The incidence of pituitary tumors is not low, but most people have no obvious clinical symptoms.
Pituitary tumors are tumors that occur in the pituitary gland, often also known as pituitary adenomas, and are one of the common neuroendocrine tumors, accounting for approximately 10-15% of central nervous system tumors. The vast majority of pituitary adenomas are benign tumors.
With the increasing level of pituitary tumor detection, the incidence of pituitary tumors has been increasing year by year in recent years. There is a lack of epidemiological survey data on pituitary tumors in China. According to the American epidemiological survey, the incidence of pituitary adenoma is 7.5-15/100,000. The incidence of pituitary adenoma during autopsy of normal deceased patients varies, ranging from 9% to 65%. In a foreign study, a random sample of 100 normal individuals underwent MRI of the saddle area, and the detection rate of pituitary adenoma was 16%, indicating that the detection rate of pituitary adenoma is very high, but most patients do not show clinical symptoms.
Pituitary tumors usually occur during young adulthood and often affect the patient’s growth, reproductive function, learning and working ability. The clinical manifestations of pituitary tumors vary widely, and the departments where patients are first seen can be relatively fragmented. In some primary and specialized hospitals, due to the lack of centers for comprehensive pituitary tumor treatment, patients are often transferred to multiple departments and are not properly diagnosed and treated for a long time, thus delaying their illness and causing unnecessary mental and physical stress to patients.
Classification of pituitary tumors
Pituitary tumors can be classified according to the size of the tumor and the different functions of hormone secretion. Depending on the size of the tumor, pituitary tumors are classified as pituitary microadenomas (tumors less than 1 cm in diameter) and pituitary adenomas (tumors greater than or equal to 1 cm in diameter). According to the different secretion of hormones, they can be further classified into hormone-secreting pituitary tumors and non-functional adenomas.
The size of pituitary tumor is closely related to the prognosis of treatment. Approximately 70% or more of non-functioning pituitary tumors do not require treatment and can be clinically followed for a long time if there is no corresponding hypopituitarism. If the corresponding clinical symptoms appear during the follow-up, the tumor grows faster and compresses the surrounding tissues (e.g., visual field defects), surgery may be considered.
Four types of hormone-secreting pituitary tumors
Hormone-secreting tumors are the most complex type of pituitary tumors among pituitary tumors in terms of clinical manifestations, diverse treatment options, and different clinical prognostic regression.
Depending on the type of hormone secretion, hormone-secreting pituitary tumors can be divided into the following categories.
1) Prolactin-secreting pituitary tumors. Most female patients mainly present with amenorrhea, lactation, and infertility. Male patients mainly present with male hypogonadism, such as decreased libido, impotence and infertility.
2) Growth hormone-secreting pituitary tumors. The main manifestations are gigantism (occurring in adolescent patients with unclosed epiphyses), facial changes, enlarged hands and feet (increased shoe size), excessive sweating, bone and joint lesions, carpal tunnel syndrome, swelling of the soft tissues and joints of the fingers (toes) of the hands and feet, increased blood pressure, increased blood sugar, coronary heart disease, and tumors of the thyroid gland and colon.
(3) Adrenocorticotropic hormone (ACTH)-secreting pituitary tumors. The main manifestations are centripetal obesity, full-moon face, acne, hirsutism, and purple lines (purple-red skin lines on the body).
(4) Thyrotropic hormone (TSH)-secreting pituitary tumor. The main symptoms of hypermetabolism are feverishness, excessive sweating, weight loss, and atrial fibrillation.
(5) There are also FSH and LH pituitary tumors, which mainly manifest clinically as menstrual disorders and infertility in women and hypogonadism and infertility in men. Hormone-secreting tumors can occur alone or be mixed tumors with increased secretion of two or more hormones, and the clinical manifestations also have corresponding mixed symptoms.
There are four main types of clinical symptoms of pituitary tumors
1) Clinical manifestations caused by increased secretion of hormones.
(2) Clinical manifestations of decreased secretion of corresponding hormones caused by pituitary tumors compressing surrounding cells and tissues: for example, hypoadrenocorticism may manifest as decreased appetite, weakness, emaciation, hypotension, hypoglycemia, and easy to catch cold, etc.; hypothyroidism may manifest as fear of cold, decreased appetite, rough skin, hair loss, constipation, etc.; in children, it may manifest as dementia, growth retardation, etc.; hypogonadism may manifest as Hypogonadism can be manifested as infertility in men and women, decreased libido, menstrual disorders or even amenorrhea in women, impotence in men, etc. In children, it can be manifested as short stature, and in adults, it can be manifested as concentration of body fat in the abdomen, muscle relaxation and atrophy, aging, decreased self-awareness, osteoporosis, decreased resistance, and low sexual function.
(3) Symptoms of compression of peripheral structures: if the tumor grows upward to the saddle and presses the visual cross, it will manifest as vision loss and visual field defects, etc. Clinically, patients usually complain of frequent bruises, etc. If the tumor invades the cavernous sinus of the neurovascular plexus around the pituitary gland, it will show symptoms of nerve compression such as ptosis and pupil enlargement.
(4) Pituitary stroke: due to poor vascular supply or abnormal growth of tumor blood vessels during the growth process, tumor bleeding and necrosis of tumor tissue will occur under certain inducements. If the tumor is completely bleeding and necrosis, the tumor envelope will rupture, there will be severe headache, nausea and vomiting or even blindness and coma, which needs emergency surgical treatment. Most strokes of pituitary tumors present as incomplete or partial pituitary strokes, which can be mild headache, nausea and vomiting with general discomfort, requiring no special treatment. Patients’ symptoms will resolve on their own within a few weeks, and clinical symptoms of certain hormone-secreting tumors are reduced.
Diagnosis of pituitary tumor
The diagnosis of pituitary tumor is based on the corresponding clinical symptoms, physical signs, pituitary hormone tests and imaging examinations.
Pituitary hormones can be detected in many laboratories and even in primary hospitals. However, in the process of clinical diagnosis and treatment, they often rely too much on laboratory tests and ignore the special requirements of the secretion rhythm of pituitary hormones on the time of blood collection, which makes the hormone measurement results of many patients impossible to judge.
Among the hormones secreted by the pituitary gland, GH, ACTH and PRL have obvious circadian rhythms and are all stress hormones. The clinical time for GH and ACTH should be 8AM (fasting), and the blood should be taken at rest for more than half an hour in a quiet state before taking blood. The measurement of blood PRL should be taken between 10AM and 2PM, and the measured PRL results should be valley values, so that the measured values can reflect the patient’s serum PRL levels under non-stressful conditions.
Imaging is a very important tool in the diagnosis of pituitary tumors. Among them, magnetic resonance imaging (MRI) of the saddle area has the highest detection rate of pituitary tumors. MRI of the saddle area with thin layers (one layer every 1 mm) of enhanced images, combined with dynamic contrast MRI, can also reveal pituitary microadenomas as small as 2-3 mm in diameter. Enhanced CT imaging of the saddle area is good for some of the pituitary macroadenomas, and can provide insight into the degree of destruction of the saddle base bone and the degree of pneumatization of the pterygoid sinus.
The diagnosis of pituitary tumor is not difficult to determine by detailed clinical interview, physical examination, pituitary hormone measurement and imaging.
A multidisciplinary pituitary tumor treatment center is significantly more effective than a single specialty
Regarding the treatment of pituitary tumors, the treatment plan is determined by the size of the tumor, whether or not it secretes hormones, and the patient’s complications. The treatment of pituitary tumors is a comprehensive treatment process with multi-disciplinary collaboration. The departments involved in pituitary tumor treatment are mainly endocrinology, neurosurgery, radiotherapy, ophthalmology, and diagnostic imaging. From retrospective clinical data in China and abroad, it can be seen that a multidisciplinary collaborative pituitary tumor treatment center has a much different effect on improving the treatment of pituitary tumor patients than a purely specialized treatment center. Therefore, it is recommended that patients with pituitary tumors should be seen at medical centers with comprehensive treatment for pituitary tumors.
The three main treatments for pituitary tumors include surgery, medications and radiation therapy. Because no single method can achieve a complete cure for every pituitary tumor, each treatment method has its own advantages and disadvantages, and an individualized treatment plan should be developed based on the patient’s pituitary tumor size, hormone secretion, complications and co-morbidities, the patient’s age, whether the patient has fertility requirements, and the patient’s financial situation.
Surgical treatment of pituitary tumors is the traditional treatment method. Since the widespread use of the transoral pterygoid sinus approach for pituitary tumors 20 years ago, there has been a significant decrease in the number of postoperative injury and infection cases in patients with pituitary tumors, and the cure rate has increased significantly. In recent years, the application of advanced neurosurgical navigation techniques has led to a significant increase in the rate of neurosurgical resection of pituitary tumors. However, for invasive pituitary tumors, especially hormone-secreting pituitary tumors, the recurrence rate after surgery can however be as high as 50% or more, so it needs to be supplemented with drug and radiation therapy.
Regarding radiotherapy, because pituitary tumors are adenomas and are inherently less sensitive to radiotherapy, nearly 70-80% of patients experience hypopituitarism after radiotherapy, which reduces the quality of life of patients, so radiotherapy is only indicated for patients with surgical residuals, those who cannot tolerate surgery, those who are insensitive to drugs, and those with co-morbidities that cannot be treated with surgery or drugs.
Drug treatment strategies and outcomes for pituitary tumors
The pharmacological treatment of hormone-secreting pituitary tumors has made great strides in recent years as the level of drug development has continued to improve.
In the case of pituitary prolactin-secreting tumors, the current view is that more than 90% of patients (both microadenomas and macroadenomas) can be treated with dopamine agonists (short-acting agents bromocriptine, long-acting agents cabergoline) to control PRL levels and reduce tumor size. Surgery is an option only for patients with prolactinomas who are allergic or drug intolerant to this class of drugs, who have acute symptoms due to tumor compression requiring emergency surgical decompression, or for patients who do not wish to undergo surgical treatment. During treatment with bromocriptine, the dose of bromocriptine should be gradually increased until the serum PRL level drops to normal level and then the dose is adjusted for long-term maintenance treatment. For patients with fertility requirements, bromocriptine should be discontinued after pregnancy. The vision should be reviewed regularly during pregnancy until bromocriptine treatment is resumed after delivery. For patients who experience miscarriage or stillbirth when bromocriptine is discontinued after pregnancy, the drug should be maintained until the dose of bromocriptine is adjusted after delivery. It has been clinically proven that no significant malformations or mental retardation have been observed in children born to pregnant women while taking bromocriptine.
For growth hormone-secreting pituitary tumors, the major advance in the last 20 years has been the use of growth inhibitory analogs. The clinical application of this drug has led to a significant increase in the cure rate of GH-secreting tumors. The use of long-acting preparations of growth inhibitor analogs such as long-acting octreotide and somatuline in recent years has led to a significant increase in patient compliance. Preoperative application of these drugs can rapidly reduce the patient’s serum GH level, alleviate the patient’s symptoms, reduce the size of the tumor, and create good preoperative conditions for the complete removal of the tumor. Additional indications for the use of growth hormone analogs in GH-secreting tumors include: postoperative residual patients, and transitional treatment of patients whose GH has not been reduced to normal after radiotherapy. The application of growth hormone analogs provides the opportunity to prepare treatment before surgery for those patients who are unable to tolerate anesthesia due to concomitant heart failure, respiratory sleep apnea, poorly controlled hyperglycemia, and hypertension. In foreign countries, many patients who do not want to undergo surgical treatment have also achieved satisfactory therapeutic results with long-term application of growth inhibitor therapy for tumor control because they do not have to worry about medical costs. Growth inhibitor analogs for thyrotropin-secreting tumors have also achieved satisfactory therapeutic results. After application of drug therapy for GH-secreting pituitary tumors, it is now accepted that reduction of GH levels to less than 1ng/dl (GH value after glucose administration) and insulin-like growth factor (IGF-1) to the level of age-matched normal individuals in patients with GH-secreting tumors is the goal of biochemical cure. Patients with growth hormone-secreting tumors, regardless of the treatment they receive, should achieve several therapeutic goals: elimination of the tumor, reduction of tumor recurrence, GH attainment, relief of clinical symptoms, preservation of pituitary function as much as possible, improvement of the patient’s quality of life, and extension of the patient’s survival.
All pituitary tumor patients should be followed for life
All patients treated for pituitary tumors should be followed up for life. Anterior pituitary function should be reviewed regularly (every 3-6 months) before and after surgery, and MRI of the saddle area should be reviewed when necessary to monitor tumor recurrence and growth.
The level of anterior pituitary hormone secretion varies with age, so one year after surgery, pituitary hormone measurement should be done annually according to the patient’s specific condition to replace the already low reduced pituitary hormone according to the situation. Especially in patients with hypoadrenocorticism, the dose of prednisone (usually 2.5-7.5 mg/d for replacement therapy) should be increased to 3-5 times the replacement therapy dose in stressful situations (fever, exertion, illness, etc.) to prevent pituitary crisis. The replacement dose of other hormones is usually 50-150ug/day of thyroid hormone (L-T4), and it is safer to start replacement therapy with normal adrenocortical function. As for sex hormone replacement therapy, it is not advocated in patients with prolactinoma because the tumor is sex hormone-dependent, while controlling prolactin levels medically. In patients with other causes of hypopituitarism, when supplementing male hormones, the level of prostate antigen (PSA) in the blood should be monitored so that it is safer to maintain it at a low level. Growth hormone deficiency following surgery or radiation therapy for pituitary tumors can manifest as growth retardation in children, and GH deficiency in adults can cause corresponding clinical symptoms (see Clinical Manifestations of Pituitary Tumors). Pediatric patients can be treated with GH growth-promoting therapy when it is confirmed that the tumor has not recurred. In adult GH deficient patients, GH replacement therapy is also possible if they are financially available and do not have a pre-existing tumor or a clear family history of other tumors. There has been clinical experience with GH replacement therapy for adults for more than 10 years abroad, while China is only beginning to make a start in the treatment of GH deficiency in adults. As the price of GH preparations decreases, more patients with adult GH deficiency will benefit from it.
In summary, pituitary tumors are a group of benign neuroendocrine neoplastic diseases that can be effectively controlled by various methods of treatment such as surgery, drugs and radiotherapy. In view of the specificity of their growth sites, while diagnosing and treating the patients, the different characteristics of the nature of pituitary tumors should be addressed in close cooperation with multiple departments (endocrinology, neurosurgery, radiotherapy, ophthalmology, radiology and imaging) In addition, we should develop a personalized treatment plan according to the different needs of patients. Finally, the patient’s tumor is removed, the recurrence of the tumor is avoided during the lifelong follow-up, the pituitary function is preserved as much as possible, the elevated secretory hormone is reduced to the normal range, the reduced pituitary hormone is replaced to the age-matched normal range, the patient’s quality of life is improved, and the patient’s life expectancy is prolonged.