosis of this disease, but the diagnosis depends on special laboratory and imaging examinations.
1. Diagnosis of adrenal insufficiency
(1) The basic level of cortisol: whether in primary or secondary adrenal insufficiency, the secretion of cortisol should be significantly lower, such as blood cortisol (F) is lower than 82.8nmol / L (3g / dl ), the diagnosis of this disease can be established, but the blood F level is affected by many factors, and its own fluctuation is very large, so the blood F is between 82.8 ~ 552mmol / L (3 ~ 20g / dl), can not rule out the adrenal cortex The presence of hypofunction, 24h urinary free cortisol (UFC) or 17-hydroxycorticosteroid (17-OHCS) can avoid the circadian rhythm of blood F and fluctuations, more can reflect the actual situation of adrenal function, the patient's UFC or 17-OHCS should be significantly lower than normal.
(2) blood ACTH level: blood ACTH level in patients with primary adrenal insufficiency should be significantly higher than normal, at least above 22pmol / L (100pg / ml), according to our experience, most Edison patients blood ACTH level Above 220 pmol/L (1000 pg/ml), the level of blood ACTH in patients with secondary adrenal insufficiency should be lower than normal, but the sensitivity of the current ACTH assay is not high enough, the actual measured value of blood ACTH may be at the normal low limit.
(3) Determination of blood renin activity, angiotensin II and aldosterone: patients with primary adrenal insufficiency due to spheroidal involvement, blood aldosterone levels are low, renin activity can be elevated or in the normal range, angiotensin II Significantly elevated, no change in patients with secondary adrenal insufficiency.
(4) ACTH stimulation test: rapid ACTH124 excitatory test, intravenous injection of 250g ACTH124, blood samples were taken at 0, 30 and/or 60min respectively. The results were judged as: 1 normal reaction, 552nmol/L after basal or excitatory blood (F20g/dl), 2 primary adrenal insufficiency, because endogenous ACTH has maximally excited the adrenal gland to secrete cortisol, therefore, exogenous ACTH can not further stimulate cortisol secretion, blood F basic value Below normal or at normal low limit, blood F rarely rises or does not rise after stimulation, 3 secondary adrenal insufficiency, long-term and severe secondary adrenal insufficiency, blood F is low or No response, such as continuous injection for 3 to 5 days, blood F can gradually improve, is a delayed response, but in mild or early patients, such as inhaled glucocorticoid-treated asthma patients and Cushing's syndrome pituitary, adrenal gland After the tumor resection, even if there is abnormality in the stimulation test of metyrapone or insulin hypoglycemia at this time, the ACTH1-24 stimulation test can be normal, because in normal people, 5-10 g ACTH can stimulate the kidney. Adrenocortical secretion close to the maximum, and used in the test 250gACTH far exceeds this amount, thus, there is proposed with a small dose of ACTH1 ~ 24 stimulation test detected early mild or secondary adrenocortical hypofunction.
Low-dose rapid ACTH124 stimulation test: intravenous injection of 0.5g/m2 body surface area or 1g ACTH124, blood samples were taken at 0, 20 and/or 60min respectively. The results were judged: 1 normal reaction, basic or excitatory blood F 496.8nmol/L (8g/dl), 2 secondary adrenal insufficiency, blood F does not rise, should pay attention to mild abnormality, when blood F basic value is 441.6nmol / L (16g / dl) or after stimulation At 469.2 nmol/L (17 g/dl), further melitrone or insulin hypoglycemia stimulation test was performed.
Classic ACTH excitatory test, ACTH139 intravenous infusion method, static ACTH13925U every day, add 5% glucose solution 500ml, evenly maintained for 8h, total 3~5 days, measure 24h urine UFC or 17- on control day and stimulation day OHCS, if the UFC or 17-OHCS response is low after 3 to 5 days of continuous stimulation, <0.552mol/24h (200g/24h) or <27.6mol/24h (10mg/24h), respectively, support primary chronic adrenal insufficiency UFC or 17-OHCS in patients with secondary adrenal insufficiency has a low or delayed response. Since ACTH1 to 39 is extracted from the pituitary of animals, it contains more impurities and is prone to allergic reactions. The method is cumbersome and has poor sensitivity. In recent years, it has been replaced by the fast ACTH1~24 excitatory test.
(5) Insulin hypoglycemia stimulation test (ITT): intravenous insulin 0.1-0.15 U / kg; blood samples were taken at 0, 15, 30, 45, 60, 90 and 120 min, ACTH and F were measured simultaneously, and the results were judged: blood glucose Should be less than 2.2mmol / L (40mg / dl), the normal reaction is excitatory blood F 552nmol / L (20g / dl); in the secondary adrenal insufficiency: blood ACTH and F do not rise, due to the test Patients with coronary heart disease and epilepsy are unsafe, so this test is only done when necessary.
(6) Simplified melitrone test: oral metoprolone 30 mg/kg was taken at midnight, and plasma 11-deoxycortisol (S) and F were measured at 8 am the next day. The results were judged: plasma F should be 8 g / Dl, to confirm that the synthesis of adrenal cortical hormone is inhibited, the normal reaction is excitement, blood S rises 232nmol / L (7g / dl), ACTH is generally > 33pmol / L (150pg / ml); and in secondary adrenal insufficiency Symptoms, blood S and ACTH do not rise.
(7) oCRH124 stimulation test: intravenous injection of 1g/kg body weight or 100goCRH124, blood samples were taken at 0, 15, 30, 45, 60, 90 and 120min, and ACTH and F were measured simultaneously. After stimulation, the ACTH and F peaks were increased by 100% from the baseline value, and ACTH and F were insufficiently increased after stimulation of secondary adrenal insufficiency caused by pituitary diseases.
2. Diagnosis of etiology and comorbidities
After the diagnosis of primary and secondary adrenal insufficiency, the cause should be determined, the adrenal, thyroid and pancreatic autoantibodies, adrenal and sella CT, MRI and other pituitary functional tests.
(1) Adrenal autoantibody assay: It is helpful for the etiological diagnosis of autoimmune adrenal gland, about 60% positive. The most classic method for measuring autoantibodies is to use indirect immunofluorescence staining with bovine or human adrenal gland slices. The sensitivity and specificity of the labeled recombinant human 21-hydroxylase simple binding assay for determination of adrenal autoantibodies were higher than indirect immunofluorescence methods.
(2) Image examination: chest X-ray examination shows that the heart shadow is reduced, and tuberculosis can be confirmed. CT, MRI examination of adrenal calcification may indicate tuberculosis and fungal infection; adrenal enlargement suggests tuberculosis or other infection or invasive disease, Hypothalamus and pituitary space-occupying lesions, can be done with sella CT, MRI, CT guided fine needle puncture can help the diagnosis of adrenal gland.
3. Diagnosis of adrenal cortical crisis
For patients with clinical features of typical adrenal cortical crisis, it is not difficult to combine laboratory tests. However, if the incidence is sharp, the clinical manifestations are insufficient, and the symptoms of other diseases are staggered and concealed, it is not easy to judge correctly. Therefore, in the following The possibility of adrenal cortical crisis should be considered in the case: 1 patients with chronic primary adrenal insufficiency have been diagnosed, such as fever, anorexia, nausea, vomiting and abdominal pain, diarrhea, should be alert to the early possibility of adrenal crisis, Timely treatment can avoid the development of crisis, so that the disease can be controlled early; 2 for unexplained shock or coma patients, should pay attention to the history of adrenal insufficiency and check for signs of hyperpigmentation, and blood potassium Determination of sodium chloride, blood sugar, blood gas, cortisol and ACTH; 3 in patients with thrombotic disease, coagulopathy, and postoperative DIC, if the condition is sharp, the blood pressure drops shock and chest and abdomen back pain should be considered, acute adrenal cortical bleeding should be considered Necrosis leads to the possibility of adrenal cortical crisis.
Differential diagnosis
1. Identification of primary, pituitary and hypothalamic adrenal insufficiency:
(1) Plasma ACTH basic value: patients with primary adrenal insufficiency in the morning (8 am) plasma ACTH basic value is higher than normal, sometimes up to 4000pg / ml or more, secondary adrenal insufficiency patients early morning plasma The ACTH baseline value can be at or below normal. The blood sample for testing ACTH must be sampled before glucocorticoid therapy or after treatment with a short-acting glucocorticoid such as hydrocortisone for at least 24 hours. Otherwise, ACTH levels may be due to glucocorticoids. Negative feedback inhibition is reduced. For patients with long-term treatment with glucocorticoids, the plasma ACTH basal value must be replaced with hydrocortisone for a few days. If the blood sample is taken at the appropriate time and the ACTH method is reliable, plasma ACTH The baseline value can be used to identify primary and secondary adrenal insufficiency.
(2) Continuous ACTH stimulation test: Continuous ACTH stimulation test can also be used to identify primary and secondary adrenal insufficiency. In continuous ACTH stimulation test, ACTH continuous slow stimulation, secondary adrenal cortex The adrenal gland with atrophy of dysfunction can restore cortisol secretion; whereas patients with primary adrenal insufficiency have partial or complete destruction of the adrenal gland, secondary ACTH secretion has reached a maximum, so there is no response to exogenous ACTH stimulation. During the continuous ACTH stimulation test or at least 24 hours before the test, glucocorticoid replacement therapy can be given dexamethasone 0.5 ~ 1.0mg / d, this treatment can not affect the test results, secondary adrenal insufficiency cortisol secretion The daily increase, and the primary chronic adrenal insufficiency did not change significantly. The short-term identification of primary and secondary adrenal insufficiency was the first choice for 48h continuous ACTH stimulation test.
2. Identification of pituitary and hypothalamic adrenal insufficiency:
CRH stimulation test can be used to identify pituitary and hypothalamic adrenal insufficiency, but has little significance for treatment guidance. Patients with pituitary adrenal insufficiency have no obvious ACTH response under CRH stimulation, and hypothalamic adrenal insufficiency The ACTH response is excessive and delayed.
3. Identification of the cause of adrenal insufficiency:
After the diagnosis of primary and secondary adrenal insufficiency, the cause should also be determined to guide treatment.
(1) Primary adrenal insufficiency: the age of the patient, the presence or absence of long-term high-dose anticoagulant therapy or other autoimmune endocrine diseases have a certain significance for the identification of the cause. Adrenal CT scan is helpful for the cause Diagnosis, such as adrenal enlargement or calcification, suggest adrenal infection, hemorrhage, metastatic cancer and rare lymphoma invasion, generally can rule out autoimmune adrenal lesions, but no adrenal enlargement or calcification can not rule out tuberculosis. Tuberculosis-induced adrenal insufficiency usually has active tuberculosis syndrome, chest X-ray, urinary tuberculosis culture and skin tuberculin test to help diagnose tuberculosis, can be performed by histoplasma complement test to check whether there is tissue cell For bacterial infection, detection of anti-adrenal antibodies may assist in the diagnosis of autoimmune adrenal insufficiency. The diagnosis of other endocrine gland dysfunction of primary autoimmune adrenal insufficiency should be based on blood calcium, blood phosphorus, blood sugar, FT3, TSH and thyroid antibodies are used to determine if blood calcium is found to be low, further Blood FTH level, if there is rare menstruation or amenorrhea, FSH and LH should be measured. CT-guided percutaneous fine needle aspiration can be used to determine the cause of the enlarged adrenal gland. It is suspected that ALD/AMN patients should be tested for extremely long serum chains. Fatty acid levels (increased serum very long chain fatty acid levels).
(2) secondary adrenal insufficiency: pituitary CT or MRI can determine the nature and location of the pituitary lesions.
4. Identification with other diseases:
(1) Chronic weight loss: chronic hepatitis, liver cirrhosis caused by weight loss can detect hepatitis virus, liver function abnormalities; tuberculosis, malignant tumors have systemic weight loss, cachexia, etc., and can find the primary lesion; hyperthyroidism is the most common cause of weight loss One of the endocrine diseases, according to typical symptoms and signs and T3, T4 can be diagnosed; diabetes caused by weight loss can be diagnosed according to "three more than one less" symptoms and FPG and OGTT; neurological anorexia weight loss without organic disease.
(2) hypotension: mucinous edematous hypotension can be diagnosed according to T3, T4, TSH and TRH stimulation test; hypotension caused by pheochromocytoma can be manifested as orthostatic hypotension or alternating hypertension and hypotension. Blood, urinary catecholamine and VMA abnormalities may have cold-pressurization test, abnormal glucagon test, imaging examination, adrenal cortex or extra-adrenal tumor; diabetic patients are prone to orthostatic hypotension.
(3) hypoglycemia: should be differentiated from insulinoma hypoglycemia, hepatogenic hypoglycemia, drug-induced hypoglycemia.
(4) chronic fibromyalgia (fibromyalgia): chronic fibromyalgia is an unknown cause of musculoskeletal pain in young women. The main clinical features are extensive musculoskeletal pain, multiple tender points. , depression, fatigue and insomnia, functional disability, must be ruled out by other diseases to confirm the diagnosis, and because the symptoms are generally ignored and not understood and easily misdiagnosed.
(5) chronic fatigue syndrome (chronic fatigue syndrome): chronic weakness syndrome is common in women aged 20 to 50 years, with severe fatigue, myalgia, lymphadenopathy, joint pain, chills, fever, fatigue after exercise is the main Clinical manifestations, whose etiology is unknown, may be related to infection, immunity, neurological and psychiatric factors, have a genetic predisposition, and are mainly diagnosed based on clinical symptoms.
