Pituitary tumors, also commonly referred to as pituitary adenomas, are one of the common neuroendocrine tumors, accounting for approximately 10 – 15% of central nervous system 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 of 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%. A group of foreign studies showed that the detection rate of pituitary adenoma was 16% in a random sample of 100 normal people who underwent MRI of the saddle area.
Classification of pituitary tumors
Pituitary tumors can be classified according to the size of the tumor and the function 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). The size of pituitary tumor is closely related to the prognosis of treatment. According to the secretion of hormones, it can be further divided into hormone-secreting pituitary tumors and non-functional adenomas. According to different types of hormone secretion, they can be divided into the following categories: prolactin pituitary tumors; growth hormone pituitary tumors; adrenocorticotropic hormone pituitary tumors; thyrotropic hormone pituitary tumors and gonadotropin pituitary tumors. Hormone-secreting tumors can occur alone or as a mixture of two or more hormones with increased secretion.
Clinical manifestations of pituitary tumors
The clinical manifestations of pituitary tumors vary widely, usually occurring in young adulthood and often affecting the patient’s growth and development, reproductive function, and ability to learn and work. The most common departments are endocrinology, neurosurgery, gynecology, ophthalmology, dermatology, orthopedics, male medicine, and dermatology. 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.
The common symptoms of pituitary tumor are mainly the following four kinds.
1. Clinical manifestations caused by increased hormone secretion.
Most female patients with prolactin-type pituitary tumors mainly show amenorrhea, lactation and infertility. Male patients mainly show hypogonadism in men. The main manifestations of growth hormone-secreting pituitary tumors include gigantism, facial changes, enlarged hands and feet, excessive sweating, osteoarthrosis, carpal tunnel syndrome, swelling of soft tissues and joints of hands and feet, increased blood pressure, increased blood sugar, coronary heart disease, and tumors of the thyroid and colon. The main manifestations of thyrotropic hormone pituitary tumors are hyperthermia, hyperhidrosis, weight loss and atrial fibrillation, etc. The main manifestations of sex hormone pituitary tumors are menstrual disorders and infertility in women and hypogonadism and infertility in men. Hormone-secreting tumor can occur alone, or it can be a mixed tumor with increased secretion of two or more hormones, and the clinical performance also has corresponding mixed symptoms.
2. Clinical manifestations caused by tumor expanding outside the saddle and pressing adjacent tissue structures.
These symptoms are the most common and are often the main reason for patients to seek medical treatment. Headache. It is seen in about 1/3 – 2/3 of patients. Initially, the headache is not very strong, mainly distending pain, and may be intermittently aggravated; the headache site is mostly in the bilateral temporal region, frontal region, behind the heel ball or nasal root. The main reason for headache is that the saddle septum and surrounding dura mater are strained by the upward growth of tumor. This is due to the different growth direction of the tumor and/or the variation of the anatomical relationship between the optic cross and the adenopituitary gland.
3.The performance of anterior pituitary hypofunction.
Patients with pituitary tumors generally have milder manifestations of reduced pituitary hormone secretion and progress more slowly until 3/4 of the gland is destroyed, then clinically significant symptoms of anterior pituitary hypoplasia appear. However, sometimes reduced pituitary hormone secretion can also become a prominent manifestation of the disease, especially in childhood, manifesting as short stature and sexual underdevelopment. The tumor can also affect the hypothalamus and the posterior pituitary gland. Impaired synthesis and excretion of vasopressin can cause uremia. Hypogonadism is seen in approximately 3/4 of patients with pituitary tumors presenting with anterior hypopituitarism. Due to pituitary adrenocortical hormone deficiency, acute hyperalgesia can occur in times of stress called adrenal crisis.
4. Pituitary stroke.
Pituitary tumors are prone to intratumoral hemorrhage called pituitary stroke, the incidence of which is 5% – lO%. The onset of pituitary stroke is rapid, manifesting as severe pain in the frontal area or one side of the retro-orbital area, which may radiate to the face, and rapid visual loss of varying degrees, and in severe cases, double vision within a few hours, often accompanied by extraocular muscle paralysis, especially the articulatory nerve is most commonly involved, and may also involve the talocrural nerve and facial nerve. Some patients show acute pituitary failure. Pituitary tumors with hormone-secreting function also have clinical manifestations of hyperproduction of one or more pituitary hormones.
Diagnosis of pituitary adenoma
The diagnosis and staging of pituitary adenoma is the basis for choosing the correct treatment plan: clinical manifestations, imaging and endocrinological examination are three important methods for the correct diagnosis of pituitary adenoma, one of which is indispensable. It is important to understand in detail the changes in the patient’s symptoms and signs and to determine whether they are related to pituitary lesions. Since most pituitary tumors have the function of hormone secretion, sometimes when the clinical manifestations are not obvious and imaging is not yet suggestive of a tumor, the patient’s relevant hormone levels have already changed, and some pituitary tumor cases can be diagnosed by endocrine testing alone. Among the hormones secreted by the pituitary gland, growth hormone, adrenocorticotropic hormone and prolactin have obvious circadian rhythms and are all stress hormones. For example, the clinical time of blood collection for growth hormone and adrenocorticotropic hormone should be 8AM (fasting), and the blood should be taken in a quiet state for more than half an hour before collection. For prolactin, blood should be taken between 10AM and 2PM. If necessary, hormone stimulation or suppression tests should be performed.
Imaging test methods include cranial X-ray plain film, CT scan, and MRI. Among them, MRI is the most important tool to diagnose pituitary tumor, which can clearly show the size, shape, location, and the relationship of the rest of the surrounding structures. Even tumors of 2 – 3 mm in diameter can be shown. However, there are also some tumors with signals close to the surrounding normal pituitary tissues, and it is difficult to distinguish between the two. Through detailed clinical questioning, physical examination, measurement of pituitary hormones and imaging tests. The diagnosis of pituitary tumor is not difficult to determine.
Pituitary tumor treatment
The main treatment methods for pituitary tumors are surgery, medication, and radiotherapy. No single method can achieve a complete cure. An individualized treatment plan should be developed based on the size of the pituitary tumor, hormone secretion, complications and co-morbidities, the patient’s age, whether he or she has fertility requirements, and the patient’s financial situation. Treatment of pituitary tumors is a multidisciplinary collaborative and comprehensive treatment process. A multidisciplinary pituitary tumor treatment center has a much different effect on improving the treatment of pituitary tumor patients than a purely specialized treatment center, so it is recommended that pituitary tumor patients should be seen at a medical center with comprehensive treatment for pituitary tumors.
The current treatment for pituitary tumors is still mainly surgery, supplemented by medication and stereotactic radiation therapy. The location of pituitary tumor is in the saddle area, surrounded by the optic nerve, internal carotid artery, hypothalamus and other important nerve structures, so surgery still has certain risks. Currently, the main surgical methods are transsphenoidal pituitary tumor resection through single nostril and open pituitary tumor resection. For patients with impaired vision or tumor diameter greater than 3 cm and optic nerve adhesions can be treated surgically first, the operation must achieve sufficient decompression of the optic nerve, and then gamma knife treatment after the operation, but there is still a possibility of recurrence after the operation, so regular review is required.
No substantial progress has been made in radiotherapy research.
It is still controversial whether radiation therapy (including gamma-knife and X-knife) can be used as the first choice of treatment, and most scholars believe that radiotherapy measures can be used as an adjuvant treatment after the initial surgical and pharmacological interventions. Since pituitary tumors are adenomas, which are inherently less sensitive to radiotherapy, and 70% – 80% of patients experience reduced pituitary function after radiotherapy, which reduces the quality of life of patients, radiotherapy is only indicated for patients who have surgical residuals, cannot tolerate surgery, are insensitive to medications, and have co-morbidities that cannot be treated with surgery or medications.
The advantages of drug therapy include the fact that it does not cause further pituitary hypoplasia and can selectively and permanently suppress hormonal overproduction resulting in improvement of their clinical symptoms. The disadvantages of drug therapy include serious side effects, long-term use, and increasing costs. In recent years, pharmacological treatment of pituitary adenomas has progressed rapidly and has shown significant results in inhibiting tumor cell growth and suppressing hormone overproduction.
For prolactinomatous pituitary tumors, more than 90% of patients (both microadenomas and macroadenomas) can have their prolactin levels controlled with dopamine agonists (short-acting agents bromocriptine, long-acting agents cabergoline).
It reduces the size of the tumor. Surgical treatment is chosen only for those patients who are allergic or intolerant to this class of drugs and whose acute symptoms due to tumor compression require emergency surgical decompression. During treatment with bromocriptine, the dose of bromocriptine should be gradually increased until after the serum prolactin level drops to normal, and then the dose is adjusted for long-term maintenance treatment. 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 pituitary tumors, the main progress in the last 20 years has been the use of growth inhibitor analogs.
The use of long-acting preparations of growth inhibitor analogues 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 growth hormone 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 growth hormone pituitary tumors include: postoperative residual patients, and transitional treatment of patients whose growth hormone has not been reduced to normal after radiation therapy. The application of growth hormone analogs provides the opportunity for preoperative preparative therapy in patients who are unable to tolerate anesthesia due to concomitant heart failure, sleep apnea, poorly controlled hyperglycemia, and hypertension. Growth-suppressing hormone analogs have also been used for thyrotropic pituitary tumors with satisfactory therapeutic results.
It is important to note that physiological hyperplasia of the pituitary gland occurs during puberty and pregnancy, while pathological pituitary hyperplasia occurs when the target glands (thyroid, adrenal, gonads) are hypofunctional. Physiological hyperplasia does not require any treatment, while in pathological hyperplasia, the pituitary gland will recover naturally with treatment that only targets the function of the target gland. For patients with incidental pituitary adenomas, especially non-functioning pituitary microadenomas, follow-up is the best option, as many patients with pituitary adenomas remain clinically inactive throughout their lives and their quality of life and lifespan are not affected. Due to the biological characteristics of pituitary adenoma cells, some tumor cells grow to a certain level and do not continue to grow, resulting in what is known clinically as a “quiescent tumor”. Any intervention is suspected to be “overtreatment” and can do more harm than good. Only if there are clear symptoms related to pituitary adenoma or if there are signs of tumor enlargement during the follow-up, treatment is needed. For some menopausal women with prolactin adenoma, they can also be followed up and observed, as decreasing estrogen levels can slow down the growth of the tumor.
We found some problems in the diagnosis and treatment of pituitary adenoma, such as.
(1) The “detection rate” of pituitary adenoma is increasing: 7.5 cases per 100,000 population, 1.5% – 84% (average 14.4%) of pituitary adenomas are detected at autopsy; the detection rate of pituitary adenomas at random MRI in normal population is 10% – 38%. The detection rate of pituitary adenomas in the normal population at random MRI was 10% – 38.5% (mean 22.5%). With the development of medical technology, the “incidental detection rate” of pituitary adenomas will become higher and higher.
(2) Some patients with pituitary hyperplasia are mistakenly treated as pituitary adenomas.
(3) Some patients with “aggressive” pituitary adenomas are difficult to cure with a single treatment.
(4) Even though some patients are cured after treatment, they may have recurrence after several years or years, etc. Due to the complex function of pituitary gland, the tumor cells grow in a “stationary” or “invasive” manner, and the performance of patients varies. It is important to analyze and summarize past experiences in diagnosis and treatment, and to adjust the thinking appropriately from the perspective of evidence-based medicine to choose an appropriate treatment plan for patients.
The ideal treatment goals for pituitary adenomas are.
(1) To control tumor growth.
(2) To eliminate or reduce the occupying effect and prevent its recurrence.
(3) To control hormone levels in the normal range.
(4) to alleviate complications due to hormonal disorders.
Due to the diversity of clinical manifestations, complexity of diagnosis and selectivity of treatment, patients with pituitary adenoma or suspected pituitary adenoma should visit a pituitary adenoma treatment center with neurosurgeons, endocrinologists, radiologists, radiologists, anesthesiologists and nurse specialists to ensure accurate diagnosis and the most appropriate treatment. Emphasis should be placed on follow-up of patients with pituitary adenoma to understand the whole course of treatment and provide appropriate guidance; establishing a database of patients with pituitary adenoma; and disseminating knowledge about pituitary adenoma so that patients and their families can understand the disease and make the right choice.
Lifetime follow-up
All patients treated for pituitary adenoma should be followed up for life. Anterior pituitary function should be reviewed regularly (every 3 – 6 months). Review saddle MRI if necessary to monitor tumor recurrence and growth. The level of anterior pituitary hormone secretion varies with age, so one year after surgery, pituitary hormone measurements should be done annually, depending on the patient’s specific condition, to replace the already hypotensive pituitary hormone as appropriate. Especially in patients with hypoadrenocorticism, the dose of prednisone 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 generally 50 – 150ug/day of thyroid hormone, and it is safer to start replacement therapy when the adrenal cortex is functioning normally. As for sex hormone replacement therapy, in patients with lactogenic pituitary tumors, sex hormone replacement therapy is not recommended while controlling prolactin levels medically because the tumor is sex hormone-dependent. In patients with other causes of hypopituitarism, male hormone supplementation should be done by monitoring the level of prostate antigen in the blood 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 can cause corresponding clinical symptoms in adults with growth hormone deficiency. Patients can be treated with growth hormone replacement therapy when it is confirmed that the tumor has not recurred.
In summary, pituitary tumors are a group of benign neuroendocrine tumors 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 patients, they should be treated according to the different characteristics of the nature of pituitary tumors and in close cooperation with multiple departments (endocrinology, neurosurgery, radiotherapy, ophthalmology, radiology imaging, etc.), according to The individualized treatment plan should be formulated according to the different needs of the patients. In the lifelong follow-up, we avoid tumor recurrence and try to preserve the pituitary function of patients, so that the elevated secretory hormones are reduced to the normal range and the reduced pituitary hormones are replaced to the age-matched normal range. To improve the quality of patients’ survival and prolong their life span.