Pituitary tumours are a group of tumours arising from the anterior and posterior lobes of the pituitary gland and the remnants of the epithelial cells of the craniopharyngeal duct. The majority of tumours in this group are adenomas from the anterior lobe, with those from the posterior lobe being rare. According to incomplete statistics, PRL tumours are most common in 50-55% of cases, followed by GH tumours in 20-23%, ACTH tumours in 5-8%, and TSH and LH/FSH tumours in less common cases. Non-functioning pituitary adenomas account for 20-25% of cases. Pituitary tumours account for approximately 10% of intracranial tumours. The majority of pituitary tumours are benign adenomas, with very few being cancerous.
Pathogenesis
The pathogenesis of pituitary tumours is a complex multi-step process involving multiple factors, which has not yet been clarified. There are two main hypotheses: one is that the hypothalamus is deregulated and the other is that the pituitary cells themselves are defective. The former suggests that the cause of the disease originates in the hypothalamus and that the abnormal regulation of the hypothalamus causes hyperfunction and hyperplasia of the pituitary gland, resulting in adenomas; pituitary adenomas are merely one of the manifestations of hypothalamic-pituitary dysfunction. In the latter case, it is thought that local factors in the pituitary gland cause a state of hyperfunction of pituitary cells, leading to the formation of adenomas. There is now growing support for the idea that pituitary adenomas originate in the pituitary gland itself, as the overproduction of hypothalamic-releasing hormones rarely causes true adenoma formation, but merely stimulates hyperplasia of the corresponding pituitary endocrine cells and an increase in the secretion of the corresponding hormones. Histological studies have shown that pituitary adenomas are not surrounded by hyperplastic tissue, suggesting that they are not caused by hypothalamic hormonal overstimulation.
In recent years, with advances in molecular biology, research into the relevance of gene mutations to the development of pituitary adenomas has intensified. The gsp gene is a new proto-oncogene formally defined by mutations in Gsαa, a 20 Kb long independent gene sequence consisting of 13 exons and 12 introns, whose base sequence and structure and function are largely understood, and whose point mutations result in mutations in the Gsαa2 subunit (Gsαa). The Gs protein is a member of the G protein family, whose function is to transmit stimulus signals from cell surface receptors to the catalytic unit of adenylate cyclase, facilitating the synthesis of cyclic adenosine monophosphate (cAMP). Since the secretion of growth hormone is cAMP-dependent, Gs proteins are closely associated with GH secretion; and there is growing evidence that cAMP is also a growth mediator, such that alterations in Gs proteins may in turn be directly or indirectly associated with tumour growth. Many clinical studies have found that gsp mutations are more frequently present in patients with pituitary GH adenomas, that they are found only in tumour cells but not in surrounding cells, and that the mutations are significantly active. These results suggest that there may be specific gsp proto-oncogene mutations during the development of pituitary GH adenomas. In addition to the gsp gene, numerous studies have shown that ras gene mutations and aberrant expression of the c-myc gene may be associated with the aggressive development and malignancy of pituitary adenomas. In addition, numerous studies have shown that many oncogenes may also be involved in the development of pituitary adenomas, such as the multiple endocrine neoplasia type 1 (MEN-1) gene, the cyclin-dependent kinase (CDK) suppressor p27Kipl gene, the retinoblastoma (Rb) gene, and the p53 gene. In addition, recent studies have shown that numerous growth factors and their receptors, hypothalamic receptors and neuroendocrine protein-7B2 may also be involved in the development and progression of pituitary tumours.
Classification of the disease
1. Functional classification
Functional pituitary tumours are classified into functional pituitary tumours and non-functional pituitary tumours. This classification is most commonly used in clinical practice.
2. Tumour size classification
Tumours are classified according to their diameter, with those less than 1 cm being referred to as microadenomas; 1-4 cm as large adenomas; >4 cm as giant adenomas.
3. Biological behaviour
There are invasive pituitary adenomas and non-invasive pituitary adenomas. Invasive pituitary adenoma is defined as “a pituitary adenoma that grows through its envelope and invades the dura mater, optic nerve, bone and other adjacent structures”. It is a tumour between benign pituitary adenoma and malignant pituitary carcinoma, with a benign histological pattern but a malignant biology. The clinical presentation and prognosis of invasive and non-invasive pituitary adenomas are distinctly different. The incidence of necrosis, stroke and cystic transformation is significantly higher in aggressive pituitary adenomas than in non-invasive pituitary adenomas. One study showed that 70% of pituitary strokes occur in invasive pituitary adenomas. Aggressive pituitary adenomas have a high recurrence rate after surgery because they are difficult to cut out and because the proliferation index is high and the residual tumour tissue grows quickly.
4. World Health Organization classification criteria
Kovacs et al. concluded from a study of 8,000 surgically resected pituitary adenomas that the classification of pituitary adenomas should include five aspects, namely clinical presentation and blood hormone levels, neuroimaging and intraoperative findings, light microscopic presentation of tumour sections, immunohistochemical typing and ultrastructural features of tumour cells under electron microscopy. Each of these classification criteria is valuable in determining the diagnosis and analysing the biological manifestations of the tumour, and has been recommended as the World Health Organisation classification of pituitary adenomas. However, the classification is complex and has not been widely promoted in clinical work.
5. Classification according to cytoplasmic staining properties
Based on the results of hematoxylin and eosin staining (HE staining), pituitary adenomas can be classified into four categories: eosinophilic, basophilic, suspicious and mixed. In the past, eosinophilic adenomas were thought to present with acromegaly or gigantism, basophilic adenomas with Cushing’s syndrome, and suspicious adenomas with no obvious clinical endocrine symptoms. In fact, classification based on the chromophobic properties of pituitary adenoma cells alone does not reflect the endocrine features of pituitary adenomas and the relationship between clinical and pathological features
6. Classification by tissue structure
In other words, according to the arrangement of the tumour cells and the number of blood vessels, they are classified into diffuse, sinusoidal, papillary and mixed types.
Clinical presentation
Pituitary tumours may have clinical manifestations of hyperproduction of one or more pituitary hormones. In addition, there may be different degrees of hypopituitarism due to compression and destruction of the normal pituitary tissue surrounding the tumour, as well as out-of-saddle expansion of the tumour to compress adjacent tissue structures.
1. Hormone overproduction syndrome.
(1) PRL tumour: It is more common in women and typically manifests as amenorrhoea, breast discharge and infertility. In males, the symptoms are hypoactive sexual desire, impotence, breast development and infertility.
(2) GH tumour: In adolescents, the tumour can become overgrown and gigantic. In adulthood, it is a manifestation of acromegaly.
(3) ACTH tumour: clinical manifestations include centripetal obesity, full-moon face, buffalo back, polycythemia, purplish skin and increased fine hair. Some patients also have hypertension, diabetes, hypokalemia, osteoporosis and fractures.
(4) TSH tumour: Rarely seen due to overproduction of thyroid stimulating hormone by the pituitary gland, causing hyperthyroidism.
(5) FSH/LH tumour: very rare, with hypogonadism, amenorrhoea, infertility, reduced sperm count, etc.
2. Decreased hormone secretion
The secretion of certain hormones may interfere with the secretion of other hormones, or the tumour may compress the normal pituitary tissues and reduce hormone secretion.
3. Peripituitary Tissue Compression Signs
(1) Headache: Because of the increased pressure in the saddle caused by the tumour, the pituitary dural sac and saddle septum are compressed.
(2) Visual loss and visual field defects: the tumour develops anteriorly and superiorly compressing the visual cross, mostly temporal hemianopia or bilateral superior temporal hemianopia.
(3) Cavernous sinus syndrome: The tumour develops laterally and compresses the third, fourth and sixth pairs of cranial nerves, causing ptosis, extraocular muscle paralysis and diplopia.
(4) Hypothalamic syndrome: the tumour develops superiorly and affects the hypothalamus which may lead to uveitis, sleep abnormalities, thermoregulation disorders, eating abnormalities and personality changes.
(5) If the tumour destroys the saddle base it may lead to cerebrospinal fluid nasal leakage.
(6) Pituitary stroke: caused by hemorrhage and necrosis within the tumour. The onset of stroke is rapid, with severe headache and rapid visual loss of varying degrees. In severe cases, both eyes may be blinded within a few hours, often accompanied by extraocular muscle paralysis.
Ancillary tests
1. Hormone measurements.
As different functional adenomas secrete different pituitary hormones, the corresponding pituitary hormone secretion varies, as detailed in the relevant chapters.
The following factors should be taken into account when assessing the results of endocrine function tests: (1) all pituitary hormones are secreted and released in a pulsatile manner; (2) there are many factors affecting pituitary hormone secretion (especially PRL), including the time of blood sampling, whether or not the patient is eating, whether or not there is stress, whether the patient is asleep or awake, age and stage of growth and development, and the effects of medication; (3) if a pituitary hormone secretion is suspected to be abnormal, other hormones should be tested as well. When abnormalities in the secretion of a particular pituitary hormone are suspected, other pituitary hormones should be tested simultaneously and, if necessary, dynamic tests, such as rhythm tests and hormone excitation and inhibition tests, should be considered to assist in the diagnosis. (5) Since the normal range of pituitary hormone values is not entirely consistent from one laboratory to another due to the different testing methods used, the interpretation of results can only be based on the normal reference range provided by the laboratory in which they are performed. (vi) The heterogeneity of the pituitary hormone fractions in the circulation can result in incomplete concordance between their immunological and biological activities, leading to discrepancies between laboratory tests and the clinical presentation. (vii) The hormone values may not be parallel to the size of the adenoma and the clinical symptoms, the latter depending on the duration of the disease, the type of hormone, the presence of degenerative and cystic changes in the tumour and other substances affecting the hormonal activity.
2. Imaging tests
(1) MRI: MRI is preferred for imaging of pituitary tumours because it is sensitive and can better show the tumour and its anatomical relationship with the surrounding tissues. MRI is more sensitive than CT and can better show the tumour and its anatomical relationship with the surrounding tissues.
Pituitary microadenomas appear as a round, low-density signal on T1-weighted images and as a high-density signal on T2-weighted images, with the pituitary stalk usually off to the side of the tumour. Gd-DTPA (gadolinium-diethylenetriaminepentaacetic acid) is commonly used as an enhancement contrast in MRI, preferably with dynamic enhancement scans, to greatly improve the detection rate of pituitary tumours. …… Normal pituitary tissue can appear after about 30 minutes. The time to develop enhancement in adenomas is not only slow, but also longer. The MRI of intra-adenopituitary haemorrhage may show different features depending on the duration of the haemorrhage and the degree of disruption of the blood-brain barrier. The subacute hemorrhagic foci within 1 to 4 weeks show a high density signal on both T1- and T2-weighted images due to the gradual formation of methemoglobin from the periphery to the centre. chronic hemorrhagic foci over 4 weeks show a uniform high density signal on both T1- and T2-weighted images, surrounded by a low density ring formed by iron-containing haemoglobin. In normal subjects, 80% of the optic cross is located directly above the pituitary fossa and is well defined on MRI. The sphenoid sinus is located on both sides of the pituitary gland and has a similar density to that of the pituitary gland. It contains the first and second branches of the third, fourth and sixth pairs of cranial nerves and the fifth pair of cranial nerves, all of which are less dense than the adenopituitary. MRI has the disadvantage of not showing bone destruction and tissue calcification.
(2) CT: Conventional 5-mm fractionated CT scans can only detect larger pituitary occupying lesions. High-resolution multi-thin-layer (1, 5mm) coronal reconstruction CT can detect smaller pituitary tumours on enhanced scanning examinations. The posterior pituitary lobe may not appear dense in patients with central uveitis. The hypothalamic funnel is located behind the optic cross.
(3) Radiograph: In larger cases, the radiograph shows enlargement of the pterygoid saddle, increase in all diameters of the pterygoid saddle, thinning of the saddle wall, subsaddle shift, destruction of the dorsal saddle bone, and enlargement of the saddle opening due to thinning of the anterior and posterior beds. A lateral view shows a double saddle base.
(4) Radionuclide imaging techniques for saddle area disease have also developed rapidly, such as positron tomography (PET), 111In-DTPA-octreotide and 123I-Tyr-octreotide scans have begun to be used in the clinical diagnosis of pituitary tumours. The diagnosis of pituitary tumours is now being made.
3. Other tests
Special tests for pituitary tumours mainly refer to ophthalmologic examinations. The ophthalmologic examination includes visual field examination, visual acuity examination and eye mobility examination. Tumour compression of the optic cross or optic bundle or optic nerve may cause visual field defects or loss of visual acuity. Pituitary tumours invading the cavernous sinuses on both sides can cause impaired eye movement, diplopia and ptosis (cavernous sinus syndrome), with the articulating nerve being the most commonly involved. Patients with pituitary tumours often show signs of cranial nerve compression. Pairs I to VI cranial nerves can be involved, and olfactory and facial sensory examinations must be performed if necessary. If the tumour ruptures and bleeds and involves the subarachnoid space, a cerebrospinal fluid examination may also be useful in determining the condition.
Plasma ACTH levels are measured in a blood sample taken from the inferior petrosal sinus and compared to the plasma ACTH levels in the surrounding veins. If the ratio is greater than 2, a pituitary ACTH tumour is indicated; if the ratio is <1, ectopic ACTH syndrome should be considered. This method of measuring the gradient of ACTH concentration by intravenous cannulation helps to confirm the diagnosis of ACTH tumours and is one of the differential diagnostic tools for the etiology of cortisolism.
Disease diagnosis
The diagnosis of pituitary adenoma is based on a detailed history, careful physical examination, clinical symptoms and signs, pituitary imaging and endocrine function tests including those of the appropriate target gland. The diagnosis of pituitary tumours is generally not difficult, and in some cases the diagnosis can be made solely on the basis of the typical clinical presentation. More difficult are microadenomas where the increase in hormone secretion is not significant and where the hormone test is not much above the upper limit of the normal range. In this case, multiple measurements are required, sometimes in combination with dynamic tests, to assess the endocrine function of the pituitary gland.
Differential diagnosis
The diagnosis of pituitary tumours should be differentiated from the following diseases: pituitary hyperplasia, inflammation (infectious, non-infectious), tumours, others.
1. Hyperplasia.
(1) Compensatory: hypothyroidism and hypoadrenocorticism cause pituitary hyperplasia, especially pituitary hyperplasia caused by hypothyroidism. The patient has typical hypothyroidism, with a markedly elevated TSH and a markedly decreased FT4 on thyroid function tests, and a uniformly enlarged pituitary gland on MRI with uniform enhancement on enhanced scans. When thyroid hormone is supplemented, the pituitary hyperplasia disappears quickly.
(2) Physiological: Growth hormone cells are actively secreted during puberty, and children have temporary thickening of the lips and large proportions of the hands and feet. In women who are pregnant and breastfeeding, PRL secretion increases and there is an increase in serum PRL. Pregnant women have lactation and temporary amenorrhoea. Enlarged pituitary gland is seen on MRI during this period.
(3) Pharmacological: Sedative and sleeping medications for psychiatric disorders are most evident.
2. Tumours.
(1) Craniopharyngioma: This can occur at all ages, with children and adolescents being the most common. In addition to visual acuity and visual field disorders, there are also manifestations of hypopituitarism and subthalamic involvement such as growth arrest, failure to develop sexual organs, obesity and enuresis, and symptoms of increased intracranial pressure in large tumours. In most cases, the tumour has cystic changes and calcification. The main body of the tumour is located in the suprasellar region, with the pituitary tissue at the base of the saddle.
(2) Germ cell tumour: also known as ectopic pineal tumour, mostly occurring in children, with rapid development and obvious clinical symptoms, often with enuresis, precocious puberty, wasting and some with hypopituitarism. The lesions are usually located in the suprasellar region and are clearly enhanced. Some patients have elevated blood hCG, cerebrospinal fluid hCG and are sensitive to radiotherapy.
(3) Meningioma of the saddle node: Mostly in middle-aged people, the disease progresses slowly and the initial symptoms are progressive visual loss with irregular visual field defects, headache and no endocrine abnormalities. There is often only mild hyper-PRLemia due to pituitary stalk compression, which is easily misdiagnosed as a non-functioning pituitary adenoma. The tumour is located in the suprasellar region with pituitary tissue at the base of the saddle.
(4) Optic nerve glioma: Most commonly seen in children, especially in girls. Visual changes often occur first on one side, and visual loss progresses more rapidly. Patients may have proptosis but no endocrine dysfunction. The pterygoid saddle is normal and the lesion is mostly suprasellar with poorly defined borders and mixed signals. The optic foramen is enlarged.
In addition, pituitary tumours need to be differentiated from granulosa cell tumours, metastatic carcinoma of the pituitary gland, lymphoma, malignant tumours, nerve sheath tumours and teratomas.
3. Inflammatory conditions.
(1) Lymphocytic pituitaryitis: This disease is most commonly seen in women of childbearing age. The cause is unknown and may be an autoimmune disease caused by a virus. Urachalgias are the main clinical manifestation. It is partially associated with hypopituitarism. Imaging shows marked thickening of the pituitary stalk. Pituitary tissue is enlarged to varying degrees.
(2) Pituitary abscess: recurrent fever, headache, significant visual loss, and may be accompanied by other cranial nerve damage, usually with rapid progression. The imaging is usually small and does not correspond to the clinical symptoms. There is significant enhancement of soft tissue structures around the butterfly saddle.
3) Eosinophilic granuloma: Typical presentations include proptosis, uveitis and cranial defects. MRI often shows abnormal hypothalamic signal and loss of normal high signal in the posterior pituitary lobe (central uveitis), with a long T1 and long T2 signal, usually with marked enhancement. The dura mater surrounding the lesion is clearly enhanced on imaging.
4) Mycotic inflammation: Symptoms resemble pituitary abscesses and there is a history of prolonged use of hormones and antibiotics. In some cases other cranial nerves are damaged.
5) Tuberculous meningitis: in young people or children, with headache, fever, history of meningitis and imaging showing adhesive hydrocephalus.4. Other.
Pituitary adenoma also needs to be differentiated from other diseases such as vacuolated pteroid saddle syndrome, suprasellar germ cell tumour, metastatic pituitary carcinoma and internal carotid aneurysm.
Treatment of the disease
The goals of pituitary adenoma treatment: to suppress the autonomic hormone secretion of the tumour, to maximise removal of the tumour, to maintain normal pituitary function, to reduce the impact of the tumour on vision, to prevent recurrence of the tumour and to prevent and manage complications.
Currently, there are three main treatments for pituitary tumours: medication, surgery and radiotherapy. The choice of treatment depends mainly on the type of pituitary tumour. Generally, drug treatment is preferred for PRL tumours, while surgery is preferred for most GH tumours, ACTH tumours, TSH tumours and non-functioning macroadenomas. Patients with GH tumours with persistently elevated postoperative GH and IGF-1 levels should be treated with octreotide or dopamine agonists, while radiation therapy may be considered for those who have had poor results with drug therapy. The treatment of ACTH tumours may be supplemented with radiotherapy.
Pharmacological treatment
The most established pharmacological treatments for pituitary adenomas are PRL tumours and GH tumours. A class of dopamine D2 agonists, represented by bromocriptine, has become the treatment of choice for PRL tumours. The efficacy of pharmacological treatment of other adenomas is uncertain and relies mainly on surgical resection and radiotherapy. Pharmacological treatment is mainly indicated for patients who have contraindications to surgery or who require adjuvant therapy before and after surgery.
The following are highlights of the dopamine agonists, growth inhibitor analogues and GH receptor antagonists.
(1) Bromocriptine
A semi-synthetic derivative of ergot alkaloids, it is a dopamine agonist that effectively inhibits the secretion of PRL and partially inhibits the release of GH. In female patients, breast discharge is reduced after 2 weeks and normal menstruation can be resumed after about 2 months of treatment. In men, the blood testosterone concentration increases after 3 months and returns to normal within 1 year, with an increase in sperm count. Bromocriptine not only reduces PRL levels, but also shrinks tumours, reduces headaches and improves visual field defects. The disadvantage of bromocriptine is that tumours tend to recur after discontinuation of the drug. Its side effects are mild and include nausea, vomiting, weakness and upright hypotension. As long as the patient is not allergic to bromocriptine and can tolerate it, it is suitable for any patient with PRL tumours, and can also be used for other causes of hyper-PRL haemorrhage.
(2) Growth inhibitor analogues
At present, there are two main types of growth inhibitor analogues: short-acting and long-acting. The former are mainly octreotide, while the latter are mainly Zantacin – long-acting release formulation and lanotide – extended release formulation. Of these, octreotide was the first to be used in clinical practice. The long-acting formulations have a much longer half-life compared to octreotide and can maintain the growth inhibitor analogues in the patient’s body at therapeutic levels for a longer period of time, making them more suitable for long-term use. The dose of Zendradine Long Release is typically 20-40mg/30d, equivalent to 750-1250ug/d of octreotide, and has recently been shown to be adequate for treatment even if the frequency of administration is reduced to once every 6 weeks. There are two extended release formulations of lanolin, Somatuline LA, which is administered subcutaneously at 30mg every 10-14d, and Somatuline Autogel, which can be administered subcutaneously as often as once a month and has approximately the same efficacy as octreotide.
Even if the frequency of administration is reduced to every 6 weeks, the treatment requirements can be fully met. There are two extended-release formulations of lanolin, Somatuline LA, which is administered subcutaneously at 30 mg every 10-14 d, and Somatuline Autogel, which is administered subcutaneously only once a month and is approximately as effective as octreotide.
In the pharmacological treatment of acromegaly, growth inhibitor analogues are mainly useful in the following phases: 1). Preferred treatment: for patients with complications, severe metabolic disturbances, who are not suitable for surgery or who are afraid of surgical treatment. ②. Pre-operative pre-emptive treatment: the aim is to reduce the size of the tumour, to create the conditions for complete surgical removal of the tumour and to improve surgical efficacy. ③. Post-operative adjuvant therapy: for patients whose GH levels remain substandard after surgery. ④. Post-radiotherapy transition therapy: GH levels are slowly reduced after radiotherapy, during which growth inhibitor analogues can be used as transition therapy. ⑤. Treatment of complications: growth hormone receptor antagonists.
(3) Antagonists of the GH receptor
Pegvisomant is a new class of drugs used in the treatment of GH adenomas in recent years, its affinity for the GH receptor is higher than that of GH and its half-life is longer. Experimental results have shown that Pegvisomant can normalize serum IGF-I in 75-80% of GH adenoma patients by subcutaneous injection of 15-20mg/d in a dose-dependent manner. In addition, Pegvisomant is currently used mainly for the surgical treatment of radiotherapy. In addition, it is currently used mainly in patients who have had poor results from surgical treatment with radiotherapy. However, it has also been reported to cause asymptomatic hepatocellular damage and to cause GH and Pegvisomant antibodies in 1/5 of patients. As a new drug, the dosage, exact effects and safety of Pegvisomant need to be further investigated.
Surgical treatment
Surgery remains the treatment of choice for pituitary tumours other than PRL tumours. Long-term clinical observations have shown that surgical treatment of pituitary tumours is safe and effective. The aim of treatment is not only to remove the tumour completely, but also to preserve as much normal pituitary tissue as possible to avoid postoperative hypopituitarism. Surgery should be considered when a pituitary tumour shows clinical signs of increased pituitary hormone production and/or mass-occupying effects such as compression of cranial nerves and peripituitary structures.
The surgical approach to pituitary tumours has improved considerably from the previous approach, with the transsphenoidal sinus approach now being the main one. It involves the selective removal of the tumour under conditions of a wider surgical field of view (operating under a microscope). The transsphenoidal approach is safe and widely used for microadenomas in the saddle and for macroadenomas that expand suprasellarly and develop into the cavernous sinus. Post-operative adjuvant radiotherapy is also generally indicated for macroadenomas that extend suprasellarly. Once the tumour is found to have invaded the dura of the saddle during surgery, it is considered that the patient is more likely to have a recurrence of the tumour after surgery and postoperative radiotherapy is necessary. In recent years, the transsphenoidal sinus procedure has been further improved by using an endoscope to fully expose the internal nasal cavity and pterygoid sinus through the unilateral nostril for selective pituitary tumour resection. This endoscopic transsphenoidal approach is not only suitable for microadenomas, but also for large adenomas.
Surgical complications have been significantly reduced since the widespread introduction of the transsphenoidal sinus approach, with a mortality rate of no more than 2.5%. Surgical complications can include nasal leakage of cerebrospinal fluid, loss of vision, stroke or cerebrovascular injury, meningitis or abscess, ophthalmoplegia and hypopituitarism. The incidence of these complications is low and the incidence of postoperative hypopituitarism is about 3% in microadenomas and only slightly more than 3% in invasive macroadenomas.
Radiation therapy
Pituitary radiotherapy stops further tumour growth and eventually reduces the level of hormones that are being produced. Radiotherapy takes longer to achieve results and does not reduce the size of the tumour and normalise hormone levels as quickly as surgical treatment. There are many types of radiotherapy, including conventional external radiation, conformal or intensity-modulated external radiation, stereotactic conformal radiotherapy (SCRT), and proton external radiation.
In recent years, the precise estimation and arrangement of the irradiation site, the total amount of irradiation and the individual dose have greatly reduced the errors and ensured the effectiveness of radiation therapy. In principle, conventional pituitary radiotherapy is not used alone, but is often used in conjunction with surgery or medication, and may be considered in cases of incomplete surgical excision and post-operative recurrence. This is because incomplete excision of a macroadenoma can easily lead to recurrence of the tumour, which is dangerous to treat again surgically, and postoperative radiotherapy can avoid this risk. Combination of radiotherapy and drug therapy can also be considered for those who are not allowed to undergo surgery. Complications of radiotherapy are uncommon, with the exception of hypopituitarism, and include manifestations of optic cross and/or optic nerve and other cranial nerve damage (blindness or oculomotor paralysis), cerebral ischaemia, seizures and pituitary or brain malignancies. Hypopituitarism is more likely to occur in those who have postoperative adjuvant radiotherapy. Hypopituitarism can continue to occur long after radiotherapy, so the endocrine status of the pituitary gland should be monitored after radiotherapy so that HRT can be given in a timely manner.