Mental disorders associated with adrenal cortex dysfunction

　　One, the cause of the disease

　　Overall, the etiology and pathogenesis of mental disorders associated with adrenal cortex dysfunction are not yet fully clear at present.

　　1. Mental disorders associated with hypercortisolism:The main cause is the increased secretion of corticosteroids. For example, Cushing's syndrome is due to excessive secretion of cortisole hormones over a long period of time, and primary adrenal tumors excessively secrete cortisole, as well as hypersecretion of ACTH in pituitary or non-pituitary cases.

　　(1) The theory of excessive adrenaline secretion: Cohon emphasized in 1980 that there is a pathological connection between depressive states and hypercortisolism, pointing out that depressive diseases and hypercortisolism have similar susceptibility, that is, the family history of depression and suicide is higher than that of the control group. Some people also propose that the occurrence of mental disorders is due to alkalosis, hypertension, and other symptoms caused by decreased blood potassium and chloride levels during hyperadrenalism.

　　(2) Neurotransmitter theory: In 1972, Mass pointed out that there is an intrinsic connection between the pituitary-adrenal system and the metabolism of catecholamines. Endocrine disorders can lead to a depressive state, and a depressive state can also cause endocrine disorders, with both being intercausal. Rubin used the pathogenesis of endogenous depression to explain the cause of mental disorders, believing that increased adrenaline concentration in the blood can activate tryptophanase, leading to a decrease in 5-hydroxytryptamine in the brain, causing a vicious cycle.

　　(3) Genetic factors and pre-morbid personality characteristics: There may also be a certain relationship with the occurrence of mental disorders.

　　2. Psychiatric disorders associated with adrenal cortical insufficiency

　　(1) It is believed to be related to factors such as trauma, surgery, pregnancy, and bleeding, thrombosis, arteritis, fungal infection, metastatic tumors, etc.

　　(2) Autoimmune factors: Due to immune deficiency, adrenal atrophy is caused by adrenal destruction. Therefore, some people believe it is an autoimmune disease.

　　(3) Tuberculosis infection factors: Some believe that adrenal cortical insufficiency is one of the main causes.

　　Second, pathogenesis

　　Mental disorders associated with adrenal cortical hyperplasia are defined as hyperfunction of the adrenal glands, increased secretion of cortisol, leading to somatic, mental symptoms, and disorders of consciousness. Mental disorders associated with adrenal cortical insufficiency are mainly due to insufficient secretion of adrenal cortical hormones, leading to somatic, mental symptoms, and disorders of consciousness. The exact pathogenesis is still unclear.

　　This disease has two states, one is increased adrenal cortical hormones, and the other is decreased adrenal cortical hormones. Complications usually occur in patients with reduced adrenal cortical function. This disease requires lifelong hormone replacement therapy. In stress states (trauma, infection, etc.) or sudden discontinuation of hormone replacement therapy, adrenal crisis may be induced, and symptoms such as nausea, vomiting, fainting, shock, and coma may occur.

　　1. Chronic adrenal cortical insufficiency:Chronic adrenal cortical insufficiency has an insidious onset, the condition gradually worsens, and various clinical manifestations can be seen in many chronic diseases, making diagnosis difficult. Primary and secondary adrenal cortical insufficiency have common clinical manifestations, such as gradually worsening general discomfort, lack of energy, fatigue, drowsiness, decreased appetite, nausea, weight loss, dizziness, and orthostatic hypotension.

　　Hyperpigmentation of the skin and mucous membranes is a characteristic manifestation of chronic primary adrenal cortical insufficiency, the pigment is brownish, with luster, does not protrude above the skin surface, and the distribution of hyperpigmentation is systemic, but it is more obvious in exposed areas and areas prone to friction, such as the face, hands, palm creases, areola, nail bed, dorsum of the foot, scars, and areas of a girdle; white spots are often interspersed in the skin with hyperpigmentation, the gums, tongue surface, and buccal mucosa also often have obvious hyperpigmentation, and sometimes other autoimmune endocrine and non-endocrine diseases are combined. In patients with adrenal brain white matter dystrophy, central nervous system symptoms may occur.

　　Patients with secondary adrenal insufficiency have a paler complexion. Other hypopituitarism may have clinical manifestations of hypothyroidism and hypogonadism, manifested as cold intolerance, constipation, amenorrhea, sparse axillary and pubic hair, decreased libido, impotence; in adolescent patients, there is often delayed growth and delayed puberty. Suprasellar or pituitary lesions can have headache, diabetes insipidus, vision loss, and field defects.

　　2. Acute adrenal cortical crisis:When the primary adrenal cortical insufficiency appears a crisis, the condition is serious: most patients have fever, some of whom may have a body temperature above 40℃, which is very likely to have an infection, and the adrenal crisis itself can also cause fever. There is severe hypotension, even hypovolemic shock, accompanied by tachycardia, cold extremities, cyanosis, and collapse. Patients are extremely weak and listless, apathetic, and drowsy. They may also show irritability, delirium, convulsive seizures, and even coma. Gastrointestinal symptoms are often prominent, manifested as nausea, vomiting, and abdominal pain, diarrhea. Abdominal pain is often accompanied by deep tenderness and rebound pain, and is misdiagnosed as acute abdomen, but often lacks specific localization signs. Patients with adrenal hemorrhage can also have pain in the abdominal, side, and back, and a rapid decrease in hemoglobin.

　　Secondary adrenal cortical insufficiency rarely causes crises. When a crisis occurs, hypoglycemic coma is more common than in primary cases. There may be hyponatremia, but there is no obvious hyperkalemia. Pituitary tumor stroke often has severe headache, sudden vision loss, sudden narrowing of the field of vision, and can also have other cranial nerve injuries. The sudden absence of ACTH secretion can also cause shock.

　　In general, the etiology and pathogenesis of mental disorders associated with abnormal adrenal cortical function are not yet fully clear. Since the pathogenesis is not clear, it is not possible to target the cause for targeted prevention. Early detection, early diagnosis, and early treatment are of great significance for indirect prevention of the disease. At the same time, it can also reduce the occurrence of complications such as infection and adrenal crisis. For patients with infection, antibiotics should be used as soon as possible. For patients with adrenal cortical insufficiency, it is not allowed to discontinue adrenal cortical hormone drugs arbitrarily.

　　1. General examination

　　There may be hyponatremia, hyperkalemia, and severe dehydration. Hyponatremia may not be obvious in severe cases of dehydration, and hyperkalemia is generally not severe. If it is very obvious, consider renal dysfunction or other causes. A small number of patients may have mild or moderate hypercalcemia (glucocorticoids can promote calcium excretion by the kidney and intestines), and if there is hypocalcemia and hypophosphatemia, it suggests concurrent hypoparathyroidism. There are often normocytic, normochromic anemia, and a few patients may have pernicious anemia. White blood cell classification shows a decrease in neutrophils, a relative increase in lymphocytes, and a marked increase in eosinophils.

　　2. Blood sugar and glucose tolerance test

　　May have fasting hypoglycemia, and the oral glucose tolerance test shows a low flat curve.

　　3. Hormone Measurement

　　1. Plasma cortisol:It is generally considered that a plasma total cortisol baseline value ≤3μg/dl can be diagnosed as adrenal cortical insufficiency, and ≥20μ/dl can exclude this disease. However, for critically ill patients, if the baseline plasma total cortisol is within the normal range, adrenal cortical insufficiency cannot be excluded. Some scholars propose that only when the baseline plasma total cortisol ≥25μg/dl in sepsis and trauma patients can adrenal cortical insufficiency be excluded.

　　2. Plasma ACTH:In primary adrenal cortical insufficiency, the plasma ACTH is often elevated, and the plasma total cortisol is within the normal range. The plasma ACTH is often ≥100pg/ml. Normal plasma ACTH excludes chronic primary adrenal cortical insufficiency, but cannot exclude mild secondary adrenal cortical insufficiency because the current measurement method cannot distinguish between low levels and lower limits of normal blood ACTH levels.

　　3. Blood or urine aldosterone:In primary adrenal cortical insufficiency, the level of aldosterone in blood or urine may be low or at the lower limit of normal, while the activity or concentration of plasma renin activity (PRA) is increased; in secondary adrenal cortical insufficiency, the level of aldosterone in blood or urine is normal, and its level varies according to the location and extent of the lesion, such as when the glomerular zone of the adrenal gland is severely damaged, its content may be lower than normal, and when the fascicle zone is mainly damaged, its content may be normal or close to normal.

　　4. Urinary free cortisol:Generally lower than normal.

　　5. Urinary 17-OHCS and 17-KS:Generally, it is often lower than normal, and a few patients may be within the normal range. Partial Addison's disease should be considered, as well as partial pathological adrenal cortex that can still secrete close to normal or slightly more than normal steroid hormones under ACTH stimulation.

　　4. ACTH Stimulation Test

　　1. ACTH Stimulation Test:Primary adrenal cortical insufficiency is due to the endogenous ACTH having already maximally stimulated the adrenal secretion of cortisol, therefore exogenous ACTH cannot further stimulate cortisol secretion. The plasma total cortisol baseline value is often lower than normal or at the lower limit of normal, and the plasma total cortisol rarely rises or does not rise after stimulation; in patients with secondary adrenal cortical insufficiency, in the case of long-term and severe secondary adrenal cortical insufficiency, the plasma total cortisol rarely rises or does not rise, but in mild or early patients, such as asthmatic patients who inhale inhaled corticosteroids and patients with Cushing's syndrome after pituitary and adrenal tumor resection, even if there is already metyrapone (metyrapone) or insulin hypoglycemia stimulation test abnormalities at this time, but the ACTH stimulation test can be normal, because in normal people, 5-10μg ACTH can stimulate the adrenal cortex to approach the maximum secretion level, so the 250μg ACTH used in the test is far beyond this amount. Therefore, some scholars propose that a low-dose ACTH stimulation test can detect mild or early secondary adrenal cortical insufficiency (such as asthmatic patients treated with inhaled corticosteroids).

　　2. Low-dose rapid ACTH stimulation test:The baseline or post-stimulation plasma cortisol in normal individuals is ≥18μg/dl (496.8nmol/L); in individuals with secondary adrenal insufficiency, the plasma cortisol does not rise. It should be noted that when the baseline plasma cortisol value is 16μg/dl, further metyrapone or insulin hypoglycemia stimulation tests should be performed.

　　3. Continuous ACTH stimulation test:The ACTH intravenous injection method is used, i.e., 25μg of ACTH is added to 500ml of 5% glucose solution and infused intravenously for a total of 8 hours daily for 3 to 5 days; or ACTH is continuously infused intravenously for 48 hours, and the 24-hour urine free cortisol or 17-OHCS on the control day and stimulation day are measured. If the response of urine free cortisol or 17-OIHCS is low after continuous stimulation for 3 to 5 days, the following

　　4. ACTH diagnostic and therapeutic test:This test is used for severe cases with high suspicion of the disease, and dexamethasone (intravenous injection or infusion) and ACTH are administered. Before and after medication, plasma cortisol is measured, which has both therapeutic effects and can be used as a diagnostic tool.

　　5. Insulin hypoglycemia test:At 10 am, after intravenous injection of insulin 0.1/kg, blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 minutes, and ACTH and cortisol were simultaneously measured. The normal blood glucose should be below 40mg/dl, and the normal response is that the blood cortisol after stimulation is ≥20μg/dl (55mmol/L), while in secondary adrenal insufficiency, the blood ACTH and cortisol do not rise.

　　6. Simplified metyrapone (mephenytoin) test:At midnight, 30mg/kg of metyrapone (mephenytoin) was orally administered, and at 8 am the next morning, plasma 11-deoxycorticosterone, cortisol, and ACTH were measured. The plasma 11-deoxycorticosterone in normal individuals should be ≤8μg/dl to clarify whether the synthesis of adrenal cortical hormones is suppressed. The normal response is that the plasma 11-deoxycorticosterone rises ≥7μg/dl after stimulation, and ACTH is generally greater than 150pg/ml; while in secondary adrenal insufficiency, the plasma 11-deoxycorticosterone and ACTH do not rise.

　　7. oCRH1-41 stimulation test:After intravenous injection of 1U/kg or 100μg CRH1-41, blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 minutes, and ACTH and cortisol were simultaneously measured. The normal response is that the peak of ACTH and cortisol after stimulation is ≥100% of the original baseline value, while the secondary adrenal insufficiency shows insufficient rise of ACTH and cortisol after stimulation.

　　8. Measurement of adrenal autoantibodies:The most classic method to determine autoantibodies is to use slices of bovine or human adrenal glands for indirect immunofluorescence staining. There are reports that the sensitivity and specificity of measuring adrenal autoantibodies by simple binding analysis with radio-labeled recombinant human 21-hydroxylase are higher than those of the indirect immunofluorescence method.

　　Fifth, Electrocardiogram:It can show low voltage, flat or inverted T waves, and PR interval and QT time can be prolonged.

　　Sixth, Imaging examination:X-ray examination may show heart shrinkage (vertical), adrenal area radiography and CT examination may show adrenal enlargement and calcification shadows in patients with tuberculosis, other infections, hemorrhage, and metastatic lesions also show adrenal enlargement (adrenal enlargement, the general course is within 2 years), adrenal glands do not enlarge in patients with autoimmune etiology, for hypothalamic and pituitary占位病变，可做蝶鞍CT和MRI，B超或CT引导下肾上腺细针穿刺活检有助于肾上腺病因诊断。

　　In terms of diet, attention should be paid to the intake of sodium and potassium, and it is advisable to eat more foods rich in high-quality protein, maintain adequate intake of carbohydrates, and eat more calcium-rich foods.

　　When adrenal cortical insufficiency occurs, it is necessary to actively use hormone drugs for supplementation and treatment. After the condition is controlled and stabilized, the dose can be gradually reduced and the drug stopped, while avoiding abrupt increases and decreases.

　　I. Treatment

　　1. Psychiatric disorders associated with hyperadrenocorticism

　　(1) Radiotherapy, surgery, and chemotherapy can be performed.

　　(2) Treatment of psychiatric disorders: Symptomatic treatment can be used, such as antidepressants such as amitriptyline, amitriptyline, fluoxetine (Prozac), etc. Desoxyn (Diazepam), hydroxyzine (Atarax) can also be used.

　　2. Psychiatric disorders associated with adrenal cortical insufficiency

　　(1) Hormonal therapy: Adrenal cortical hormones can be used for substitute therapy. It is effective for both psychiatric disorders and somatic diseases. However, this condition is prone to cause hormonal psychiatric disorders after excessive use of hormones, so it is necessary to prevent excessive use. Do not cause hormonal psychiatric disorders.

　　(2) Treatment of psychiatric disorders: Antianxiety drugs or antidepressants can be used. Antipsychotic drugs should be used with caution, as they are prone to induce hypotensive collapse.

　　II. Prognosis

　　The prognosis depends on the outcome of the primary disease. If the primary disease improves or is controlled, the psychiatric symptoms can be relieved.