Adrenal insufficiency in children

Introduction to pediatric adrenal insufficiency Pediatric adrenal cortical insufficiency (pediatricadadrenocorticalinsufficiency) is caused by a number of congenital or acquired causes of adrenal cortex secretion of cortisol and / or aldosterone deficiency, resulting in a series of clinical manifestations. Due to the different etiology and pathology, the clinical manifestations vary greatly. The onset of the disease, the age of the onset, the duration of the disease, and the severity of the disease are all significantly different. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: dehydration, low blood sugar

Pediatric adrenal insufficiency etiology

(1) Causes of the disease

Defects or lesions on any part of the hypothalamic-pituitary-adrenal axis may cause adrenal insufficiency, such as

1 congenital pituitary hypoplasia or non-development.

2 primary adrenal gland hypoplasia or not developed.

3 Congenital defects in the synthesis of adrenocortical hormone.

4 familial glucocorticoid deficiency.

5 Addison disease: Adrenal insufficiency caused by adrenal destructive lesions such as tuberculosis, histoplasmosis, coccidioidomycosis, fungal disease, amyloidosis and metastatic cancer in children, called Addison (Addison) is sick.

6 adrenal white matter malnutrition.

7 adrenal hemorrhage: bleeding in the neonatal period due to dystocia or asphyxia.

8 Huafo syndrome.

9 Sudden withdrawal of corticosteroids or ACTH.

10 simple aldosterone synthesis is insufficient, is autosomal recessive inheritance.

11 pseudo-low aldosteronism, autosomal recessive inheritance.

(two) pathogenesis

Described in the following:

1. Pituitary and hypothalamic defects: congenital hypoplasia or aplasia of the pituitary is often accompanied by adrenal insufficiency and other hormone deficiency, congenital developmental disorders of the pituitary often combined with abnormalities of the skull and brain Such as noence of the brain (anencephaly) and complete forebrain malformation (holoprosencephaly), such patients often retain part of the pituitary function, pituitary hypoplasia may also be secondary to the lack of CRF in the hypothalamus, ACTH deficiency alone is rare Often, with the reduction of idiopathic pituitary function and the lack of growth hormone, indirect experiments can be used to prove that pituitary dysfunction is secondary to the lack of CRF in the hypothalamus (see pituitary pygmy), destructive lesions of the pituitary, craniopharynx Tumor is the most common cause of ACTH deficiency in children, and a small number of cases are suspected of insufficient secretion of ACTH caused by pituitary autoimmunity.

2. Primary adrenal hypoplasia or non-development: for the defects of organogenesis, the same patient or its siblings can be seen in other organs of non-development and hypoplasia, pituitary function and ACTH secretion are normal, adrenal cortex Defects affect the production of cortisol and aldosterone. Adrenal hypoplasia can be seen in histological destruction of tissue structure and cell changes. This disease may be related to genes, and its genetic pattern is reported by X-linked recessive inheritance and autosomal recessive inheritance. X-linked hereditary boys lack spontaneous puberty due to lack of gonadotropin. The mechanism is not certain. It may be that the fetus lacks adrenal androgen to activate hypothalamic-pituitary secretion of gonadotropin or primary congenital gonadotropin. Hormone deficiency is often accompanied by cryptorchidism, but the hCG stimulation test is normal, and the adrenal insufficiency X-linked genetics are located in Xp21, 2, which also has the Duchenne spinal muscular atrophy gene.

3. Congenital defects in adrenal cortical hormone synthesis: The most common adrenal insufficiency in infants is due to loss of congenital cortical hyperplasia, all children with lipid adrenal hyperplasia, most patients with 3-hydroxydehydrogenase deficiency and Half of the 21-hydroxylase-deficient infants showed loss of salt, and the synthesis of cortisol and aldosterone was reduced in these children.

4. Familial glucocorticoid deficiency: is a chronic adrenal insufficiency, characterized by insufficient glucocorticoids, elevated ACTH and normal aldosterone, so there is no symptoms of salt loss and primary hypoglycemic convulsions and skin pigmentation, feeding difficulties And growth stagnation, both sexes are onset, autosomal recessive inheritance, when ACTH stimulates the adrenal gland, cortisol secretion does not increase; when given a low-salt diet, aldosterone secretion increases, pathological changes are adrenal cortical bundles and reticular bands Atrophy, but still retains fewer globular bands, the cause may be the lack of ACTH receptors in the adrenal cortex cell membrane, or the defects in the enzyme system that activates ACTH, forming a congenital adrenal gland that does not respond to ACTH.

5. Addison disease: Adrenal insufficiency in older children is generally caused by destructive lesions of the adrenal gland. It is called Addison disease. Tuberculosis is the most common cause in the past. Adrenal insufficiency has been reduced, histoplasmosis, coccidioidomycosis, fungal disease, amyloidosis and metastatic cancer may be the cause of the disease, but rare in childhood, children occasionally adrenal gland "idiopathic atrophy" (idiopathic Atrophy), shrinking to the residual cortex can not be found at autopsy, lymphocytic infiltration in the medulla, about half of the patients can also see anti-adrenal antibodies in the blood, it is believed that this disease may be the formation of autoimmune adrenal inflammation Incomplete function.

Idiopathic Addison's disease has proven to be an autoimmune disease, along with other autoimmune diseases, mainly hypoparathyroidism, pernicious anemia, hypogonadism, alopecia areata, vitiligo, intestinal Absorption of dysfunction and chronic mucocutaneous candidiasis, etc., is autoimmune polyglandular syndrome type I, often accompanied by thyroid disease and insulin-dependent diabetes mellitus, HLA-DR3 and DR4 are autoimmune polyglandular syndrome Type II, the above diseases can occur before or after Edison's illness, idiopathic Edison disease can have autoimmune diseases in the same family siblings, Beijing Xuanwu Hospital has reported from 66 families to investigate, It is proved to be autosomal dominant inheritance, and there is no similar report at home and abroad.

6. Adrenal white matter malnutrition: Adrenal cortical atrophy and extensive brain nodule sclerosis are pathological features, a rare X-linked genetic disease, most patients start to appear symptoms from 3 to 12 years old, and only when they are adults At the beginning, the central nervous system symptoms are the main clinical manifestations, which may have behavior, personality changes, gait disturbances, difficulty in pronunciation, difficulty in swallowing, blindness, late convulsions, spastic quadriplegia and cortical-like body position, about 1 /3 children with symptoms and signs of adrenal insufficiency, often onset after 4 years of age, symptoms appear slowly, such as increased skin pigmentation can occur before or at the same time as nervous system symptoms, the disease develops slowly, Beijing Children's Hospital I have seen dozens of cases, and there is a mild adrenal leukoencephalopathy. The onset is often after 20 years of age. It is characterized by progressive leg stiffness, convulsions, ataxia and multiple neuropathy. Both types occur in men and are X-linked. Inheritance, the gene is close to the G6PD gene color blindness and hemophilia gene locus on the X chromosome. This disease is a defect of peroxidase in long-chain fatty acid oxidation such as 26-alkanoic acid (hex The oxidative defects of icosanicacid, cultured adrenal and cerebral cortex, amniotic fluid and chorionic mucosa biopsy have all found this acid increased, and women carrying genes can also be confirmed, can do prenatal diagnosis.

7. Adrenal hemorrhage: In the neonatal period, hemorrhage may occur due to dystocia or asphyxia. When hemorrhage is extensive, he may die due to decreased cortical function or blood loss. Some bleeding is asymptomatic at the beginning, and adrenal calcification occurs later. A small number of patients may have progressive fibrosis. Or cystic changes gradually produce a decrease in adrenal function, and the symptoms develop significantly in infants or children.

8. Huafo Syndrome: It is a shock caused by bacterial infection.

9. Sudden discontinuation of corticosteroids or ACTH Long-term use of high-dose ACTH or corticosteroids inhibits the physiological function of the adrenal gland or pituitary gland, causing adrenal insufficiency, and can not be recovered in a short period of time after stopping the drug. Symptoms often occur in In the state of agitation, such as infection, surgery, etc.

10. Insufficient synthesis of simple aldosterone: Very rare, due to two mixed functional oxidases: corticosteroid methyl oxidase type I and type II (CMO I or CMOII) defects, unable to synthesize aldosterone, increased production of deoxycorticosterone Cortisol synthesis is normal, aldosterone and its metabolites are significantly reduced, CMOII lacks 18-hydroxycorticosteroids, and salt-loss symptoms are only seen in small infants. Children grow behind, and salt-alteration symptoms improve with age. When salt-loss symptoms occur in infancy, A sufficient amount of salt and/or mineralocorticoid to the blood renin restores normal, CMOII deficiency, autosomal recessive inheritance, requiring a significant increase in the ratio of 18-hydroxycorticosteroids and aldosterone to diagnose.

11. Pseudohypoaldosteronism: Infants exhibit salt loss, doca and aldosterone can not correct sodium loss, salt may sustain life, blood and urinary renin-angiotensin activity and secondary aldosterone increase, presumably a far ball Renal tubules, salivary glands and colonic mucosa are not responsive to aldosterone and are autosomal recessive.

Pediatric adrenal insufficiency prevention

The etiology of adrenal insufficiency is more complicated and diverse. First, the occurrence of iatrogenic adrenal insufficiency should be prevented. Long-term use of exogenous corticosteroids can lead to atrophy and dysfunction of the adrenal cortex, and suddenly stop the drug after long-term use. When stress is encountered after stopping the drug (such as infection, vomiting, dehydration, cold stimulation, hunger, trauma, surgery, overwork, etc.), acute adrenal insufficiency occurs due to insufficient secretion of corticosteroids in the body, and even a crisis occurs. Waiting for the drug withdrawal reaction, the preventive measures are to gradually withdraw the drug reasonably, and if necessary, a certain amount of adrenocorticotropic hormone can be administered.

Adrenal cortical tuberculosis, histoplasmosis, coccidioidomycosis, fungal disease, amyloidosis and metastatic cancer, etc. Adrenal insufficiency, Huafo syndrome is caused by bacterial infection, adrenal insufficiency, should actively prevent infection The occurrence includes a variety of vaccination work.

In the neonatal period, due to dystocia or asphyxia may cause adrenal hemorrhage to the disease, should do perinatal medical work, reduce dystocia or suffocation, do a good job in the rescue of newborns.

Congenital pituitary hypoplasia or non-development, primary adrenal insufficiency or non-development, familial glucocorticoid deficiency, adrenal white matter malnutrition, etc., for X-linked inheritance and autosomal inheritance, genetic prevention should be done. By preculturing the fibroblast amniotic fluid and chorionic membranous biopsy of the adrenal gland and cerebral cortex, prenatal diagnosis can be performed to take corrective measures.

Pediatric adrenal insufficiency complications Complications dehydration and hypoglycemia

In acute children, dehydration, hypoglycemia, circulatory failure, etc. can occur, and if the diagnosis and treatment are not timely, they can die quickly. Chronic children can be thin, low blood pressure quickly expand into a large ecchymosis, blood pressure drops, pulse growth, difficulty breathing, skin blue and purple cold, insufficient salt intake and treatment is not timely can cause adrenal crisis, convulsions And coma; Huafu syndrome can occur when acute infection, especially meningococcal sepsis.

Pediatric adrenal insufficiency symptoms Common symptoms Diarrhea, loss of appetite, weight loss, infant feeding difficulties, abdominal pain, lethargy, pigmentation, skin bleeding, nausea, microcirculation

The age and performance of symptoms vary according to the disease. The clinical can be divided into salt loss manifestations in infants, chronic adrenal insufficiency, and acute adrenal crisis.

Acute adrenocortical insufficiency

Infants often occur when the adrenal gland is not developed, steroid hormone synthesis defects and pseudo-aldosteronism, salt loss symptoms can begin soon after birth, vomiting, nausea, feeding difficulties, weight loss, lethargy, dehydration, hypothermia, Symptoms such as hypoglycemia and circulatory failure can quickly die if the diagnosis and treatment are not timely.

2. Chronic adrenal insufficiency (Addi's disease)

Slow onset, early symptoms are gradually feeling tired and weak, long-term loss of appetite, nausea, vomiting, diarrhea, weight loss, hypotension, etc., abdominal pain symptoms similar to acute abdomen, more than salt and water, if the intake of salt is insufficient and treatment is not timely Can cause adrenal crisis, cyanosis, skin chills, weak and fast pulse, lower blood pressure, quick and laborious breathing, skin pigmentation often occurs in the face, palm prints and fingerprints, perineum, nipple, umbilicus and joints ( Some patients do not increase the number of ACTH without skin pigmentation), sometimes white spots appear on the skin, melanoma spots appear in the mucosa, under stress, the condition can suddenly deteriorate, and the adrenal crisis occurs in convulsions and coma.

Children's familial glucocorticoid deficiency begins without salt loss, but hyperpigmentation and hypoglycemia. Symptoms can occur shortly after birth, but most begin at age 5, and many children do not diagnose hypoglycemia due to seizures. Receive other treatments.

3. Adrenal crisis

Adrenal crisis occurs in acute infection, especially in meningococcal septicemia (also seen in pneumococcal, streptococci, etc.), and soon severe shock into coma, and acute purpura, starting to be skin bleeding, It will soon expand into a large ecchymosis, blood pressure drops, pulse growth, difficulty breathing, skin blue and purple, and blood sodium reduction can be concealed by blood concentration, clinically known as fulminant meningitis or Huafo syndrome, Adrenal hemorrhage is only a pathological diagnosis, and the main cause of circulatory failure is microcirculatory disorder caused by toxemia.

X-ray examination: X-ray abdominal plain film may find calcification in the adrenal gland, indicating that the lesion is adrenal hemorrhage, cystic lesion, tuberculosis, etc., chest seeing small and slender heart shadow, reflecting blood volume reduction.

Pediatric adrenal insufficiency examination

When there is salt loss performance:

1. Electrolyte: Blood sodium, chlorine concentration is reduced, blood potassium is increased, urinary sodium is excreted, chlorine is increased, potassium is reduced, blood urea nitrogen can be dehydrated, NPN is increased, plasma renin is increased, and general hypoglycemia is not obvious, prolonged Hypoglycemia can occur in fasting time.

2. Peripheral blood: Increased eosinophils.

3. Determination of corticosteroids in blood and urine: In general, blood or urinary cortisol levels are reduced or normal, which is an important diagnostic basis.

4. ACTH stimulation test: The secretion of corticosteroids can not be increased during the experiment, indicating that the lesion is in the adrenal gland, lack of reserve capacity; if there is a significant increase in corticosteroids after ACTH, the lesion is not in the adrenal gland but in the pituitary or hypothalamus, in order to test the pituitary ACTH The reserve function can also be tested with metyrapone, which does not reflect the reserve capacity of the pituitary gland if there is a primary lesion in the adrenal cortex.

5. ACTH concentration in the blood: elevated to primary cortisol deficiency, such as reduced cortical function secondary to the pituitary or hypothalamus, CRH test is helpful for the diagnosis of lesions.

6. Blood test and urinary aldosterone: When it is suspected that aldosterone is insufficiently secreted, blood and urine aldosterone should be measured, which is meaningful for the differential diagnosis of aldosterone alone and pseudo-low aldosteronism.

7. Electrocardiogram: It can be seen that there is a change in hyperkalemia, T-wave high-pitched, ST-segment decline, prolonged PR interval, arrhythmia and so on.

8. EEG: normal or low voltage, fast frequency wave reduction.

9. Others: Abdominal ultrasound or CT examinations are sometimes helpful for diagnosis.

Diagnosis and diagnosis of pediatric adrenal insufficiency

diagnosis

According to the medical history, clinical and laboratory results can confirm adrenal insufficiency, according to laboratory tests can further determine whether the lesion is in the adrenal gland or in the pituitary.

Differential diagnosis

Need to consider the disease associated with adrenal insufficiency, in the neonatal period, vomiting, diarrhea, dehydration and other salt loss performance, should be differentiated from pyloric obstruction, severe dyspepsia. Skin pigmentation must be differentiated from other skin pigmentation diseases such as neurofibromatosis. Neurofibromatosis is a benign peripheral neuropathy that belongs to the autosomal dominant botanical connective tissue that histologically originates from the intima of the peripheral nerve sheath.

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