The adrenal gland is an important endocrine organ in the body and traditionally belongs to the urological disorders because of its location in close relationship with the kidneys. The human adrenal glands, one on the left and one on the right, are located behind the peritoneum, while their lower lateral side is in close proximity to the upper medial side of both kidneys. The shape of the adrenal glands: the right adrenal gland is triangular and the left adrenal gland is semilunar, with the former riding across the medial aspect of the upper pole of the right kidney and the latter dangling over the medial aspect of the upper pole of the left kidney, with a length, width and thickness of 4.0 cm to 6.0 cm, 2.0 cm to 3.0 cm and 0.3 cm to 0.6 cm, respectively. The normal adrenal gland weighs about 4.0 to 5.0 grams.
Although the adrenal gland itself is small in size, the size of the tumors that grow in it varies greatly. Those less than 3 cm in diameter are usually referred to as small tumors, the smallest being less than 1 cm, and the larger ones can be more than 10 to 30 cm.
Physiological functions of the adrenal gland
A great deal of interest and energy has been devoted to research in this area. Research on the biochemical and pharmacological aspects of the gland has made rapid progress. We know that not only adrenaline, but also norepinephrine and dopamine can be obtained from the adrenal medulla, and their side effects are less than those of adrenaline, and their effect of raising blood pressure and saving lives is often better. More importantly, in terms of adrenal cortex function, through nearly half a century of research, we know that there are more than 40 kinds of corticosteroids (chemically called steroid hormones or steroids) produced and secreted from the adrenal cortex, and if we add some available intermediate products or derivatives. There can be more than 70 species. Corticosteroids can be roughly divided into three categories, which are briefly described as follows.
1. Hormones regulating sugar and protein metabolism – corticosteroids are represented by cortisol, which is commonly used clinically as cortisone. These hormones promote amino acid deamidation into glycogen, that is, promote glycogen xenobiotic effect, maintain the concentration of blood sugar. Lack of this hormone makes hypoglycemia easy to occur. When there are too many of these hormones, gluconeogenesis is enhanced, which can destroy proteins or prevent their synthesis, resulting in excessive increase in subcutaneous fat, elevated blood glucose, thinning of skin with purple lines, muscle weakness and osteoporosis. In addition, glucocorticoids have an effect on the metabolism of various substances, which together with insulin, growth hormone and adrenomedullary hormone regulate the metabolism of substances and energy supply of the body, so that the physiological activities in the body are coordinated and balanced with each other.
2. Hormones regulating salt and water metabolism – salt corticosteroids are represented by aldosterone and clinically applied by deoxycorticosterone acetate. This hormone makes the renal aqueduct absorb sodium and chloride while excreting potassium and phosphorus. If there is a lack of this hormone, the concentration of sodium in plasma decreases, thus water is lost and blood is concentrated, while blood potassium increases. If there is too much of this hormone, the situation is reversed, i.e. sodium increases and potassium decreases. Salt corticosteroids can also have some effect on the metabolism of sugar and protein, but the effect is less severe. The production and secretion of salt corticosteroids are mainly regulated by the renin-angiotensin system in the physiological state, followed by the influence of blood potassium and adrenocorticotropic hormone.
3, sex hormones adrenal cortex also secrete weak androgens such as gliadin, androstenedione and trace testosterone, which do not play an important role in the married life of adults. However, it can contribute to the appearance of the earliest secondary sexual characteristics such as axillary and pubic hair, and the maturation of the hypothalamic-pituitary-gonadal axis in adolescents of both sexes, thus enabling healthy pubertal development. The adrenal cortex also secretes trace amounts of estrogens, which are generally of no practical significance, but in patients with adrenal tumors, their increased levels can cause impotence and infertility in male patients and menstrual disorders in female patients.
The secretion of these corticosteroids in human body is regulated by the hypothalamus|pituitary-adrenal axis and the role of neurohumoral feedback system. For example, the content of cortisol is highest in the morning at 8-9 o’clock and lowest at midnight around 24 o’clock. This can maintain the human metabolism, growth and development, physiological activities in a normal and orderly manner; and when it comes to unexpected emergencies, that is, when the human body can be a sudden strong stimulus or blow to the spirit, such as encountering some huge difficulties must be overcome immediately, trapped in a heavy siege breakthrough, tenacious athletics want to knock down the opponent, obstructed labor, major surgery, hemorrhage must be a desperate survival, etc., afterwards, even they are often I don’t know: how can I be wise in that critical moment, how can I have that extraordinary perseverance, how can I have that great life not to die. In fact, this is also thanks to the secretion of adrenocorticotropic hormone also has a stressful set of characteristics. Experiments show that when major surgery, hemorrhage, cortisol levels can rise several times or even more than ten times, while through the negative feedback regulatory mechanism, promote the release of pituitary pro-adrenocorticotropic hormone, enhance the body’s stress capacity and extraordinary ability.
Once a tumor occurs in one part of the adrenal gland, the hormones in the corresponding part will be overproduced, which is called functional adrenal tumor, causing a series of clinical symptoms related to the overproduction of hormones.
Common functional adrenal tumors
Cortisolism
A series of pathophysiological changes and clinical manifestations caused by the increase of cortisol in human body is cortisolism, or cortisolism, formerly known as Cushing’s syndrome.
1.Cause
(1) Due to the presence of adrenal tumors (adenoma or carcinoma), there is excessive secretion of cortisol autonomously; it accounts for about 25% of cases.
(2) Due to the presence of pituitary adenoma or hypothalamic or even central nervous regulation disorder, the pituitary gland secretes too much pro-adrenocorticotropic hormone, causing bilateral adrenal cortex hyperplasia and excessive secretion of corticosteroids.
(3) Increased autocrine secretion of ACTH (in the form of ectopic ACTH syndrome) during the pathogenesis of organ tumors other than the endocrine system (such as small cell lung cancer), carcinoid tumors (lung, gastrointestinal), thymoma, pancreatic tumor, medullary thyroid-like carcinoma, ganglion tumors, melanoma and prostate cancer.
(4) Increased medical-derived corticosteroids. Similar symptoms appear due to long-term heavy glucocorticoid treatment and gradually disappear after stopping the drug.
2.Symptoms
From 1980 to the end of 1998, a total of 48 cases were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences, 30 female cases and 18 male cases, aged 12-74 years old. Patients are mostly obese in body but not fat in limbs. This is the so-called “centripetal obesity”. The head was bald, the face was round, the so-called “full-moon face” was deep red and dark with sores, the back of the neck and both shoulders were fatty, such as “buffalo back”, the skin was thin, hairy, and there were purple lines in the axillae, both sides of the lower abdomen, and the femur, and the patients had high blood pressure, complained of general weakness and lumbar and leg pain. Female patients show typical symptoms such as silence, amenorrhea or menstrual disorders, and osteoporosis.
3.Diagnosis
It is generally not difficult, as long as one has common sense in this area, raises alertness to the disease, and remembers some of the above-mentioned symptoms and signs can be known at a glance, because many of her (his) symptoms are on the surface. Based on this clue, we can draw blood and urine for endocrine hormone test, and use B-ultrasound, CT and MBI for tumor localization, then we can make a clear diagnosis. Since such cases are rare, even the general medical personnel rarely see them, misdiagnosis is inevitable. In addition to routine blood and urine examination items, patients with cortisolism must have plasma cortisol, 24-hour urinary free cortisol, 24-hour urinary 17-hydroxycorticosteroid, and 24-hour urinary toxic 17-ketosteroid measured. Cortisolism is diagnosed if plasma cortisol at 8:00 am exceeds 138 micromol/ or is higher than 10 μg/dl. On the night before blood sampling
Dexamethasone 1mg is given orally at 11:00 to suppress hypothalamic-pituitary-adrenal function. In addition, blood ACTH values can be measured, which are suppressed below normal values in patients with adrenal tumors. The normal value is 20 to 100 μg/dl. Increased blood ACTH values in patients with other causes of cortisolism are not suppressed.
In addition, the size and nature of the adrenal tumor and its relationship to surrounding structures must be examined by ultrasound, CT or MRI, and the presence or absence of pituitary adenoma or microadenoma must be diagnosed by X-ray frontal and lateral views of the pterygoid saddle area of the skull, tomography and 3D pterygoid saddle area, tomography and 3D pterygoid saddle views, as well as CT scan and magnetic resonance imaging.
4.Treatment
The main treatment is to address the cause of the disease. Patients with adrenal tumors should strive to remove the tumor as much as possible, especially for benign tumors, the efficacy of which is certain. For malignant tumors, the removal of the tumor should be followed by other adjuvant treatments to improve the quality of survival and prolong the survival period after relieving the symptoms. For those whose general condition is too poor for surgical treatment or extensive metastasis, palliative treatment such as radiation, chemotherapy and immunotherapy will be given. For those diagnosed with pituitary tumors, the results are good after transsphenoidal saddle pituitary tumor resection. In cases of ectopic ACTH syndrome, ACTH can gradually subside after resection of the primary tumor. Those who cannot be controlled can be controlled with adrenal enzyme inhibitors such as albuterol, aminoglutethimide, or drugs that act directly on the hypothalamus and pituitary gland such as cephaeline and bromocriptine.
Aldosteronism
Aldosteronism can be divided into two types: primary and secondary. Primary aldosteronism is a rare disease caused by excessive secretion of aldosterone from adrenal cortical adenomas, hyperplasia and other lesions. Secondary aldosteronism is caused by aldosterone overproduction from various extra-adrenal diseases, including nephrotic syndrome with varying degrees of edema, cirrhosis with ascites, heart failure, and hypertension in the acute form. Primary aldosteronism is described in this article.
Primary aldosteronism is a syndrome in which renin secretion is suppressed due to increased secretion of aldosterone in the body, and is characterized clinically by hypertension and hypokalemia. 1954, Kong first reported a case in which an aldosterone-secreting adrenocortical adenoma was removed and cured, thus naming the disease Conn’s syndrome. The majority of adrenal glands that cause this disease are small benign adenomas located in the outermost layer of the adrenal gland. Adrenal carcinoma is rare, accounting for about 1% of cases of hyporeninogenic aldosteronism. Even less than 50 cases have been reported internationally. It is currently estimated internationally that primary aldosteronism accounts for 0.65%-2% of hypertension.
1.Symptoms
(1) Hypertension is mainly due to increased plasma volume and increased vascular resistance caused by increased sodium ions, and is the most dominant or earliest symptom of the disease. Blood pressure increases to moderate or slightly severe levels. In children, a malignant form of hypertension may occur, with a maximum pressure of 34.5/20.5 kPa. There is also normotensive prodromalgia, the mechanism of which is unknown. Due to hypertension and high blood sodium often cause dizziness, headache, fatigue, blurred vision, irritability, thirst and other symptoms.
(2) Hypokalemia hypokalemia causes muscle weakness and muscle paralysis, causing the patient to feel light-headed and weak in the limbs, more pronounced in the lower limbs, and in severe cases presenting periodic paralysis. Hypokalemia leads to cardiac arrhythmias, cerebral hypoxia syndrome, and polyuria and nocturia due to renal dysfunction. When the pancreas is affected, fasting blood glucose is increased.
(3) Water and electrolyte balance imbalance causes alkalosis, which eventually leads to loss of calcium and magnesium ions, and the right presents numbness of extremities, painful limbs must spasm, etc.
2.Diagnosis
(1) In children or table juvenile hypertensive patients, the possibility of this disease should be considered and the corresponding examination.
(2) In adult hypertensive patients who take antihypertensive drugs with no obvious effect, accompanied by hypokalemia or periodic lower extremity limb paralysis, this disease should be considered for further examination.
(3) Laboratory tests
① Measure plasma potassium and sodium concentrations and 24-hour urinary potassium excretion. If hypokalemia is spontaneous or easily induced, or if hypokalemia coexists, this disease should be highly suspected.
②Measure plasma or 24-hour urinary aldosterone concentration and plasma renin activity. Plasma renin activity in the standing position is less than 2.46 molL/h, and the ratio of plasma aldosterone concentration to plasma renin activity in the standing position is >20.
(iii) Negative aldosterone suppression test. Aldosterone secretion in proaldosteronism is autonomic. This excludes primary hypertension and secondary aldosteronism.
④Glucocorticoid secretion and excretion are most normal.
⑤ Oral sodium chloride suppression test: plasma aldosterone level above 554 pmll/L, urinary aldosterone value above 38.8 nmol/24h, and urinary sodium excretion above 200 μmol/24,can confirm the diagnosis of proaldosteronism.
Laboratory test results, such as hypertensive patients with normal glucocorticoid secretion, increased secretion of aldosterone can not be suppressed by high sodium diet, accompanied by spontaneous hypokalemia and increased urinary potassium excretion, can confirm the diagnosis of proaldosteronism.
(4) Diagnosis by imaging
In addition to adrenal adenoma and adenocarcinoma, adrenal cortical hyperplasia also accounts for a large proportion of cases of proaldosteronism. The former is mainly treated by surgery, while the latter must be treated by medication. The two methods are different, and differential diagnosis must be made by ultrasound, CT and MRI. Since the adenoma causing prodromalgia may be very small, CT scan with a dense layer of 0.5cm spacing can avoid missing the tumor. When difficulties are encountered in differentiation, adrenal isotope iodinated cholesterol scintigraphy with dexamethasone suppression test can be applied, i.e. the patient is scanned after the injection of 131I-6β iodomethyl-19 desmethyl cholesterol, the cortical adenoma absorbs more amount of radiomarkers than normal, the cortical hyperplasia uptake is normal, and the cortical cancer is not shown. Its accuracy rate can reach 70%~90%.
3.Treatment
Adrenal tumor is mainly treated by surgery. For smaller adenomas, enucleation is generally used, together with the normal tissues around the tumor at a distance of 0.5cm, because the adrenal tissues close to the tumor have polyploid abnormalities, which can cause tumor recurrence. In adenoma cases, the blood potassium and aldosterone values return to normal after surgery and the symptoms disappear; in adenocarcinoma cases, the prognosis is considered poor in the literature. Pharmacological treatment: The particulate form of spirolactone, Atixotone 120mg 3 times daily and Amclopramide 5mg 3 times daily can be used alone or in combination to normalize the blood potassium and blood pressure. Or use antihypertensive drugs such as cardiac painkillers in combination with antiseptic.
Adrenal Sexual Abnormalities
Abnormalities of the external genitalia and sexual characteristics caused by some congenital or acquired diseases of the kidneys are called adrenal gonadal syndrome or adrenal reproductive syndrome.
1. Classification
This syndrome is also rare, with about a hundred cases reported in China. It can be named according to the age of onset, gender, cause and type of abnormal sex characteristics.
2.Etiology
The cause of the disease is hyperplasia, which occurs mainly in the cortical network-related areas. The human adrenal glands produce and secrete mainly sex hormones and very little estrogen. In the process of normal development of adrenal cortex, there must be normal action of enzymes in order to complete smoothly. Lack of supply of enzymes or obstruction of their action affects the synthesis of corticosteroids, prompting the adrenal cortex to proliferate, thus increasing the action of androgens, which is equivalent to adding fuel to the fire, and a large amount of androgenic corticosteroids make female patients transform into men. If the cause is tumor, it is due to the secretion and accumulation of more sex hormone components in the body.
3.Symptoms
Abnormal adrenal sex characteristics are mainly manifested in the transformation of female patients into males. The so-called sex transformation is only a change in the appearance of the genitalia, but the real sex remains unchanged, because the gonads and sex chromosomes that determine the sex remain unchanged. Therefore, the so-called “female pseudohermaphroditism” that occurs during fetal life indicates that it is different from true hermaphroditism, in which both gonads are present in the ovaries and testes, and such cases are rare. Female pseudohermaphroditism can be seen at birth with the clitoris and labia majora shaped like the external genitalia of a male infant with congenital hypospadias. The authors have seen a case of an untreated girl with the same appearance as a boy, with dark skin, hairy and reticent, with a clitoris like a penis, erect, and labia majora like a scrotum. Its urethra is the opening of the urogenital sinus. The abnormal sexual characteristics of male infants in the fetal period are mainly manifested by larger external genitalia, and later they grow rapidly, and children aged 4 to 5 years have physical and external genitalia right as into from size. The onset of normal prepubertal period at birth, its cause is mostly caused by adrenal tumors. The main symptoms are: disappearance of subcutaneous fat, masculinization of body physique, enlarged clitoris, low voice, shrinking of breast and uterus, cessation of menstruation, loss of libido, etc.
4.Diagnosis
(1) Firstly, the type of abnormal sexual characteristics and local conditions should be checked by physical examination for reference of deformity correction surgery.
(2) Diagnose by imaging, and if necessary, perform adrenal scan by dexamethasone suppression test to identify whether it is hyperplasia, adenoma or cancer.
(3) In case of hyperplasia and Cushing’s syndrome, the 24-hour urine levels of 17 ketones, 17 hydroxyl, 21 hydroxylase, 11 hydroxylase, etc. should be checked in detail.
(4) Find out the real gender of the patient, pay attention to differentiate from male severe hypospadias combined with cryptorchidism, male pseudohermaphroditism, true hermaphroditism, mixed gonadal dysplasia, etc. If necessary, do chromosome examination, or dissection.
5.Treatment
Tumor patients should have their tumors removed, and the larger ones should be removed together with the surrounding tendons and, if necessary, the kidneys. The basic principle of treatment for patients with hyperplasia is to replenish the lack of cortisol, inhibit the overproduction of pituitary ACTH to stop the hyperplasia and hypertrophy of adrenal cortex, and reduce the overproduction of androgens to relieve or alleviate the masculinization disease.
Adrenal medullary tumors
Pheochromocytoma
The adrenal medulla is in the middle part of the adrenal gland and accounts for only about 10% of the adrenal gland. The morphology of the medullary cells varies, and they are called chromophobe cells because the granules in these cells are found to be colorable when the medullary cells are treated with a chromium-containing fluid.
Pheochromocytomas are mostly benign, accounting for about 90% of cases. Therefore, its shape is either smaller than a loquat or as large as a cantaloupe. Generally, it is the size of a mandarin, flat and round with a slight fan shape, and the cut surface is dark yellow or brown. The tumor cells are irregularly polygonal, either small or large, with multinucleated cytoskeletons and contain most chromophobic staining particles, especially dark and dark in those suspected to be malignant.
Adrenal medulla. Both sympathetic nerve endings and the central nervous system synthesize dopamine, norepinephrine and epinephrine from chromogenic acid in the blood, which are collectively known as catecholamines. In both the sympathetic nervous system and the central nervous system, catecholamines are synthesized by nerve cells and then passed to nerve terminals for release. Dopamine in the adrenal medulla is an intermediate product that must be converted to norepinephrine and further to epinephrine by the action of dopamine beta-enhancerase, both of which can be released directly into the circulation. When chromophobe tumors occur, there is a large amount of epinephrine and norepinephrine stored in the tumor. However, once the tumor releases a considerable amount of catecholamines in response to a certain stimulus, the patient will suddenly experience a sudden increase in blood pressure and heart rhythm disorder, and experience an explosive or even fatal blow.
Symptoms
The disease is predominant in young adults between 20 and 40 years of age, with the ratio of men to women being almost equal. The main symptoms are hypertension and changes in basal metabolism: hypertension may be paroxysmal or persistent, or persistent hypertension may increase paroxysmally. Persistent cases usually have dizziness, headache, chest tightness, chest pain, heartbeat panic, blurred vision, mental tension, anxiety, fear of heat, etc. In paroxysmal cases, there is a sudden severe headache, palpitation, chest tightness, pale face, sweating, shortness of breath, and the patient has a feeling of near death. At this time, if the blood pressure is measured up to 40.OkPa (200-300LHg), about half an hour or so after the possible self-remission. After recovery, a normal person. Later on, when encountering some kind of stimulus, the attack will occur again. Gradually, the number of seizures becomes more frequent, the interval is shortened, and the situation becomes heavier. The stimulus of seizure may not be very strong. There are cases when the seizure wakes up during gargling and brushing teeth or in dream, sweating profusely and having a sense of near death. There are also patients with huge tumors and high blood pressure who never have seizure symptoms, or those who die during surgery for other diseases without a mass or seizure. Therefore, patients with such symptoms should be examined and treated early.
Diagnosis
According to the literature, the presence of pheochromocytoma should be suspected in two out of five cases, including typical seizure symptoms, abdominal mass, hypertension, diabetes mellitus, and increased basal metabolism, while three out of five cases should be highly suspected and four out of five cases should be diagnosed. If the tumor is small and located outside the adrenal gland, it must be examined qualitatively. If the tumor is small and located outside the adrenal gland, the examination must be carried out from two aspects: qualitative and localization. Qualitatively, urinary norepinephrine and epinephrine, urinary 3-methoxy-4-hydroxymandelic acid (VMA) values should be measured. Their normal values are 8 to 165 micrograms/24 hours. Plasma-bound catecholamines are measured by drawing blood in the resting position to determine the value of plasma catecholamines if they are significantly elevated, and the diagnosis can be confirmed in combination with clinical findings. If the dopamine value is elevated, the tumor is usually malignant. Its accuracy is better than that of free blood catecholamine values. Localization: Generally, ultrasound, CT, MRI can be used to confirm the diagnosis of adrenal tumor, hyperplasia, hemorrhage, medullary lipoma, etc. If there is a lack of such equipment, retroperitoneal gas injection imaging can still be used to locate small pheochromocytomas outside the adrenal glands. (131IMIBG) tracer scan with gamma photography is more effective.
Treatment
Surgical resection of pheochromocytomas is recommended because they are mostly benign tumors and most have good postoperative results. However, surgery and anesthesia are more dangerous, especially for large tumors, which are rich in blood vessels and close to the surrounding large blood vessels, and the tumors contain a large amount of catecholamines, which are easily released into the blood by extrusion, causing a sharp rise in blood pressure and cardiac arrest. However, it still requires adequate preoperative preparation and postoperative care, and gentle operation during surgery to ensure the smooth and successful completion of surgery.
Adrenal malignant tumor
Adrenocortical carcinoma is rare, usually functional, and is usually larger than adenoma when found, often weighing more than 100g. It grows infiltratively, destroying or flooding normal adrenal tissue and invading outward to the surrounding adipose tissue or even the kidney on that side. Smaller adenocarcinomas may have an envelope. The cut surface is brownish-yellow in color, and hemorrhage, necrosis and cystic changes are common. Microscopically, poorly differentiated adenocarcinoma is highly heterogeneous, and the tumor cells are of different sizes, with odd-shaped nuclei and multinuclei. Metastasis to abdominal aortic lymph nodes or hematogenous metastasis to lung and liver is common. If the cancer is small and has envelope, it is difficult to distinguish it from adenoma. Some people think that if the diameter is more than 3 cm, it should be considered as highly differentiated adenocarcinoma.
Treatment of disease
Currently, laparoscopic surgery has become the most common way to remove adrenal tumors. The advantages of laparoscopy are obvious: firstly, it is minimally invasive, i.e. only a few small holes of 1 cm in diameter are needed to remove the tumor and the postoperative recovery is fast, while the incision in traditional open surgery is more than 10 cm, which makes the patient’s postoperative recovery slow and affects the aesthetics. The use of advanced cutting and separating instruments makes the surgical dissection quite fine and bleeding minimal.