Pituitary adenoma
Overview
Pituitary adenoma, referred to as pituitary tumor, is a kind of tumor belonging to the endocrine system, which mainly originates from the anterior lobe of pituitary gland (adenopituitary gland), while patients with pituitary origin are rare. Pituitary tumors account for about 10% of intracranial tumors and are common in 30-40 years old, both sexes. When the tumor is small, it is generally grayish white or grayish red, substantial and clearly demarcated from the surrounding normal tissues; when the tumor grows up, it often squeezes the normal pituitary tissue to the side and makes it shrink.
Classification
1. According to the light microscope performance of pituitary tumor
(1) Anaplastic: the most common. Initially thought to be “non-functional”, it can actually produce prolactin, GH or TSH.
(2) Acidophilic: secretes PRL, TSH, or GH (gigantism in children or acromegaly in adults).
(3) Basophilic: Secretes LH, FSH, beta-lipotropin or ACTH (Cushing’s disease).
(4) Mixed.
2. According to the secretion products
(1) Functional pituitary adenoma: with active secretion function, according to the secretion products can be divided into: ① GH type pituitary adenoma. (2) PRL pituitary adenoma. (3) ACTH pituitary adenoma. TSH type pituitary adenoma. About 70% of pituitary adenomas secrete one or two hormones, which can be measured in plasma and produce specific clinical syndromes.
(2) Non-functional pituitary adenoma: The endocrine function is not active, or the secretory products do not produce obvious endocrinological symptoms. (1) Empty cell adenoma. (2) Large eosinophilic granuloma. (iii) Gonadotropin adenoma. (4) Quiescent corticotropin-producing adenoma. ⑤ Glycoprotein-secreting adenoma.
Clinical manifestations
1. Occupational effects of pituitary tumors
(1) Usually seen in non-functional tumors. Among the functional tumors, prolactinomas are the most likely to be large enough to cause occupational effects (ACTH adenomas are the least likely).
(2) Headache: Most non-secretory adenomas may have headache complaints, which are caused by the upward development of the tumor pulling the saddle septum in the early stage. In contrast, GH type adenoma has obvious and prolonged headache symptoms, and the location is not fixed.
(3) Visual field changes: When the tumor lifts up the saddle septum or grows upward through the saddle septum, it can compress the visual cross and produce visual field changes, typically manifesting as bilateral temporal hemianopia (inconsistency), and can also lead to vision loss.
(4) Pituitary dysfunction: It can lead to different degrees of hypopituitarism. (1) hypothyroidism: fear of cold, mucinous edema, coarse hair; (2) hypoadrenalism: postural hypotension, easy fatigue; (3) hypogonadism: menopause (female), no libido, infertility; (4) uremia: very rare (look for other causes, including hypothalamic pituitary tumors, suprasellar germ cell tumors); (5) hyperprolactinemia: PRL is inhibited by the hypothalamus, and partial inhibition can be caused by pressure on the pituitary stalk (5) hyperprolactinemia: PRL is suppressed by the hypothalamus, and pituitary stalk compression can cause partial suppression.
(5) cavernous sinus syndrome: (1) cerebral nerve compression (III, IV, V1, V2, VI): eyelid ptosis, facial pain, diplopia, etc.; (2) cavernous sinus blockage: proptosis, conjunctival edema, etc.; (3) internal carotid artery wrapped by tumor: may cause mild stenosis, but complete blockage is rare.
2. Endocrinological manifestations of pituitary tumors Most functional pituitary tumors secrete one of the following hormones:
(1) Prolactin (PRL): the most common endocrine adenoma, causing menopause and lactation syndrome (Forbes-Albrigh syndrome) in female patients, impotence and non-reproductive function in male patients, and bone loss.
(2) Adrenocorticotropic hormone (ACTH): Also known as corticotropin, or Cushing’s disease, elevated ACTH can lead to: ① endogenous hypercorticotropism (Cushing’s syndrome): a series of changes caused by hypercorticotropism. The most common cause is of medical origin (use of exogenous hormones). Non-medical cushing syndrome is common in patients with acromegaly, with an incidence of about 25%. Nelson’s syndrome: 10%-30% of patients with adrenalectomy for Cushing’s disease develop hyperpigmentation [through cross-reactivity between melanotropic hormone (MSH) and ACTH].
(3) Growth hormone (GH): causes acromegaly in adults, which manifests as enlarged hands and feet, thickened heels, forehead bulge, giant tongue, hypertension, soft tissue swelling, peripheral nerve entrapment syndrome, debilitating headaches, excessive sweating (especially in the palms of the hands), and arthralgia; 25% of patients with acromegaly develop goiter, but laboratory tests are normal. Elevated GH levels in children (before epiphyseal closure) can lead to gigantism rather than acromegaly.
(4) Thyrotropin (TSH): causes thyrotoxicosis.
(5) Gonadotropins (LH/FSH): usually do not cause clinical symptoms.
Imaging tests
1. CT examination
(1) Usually replaced by MRI. It can be used when MRI examination is not appropriate (e.g., pacemaker).
(2) Axial and coronal examinations should be performed, and thin layer scans are more meaningful. Brain CT can understand the development status of frontal sinus and pterygoid sinus, the location of pterygoid sinus mediastinum and bone destruction in pterygoid saddle area, the relationship between tumor and pterygoid sinus. Cerebral angiography should be performed to show the paranasal internal carotid artery and to exclude cerebral aneurysm. The intrapituitary calcification usually indicates bleeding or infarction within the small tumor.
2. MRI examination
(1) It is the preferred imaging method for pituitary tumor.
(2) Normally, pituitary gland shows high signal in T1 image (probably because of phospholipid body). Lack of this sign is often associated with uveitis. MRI can be used to understand the relationship between tumor and brain pool, cavernous sinus, internal carotid artery and third ventricle, such as tumor invasion of cavernous sinus, showing the involvement of internal carotid artery and/or internal carotid artery. It is more meaningful for the diagnosis of microadenoma.
(3) In 75% of patients, T1 image shows low signal and T2 image shows high signal. The time dependence of intensification is very strong, and MRI must be imaged 5 minutes after drug injection to show microadenoma. Initially, the normal pituitary gland is enhanced instead of the tumor (no blood-brain barrier), and the tumor is similarly enhanced approximately 30 minutes later. Displacement of the pituitary stalk also suggests a pituitary microadenoma, and the thickness of the normal pituitary stalk corresponds to the diameter of the basilar artery. Thickening of the pituitary stalk is usually not a tumor, and the differential diagnosis is lymphoma, lymphocytic pituitary inflammation, granulomatosis, and hypothalamic glioma. In patients with Cushing’s syndrome, 25-45% of tumors cannot be visualized on MRI.
Other tests – endocrinology]
All patients with pituitary tumors should undergo endocrine tests to indicate the type of tumor, the type of hormone supplementation needed, and as a basis for comparison before and after treatment. Usually radioimmunoassay is used to measure hormone levels, including PRL, GH, ACTH, TSH, FSH, LH, MSH, T3, T4 and TSH.
Differential diagnosis
1. Craniopharyngioma
2. Meningioma.
3. Paracranial artery aneurysm
4. Optic nerve glioma
5. Chordoma
6. Epidermoid cyst
7. Vacuolar saddle syndrome
8. Ectopic germ cell tumor
9. Lacrocyte cyst
10. Pituitary abscess
Treatment plan and principles
1. Surgical indications
(1) Diagnosed prolactinoma: treatment principle ①Prolactin level (PRL) <500ng/ml, surgical treatment may correct PRL. ②PRL>500ng/ml and drug treatment cannot control tumor growth (because the chance of normal PRL after surgery for tumors with PRL>500ng/ml before surgery is rare, so the first trial should be drug treatment alone), the treatment effect should appear within 4-6 weeks after surgery. The treatment effect should appear within 4-6 weeks after surgery. Continued pharmacological treatment after surgery can correct PRL levels.
(2) Primary Cushing’s disease: the long-term effect of drug therapy is not satisfactory.
(3) Acromegaly: Surgery is recommended as the treatment of choice for most patients.
(4) Macroadenoma: ①Prolactinoma: If there is no acute development, the tumor can be significantly reduced after bromocriptine treatment ② Symptoms caused by the occupying effect of non-PRL tumors due to their large size. (3) Non-PRL macroadenomas that elevate the optic cross upward may have damage to visual structures even though there is no endocrine abnormality or visual field deficit.
(5) Acute and rapid deterioration of vision or other neurological functions. It may mean ischemia of the optic cross, hemorrhage or tumor infarction pituitary stroke). The main risk is blindness (hypopituitarism may be treated with alternative therapy). Blindness usually requires emergency surgical decompression. Craniotomy is usually used, but transsphenoidal surgical decompression can also be performed with satisfactory results.
(6) In doubtful cases, the surgically obtained tissue can be used for pathological diagnosis.
2. Transcranial approach:
(1) Indications: ① slight enlargement of the butterfly saddle, tumor is mainly located in the supra-saddle, especially the tumor is tightened by the saddle septum (girdle sign), and the supra-saddle part compresses the visual cross. ②Tumors that grow towards the middle fossa of the skull and are larger than the inner part of the saddle. ③Transsphenoidal surgery can lead to other diseases: such as paracranial aneurysm. ④When combined with other tumors in the anterior cranial fossa or saddle area that may be removed in one transcranial operation.
(2) Transcranial approach: It is suitable for tumor located mostly in the suprasellar area and not invading the anterior part of the third ventricle; it is difficult for those with anterior visual cross.
(3) Longitudinal approach: suitable for tumor located in the anterior part of the third ventricle, filling the suprasellar pool and not invading the third ventricle.
(4) Transcallosal approach: suitable for tumor invading into the third ventricle and/or lateral ventricles, with obvious hydrocephalus. The tumor is not well exposed below the visual cross and in the saddle.
(5) Trans-lateral ventricular approach: suitable for tumor invasion into the lateral ventricles with obvious obstruction of interventricular foramen. It is not good for intra-saddle exposure.
(6) Transsphenoidal approach: It is suitable for the tumor growing to the paracentral saddle and the base of the middle cranial fossa, and developing to the posterior saddle. It is not good for intra-saddle exposure.
(7) Cranio-orbital-zygomatic approach: It is suitable for tumor invading upward, outward and anteriorly extensively. It has little strain on the brain tissue.
3. Transsphenoidal approach:
(1) It is often the preferred approach, with small trauma (extra-arachnoid approach, no service marks, no need to pull the brain tissue) and short operation time.
(2) It is suitable for those whose tumor is mainly located in the saddle and develops downward (pterygoid sinus), or grows upward to the saddle with no obvious “stuck waist sign” of septal foramen. Especially for microadenoma.
(3) Commonly used approaches: ① transoral-nasal-pterine approach. (2) Single nostril approach through the nose and butterfly, which is more commonly used at present. (3) Endoscopic surgery, which is more commonly used at present, requires corresponding endoscopic equipment and is less invasive. ④Transseptal sinus approach: less often used.
4. Postoperative complications of transsphenoidal approach
(1) Antidiuretic hormone (ADH) changes: transient abnormalities are common, including diuresis (DI), but DI > 3 months is uncommon; postoperative DI is usually manifested in one of the following three ways: ① transient DI: lasting approximately 12-36 hours after surgery; ② “long-term” type DI: lasting for several months, or can be permanent; ③ triphasic reaction (the least common): normal DI or abnormal antidiuretic hormone (2) Cortisone deficiency → cortisone deficiency
(2) Cortisone deficiency → hypoadrenocorticism → Addison’s crisis in severe cases.
(3) TSH deficiency → hypothyroidism → mucinous edema in severe cases (rare).
(4) Sex hormone deficiency → hypogonadotropic hypogonadism.
(5) Secondary empty saddle syndrome (optic cross is involved in the empty saddle → visual impairment).
(6) Hydrocephalus with coma: surgical resection (transsphenoidal or transcranial) is feasible for tumors growing on the saddle, and ventriculostomy is performed if hydrocephalus is present (even if there are no symptoms). Possible causes: ①Stretching of the second ventricle. (ii) Release of pressor hormone due to pulling on the pituitary gland and/or pituitary stalk. (3) Edema after tumor removal.
(7) Infection:① pituitary abscess;② meningitis
(8) CSF nasal leak.
(9) Internal carotid artery rupture: rare. It tends to occur late after surgery, often about 10 days after surgery (due to degradation of fibronectin around the internal carotid artery, or rupture of pseudoaneurysm due to intraoperative injury).
(10) Entry into the cavernous sinus damaging structures within the cavernous sinus.
(11) Perforation of the nasal septum.
5. Postoperative management
(1) After transsphenoidal approach, due to blood and fluid leakage from the nasopharynx, the endotracheal tube should be retained for 2-3 hours to prevent misaspiration, and the endotracheal tube should be removed only after the patient is fully conscious.
(2) The patient’s urine volume should be closely observed and controlled in the postoperative period. Pay attention to the use of no urinary collapse.
(3) antibiotics: to prevent infection.
(4) Hormone: Postoperative steroid hormone supplementation is needed until there is sufficient endogenous hormone production, especially in Cushing’s disease. Use one of the following methods: ① hydrocortisone 50mg, intramuscularly or intravenously, every 6 hours; change to methylprednisolone tablets 4mg or prednisone 5mg every 6 hours on the 2nd postoperative day; change to 5mg twice daily after one day, and stop on the 6th postoperative day. (2) Hydrocortisone 5Omg, intramuscular or intravenous or oral, twice daily; then reduce the dose by lOmg daily until discontinuation.
(5) Anti-epileptic drugs: such as carbamazepine, phenytoin sodium, sodium valproate, etc., at least 3-6 months, if no seizures before considering drug reduction and gradual discontinuation; if there are seizures, should continue to take 1-2 years, and then gradually reduce the dosage and discontinue the drug.
(6) Monitor electrolyte changes, visual field changes, and pay attention to whether there is nasal leakage of cerebrospinal fluid
(7) Review brain CT or MRI, and endocrine level
6. Radiation therapy
(1) Including stereotactic radiation therapy and general external radiation therapy.
(2) The total dose is usually 40-50Gy and is completed within 4-6 weeks.
(3) As an alternative treatment to surgery: when the patient’s general condition is poor or combined with other systemic diseases, can not withstand general anesthesia surgery, or when the patient refuses surgery.
(4) As an adjuvant treatment to surgery: ①If the recurrent tumor cannot be removed by surgery again and continues to grow, radiation therapy can be considered. (2) If the tumor is huge or invasive pituitary tumor, which is difficult to be removed by surgery, radiation therapy can be considered before surgery, and then surgical treatment can be performed after the tumor shrinks.
7. Drug treatment:
(1) Dopamine inhibitors: bromocriptine (for the treatment of prolactinoma).
(2) Edema inhibiting drugs: such as glucocorticoids, dexamethasone or methylprednisolone.