What Is Secondary Adrenal Insufficiency?

Clinical manifestation

Secondary adrenal insufficiency

This disease is due to adrenal insufficiency due to lack of ACTH. Secondary adrenal insufficiency can occur in hypopituitarism. Patients with a lack of single ACTH production and receiving corticosteroids after discontinuation of corticosteroids. It is most commonly seen in women with Sheehan syndrome, but can also occur in chromocytoma, younger patients with craniopharyngioma and various tumors, granulomas, and rare trauma infections that cause pituitary tissue destruction. Patients receive More than 4 weeks of corticosteroids or several weeks to months after discontinuing treatment, insufficient ACTH secretion during the stress process stimulates the adrenal glands to produce sufficient corticosteroids, or the adrenal cortex atrophy does not respond to ACTH. This phenomenon can continue to steroid treatment 1 year after stopping. During the long-term steroid treatment, the hypothalamic-pituitary-adrenal axis integrity can be measured by intravenous injection of 5 to 250 g of tecoclatin, and the plasma cortisol level after 30 minutes should be> 20 g / dl (> 552nmol / L) .A single ACTH deficiency is idiopathic and extremely rare.

Signs and symptoms of secondary adrenal insufficiency

Clinical manifestation

The clinical manifestations of chronic adrenal insufficiency are due to a deficiency of cortisol and aldosterone.

(A) weakness

It is an early major symptom. The degree of fatigue is directly proportional to the severity of the disease. In severe cases, weakness can be achieved by turning over or reaching out. Serious muscle spasms, especially in the legs, can also be seen. These muscle lesions may be related to sodium and potassium at the nerve-muscle endplate. Related to imbalance.

(Two) weight loss

Cortisol deficiency can cause gastrointestinal dysfunction such as loss of appetite, nausea and vomiting, bloating and diarrhea, reduced fat storage and muscle wasting, and other factors can lead to weight loss. Progressive large reductions may indicate adrenal cortical crisis.

As cortisol deficiency weakens the feedback inhibition of pituitary ACTH, melanocyte stimulating hormone (MSH), and lipotropin (LPH), increasing the secretion of these hormones, and ACTH and LPH contain and -MSH structures, respectively. Therefore, pigmentation, rubbing, palm prints, areola, scars, etc. are particularly obvious on the skin and mucous membranes. Pigmentation is one of the main criteria for distinguishing primary and secondary adrenal insufficiency. Sudden deepening of the pigmentation may indicate deterioration of the condition. .

(D) cardiovascular symptoms

Due to the weakened booster response to catecholamines, which leads to lower blood pressure, orthostatic hypotension is the most common. X-rays show reduced heart shadow, ECG shows low voltage, PR and QT intervals are prolonged, and patients often have dizziness, dazzling, orthostatic syncope. .

(E) Hypoglycemia

Patients have increased sensitivity to endogenous and exogenous insulin, and are prone to hypoglycemia under hunger, gastrointestinal dysfunction, and infection.

(6) Nervous system symptoms such as indifference, drowsiness and even mental disorders.

(7) Reduced resistance to infection, trauma, and other stresses, which can easily induce adrenal crisis. They are extremely sensitive to narcotics, sleeping sedatives, and hypoglycemic drugs. A small amount can cause coma.

(Eight) sexual dysfunction

Both males and females can have sexual dysfunction. Female adrenal androgens are related to maintaining hair and sexual desire. Therefore, women's armpit hair and pubic hair are scarce or shedding. Premature testicular failure.

diagnosis

The hypothalamic-pituitary-adrenal axis integrity can be determined by intravenous administration of 5 to 250 g of teccopeptide. After 30 minutes, plasma cortisol should be> 20 g / dl (> 552 nmol / L), and a pituitary mass or atrophy of the pituitary gland strongly suggests the following Primary adrenal insufficiency.

Treatment of secondary adrenal insufficiency with medication

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treatment

Mission

Patients should be fully aware of the nature of the disease, knowing that adrenocortical hormone replacement therapy should be used for life. Once the diagnosis is clear, they should be explored and get the appropriate basic amount. In stress situations, they can see a doctor or increase the dose appropriately according to their actual situation.

Basic treatment

Chronic adrenal insufficiency requires long-term replacement therapy. The dose of replacement therapy should be individualized, because it is related to the individual's weight, body surface area, labor intensity, intestinal absorption of hormones, disease severity, hormone and plasma protein binding status, and so on. Alternative treatment should be hydrocortin or corticosteroids, usually one tablet daily, taken orally in divided doses, with a greater need in the morning. Patients with diabetes, ulcers or mental illness should reduce the dose. Children should pay special attention when adjusting the dosage. Insufficient dosage can easily lead to adrenal crisis. Excessive dosage can cause developmental delay. In particular, dexamethasone is disabled, which inhibits linear growth 80 times that of hydrocortin.

Hydrocortin has a certain natriuretic effect, but it only exerts its maximal mineralocorticoid effect at 100-200mg / 24h. Therefore, long-term replacement therapy below this dose must be added with salt or mineralocorticoid steroids. When the sodium intake is insufficient or the amount of excretion increases, such as excessive sweating in summer can not maintain the sodium balance, you must add sodium or apply sodium hormonal hormone, the intake should be sufficient.

Natriuretic hormones include 9-fluorohydrocorticoid, deoxycorticosterone acetate, and long-acting trimethylcortisol acetate. 9-fluorohydrocorticoid is the most convenient and inexpensive. The commonly used dose is 0.05 0.2mg / 24h. Deoxycorticosterone acetate, intramuscularly 2.5 to 5 mg daily or every other day. Deoxycorticosterone trimethylacetate is administered intramuscularly once a month at 50 to 100 mg each time. The dose comparison between the three preparations was 0.2 mg of 9-fluorohydrocorticoid taken orally daily, which was equivalent to 5 mg of intramuscular deoxycorticosterone acetate or 125 mg of trimethylcortisol acetate every month.

Treatment under stress

For mild stress such as colds and tooth extractions, about 40 mg of hydrocortin can be added daily. After stress, gradually reduce to maintain the amount. When there is a digestive dysfunction, increase at least 40 mg of hydrocortin daily and use intravenous drip instead. For severe infection or major surgery, the treatment is the same as acute adrenal crisis. Adequate doses of corticosteroids must be applied before, during and after major surgery.

Treatment of adrenal crisis

For details, see Acute Adrenal Insufficiency.

Etiology treatment

Patients with active tuberculosis should be actively treated with antituberculosis. The physiologically substituted amount of hydrocortin does not affect the control of tuberculosis, and individual patients can be cured.

Autoimmune diseases should be checked for the possibility of other glandular dysfunction, and if so, co-existing conditions such as hypoparathyroidism, autoimmune thyroid disease or diabetes should be treated accordingly.

In the treatment of autoimmune polyendocrine disease syndrome, if accompanied by hypothyroidism, in order to avoid thyroid hormone aggravating adrenal hypofunction or causing crisis, adrenal corticosteroids should be given until an appropriate maintenance dose. If combined with diabetes, they are mostly insulin-dependent and require insulin treatment, but they are more prone to hypoglycemia. Conversely, if the amount of adrenal corticosteroids is too large, it can cause diabetes to worsen, and even ketoacidosis. Care must be taken during treatment. When accompanied by a fungal infection, a combination of transfer factor and amphotericin can be used. ;

Secondary adrenal insufficiency

Prognosis: Pay attention to rest to prevent overwork and prevent infection or adrenal crisis.

Prevention: Educate patients to understand the nature of the disease, and adhere to life-long hormone replacement therapy, including long-term physiological dose replacement and short-term stress replacement treatment. Normally, supplement the appropriate basic amount of physiological requirements; such as the occurrence of complications or the implementation of surgery and other stress In order to prevent the crisis, it is necessary to increase the dosage by 3 to 5 times or more. Educate patients to carry disease cards with their contacts and addresses to facilitate timely treatment.

Preventive care of secondary adrenal insufficiency

Active treatment of the primary disease is the key to preventive care of this disease.

Pathological causes of secondary adrenal insufficiency

Secondary adrenal insufficiency

(1) Inadequate corticotropin-releasing hormone (CRH).

(2) Inadequate pituitary function: postpartum pituitary necrosis (Sean syndrome), pituitary tumors, post-resection or hypoplasia, insufficient selective ACTH, etc.

(3) Long-term rise in blood concentration of glucocorticosteroids or other steroid drugs causes hypothalamus and pituitary depression.

1. After resection of a functional adrenal tumor.

2. Overuse of iatrogenic corticosteroids.

3. Application of oral contraceptives or immunosuppressants.

4. Long-term ACTH treatment.

Diagnosis of secondary adrenal insufficiency

Secondary adrenal insufficiency is mainly different from primary adrenal insufficiency: most secondary adrenal insufficiency is due to pituitary destruction, so sphenoidal CT or MRI can help rule out tumors and atrophy. Saddle syndrome is not always accompanied by hypopituitarism, and functional tests must be performed when the pituitary shadow changes. Patients with primary adrenal disease have elevated plasma ACTH levels (50 pg / ml). Patients with pituitary failure or single ACTH deficiency have ACTH levels Low. If ACTH cannot be measured, a mepidone test should be performed. Because mepidone blocks 11-hydroxylation of the cortisol precursor, plasma cortisol is reduced. Normal human cortisol reduces excitatory ACTH secretion, leading to increased cortisol precursor synthesis , Especially 11-deoxycortisol (compound S), is excreted in the urine (tetrahydro-S) as a metabolite. The best and easiest way is to take orally 30 mg / kg of mepyridone in the middle of the night, while eating small amounts of food to avoid the stomach Stimulation. Plasma cortisol should be <10 g / dl (<276 nmol / L), and 11-deoxycortisol should be between 7 to 22 g / dl (0.2 to 0.6 mol / L) at 8 o'clock in the morning. No response to metyrapone The patient must undergo another test of teicotaxin. Both compounds are low in patients with reduced function, and they have no response to teicotaxin. Patients with hypopituitarism respond to synthetic ACTH, but do not respond to metyrapone. It is necessary to intramuscularly inject long-acting ACTH20u 3 days before the test , 2 times a day, to prevent adrenal atrophy in patients with pituitary failure. Inadequate response to metyrapone, but if there is a positive response, this preparation is required.

Test methods for secondary adrenal insufficiency

Laboratory inspection

(A) blood routine examination

May have mild orthocytic orthochromic anemia, occasionally large cell or malignant anemia, classification shows decreased neutrophils, relatively increased lymphocytes, and significantly increased eosinophils, sometimes due to dehydration before treatment, hypovolemia For reasons, hemoglobin can be normal.

(Two) electrolyte

Generally there is a decrease in the ratio of blood sodium and blood potassium, while low sodium and high potassium are rare, and obvious low sodium and high potassium do not appear until crisis.

(Three) glucose metabolism disorders

The fasting blood glucose is below normal in most patients, and the oral glucose tolerance test (OGTT) can show a low-level curve. Most patients have lower than 3 hours blood glucose after meals, indicating that they cannot respond to hypoglycemia caused by endogenous insulin.

(IV) Drainage Water Load Test

In the water test alone, 90% of patients excrete less than 10ml per minute, and 50% of patients excrete less than 5ml. This method can be corrected when the cortisol water test is repeated. This method is simple and easy to use, and has great diagnostic value. Test blood sodium first, those who drop blood sodium are prone to water poisoning and should not be carried out.

(E) Urine 17-hydroxy and 17-ketosteroid excretion

Normal urine 17-hydroxycorticosteroids are 5.5 to 28umol / 24h (2 to 10mg / 24h), normal urine 17-ketosteroids are 14 to 52umol / 24h (4 to 15mg / 24h) in women, and 22 to 88umol / 24 in men. 24h (7-25mg / 24h), most patients with adrenal insufficiency were lower than normal.

(Six) plasma cortisol

Plasma cortisol is pulsed and has obvious circadian rhythm changes. The blood concentration is lowest from 1 hour to midnight after falling asleep at night, and it starts to rise in the morning. Normal value: 220-660nmol / L (8-24ug / dl) in the afternoon at 8 am At 4:50 to 410 nmol / L (2 to 15 ug / dl), the midnight is less than 140 nmol / L (less than 5 ug / dl). Most patients with adrenal insufficiency are lower than normal, and the circadian rhythm disappears.

(VII) ACTH measurement

The plasma basic ACTH measurement of patients with this disease was significantly increased, exceeding 55 pmol / L (250 pg / ml), mostly between 88-440 pmol / L (400-2000 pg / ml), and normal people were lower than 11 pmol / L (50 pg / ml). However, due to the stress of a few other diseases, the plasma ACTH level can reach 132 pmol / L (600 pg / ml).

(Eight) ACTH excitement test

The ACTH stimulation test has the most diagnostic value. Regardless of whether the basic urinary free cortisol excretion or blood cortisol is decreased, which is close to normal or normal, there is no significant increase in ACTH excitement. Some patients have decreased, or even reduced to zero.

The commonly used method of this test is intravenous infusion of ACTH 25u, which is maintained at an even rate for 8 hours. If the disease is highly suspected clinically, dexamethasone 1mg should be taken before the test, which will not affect the measurement and prevent the crisis.

In order to identify primary or secondary adrenal insufficiency, a 3-day ACTH excitation test may be used, or 25 mg of synthetic ACTH 24 peptide may be injected intravenously, and plasma cortisol may be measured before and 30 minutes after injection, or intramuscularly. Plasma cortisol was measured before the same dose and 60 minutes after injection. Normal human plasma cortisol can increase 276-552nmol / L (10-20ug / dl).

(9) Image inspection

Imaging examination is of high value in tuberculous patients. Plain radiographs of the X-ray kidney area can show the following signs: Adrenal density is uniformly increased, fine-grained, with coarse granular adrenal calcification.

Adrenal tuberculosis is easier to display on ultrasound and CT examinations. Circular or oval shadows are visible during CT examinations, which are heterogeneous low-density shadows and granular calcified shadows.

Common serum electrolyte levels include low sodium (<130mEq / L), high potassium (> 5mEq / L), low HCO3-(15 ~ 20mEq / L), and high BUN along with characteristic clinical manifestations suggesting Addison's disease (Table 9- 1). Plasma renin activity and ACTH levels increase. When adrenal failure is due to insufficient pituitary ACTH production, electrolyte levels are generally normal.

Adrenal insufficiency test Cosyntropin (synthetic 24 peptide corticosteroid) 5 ~ 25g intravenous bolus. Normal plasma cortisol before injection is between 5 ~ 25g / dl (138 ~ 690nmol / L), between 30 ~ Doubled in 90 minutes, with a minimum value of 20 g / dl (552 nmol / L). Addison's disease is low or normal, and it does not increase after excitement.