Adrenal hyperplasia

Adrenal hyperplasia is a serious pathology, which is explained by the functional features of the paired gland - the production of special hormones (glucocorticoids, androgens, aldosterone, adrenaline and noradrenaline) that regulate the vital functions of the entire organism.

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Causes adrenal hyperplasia

The causes of adrenal hyperplasia depend on the type of disease. The occurrence of the congenital form of pathology, which is widespread in clinical practice, is preceded by severe functional disorders of the pregnant woman's body.

It should be noted that the causes of adrenal hyperplasia are closely related to stressful conditions, excessive mental stress and strong emotions that increase the secretion of cortisol (the main hormone of the glucocorticoid group).

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Pathogenesis

The phenomenon of hyperplasia is an active increase in cellular tissue. An organ undergoing such changes increases in volume, while maintaining its original shape. The adrenal glands include the cortex and medulla. Hyperplasia processes most often affect the adrenal cortex, and tumors are detected mainly in the medulla.

As a rule, the disease is congenital, inherited or formed as a result of negative external/internal factors. Some diseases are accompanied by the phenomenon of hyperplasia of both adrenal glands. For example, adrenal hyperplasia is diagnosed in 40% of cases of Cushing's pathology, which is detected in middle and old age. The nodular form of hyperplasia is characterized by the presence of one or more nodes, the size of which varies from a couple of millimeters to several centimeters.

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Symptoms adrenal hyperplasia

Adrenal hyperplasia occurs under conditions of metabolic disorders and with symptoms that depend on a deficiency or excess of the glucocorticoid hormone.

Non-classical forms of hyperplasia are characterized by the following signs:

• early hair growth in the pubic area and underarms;
• excessive and inappropriate growth for age;
• androgen excess;
• manifestation of terminal hair growth on the body ( hirsutism );
• early closure of growth zones;
• detection of amenorrhea (absence of menstruation);
• presence of acne;
• bald spots in the temple area;
• infertility.

Symptoms of adrenal hyperplasia are varied and depend on the type of pathology. The most common manifestations of the disease include:

• blood pressure surges;
• muscle atrophy, numbness;
• development of diabetes;
• weight gain, appearance of signs of a “moon-shaped” face;
• stretch marks;
• osteoporosis;
• mental changes (memory loss, psychosis, etc.);
• gastrointestinal tract disorders;
• a decrease in the body's resistance to viruses and bacteria.

Thirst and frequent urge to urinate at night are also alarming factors.

Nodular hyperplasia of the adrenal gland

About 40% of patients with Cushing's syndrome are subject to bilateral nodular hyperplasia of the adrenal glands. The nodules grow to several centimeters and can be single or multiple. The nodules are often characterized by a lobular structure, and the pathology is more often detected in old age.

Being a consequence of prolonged stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), nodular hyperplasia of the adrenal gland affects the formation of an autonomous type of adenoma. The pathology of the nodular type belongs to the hereditary autosomal dominant type of transmission. A clear clinical picture of the formation of nodular hyperplasia has not been established, however, doctors are inclined to the autoimmune theory of pathogenesis. The severity of the symptoms of the disease increases gradually in accordance with the maturation of the patient. In its development, the disease combines signs of an extra-adrenal nature - congenital spotted pigmentation of the skin (Carney syndrome), manifestations of mucous neurofibromatosis and atrial myxoma. Among other signs of pathology, the following are noted:

• symptoms of arterial hypertension (headache, dizziness, black spots before the eyes);
• dysfunctions of conduction and excitation of neurons of muscle structures (convulsive state, weakness, etc.);
• kidney dysfunction (nocturia, polyuria).

Nodular adrenal hyperplasia is differentiated by stigmas of dysembryogenesis or minor developmental anomalies. These criteria are crucial for establishing the correct diagnosis and represent a difficulty in identifying the pathology, since sometimes doctors do not focus on them as much as they should.

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Diffuse adrenal hyperplasia

Adrenal hyperplasia is divided into diffuse, in which the shape of the gland is preserved, and local with the formation of one or more nodules.

It is quite difficult to diagnose diffuse adrenal hyperplasia using ultrasound; magnetic resonance imaging and computed tomography are considered the main methods for recognizing the pathology. Diffuse hyperplasia may be characterized by the preservation of the gland shape with a simultaneous increase in volume. The results of the studies reveal hypoechoic triangular structures surrounded by fatty tissue. Mixed types of hyperplasia are often diagnosed, namely: diffuse-nodular forms. The clinical course may be washed out or have pronounced symptoms with constant weakness, panic attacks, high blood pressure, excessive hair growth, obesity.

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Nodular adrenal hyperplasia

Bilateral nodular adrenal hyperplasia (aka nodular) is more often detected in children and adolescents. The pathology is associated with the phenomenon of hypercorticism and Itsenko-Cushing syndrome. The causes of increased cortisol production are rooted in dysfunction of the adrenal glands themselves or are caused by an overdose of glucocorticoids.

Clinical picture:

• obesity - uneven type, fatty tissue is deposited mainly in the neck, abdomen, chest, face (hence the “moon-shaped” oval of the face, “climacteric” hump);
• muscle atrophy - clearly visible in the legs and shoulders;
• dry, thinned skin, with marbled and vascular patterns, purple or violet stretch marks, areas of hyperpigmentation;
• development of osteoporosis - thoracic and lumbar spine, compression fractures in combination with severe pain syndrome;
• the occurrence of heart failure and heart rhythm disturbances;
• changes in the nervous system - a depressive state along with lethargy or, on the contrary, complete euphoria;
• presence of diabetes mellitus;
• Excessive hair growth in women according to the male pattern and the development of amenorrhea.

Nodular adrenal hyperplasia has a favorable prognosis with early diagnosis and treatment.

Micronodular hyperplasia of the adrenal gland

Local or nodular forms of hyperplasia are divided into micro- and macronodular pathologies. Micronodular hyperplasia of the adrenal gland develops against the background of the active action of adrenocorticotropic hormone on the cells of the gland with the subsequent development of adenoma. The adrenal gland produces an increased amount of cortisol, and the pathology itself is classified as a hormone-dependent form of Cushing's disease.

Hyperplasia of the medial adrenal stalk

As practice shows, information about the adrenal glands is based on morphological (postmortem) parameters. Based on the data of a medical study, in which about 500 bodies of healthy people during life (from 20 to 60 years) were studied, it is possible to judge the state of the adrenal glands. The work presents data on the shape and size of the glands thanks to axial and frontal sections (cut thickness 5-7 mm), allowing to obtain the height of the medial pedicle of the adrenal glands, as well as the length of the lateral pedicle.

Based on the results of the morphological study of the adrenal glands, it was concluded that adrenal glands with deviations from the norm without small-nodular or diffuse hyperplasia are classified as adenopathy. In turn, adenopathy is understood as a condition of the adrenal gland in which, over time and under the influence of a number of factors, hyperplasia will form or the initial stage of the disease will be stopped (for example, as a result of treatment) and the gland will return to normal functioning. It should be noted that deviations in the size of the adrenal glands, which include hyperplasia of the medial peduncle of the adrenal gland, were detected in 300 people.

Adrenal cortex hyperplasia

Adrenogenital syndrome refers to congenital hyperplasia of the adrenal cortex caused by dysfunction of the enzymes responsible for steroid biosynthesis. These enzymes regulate the hormones of the adrenal glands and sex glands, so simultaneous disorder of hormonal secretion of the genital area is possible.

Congenital adrenal cortex hyperplasia is associated with various gene mutations that lead to disruption of cortisol synthesis. The disease develops against the background of decreased cortisol levels, increased ACTH levels in the blood, and the appearance of bilateral hyperplasia.

The pathology is recognized by the following distinctive features:

• predominance of male traits against the background of hormonal imbalance;
• excessive pigmentation of the external genital area;
• early hair growth in the pubic area and under the arms;
• acne;
• late onset of first menstruation.

It is necessary to differentiate hyperplasia and tumor of the adrenal glands. For this purpose, hormonal diagnostics are carried out - laboratory tests of urine and blood to determine the level of hormones.

Adrenal hyperplasia in adults

Adrenal hyperplasia is often congenital and is detected in small children, which allows for the earliest possible start of hormonal therapy. Misidentification of sex at birth, as well as the lack of timely treatment, often leads to various psychological difficulties experienced by patients due to the development of secondary sexual characteristics.

Treatment of adult women may be necessary for feminization, and men to eliminate sterility when the testicles are atrophic and spermatogenesis is absent. Prescribing cortisone to older women helps eliminate the external signs of hyperplasia: the body contours change as a result of the redistribution of fat tissue, facial features become feminine, acne disappears, and breast growth is noted.

Adrenal hyperplasia in adult female patients requires constant maintenance doses of medications. With constant monitoring of the condition, cases of ovulation, pregnancy and birth of healthy children are described. The beginning of therapy for virilizing symptoms at the age of 30, the ovulatory cycle may not be established, uterine bleeding not associated with the cycle is often detected. In this case, estrogens and progesterone are prescribed.

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Forms

Adrenal hyperplasia is divided into:

• hypertensive;
• virile;
• salt-losing.

The virile subtype is associated with the secretory activity of androgens, which results in an increase in the external genitalia, as well as excessive and early hair growth, acne, and rapid muscle development. The hypertensive form manifests itself with increased action of androgens and mineralocorticoids, which negatively affects the vessels of the fundus, kidneys, and causes hypertension syndrome. Salt-wasting hyperplasia is caused by increased production of androgens against the background of the absence of other hormones of the adrenal cortex. This type of pathology provokes hypoglycemia and hyperkalemia, threatening dehydration, weight loss, and vomiting.

Left adrenal hyperplasia

The left adrenal gland has a crescent shape, its upper anterior surface is limited by the peritoneum. Hyperplasia of the gland tissue refers to functionally active tumors (usually benign) and causes endocrine disorders.

Modern medicine has discovered the mechanism of pathology formation at the cellular and molecular level. Facts are given that hyperplasia of the left adrenal gland and hormone production are interconnected with changes in the conditions of intercellular interaction (the presence of defects in areas of genes and chromosomes, the presence of a hybrid gene or chromosomal marker). The disease can be either hormone-dependent or independent.

An indication for surgical removal is the detection of growths over 3 cm. Retroperitoneal resection is performed by laparoscopy, which allows minimizing the postoperative period. Smaller neoplasms are observed to assess the tendency of the hyperplasia focus to spread. In addition to laparoscopic intervention, it is possible to use the lumbotomy approach according to Fedorov on the left.

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Diffuse hyperplasia of the left adrenal gland

Diffuse hyperplasia of the left adrenal gland is diagnosed in most cases of arterial hypertension. The condition is often accompanied by headaches, myocardial dysfunction, and fundus pathologies. Cardiac symptoms are explained by sodium retention, hypervolemia, vasoconstriction and increased resistance at the periphery, activation of vascular receptors to pressor effects.

The patient's condition also includes muscle weakness, the presence of convulsions, and dystrophic changes in muscle and nerve structures. "Kidney syndrome" is often detected, manifested by an alkaline urine reaction, nocturia, and intense thirst.

Diffuse hyperplasia of the left adrenal gland is differentiated using computed tomography or magnetic resonance imaging. These examination methods make it possible to detect changes in the gland with a reliability of 70 to 98%. The purpose of selective phlebography is to determine the functional activity of the adrenal gland by obtaining data on the amount of cortisol and aldosterone in the blood.

Diffuse and diffuse-nodular hyperplasia of the cortex is associated with a significant increase in adrenal activity. Conservative therapy in this case gives weak results, so unilateral adrenalectomy is recommended. The simultaneous presence of diffuse hyperplasia and aldosteronoma has the most unfavorable outcome even in the case of surgical intervention.

Nodular hyperplasia of the left adrenal gland

The phenomenon of primary hyperaldosteronism is directly related to high blood pressure, which is an important clinical sign of excess aldosterone in the adrenal cortex. Variants of the disease: diffuse or diffuse-nodular hyperplasia of the left adrenal gland/right adrenal gland (can be bilateral) in the presence/absence of a secondary adenoma. Symptoms include cardiovascular (pressure surges, hearing loss, etc.), muscular (weakness, atrophy), renal (nocturia, polyuria, etc.) and nervous dysfunctions (e.g., panic attacks).

As a result of CT or MRI, a rounded, hypoechoic formation is determined, which is easily mistaken for an adenoma. According to the results of the tests, an increase in the production of cortisol, aldosterone and renin in the blood is confirmed. Studies of daily urine reveal elevated values of 17-KS and 17-OKS. Externally, increased hair growth, excess weight, and stretch marks on the body are observed.

Nodular hyperplasia of the left adrenal gland can be treated with surgical methods followed by maintenance of a stable condition with hormone-containing medications.

Nodular hyperplasia of the left adrenal gland

The concepts of "Itsenko-Cushing's familial pathology", "familial Cushing's syndrome with primary adrenocortical adenomatosis", "primary adrenocortical nodular hyperplasia disease", "ACTH-inactive Cushing's disease", etc. are widely used in clinical practice. This set of terminology refers to nodular hyperplasia of the left adrenal gland or the right adrenal gland. In most cases, the pathology is hereditary in nature and is transmitted in an autosomal dominant manner. The development of nodular hyperplasia is supported by the autoimmune theory. A feature of the disease is the functional isolation of the adrenal cortex, which is detected in the blood by testing the level of cortisol and ACTH or by the presence of 17-OCS in the urine.

Nodular hyperplasia of the left adrenal gland, described in a number of studies, is determined by the signs of Cushingoid syndrome of manifest or developed clinical picture. Most often, the disease develops latent with a gradual increase in symptoms, depending on the patient's age. Nodular hyperplasia is characterized by manifestations of extra-adrenal origin, including pigment spots on the skin, the formation of tumor processes of various localizations and neurological symptoms.

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Hyperplasia of the right adrenal gland

The right adrenal gland resembles a triangle in shape, with the peritoneum adjacent to its lower part. Hyperplasia of the gland is a fairly common disease, often detected at an advanced stage or after the patient's death. The difficulty in differentiating the pathology, if the disease is not hereditary, is due to the asymptomatic course of the pathology. It is possible to detect a tumor at the beginning of development thanks to ultrasound, MRI or CT. The manifestations of clinical symptoms of Itsenko-Cushing's disease are often supported by echoscopy data with the definition of an echo-positive neoplasm on top of the right kidney. To finally confirm the diagnosis of hyperplasia of the right adrenal gland, laboratory tests of blood and urine are carried out.

Hyperplasia is diffuse or focal. The latter form is subdivided into macro- and micronodular, which, when examined using ultrasound, are indistinguishable from tumor processes of the gland. The symptoms of the disease vary for each specific case, including arterial hypertension, diabetes mellitus, muscle weakness, changes in the functioning of the renal apparatus, etc. The clinical picture is characterized by both a vague and crisis nature. Based on the severity of the hyperplasia, the patient's age and individual characteristics, a treatment strategy is developed, often including surgical intervention.

Nodular hyperplasia of the right adrenal gland

In Cushing's syndrome, nodular hyperplasia of the right or left adrenal gland is observed in almost 50% of clinical practice. This disease is diagnosed in patients of middle and old age. The disease is accompanied by the formation of several or one node, the size of which varies from a couple of millimeters to impressive sizes in centimeters. The structure of the nodes is lobar, and in the space between the nodes themselves there is a focus of hyperplasia.

The disease is differentiated by external signs - obesity, thinning of the skin, muscle weakness, osteoporosis, steroid diabetes, decreased chlorine and potassium in the blood, red striae on the thighs, abdomen and chest. The pathology can develop latently without pronounced clinical symptoms, which significantly complicates the task of the diagnostician. In order to classify the pathology, laboratory blood and urine tests, CT and MRI studies, histological tests are used.

Treatment of right adrenal hyperplasia is based on diagnostic data and the type of disease. In most cases, surgical resection is indicated, which allows normalizing blood pressure and returning the patient to a full life.

Congenital adrenal hyperplasia

Congenital hyperplasia is classified by classical and non-classical course. Classic manifestations of the disease include:

• lipoid form of pathology - a fairly rare disease associated with a deficiency of the enzyme 20.22 desmolase and a deficiency of steroid hormones. In case of survival, the child develops severe adrenal insufficiency and inhibition of sexual development;
• congenital adrenal hyperplasia due to a deficiency of 3β-hydroxysteroid dehydrogenase with severe salt loss. In girls, due to the active production of male sex hormones during the period of intrauterine development, external genitalia formed in accordance with the male type are sometimes detected. Boys may develop according to the female phenotype or have failures of sexual differentiation;
• diffuse subtype of hyperplasia (lack of 17α-hydroxylase) – diagnosed very rarely. The pathology is characterized by clinical manifestations of deficiency of glucocorticoids and hormones of the reproductive system. Children suffer from low blood pressure and hypokalemia associated with the lack of a sufficient number of potassium ions. For girls, this disease is characterized by delayed puberty, and for boys - signs of pseudohermaphroditism;
• Diffuse type hyperplasia with 21-hydroxylase deficiency refers to simple virilizing forms.

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Diagnostics adrenal hyperplasia

Diagnostic measures include clinical examination, laboratory tests (providing a clinical, hormonal and biochemical picture), instrumental and pathomorphological examination. Research methods for determining functional indicators of the adrenal glands include obtaining information on the concentration of hormones and their metabolites in urine and blood, as well as conducting certain functional testing.

Laboratory diagnostics of adrenal hyperplasia includes two methods – enzyme immunoassay (EIA) and radioimmunoassay (RIA). The first method detects the amount of hormones in the blood serum, and the second method detects the presence of free cortisol in the urine and cortisol in the blood. RIA, by studying blood plasma, allows determining the amount of aldosterone and the presence of renin. Indicators of 11-hydroxycorticosteroid inclusions provide information on the glucocorticoid function of the adrenal glands. It is possible to assess the functioning of the androgenic and partially glucocorticoid component by the excretion of free dehydroepiandrosterone in the urine. As for functional tests, dexamethasone tests are used, which help differentiate hyperplasia or tumor processes of the adrenal glands from conditions similar in clinical signs.

Adrenal hyperplasia is examined by X-ray methods: tomography, aorto- and angiography. The most modern diagnostic methods include: ultrasound, computed tomography, magnetic resonance imaging, radionuclide scanning, which provide an idea of the size and shape of the adrenal gland. In some situations, it may be necessary to perform aspiration puncture, performed with a thin needle under ultrasound and computed tomography control together with cytological examination.

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Differential diagnosis

Adrenal hyperplasia is differentiated immediately after birth or in the first years of life, more often the pathology is detected in female infants. An important role is given to early diagnosis of the disease, since an advanced process has the most unfavorable effect on all body systems - digestive, nervous, vascular, etc.

Treatment adrenal hyperplasia

Treatment tactics mostly come down to building a regimen for taking hormonal drugs. It is not possible to prove the advantage of a certain program for introducing substances or their combinations. Glucocorticoids are mainly prescribed - hydrocortisone, dexamethasone, prednisolone, cortisone acetate and various combinations of drugs. Moreover, treatment of adrenal hyperplasia is possible with two or three equal doses of hormonal drugs per day, as well as a general dosage in the morning or afternoon. For children with salt deficiency syndrome, mineralocorticoids and a simultaneous increase in daily salt intake to 1-3 g are recommended. In order to stimulate the formation of secondary sexual characteristics, adolescent girls are prescribed estrogens, and boys - androgens.

Severe adrenal hyperplasia requires surgical intervention. Operations are indicated when external genitalia of an intermediate type are detected. Correction of sexual characteristics in accordance with the genetic sex is preferably carried out in the first year of life of a small patient, provided that the child's condition is stable.

Treatment of nodular hyperplasia of the adrenal gland

The main treatment for nodular adrenal hyperplasia is surgical removal of the affected adrenal gland. Surgeries that preserve the altered adrenal gland (resection, enucleation, etc.) are considered ineffective due to frequent relapses.

Among modern minimally invasive surgical methods, laparoscopic adrenalectomy stands out. Endoscopic technique is safe and practical. Extraperitoneal adrenalectomy deserves special attention, on the one hand, it requires more skill from the surgeon, and on the other hand, it is better tolerated by patients. After such a surgical intervention, discharge from the hospital is possible in a few days and in a few weeks the patient returns to a full life. Among the advantages of laparoscopy is the absence of a scar surface, weakening of the muscular corset of the lumbar region.

Removal of the adrenal gland increases the load on the remaining healthy organ, which makes it necessary to introduce hormone replacement therapy for the entire period of life. The appropriate treatment is prescribed, adjusted if necessary and constantly monitored by an endocrinologist. After adrenalectomy, physical and mental impact should be minimized, and alcohol and sleeping pills should be forgotten.

Treatment of congenital adrenal hyperplasia

Congenital adrenal hyperplasia of the virilizing type is treatable with cortisol, cortisone or similar substances of synthetic origin. Therapy is carried out with constant monitoring of the daily content of 17-ketosteroids in accordance with the age norm.

Congenital adrenal hyperplasia is often treated with intramuscular cortisone injections. The initial dosage is adjusted to suppress the adrenocorticotropic function of the pituitary gland:

• children under 2 years old – 25 mg/day;
• for older children and adults – 50-100 mg/day.

The duration of therapy varies from 5 to 10 days, after which the amount of cortisone administered is reduced to a supporting function. It is possible that the dosage remains the same, but the frequency of injections changes (once every 3-4 days).

Oral use of cortisone is divided into daily doses to be taken 3-4 times. To achieve the desired effect, two or even four times more tablet substance is required compared to the liquid solution for injection.

Cortisone is indicated for babies, while prednisolone is successfully used orally for older children and adult patients. The initial daily dose, which reduces the production of 17-ketosteroids to acceptable levels, is 20 mg. After about a week, the amount of the drug is reduced to 7-12 mg/day.

The most active glucocorticoid drugs, such as dexamethasone and triamcinolone, not only have no advantages over traditional therapy, but also have pronounced side effects - psychosis, hypertrichosis, manifestations of hypercorticism, etc.

Prevention

A family history of adrenal hyperplasia of any kind is a predisposing factor for contacting a geneticist. A number of congenital forms of adrenal cortex pathology are detected by prenatal diagnostics. A medical opinion is established during the first three months of gestation based on the results of a chorionic biopsy. In the second half of pregnancy, the diagnosis is confirmed by examining the amniotic fluid for hormone levels, for example, for 17-hydroxyprogesterone levels.

Prevention of adrenal hyperplasia involves regular examinations, including screening testing of newborns, which allows, based on a study of capillary blood taken from the baby’s heel, to establish the congenital form of hyperplasia.

So, in most cases, preventive measures concern only future parents, who should:

• take a conscious approach to pregnancy planning;
• undergo a thorough examination for possible infectious diseases;
• eliminate threatening factors – the effects of toxic substances and radiation;
• visit a geneticist if adrenal hyperplasia has been diagnosed in the family before.

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Forecast

Hyperplastic changes are most often observed in both adrenal glands. An increase in the gland's volume leads to an increase in hormone levels.

Adrenal hyperplasia provokes some diseases:

• Itsenko-Cushing's pathology - visually diagnosed by obesity with an increase in the upper body and swelling of the face ("moon-shaped"), while the muscle structures and dermis atrophy. The syndrome is characterized by hyperpigmentation, acne and heavy hair growth. In addition to the fact that there are problems with the healing of injured skin, there are disturbances in the musculoskeletal system, jumps in blood pressure are observed, disorders of the sexual and nervous spheres are revealed;
• Conn's disease - does not manifest itself externally, is associated with the removal of potassium from the body and the accumulation of sodium. As a result, fluid accumulates, which increases the risk of stroke, causes decreased sensitivity, leads to cramps and numbness of the limbs.

Hyperplasia in men is treated with medications until the end of puberty, hormonal therapy for female patients is carried out throughout life. Women with adrenal hyperplasia are recommended to undergo regular examination, mandatory pregnancy planning and monitoring of labor.

In adulthood, the prognosis for adrenal hyperplasia is favorable in the case of radical surgical treatment. In some cases, constant medical monitoring and regular hormonal therapy are sufficient to stabilize the patient's condition and improve the quality of life.

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