diagram for adrenal gland disease cortisol hypercortisol or hypercortisolism

What is Adrenal Gland Disease – Hypercortisolism (Cortisolism)?

Adrenal Gland Disease, also known as Cushing syndrome, is a syndrome with excessive secretion of adrenal glucocorticoids (mainly cortisol). More common in middle and young people, more women than men. People also call this Hypercortisol or hypercortisolism, or simply cortisol.

 

What are the causes of Adrenal Gland Disease?

Adrenal Gland Diseases Causes and Onset:

 I. Primary Causes of Adrenal Gland Disease

  1. Adrenal cortex adenomas account for about 15%, which is the proliferation of functional autonomous cells and is not affected by ACTH. Most of them are unilateral, so that the adrenal cortex except adenoma is atrophic. Cortisol secretion by this adenoma is not inhibited by exogenous glucocorticoids.
  2. Adrenal cortex cancers account for about 2 to 5%, have secretory function, and are not affected by ACTH.

 

II. Secondary Causes of Adrenal Gland Disease

(1) Pituitary tumors or hypothalamic-pituitary dysfunction secondary to hypothalamic-pituitary disease can cause adrenal hyperplasia, known as hyperplastic cortisol, or Cushing’s disease, accounting for about 70%. In this group of patients, there are large anterior pituitary adenomas (> 10 mm in diameter), and about 10% of them with enlarged syllabary. In recent years, the experience of pituitary microsurgery through the sphenoid sinus has confirmed that more than 80% of those with non-enlarged sphenoidal saddles have pituitary microadenomas (those with a diameter of less than 10mm). A considerable number of patients are cured after removal of microadenomas, and another patient can relapse, indicating that the latter is related to hypothalamic-pituitary dysfunction.

 (2) Ectopic ACTH-like tumors such as lung cancer (about 50%), thymic cancer, pancreatic cancer and prostate cancer can secrete ACTH-like active substances. The pathology shows bilateral adrenal hyperplasia. Due to the poor differentiation of the primary cancer and short survival time, the clinical manifestations of increased adrenal corticosteroids are often atypical.

 (3) Iatrogenic glucocorticoids Long-term high-dose corticosteroid treatment. Such as rheumatoid arthritis, disseminated lupus erythematosus, and bronchial asthma can cause symptoms similar to Cushing’s disease, all of which are accompanied by atrophy of the adrenal cortex and reduced secretory function, and reduced blood ACTH concentration.

 

Pathology for Hypercortisolism

 1. Cortical hyperplasia: The bilateral adrenal glands are enlarged, and the cortex is thickened on the cut surface, which is yellow-brown. Microscopically, the adrenal cortex bundle bands are widened, and the cells are proliferated and enlarged. In a few cases, bundle and reticular belts proliferate simultaneously, and globular belts are compressed, shrunk, and even disappear.

 

2. Cortical adenomas and sacral adenomas are mostly round or elliptical, with diameters ranging from 2 to 5 cm, and their capsules are intact and sometimes lobular. Under the microscope, adenomas were found to contain clear cells and granulosa cells, and some cells were atypical and deeply stained. Most are granular cells.

 

3. Cortical adenocarcinomas grow fast and have a large volume (adrenal gland disease). The cut surface often has bleeding and necrosis. There are atypical adenocarcinoma cells and mitoses, which infiltrate or penetrate the capsule. It can metastasize to the lymph nodes, liver, and lungs in advanced stages.

 

4. Other osteoporosis, muscle and fibrous tissue atrophy, arteriosclerosis, left ventricular hypertrophy, calcium salts may appear in the renal tubules, urinary stones, liver infiltration and so on.

 

Clinical Manifestations of Hypercortisolism (Cortisolism)

 The onset is slow, and individual cases may show typical clinical signs within weeks.

 1. Appearance: Concentric obesity on the face and torso is the characteristic shape of the disease. Including full moon face, neck and back fat accumulation, bulge, and belly bulging. The limbs appear relatively small due to fat and muscle atrophy, and their complexion is rosy and shiny, with this fat overflow phenomenon. The skin becomes thinner, prone to purpura and petechiae, and the capillary fragility test is mostly positive. Purple stripes are also specific signs of this disease, about 56% positive, often distributed in the lower abdomen, buttocks, shoulders, anterior axillary, etc. The purple stripes are wide in the center, thin at the ends, and purple-red. Acne often occurs on the face and back skin. Body hair increased, thickened, and blackened, and some patients had signs of hair loss.

 

2. Hypertension: About 80% of patients have elevated systolic and diastolic blood pressure. After reasonable treatment, blood pressure can drop or return to normal.

 

3. Musculoskeletal system: Due to negative nitrogen balance, muscle atrophy, especially striated muscle is obvious. There are osteoporosis, decalcification, and obvious support for heavy bones, such as spine and pelvic pathological fractures may occur. Patients are more conscious of low back pain, weak limbs, and difficult wound healing. Symptoms can be improved to varying degrees after proper treatment.

 

4. The gonad and reproductive system: Female patients often have reduced menstruation or amenorrhea, breast atrophy, and increased clitoris. If there is obvious virilization, more adrenal cancer. Male patients have impotence and testicular atrophy.

 

5. Mental symptoms: Emotional instability, easy impulsivity, insomnia, disorientation. Severe cases can be depressed, and individual cases can appear hallucinations and fantasies. After treatment, general mental symptoms can disappear quickly, while depressive symptoms can last for months to two years, and individual patients may last longer.

 

6. Glucose emission disorders: About 70% of patients may have glucose metabolism disorders, show steroid diabetes, and are not sensitive to insulin. Treatment can restore normal glucose metabolism. But if the course is too long and the islet beta cells degenerate, it will lead to permanent diabetes.

 

7. Electrolytes: Sodium is normal or high, serum potassium is mostly low, if the changes are significant, adenocarcinoma should be considered. Blood calcium and phosphorus are in the normal range, and there can be mild radon poisoning.

 

8. Patients with skin pigmentation and ectopic ACTH syndrome have obvious pigmentation, which has diagnostic significance. Patients with severe adrenal hyperplasia also have darker skin pigments.

 

Laboratory and other inspections for Hypercortisolism (adrenal gland disease)

I. The general inspection (adrenal gland disease): Red blood cell count and high hemoglobin content. Total white blood cells and neutrophils increased, and absolute values ​​of lymphocytes and eosinophils decreased.

 

II. The 24-hour content of urine 17 hydroxycorticosteroids increased significantly over 38.4 μmol / 24h (13.9mg / 24h) (male) and 30.9 μmol / 24h (11.2mg / 24h (female). 17 ketosteroids often also exceed 40.3 μmol / 24h (11.6mg / 24h) (male) and 37.3 μmol / 24h (8.5mg / 24h) (female).

 

III. The increase in serum cortisol concentration: 0.28 μmol / L (10.1 mg / dl) at midnight, and the quiet state at 8 am exceeded 0.69 μmol / L (24.9 mg / dl).

IV. Blood cortisol disappears day and night. That is, the concentration of cortisol at midnight exceeds the level of 8 am. Circadian rhythm disappears early in the onset of illness.

 

V. Low-dose dexamethasone inhibition test Cortisol is not inhibited, other reactive or functional cortisol can reduce blood cortisol concentration or 24-hour urine 17 hydroxycorticosteroid content by more than 50% of the basic value , Mainly used to identify with simple obesity. Methods: Simplified method; the blood cortisol concentration was measured as the basic value at 8 am on the first day. Take dexamethasone at midnight: 1.5mg, and re-evaluate blood pilotanol at 8 am the next day. Regular method: On the first day, the blood cortisol concentration at 8 am or the 17-hour urine 17-hydroxycorticosteroid content was measured. The next day, dexamethasone 0.75 mg was taken three times a day for a total of 4 days. The blood cortisol concentration or urine 17-hydroxyl group will be reviewed later. Corticosteroid content and compared with before taking the drug.

 

VI. High-dose dexamethasone inhibition test Adrenal hyperplasia is more than 50% inhibited, while adrenal adenoma or adenocarcinoma is not significantly inhibited. Methods: The blood cortisol or urine 17 hydroxycorticosteroid content was measured one day before the test, and dexamethasone 2 mg was taken thereafter, every 6 hours for a total of 5 days. The blood cortisol concentration or urine 17 hydroxycorticosteroid content was then re-examined and taken with the medication. Before comparison.

 

VII. ACTH excitation test normal people, simple obesity and adrenal hyperplasia after ACTH injection can increase blood cortisol concentration or urine 17 hydroxycorticosteroid content more than doubled, but no significant increase in adrenal adenoma or adenocarcinoma high. Methods: Simplified method. Blood was drawn at 8 am to measure the concentration of cortisol. Immediately after injection, 25 mg ACTH was injected intramuscularly or intravenously. Blood was measured at 8:30 and 9 am. Formal law. On the first and second days, the urine was measured for 17 hydroxycorticosteroids for 24 hours. On the third and fourth days, an intravenous infusion of ACTH24mg (within 5% glucose solution 500ml) was started for 8 hours, and the 24-hour urine was measured daily. 17 hydroxycorticosteroid content.

 

VIII. Imaging examination: It is a localized examination, including B-ultrasound, CT scan, adrenal angiography, magnetic resonance examination, segmental blood collection of venous catheters, and determination of cortisol. When possible, 131 iodine-labeled cholesterol isotope scans or gamma imaging are also used to assist diagnosis.

 

Diagnosis and Differential Diagnosis for Adrenal Gland Diseases

 Adrenal Gland Disease: Careful analysis of laboratory results and other test results makes diagnosis difficult. It should be mainly distinguished from simple obesity, ectopic ACTH-like tumors, diabetes, and other secondary lesions of the adrenal cortex.

 

Laboratory and X-ray Differential Diagnosis of Cortisol Disease with Different Etiologies (adrenal gland disease)

 Bilateral adrenal hyperplasia (hypothalamic-pituitary dysfunction) Adrenal cortical adenoma Adrenal cortical cancer Ectopic ACTH syndrome

Urine 17-hydroxyl (mg / 24 hours) generally moderately increased, about 30mg with hyperplasia significantly increased, up to more than 50mg with cancer

Urine 17-ketone (mg / 24 hours) Moderate increase, about 20mg can be normal or increased Obviously increased, can reach above 50mg Obviously increased, above 50mg

Serum cortisol (μg / dl) 8 am 30 35 35 50

4 pm 25 25 ~ 35 35 50

Large-dose dexamethasone inhibition test + most can be inhibited, a few cannot be inhibited cannot be inhibited cannot be inhibited cannot be inhibited, a few ectopic CRF can be inhibited

ACTH excitement test + Response, higher than normal. About half of them have no response, half of them have responded.

Methylpyridone test +++ There is a response, often higher than normal. Generally there is no response. A few have a response.

Hypokalemia poisoning may occur in severe cases.

Photo of Sella Saddle Scaling of a small number of patients

Retroperitoneal gas angiography: Adrenal shadows increase on both sides. Adenoma shadows on one side are generally 2 to 6 cm in diameter. One side of the tumor is usually larger than 6 cm in diameter.

Scanning or taking pictures of radioactive iodized cholesterol adrenal glands. Adrenal glands imaging on both sides, enlarge tumor side imaging, enlarge cancer side imaging, or no imaging.

Adrenal ultrasound and CT scan Adrenal glands enlarged on both sides Show tumors Tumors Adrenal enlarged on both sides

Plasma ACTH measurement is slightly higher than normal in the morning and does not decrease at night as normal.

 

Note (ref. adrenal gland disease): + 2mg each time, orally once every 6 hours for 2 consecutive days. On the second day, the urine 17-hydroxyl decreased to less than 50% of the control value, indicating that it was inhibited.

 

+ ACTH25u, dissolved in 500ml of 5% dextrose aqueous solution, was intravenously infused for 8 hours for a total of 2 days, and the basal value of urine 17-hydroxyl on the day of normal infusion increased by more than 2 times.

 

+ + + Mepyrapone 2 to 3 g per day, orally in divided doses for 2 consecutive days, the second day or the first day after discontinuation of the drug, the urinary 17-hydroxy or 17-ketogenic steroids more than doubled the control value, indicating a response.

 

Treatment for Adrenal Gland Diseases

 I. General treatment of Cortisol (adrenal gland disease):

i. Correct hypokalemia, orally take potassium chloride or potassium citrate 3-9g every day, if necessary, you can take Anti Shutong.

ii. To correct the disorder of glucose metabolism, insulin injection can be used for treatment. Patients are often not sensitive to insulin, so the dose should be gradually increased according to the condition.

iii. Correct the negative nitrogen balance, because protein breakdown is greater than synthesis, testosterone propionate or nandrolone phenylpropionate can be given as appropriate.

 

II. Adrenal cortex adenoma or adenocarcinoma After surgical correction of electrolyte disorders and acid-acid balance disorders, maintaining normal blood pressure and controlling glucose metabolism disorders, surgery should be performed to remove the tumor. Corticosteroids were given intraoperatively to maintain stress. After hormone replacement therapy, daily intramuscular long-acting ACTH60 to 80U should be used to restore the function of the atrophic adrenal cortex. After two weeks, the dose is gradually reduced, and those who have not responded well need to use cortisone instead for a longer period of time. Most patients can gradually discontinue replacement therapy within 3 months to 1 year.

 

III. Adrenal hyperplasia In the past, subtotal adrenalectomy was performed on both sides, but the postoperative remission was poor and the recurrence rate was high. Some people advocate bilateral adrenalectomy for better remission, but need to use corticosteroid replacement therapy for a lifetime, some patients (approximately 10%) after a few years (approximately 10%) develop ACTH adenoma, which is Nelson syndrome, and needs surgery.

 

Adrenal cortical hyperplasia, such as CT scan and magnetic resonance examination, can confirm the diagnosis of pituitary adenomas, microsurgery of pituitary adenomas can be performed through the sphenoid sinus. Replacement therapy should also be given after surgery.

 

IV. For adrenocortical hyperplasia or adenocarcinoma that cannot be treated surgically, 0.4 g of aminohypnotic energy can be taken orally three times a day, with less side effects, mainly gastrointestinal reactions, rashes, and lethargy. It can also be used as preparation before surgery. Can also try 2 to 6 g of mepidone daily, orally. You can also try O, P-DDD 2 to 10 g per day, divided into oral administration, but the side effects are large, interrupting treatment will affect the efficacy. Those who respond can get clinical relief, but they cannot cure it.

 

  

Primary Aldosteronism

Hyperaldosteronism is divided into two categories: primary and secondary. Primary aldosteronism is caused by an adrenal cortex tumor or an increase in aldosterone secretion, resulting in retention of water and sodium, and expansion of body fluid volume, which inhibits the renin-angiotensity system. The cause of secondary aldosteronism is outside of the adrenal gland, mostly due to decreased effective blood volume, decreased renal blood flow and other reasons. The renin-angiotensin-aldosterone system is hyperfunctional. Excessive angiotensin excites the spheroidal zone of the adrenal cortex, so that aldosterone is secreted too much. This article describes only primary aldosteronism. This disease is more common in adults, and more common in women than men, accounting for about 0.4 to 2.0% of patients with hypertension.

 

Cause of Primary Aldosteronism

 1. Adrenocortical aldosterone tumors account for about 80 to 90%. Also known as Conn syndrome, mostly unilateral. The extratumor glands are mostly atrophic.

 

2. Adrenocortical aldosterone cancer is rare, with tumor cells infiltrating outside the envelope. Cancers often secrete a lot of other steroid hormones in addition to aldosterone. Clinical manifestations are mostly mixed syndromes.

 

3. Adrenal cortical hyperplasia accounts for about 10-40%, are bilateral, also known as idiopathic hyperaldosteronism, the etiology is unknown, may be caused by extra-adrenal factors. In severe cases, there is nodular hyperplasia without encapsulation. More common in children.

 

Pathophysiology and clinical manifestations

 I. Hypertension is related to factors such as sodium retention, increased plasma volume, and increased calcium ion concentration in the blood vessel wall. Although it often increases gradually with the duration of the disease, it is generally 22.6-28.0 / 13.3-17.3kpa (170-210 / 100- 130 mmHg), but rarely show malignant hypertension.

 

II. Sodium retention increased blood sodium: Increased blood volume. However, after the sodium retention and blood volume increase to a certain extent, it causes the activity of the sodium excretion system in the body. Although there are many secretions of aldosterone, it no longer presents a positive sodium balance, that is, “escape” phenomenon.

 

III. Loss of potassium: The sodium-potassium exchange in non-curved tubules, a large amount of potassium is excreted by the kidneys, the body is deficient in potassium, and the blood potassium is reduced. Can be exacerbated by lowering blood pressure with thiazide diuretics. The main clinical manifestations are:

i. Muscles, which can change from muscle weakness to typical periodic paralysis, which occurs at rest after exertion, and the lower limbs are obvious. In severe cases, there is limb paralysis and difficulty breathing and swallowing. Paralysis can last for several hours to several days or more. Paralysis is related to the degree of blood potassium reduction, but also to changes in the ratio of potassium ion concentration on both sides of the cell membrane. Muscle paralysis can occur.

ii. In the heart, the electrocardiogram can show Q ~ T time extension, T wave widening, reduction, or inversion, and U wave is significant. Premature beats or tachycardia may occur, and ventricular tachycardia may occur in severe cases.

iii. Kidney For a long time, severe sodium deficiency can cause tubule-like vacuole degeneration, renal concentrating dysfunction, and polyuria, which is more obvious at night, urine specific gravity and osmotic pressure, and thirst.

 

iv. Disorders of acid and tritium balance A large amount of potassium ions are lost in the cell, and sodium and hydrogen ions are stored in the cell, which causes the pH to decrease, and the extracellular liquid hydrogen ions are relatively reduced, showing radon poisoning. When tadpole poisoning is obvious, free calcium decreases, causing numbness of the extremities, convulsions in the hands and feet, and potassium supplementation increases the neuromuscular stress energy and exacerbates the convulsions. At this time, calcium supplementation should be made at the same time.

 

v. Others It can be caused by long-term potassium deficiency, which can cause growth and development disorders, which can be accompanied by hypomagnesemia, which also induces or trembling tremors, and in severe cases, impaired glucose tolerance. There may be lower limb edema when there is heart failure.

 

Laboratory and other inspections for Cortisol

First, the general examination of continuous or intermittent hypokalemia, blood sodium in the upper limit of the normal range or slightly higher, blood PH slightly increased, urine pH neutral or partial. Increased urinary potassium, often exceeding 25mmol / 24h, (for hypokalemia caused by gastrointestinal loss of potassium, urinary potassium is less than 15mmol / 24h) decreased renal concentration, nocturia more than 750ml. The saliva Na + / K + ratio is less than 1, and if it is less than 0.4, it has diagnostic significance (normal human saliva Na + / K + ratio is greater than 1).

 

Special inspections for Cortisol

 (1) Determination of renin-angiotensin basal value and stress test Firstly, blood was collected after resting for 4 hours in the morning and the basal value was measured. The renin activity and angiotensin level of the disease were significantly lower than the normal range. Then the patient stood up for 4 hours, and intramuscularly injected furosemide 20mg, and the blood renin activity and angiotensin level were measured. Both of them were significantly increased in normal people. In the patients with this disease, neither of them was significantly increased.

 

(2) Determination of basic aldosterone in blood plasma and load test Before blood gets up in the morning to measure the basic value of aldosterone concentration (normal value: 28-138pmol / L) (1-5mg / dl), the disease is significantly elevated, and then stand for 2 hours to collect blood After loading, the concentration of aldosterone (normal value: 138-415 pmol / L) (5-15 mg / dl) is still close to the basic value, and there is no significant increase.

 

(3) spironolactone test spironolactone can inhibit the promotion effect of aldosterone on renal tubular sodium reabsorption. Therefore, take 320-400mg daily, orally in 4 divided doses for 2 to 3 weeks. Both blood pressure and potassium should return to or close to normal, or hyponatremia and hypertension caused by kidney disease. This does not work.

 

(4) Sodium and potassium balance test Low sodium and high sodium load test to determine the amount of sodium and potassium excreted in urine. Potassium metabolism is negatively balanced and sodium metabolism is positively balanced. Due to the tedious procedures and difficult to accurately control the intake, it has rarely been done.

 

Localization examination: choose different imaging examinations, including magnetic resonance, CT scan, selective adrenal angiography, B-mode ultrasound and so on. And inferior vena cava blood sampling to determine aldosterone to determine the tumor site.

 

Diagnosis and Differential Judgment

 Based on clinical manifestations and special laboratory tests, the diagnosis of primary aldosteronism is not difficult. It should be mainly distinguished from secondary aldosteronism, including renal stenosis hypertension, malignant hypertension, renal hypertension and so on. Plasma renin activity and angiotensin II in these secondary aldosteronism patients were significantly increased, and the identification was not difficult.

 

 Treatment

 First, the general treatment to correct hypokalemia, can be based on blood potassium determination and negative ECG monitoring. Proper potassium chloride supplementation and avoid the use of drugs that promote potassium excretion. Such as dihydrocorsa.

 

2. Surgical treatment Surgical resection of adrenal adenoma and adenocarcinoma is the selected treatment. Before the operation, take Anshushutong to correct hypertension and hypokalemia to ensure smooth and safe operation.

 

3. For patients who can not undergo surgery and two patients with adrenal hyperplasia, they can take amphitamine for a long time to create conditions and strive for opportunities for further treatment.

 

 Chronic Adrenal Cortical Insufficiency

 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 of Chronic Adrenal Cortical Insufficiency

First, adrenal tuberculosis Only bilateral adrenal tuberculosis, most of the adrenal tissue is destroyed before 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. 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), which can include, for example, adrenal insufficiency, hypothyroidism, hypoparathyroidism, gonadal failure, diabetes, hypopituitarism, positive gastric wall cell antibodies, and malignant anemia , Hyperthyroidism, colon tumors, myasthenia gravis, solitary red blood cell regeneration disorders, etc.

 

3. Other adrenal metastases of malignant tumors, accounting for about 10% of patients with cancer metastasis, 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.

 

Clinical Manifestations of Chronic Adrenal Cortical Insufficiency

1. The slow onset may not be noticed until many years later. 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. It is obvious that exposed parts, frequently rubbing parts and roots of nails, scars, areola, external genitals, 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.

 

3. Fatigue The degree of fatigue is parallel to the severity of the disease. Those who are weak only have poor labor tolerance, and those who are severe cannot stay in bed. It is caused by electrolyte disorders, dehydration, and protein and sugar metabolism disorders.

 

4. 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, multi-tolerance, 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, lethargy. Some patients have insomnia, irritability, and even delirium and mental disorders.

 

8. Adrenal crisis Patients have low resistance, and any stress load such as infection, trauma, surgery, anesthesia, etc. can induce acute hypoadrenal crisis.

 

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

 

10. Primary symptoms such as tuberculosis, various autoimmune diseases and various symptoms of glandular failure syndrome.

 

Laboratory and other inspections
I. The general examination:

  i. Blood image examination has mild positive cell positive pigment anemia, lymphocytes and eosinophils are high.

ii. Blood biochemical examination, some patients have low serum sodium and high potassium. Blood sugar is low, about one-third of the cases are below the normal range. The glucose tolerance test showed a low-level curve or reactive hypoglycemia.

iii. The low voltage of the electrocardiogram and the low or T-wave of the T wave were flat or inverted.

iv. X-ray examination showed that the heart shadow was reduced and was vertical.

 

II. Special inspections (adrenal gland disease)

 (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.

 

(2) 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. Simplified method: Blood was collected at 8 am to determine the basic concentration of plasma cortisol, and ACTH 25 mg was injected intramuscularly or intravenously. After 60 minutes, the plasma cortisol concentration was re-examined. Cortisol concentration in normal people increased by more than 2.5 times after ACTH injection, but the disease did not increase significantly.

In intravenous drip method, 24 hours urine 17 hydroxycorticosteroid content is used as the basic value on the 1st and 2nd consecutive days. On the 3rd or 4th or 3th to 7th days, ACTH25mg and 5% glucose solution are added slowly in 500ml daily. For 8 hours, the urine 17 hydroxycorticosteroid content was re-measured for 24 hours on the last two days of intravenous drip, which was 1 to 2 times higher in normal people, but the disease was not significantly increased. Secondary chronic adrenal insufficiency The response is normal or slightly delayed.

 

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

 

The cause of examination tuberculosis in the adrenal gland X-ray film may see 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.

 

Diagnosis and Differential Diagnosis (adrenal gland disease)

 The clinical manifestations of extensive pigmentation of the skin and mucous membranes should be considered when symptoms such as fatigue, digestive system and mental system are present. Confirmation of the diagnosis mainly depends on the determination of adrenal corticosteroids, excitability tests and etiological examination. This disease needs to be distinguished from other pigmented diseases. Such as melanosis, hemochromatosis, pellagra, scleroderma, dermatomyositis, multiple colon polyps, multiple neurofibromatosis, cirrhosis, ectopic ACTH secretion syndrome, drugs (heavy metals such as arsenic, mercury, and Chlorpromazine, A equality) caused by pigmentation.

Adrenal crisis should be considered for acute patients with the following conditions: The disease is not too serious and severe circulatory collapse occurs, dehydration, shock, failure, unexplained hypoglycemia, unexplained vomiting, pigmentation, whiteness found during physical examination Purpura, scarce body hair, and weak constitution, those with chronic consumption should consider renal crisis. You can give sugary saline and glucocorticoids, and check them when the condition improves.

 

Prognosis

 It depends on the cause, concomitant disease and treatment. The prognosis of tuberculosis patients can be relieved by effective anti-TB treatment. People with autoimmunity can get better results by immunosuppressive therapy. The etiology is unknown, and alternative therapies are given alone, especially if the dose is improper, and infection may spread. Corticosteroid dose should be increased during stress to prevent crisis.

 

Treatment of Chronic Adrenal Cortical Insufficiency

 I. Basic treatment usually enter a high-sodium diet, alternative therapy can take hydrocortisone 20-30mg per day, or prednisone 5-7.5mg, should be taken in the morning 2/3 of the total dose, 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 9α-fluhydrocortisone 0.2 mg daily or 125 mg of trimethylcortisol acetate.

 

II. The treatment of acute cortical functional crisis In mild stress, increase hydrocortisone by about 50mg per day, those who can not take oral administration can be administered intravenously. Severe acute adrenal crisis, which is life-threatening, must be rescued in time.

i. Replenish the saline. The saline should be replenished quickly in the first two days, 2 ~ 3L per day.

ii. Glucocorticoids. Intravenous injection of 100 mg 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. 9α-fluorohydrocortisone can be added.

 

iii. The cause of treatment, such as immunosuppressive agents, anti-TB treatment. (for adrenal gland disease)

 

Pheochromocytoma

Pheochromocytoma (adrenal gland disease) originates from pheochromocytosis that migrates from the neural crest. Chromaffin tissue can synthesize catecholamines, which are widely distributed during the embryonic period, and only a small amount remains in the adrenal medulla, sympathetic ganglia, and other parts of the body after birth. Can form tumors and synthesize and release catecholamines, causing symptoms such as hypertension.

 

Pathology (adrenal gland disease)

About 85 to 90% of pheochromocytomas originate from the adrenal medulla, mostly unilateral, and a few originate from both adrenal glands. Tumors outside the adrenal gland can be from the carotid body to the pelvic cavity, and are often associated with sympathetic ganglia, such as the abdomen Both sides of the aorta (10-15% of patients) and posterior mediastinal barrier. Multiple pheochromocytomas are more common in children and patients with familial pheochromocytoma.

 

About 10% of pheochromocytomas are malignant, and the diagnosis of pathological morphology is difficult to determine. The diagnosis is based on:

i. Infiltration of the capsule

ii. Intramuscular tumor thrombus formation

iii. Tumor metastasis in the site without chromaffin tissue.

 

The catecholamines synthesized by normal adrenal medulla are mainly epinephrine, and norepinephrine only accounts for 15%. The catecholamine released by adrenal pheochromocytoma accounts for about three quarters of norepinephrine, and almost all of the release from extra-adrenal tumors is norepinephrine. So the performance is different.

 

Clinical manifestations (adrenal gland disease)

 I. Hypertension can have different manifestations:

(1) Paroxysmal hypertension is approximately one-third. It can be caused by various reasons such as emotional excitement, change of body position, manual labor, smoking, pressure on tumor mass, injection of histamine, anesthesia, etc., or there is no obvious cause. Seizures include limb numbness, visual abnormalities, muscle tremors, and abdominal cramps. The blood pressure rises sharply at the onset, systolic blood pressure often exceeds 28 kpa (220 mmHg), and diastolic blood pressure rises accordingly. The duration of the attack varies, ranging from a few seconds to tens of minutes or even more than 24 hours, after which blood pressure drops to normal. Conscious severe headache during the attack, pain in the anterior heart area and upper abdomen, pain in the anterior heart area, sweating, nausea, vomiting, blurred vision, double vision, etc. At the beginning of remission, symptoms of vagus nerve excitement may occur, such as flushing of the skin, fever feeling throughout the body, salivation, shrinking pupils, and increased urine output. Feeling weak and sleepy after the attack. The attack occurs once a few weeks to several months at the beginning, after which the interval is short and the attack gradually becomes serious. It can occur dozens of times a day.

 

(2) About two-thirds of persistent hypertension. There may be paroxysmal exacerbations and orthostatic hypotension. The systolic blood pressure is more than 28Kpa (220mmHg). Taking general antihypertensive drugs is not effective, taking catecholamine releasing drugs such as reserpine, antihypertensive, guanethidine, methyldopa, etc. can have abnormal reactions, but blood pressure has increased. Some patients have aggressive hypertension, accompanied by rapidly progressing heart, kidney, and brain damage and acute myocardial infarction. Hypertensive crisis may also occur.

 

(3) Hypotension and shock can occur suddenly or alternately with hypertension. May be accompanied by acute abdominal pain, anterior heart pain, high fever and so on. Reasons:

  1. Sudden bleeding in the tumor and necrosis.
  2. A large number of catecholamines cause severe arrhythmia or cardiac insufficiency.
  3. A large number of catecholamines cause strong blood vessel contraction, tissue hypoxia, increased vascular permeability, plasma extravasation, and severely insufficient blood volume.
  4. Epinephrine excites the adrenergic β receptors and expands the surrounding blood vessels.

 

II. The cardiovascular system Insufficient blood volume, blood pressure decreases after vasoconstriction is relieved, and shock may occur. Due to the effects of excessive catecholamines, especially norepinephrine, the myocardium is degenerative, necrotic, edema and fibrosis. Therefore, severe acute heart failure can occur, with left heart failure and pulmonary edema being more common. A variety of arrhythmias can occur, such as premature beats, atrioventricular block, paroxysmal tachycardia and ventricular fibrillation, and can cause sudden death.

 

III. Gastrointestinal system Constipation often occurs due to intestinal motility and weakened tension. Severe blood vessel constriction and gastrointestinal ischemia can cause gastrointestinal bleeding, ulcers, perforation, and intestinal obstruction. About 20% of all cases are cholelithiasis. Pheochromocytoma is located in the latter of the rectum and can cause high blood pressure during defecation.

 

IV. Urinary system Renal failure will occur in those with a longer course of disease. If a pheochromocytoma is located in the bladder, high blood pressure may occur during urination.

 

V. Metabolic disorders: Diabetes is about 60% of the glucose tolerance curve. Half of the patients have hyperlipidemia, some patients have low potassium, and nearly half of the patients have a high basal metabolic rate.

 

VI. Other often have headaches, insomnia, bathing, anxiety and other symptoms, hypertension can induce cerebrovascular accidents, but also the disease and an important cause of death. A few patients can reach a larger mass in the abdomen-pheochromocytoma. Hypertension can be caused by pressure, but larger pheochromocytomas usually have no significant endocrine function.

 

Laboratory and other inspections (adrenal gland disease)

 I. Urinary vanilloid ursolic acid (VMA) For patients with persistent hypertension and paroxysmal hypertension with frequent daily episodes, 24-hour urine VMA excretion can be measured, which is <32 μmol / 24h (<5.8mg / 24h), higher than 50μmol / 24h (9.1mg / 24h) is suspicious, more than two times higher than 100μmol / 24h (18.2mg / 24h) is diagnostic. In occasional short-term authors, you can measure the urine VMA content within 3 hours including the onset period and the 3-hour urine VMA content during the intermittent period. Such as a significant increase is also meaningful.

 

2. The determination of renin activity and angiotensin due to the feedback relationship, they were significantly low, have a better value in identifying the etiology of high blood.

 

3. Determination of catecholamines and metabolites in blood and urine The determination of epinephrine and norepinephrine, and methoxyadrenaline (MN) and methoxynorepinephrine (NMN) were significantly higher than the normal range. If it is measured repeatedly, NMN is significantly increased, and MN is close to normal, which indicates that the possibility of extra-adrenal pheochromocytoma is greater.

 

All the drugs that affect catecholamines must be stopped during the above inspections, so as not to affect the reliability of the measurement.

 

4. Induced test Induced test can be performed on the author without observation during the observation period. Antihypertensive drugs and sedatives must be stopped for 7 to 10 days before the test. Methods: The patient rested in a supine position, intravenously injected histamine 0.025-0.05mg (equivalent to histamine phosphate 0.069-0.138mg) or glucagon 0.5 ~ 1mg, measured blood pressure every 30 seconds, and every minute after 5 minutes . Positive blood pressure was raised above 6.0 / 2.7kpa (45 / 20mmHg). Precautions:

i. There may be overdose of drugs and histamine reaction.

ii. It may cause sudden increase in blood pressure and cause cerebrovascular accidents, myocardial infarction, acute heart failure, and severe arrhythmia (such as ventricular fibrillation).

iii. Hypotension and shock. Therefore, blood pressure monitoring should be used during this test, and phentolamine injection and defibrillator should be prepared to prevent accidents. The positive rate is about 50%, and the false positive rate is about 10%. You can also use tyramine 0.5-2.0mg intravenously instead of histamine. The side effects are lighter, but the false positive rate is about 15%.

 

5. Phentolamine test The preparation is the same as the challenge test, which is suitable for blood pressure higher than 24 / 14kpa (180 / 106mmHg). For example, dilute 5mg of phentolamine in 10-20ml of normal saline, inject it slowly, and measure blood pressure once every 30 seconds, and once every 5 minutes. If the drop in blood pressure is not noticeable, you can speed up the injection. If the blood pressure drops more than 4.6 / 3.3kpa (36 / 25mmHg), it is positive.

The reduction in blood pressure can last from minutes to hours. The false negative rate is low, but the false positive rate is high, especially those who have recently taken antihypertensive agents such as reserpine and guanethidine, which are prone to false positives.

Note: A significant decrease in blood pressure, hypovolemia and shock may occur, causing myocardial infarction and cerebrovascular accidents.

 

6. Localization examination: mainly imaging methods, such as B-mode ultrasound, CT scan, magnetic resonance imaging, etc., can also be done angiographic examination, but it is meaningful to those located in the adrenal glands. Extra-adrenal tumors can be used as vena cava catheters and segmented blood to measure catecholamines (MN and NMN) to roughly estimate the tumor site. This is meaningless during the intermittent period.

 

Pheochromocytoma in specific sites can be found due to special symptoms and local examination. If the latter is more frequent in the rectum than in bowel movements, a barium enema can detect mass. Those in the bladder often experience seizures during urination, and cystoscopy is often found.

 

Diagnosis and Differential Diagnosis (adrenal gland disease)

 Paroxysmal or persistently elevated blood pressure, exceeding 28 / kpa (220 / 106mmHg), accompanied by sympathetic symptoms, has been confirmed by laboratory tests, and diagnosis is not difficult (sometimes difficult to locate). It should be distinguished from hypertension, hyperthyroidism, diabetes, and menopausal syndrome of other causes.

 

Treatment (adrenal gland disease)

1. General Treatment: Quiet rest- Avoid excessive pressure on the mass or suspicious area to reduce seizures. Intensify nursing and be prepared to deal with hypertension crisis and acute heart failure at any time.

 

2. Adrenergic receptor blockers: Preferred alpha blockers such as phenbenzamine (benzylamine) are orally administered twice a day at 10 to 60 mg for 24 hours to 5 days. The vasoconstriction disappears during medication, so hypovolemia should be corrected at the same time. Due to the long duration of action of this drug, patients treated with surgery must be discontinued 2 to 3 days before surgery to avoid difficult-to-control hypotension and shock during surgery. Preoperative and intraoperative use of phentolamine (Rigitine) continuous intravenous drip to control blood pressure. The main side effects are nasal congestion and nasal obstruction. In the case of hypertension crisis, phentolamine 5mg was intravenously injected, and the infusion rate was adjusted according to blood pressure.

 

β-blockers: α-blockers must be used for 1 to 3 days before application. Otherwise, β-blockers eliminate the vasodilator effect of catecholamine β-receptors, and the vasoconstriction of α-receptors No longer being antagonized, blood pressure will rise even further, and even myocardial infarction and cerebrovascular accidents must be observed.

 

3. Catecholamine blocker: α-methyltyrosine can compete with butyric acid, inhibit tyrosine hydroxylase, and block the synthesis of catecholamines. The dose is 600-1200mg per day. There may be side effects such as drowsiness, anxiety, tremor, dry mouth, and galactorrhea. The effect gradually worsens after several months of continuous medication.

 

4. Blood volume supplementation: After the excessive contraction of blood vessels, blood volume must be replenished in time. The crystal solution can only maintain blood volume for a short time, and colloidal liquid can maintain it for a long time, such as whole blood, plasma, and plasma replacement. Created conditions.

 

5. Surgical treatment: Pheochromocytomas that can or can be located should be surgically removed or explored. Preoperatively, alpha blockers were used to control blood pressure, correct hypovolemia, and control glucose metabolism disorders. Intravenous infusion of phenhydramine and dopamine was used during the operation to maintain stable blood pressure. If the main vein of the tumor is cut, the blood pressure should drop immediately. If it does not drop, the possibility of multiple pheochromocytoma should be considered and explored.

 

 

 

 

Refer also:

 

 

 

 

 

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