CHOOSE YOUR LANGUAGE

  • Pituitary Gland
  • Pituitary Tumors
  • Acromegaly, Gigantism
  • Prolactinoma
  • Cushings Disease
  • Non-Secreting Tumour
  • Overview of Surgery
  • Our Technique & Results
  • Pituitary Gland

    The pituitary gland is a small gland found at the base of the brain just below the hypothalamus, to which it is attached via nerve fibers. It produces many hormones that travel throughout the body and directly affect the body function and also indirectly by controlling other endocrine glands in the body.


    Pituitary gland has 2 lobes, the anterior, or front, and the posterior, or back. Each lobe is responsible for releasing specific hormones. The following hormones are made in the anterior (front part) of the pituitary gland:


    1. Prolactin - Prolactin stimulates breast milk production after childbirth. It also affects sex hormone levels from ovaries in women and from testes (testicles) in men, as well as fertility.

    2. Growth Hormone(GH) - GH stimulates growth in childhood and is important for maintaining a healthy body composition and well being in adults. In adults, GH is important for maintaining muscle mass and bone mass. It also affects fat distribution in the body.

    3. Adrenocorticotropic Hormone(ACTH) - ACTH stimulates the production of cortisol by the adrenal glands—small glands that sit on top of the kidneys. It helps maintain blood pressure and blood glucose levels, and is produced in larger amounts when we’re under stress—especially after illness or injury.

    4. Thyroid-Stimulating Hormone(TSH) - TSH stimulates the thyroid gland to produce thyroid hormones, which regulate the body's metabolism, energy balance, growth, and nervous system activity.

    5. Luteinizing Hormone(LH) - LH stimulates testosterone production in men and egg release (ovulation) in women.

    6. Follicle-Stimulating Hormone(FSH) - FSH promotes sperm production in men and stimulates the ovaries to produce estrogen and develop eggs in women.


    The Following Hormones are Stored in the Posterior (back part) of the Pituitary Gland:

    1. Antidiuretic Hormone (ADH) - ADH, also called vasopressin, conserves body water by reducing the amount of water lost in urine. Underproduction of ADH results in a disorder called diabetes insipidus characterized by inability to concentrate the urine and, consequently, excess urination leading potentially to dehydration.

    2. Oxytocin - Oxytocin causes milk to flow from the breasts in breastfeeding women, and may also help labor to progress.


  • Pituitary Tumors

    The most frequent type of pituitary disorder is a pituitary gland tumor. These tumors are fairly common in adults. They are almost always benign (that is, not cancer).


    There are two types of tumors—secretory and non-secretory. Secretory tumors produce too much of a hormone normally made by the pituitary, and non-secretory tumors do not. Both types of tumors can cause problems if they are large and interfere with normal function of the pituitary gland and/or nearby structures in the brain.


    The problems caused by pituitary tumors fall into three general categories:


    1. Hypersecretion - Too much of any hormone in the body is caused by a secretory pituitary tumor. Examples include acromegaly, Cushing's disease and prolactinoma.

    2. Hyposecretion - Too little of any hormone in the body can be caused by a large pituitary tumor, which interferes with the pituitary gland’s ability to produce hormones. Hyposecretion can also result from surgery or radiation of a tumor.

    3. Tumor Mass Effects - As a pituitary tumor grows and presses against the pituitary gland or other areas in the brain, it may cause headaches, or push upwards and interfere with vision – a visual field defect. Very occasionally, the tumor may expand sideways and cause double vision as it affects the nerves, which control eye movements.


    Injuries, certain medications, bleeding inside or close to the pituitary, and other conditions can also affect the pituitary gland. Loss of normal pituitary function also can occur after major head trauma.


  • Acromegaly, Gigantism

    Gigantism and acromegaly are hormonal disorders that result from too much growth hormone (GH) in the body. In these conditions, the pituitary produces excessive amounts of GH. Usually the excess GH comes from benign, or noncancerous, tumours on the pituitary.


    When GH-producing tumours occur in childhood, the disease that results is called gigantism. In response to GH, the long bones grow in length at the growth plate—areas near either end of the bone. Prolonged exposure to excess GH before the growth plates fuse causes increased growth of the long bones and thus increased height(Fig.1& 2). In more than ninety percent of individuals, the underlying cause is a benign pituitary tumour. Occasionally it may present as a feature of other conditions such as multiple endocrine neoplasia (MEN) type I, McCune-Albright syndrome (MAS), neurofibromatosis, tuberous sclerosis or Klinefelter syndrome.


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    Fig.1. Patient with gigantism standing beside a nurse who is 5ft 2inches tall.

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    Fig.2. Hand of the gigantism patient beside a normal
    adult hand for comparison.

    Since growth plates fuse after puberty, excessive GH production in adults does not result in increased height. It produces a condition known as acromegaly. The name acromegaly comes from the Greek words for “extremities” and “enlargement,” reflecting one of its most common symptoms—the abnormal growth of the hands and feet. Symptoms may include, coarse facial features as protruding jaw, enlarged lip, nose, and tongue(FIG.3), swelling of the hands and feet(Fig.4)degenerative arthritis, enlarged heart, fatigue and weakness, headaches, loss of vision, irregular menstrual cycles in women, diabetes and high blood pressure.


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    Fig.3. Facial appearance of acromegaly.

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    Fig.4. Thickened hand and fingers of acromegaly patient.


    In few patients, acromegaly is caused not by pituitary tumours but by tumours of the pancreas, lungs and adrenal glands that also lead to an excess of GH either because they directly produce GH or, more frequently, because they produce GHRH. Mostly, the overproduction of GH is caused by a benign tumuor of the pituitary gland.


    Treatment :

    The goal of treatment is to restore the pituitary gland to normal function, producing normal levels of growth hormone. Treatment may include removal of the tumor, radiation therapy, and injection of growth hormone blocking drugs.


    Surgical removal of the pituitary gland tumor should be considered as the primary treatment for most patients with acromegaly. Medical therapy should be administered only to patients with persistent postoperative disease. Somatostatin (octreotide) and Dopamine-receptor agonists (eg, bromocriptine, cabergoline), and GH receptor antagonists (pegvisomant) are the mainstays of medical treatment. Radiation treatment usually is reserved for recalcitrant cases.


  • Prolactinoma

    Prolactin is a hormone produced by the pituitary gland that stimulates breast milk production in pregnant and nursing women and its level falls with cessation of breast-feeding. Very high levels of prolactin (hyperprolactinemia) can cause hormonal disturbances including milk production to occur in men as well as in non- pregnant women.


    Prolactinomas, the most common type of pituitary adenomas (30% of all pituitary adenomas), cause excess secretion of the hormone prolactin (PRL).Prolactinomas are 5 times more common in women than in men and it occurs in the third and fourth decades of life.


    Prolactinomas cause symptoms either due to the hormonal effects of excess PRL or due to the pressure effect on the pituitary gland and the critical neurovascular structures that surround it such as the optic nerves. The hormonal symptoms resulting from hyperprolactinemia are different in males than in females.


    Prolactinomas are the most common cause of hyperprolactinemia. Prolactin secretion in the pituitary is normally suppressed by the brain chemical dopamine. Use of certain drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin.These include Metoclopramide, or anti-depressants such as Fluoxetine, an underactive thyroid gland (hypothyroidism), some growth hormone (GH)-producing tumours and other types of pituitary tumours that arise in or near the pituitary gland- as those may compress the pituitary stalk and block the flow of dopamine from the brain to the prolactin-secreting cells causing hyperprolactinemia, this is commonly known as “stalk effect”.


    Symptoms :

    In women, abnormal milk flow from the breast in a woman who is not pregnant or nursing (galactorrhea), breast tenderness, decreased sexual interest, headache, infertility, stopping of menstruation (amenorrhoea) not related to menopause, and vision changes


    In men, decreased sexual interest, enlargement of breast tissue (gynecomastia), headache, impotence, infertility and vision changes.


    Symptoms caused by pressure from a larger tumour may include headache, lethargy, nasal drainage, nausea and vomiting, problems with the sense of smell and vision changes (double vision, ptosis and visual field loss).


    If untreated, prolactinomas may enlarge, producing mass effects such as visual deficits or total blindness, cranial nerve palsies, hydrocephalus, pituitary apoplexy, and hypopituitarism. The effects of prolonged untreated hyperprolactinemia can include hypogonadism, infertility and osteoporosis.


    Diagnosis :

    1. A thorough medical history and neurological examination.
    2. Prolactin level in blood.Other pituitary hormones.
    3. Other pituitary hormones.
    4. MRI scan.
    5. Neuroopthalmological assessment of visual acuity (VA) and visual fields (VF).

    Treatment :

    Treatment is indicated if mass effects from the tumor, significant effects from hyperprolactinemia, or both are present. The goal of treatment is to return prolactin secretion to normal, reduce tumour size, correct any visual abnormalities, and restore normal pituitary function. Treatment options include medical, surgical and pituitary irradiation. In Prolactinoma patients with minimal symptoms or no symptoms, the patient can be monitored closely with serial estimations of serum PRL levels combined with imaging studies at yearly intervals.


    As dopamine is the chemical that normally inhibits prolactin secretion by the pituitary gland, drugs that act like dopamine or dopamine agonists e.g. Bromocriptine , pergolide , and cabergoline are used in the treatment of prolactinomas. Once started, these drugs must be continued for life as prolactin levels often rise again in most people when the drug is discontinued and failure is more likely with large prolactinomas. Using bromocriptine or one of the other drugs over time can reduce the chance of a cure using surgical removal. Therefore, if surgery is to be performed, its best timing is during the first six months of using medical therapy.


    Surgical treatment is reserved for women who have a microaprolactinoma, desire pregnancy and cannot tolerate or do not wish to take bromocriptine or one of the other drugs, patients who do not respond to medical treatment, or those who show progression of symptoms after an initial response to medical treatment.


    The use of radiotherapy for prolactinomas has declined in recent years due to the remarkable effectiveness of other treatments such as medications and surgery, hence it is usually reserved for patients who have persistent and progressive symptoms that were not cured by medications or surgery, or patients who cannot tolerate them.


    Even with successful treatment, careful monitoring of clinical signs and symptoms, serial measurements of serum PRL levels and pituitary imaging on yearly basis for the rest of the follow-up period are essential.


  • Cushings Disease

    Cortisol is a steroid hormone, produced by the adrenal gland.It is released in response to stress and low blood-glucose concentration. It functions to increase blood sugar, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates.It also decreases bone formation. Cortisol levels normally fluctuate throughout the day and night in a circadian rhythm that peaks at about 8 AM and reaches it lowest around 4 AM. Secretion of the hormone is controlled by the hypothalamus, the pituitary gland and the adrenal gland. Hypothalamus secretes CRH (corticotropin-releasing hormone) that stimulates the pituitary gland to secrete ACTH (adrenocorticotrophic hormone), which in turn stimulates adrenal gland to secrete cortisol. Release of CRH is controlled by the level of cortisol in blood.


    Prolonged exposure of the body to cortisol results in a condition known as Cushing's syndrome. The most common cause is the taking excessive cortisol-like medication such as prednisone. Certain tumor produce or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease. It is the second most common cause of Cushing's syndrome after medication. In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. It is responsible for 70% of endogenous Cushing's syndrome.

    Tumours of the Adrenal gland, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia also produce excess cortisol. Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. It is called ectopic or paraneoplasticCushing’s disease and is seen in diseases such as small cell lung cancer.Rare cases of CRH-secreting tumors have been reported, which stimulates pituitary ACTH production.


    Clinical Picture :

    Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, fatty deposits, especially in the midsection, the face (causing a round, moon-shaped face)(Fig.5)and between the shoulders and the upper back (causing a buffalo hump), weak muscles, weak bones, acne, and purple stretch marks on breasts, arms, abdomen(Fig.6), and thighs. Skin becomes thin and gets bruised easily. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headache, and a chronic feeling of tiredness.


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    Fig.5. Moon shaped face in Cushing's disease.

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    Fig.6. Purple stretch marks in abdomen.

    Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done to determine if the pituitary is involved.


    Treatment:

    Treatment of Cushing syndrome is directed by the primary cause of the syndrome. In general, therapy should reduce the cortisol secretion to normal to reduce the risk of comorbidities associated with hypercortisolism. The treatment of choice for endogenous Cushing syndrome is surgical resection of the tumor. The primary therapy for Cushing disease is transsphenoidal surgery. The goal of surgery is to remove the adenoma, preserving as much pituitary function as possible. Pituitary irradiation is employed when transsphenoidal surgery is not successful or not possible. The primary therapy for adrenal tumors is adrenalectomy.


    When surgery is not successful or cannot be undertaken, as in ectopic adrenocorticotropic hormone (ACTH) or metastatic adrenal carcinoma, control of hypercortisolism may be attempted with medication. However, medication failures are common, and adrenalectomy may be indicated in ACTH-mediated Cushing syndrome.


  • Non-secreting Tumour

    As non-functioning pituitary adenomas, also known as non-secretory adenomas do not produce any hormones, they tend to grow large before producing symptoms. Non-functioning pituitary adenomas represent approximately 30% of all pituitary tumours and they are usually macroadenomas (> 1 cm in diameter).


    Symptoms :

    The symptoms of non-functioning adenomas fall into two categories – tumour mass effects or hyposecretion effects.


    When they expand beyond the confines of sella, headache is commonly experienced because of the stretch on the sellar dura. Suprasellar expansion compresses optic nerve and/or chiasm causing varying degrees of visual disturbance and visual field defects (bitemporal hemianopia). Massive suprasellar growth may cause obstructive hydrocephalus and elevated intracranial pressure. Lateral growth into the cavernous sinus may cause double vision and facial pain or numbness.


    Pressure on the normal pituitary gland results in hypopituitarism. The pituitary cells that are most susceptible to pressure are the gonadotrophs, which are responsible for the production of sex hormones such as luteinizing hormone (LH) follicle-stimulating hormone (FSH) and testosterone followed by the thyrotrophs that produce the thyroid stimulating hormone (TSH), the somatotrophs that produce the growth hormone (GH), and the corticotrophs that produce adrenocorticotropic hormone(ACTH). Hypopituitarism can be partial or may lead to a complete deficiency of all pituitary hormones (panhypopituitarism). Effects are loss of appetite, weight loss or weight gain, fatigue, irregular menstrual cycle, infertility, reduced sex drive, impotence or failure to get or maintain an erection, inadequate function of the ovaries or testes, frequent urination during night, joint pains, dizziness and low blood pressure.


    Some patients with large pituitary tumours may have acute hemorrhage or infarction of the tumour (pituitary apoplexy) causing sudden onset of headache, visual loss, double vision, and/or pituitary failure, this condition is considered a surgical emergency requiring surgical decompression.


    Diagnosis :

    Hormonal evaluation is conducted to detect hypopituitarism. These blood tests evaluate baseline levels of different pituitary hormones such as TSH, ATCH, LH etc. Based on the results of the blood tests, additional hormonal studies may be required.


    Radiological evaluation includes magnetic resonance imaging (MRI) of the pituitary with and without gadolinium (a contrast agent) for visualizing the pituitary tumour, determining its size, location, and appropriate treatment plan. Neuro-ophthalmological assessment is done that includes visual acuity testing, fundus examination (fundoscopy) and visual field testing (perimetry).


    Treatment :

    Observation is sometimes appropriate for smaller tumours that do not threaten vision or cause headaches or other symptoms. But the patient must be closely followed-up with periodic MRI scans and blood testing for hormonal levels. For symptomatic pituitary adenomas, observation, as well as medical treatment, do not have a significant role. Endoscopic transnasal pituitary surgery is the treatment of choice. It effectively relieves the mass effect caused by the tumour such as the visual manifestations caused by pressure on the optic nerve(s). Radiation therapy is mostly reserved for recurrent and residual cases or if surgery could not be tolerated by the patient due to other health problems.


    Hormonal function may gradually return to normal, and a complete cure is obtainable. Postoperatively, periodic MRIs and hormonal assessment should be carried out for the rest of the follow-up period.


  • Overview of Endoscopic Pituitary Surgery

    A number of milestones have marked the development of transphenoidal pituitary tumour resection this century. The introduction of head lamp illumination, followed by the use of the operating microscope and fluoroscopy have allowed Neurosurgeons to perform this surgery in a safe and highly effective manner. This midline approach avoids the brain retraction associated with intracranial approaches to this region.


    Cushing operating on a transsphenoidal case wearing the headlight apparatus that has remained legendary for burning either his assistant or the nurse. The headlamp was made from an unshielded standard light bulb. (From Cushing H. The Weir Mitchell Lecture Surgical experience with pituitary disorders.)


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    Cushing was the first to describe the transseptal transsphenioidal approach to the sella turcica in 1912. Guiot and Hardy refined the technique and added intraoperative fluoroscopic guidance and the use of the surgical microscope. Since then, the approach has become the standard one for lesions of the sella. The most serious limitation of the standard transphenoidal approach is the very narrow surgical corridor. The narrow corridor limits the lateral and rostrocaudal view.


    This limitation can result in incomplete tumour resection or inadvertent injury to adjacent structures. Much of the dissection involved in standard transphenoidal surgery is done blindly, and the most significant mortalities result from inadvertent injury to the hypothalamus or carotid arteries. The standard transsphenoidal approach may employ a sublabial or nasal incision and requires a nasal speculum. This can result in septal perforation, tearing of the nostril, recurrent nose bleed, tooth analgesia, sinusitis and mucocoele.


    Currently endoscopic sinus surgery is accepted as a safe method of sinus surgery for inflammatory and polypoid conditions of ethmoid and sphenoid sinuses. Building on this experience, otolaryngologists accumulated considerable expertise in pituitary tumour resection aided by endoscopic techniques. The endoscope's short (5 to 15 mm) focal length enables a panaromic view of the sella with excellent magnification and illumination superior to the operative microscope. Angled scopes allow the surgeon to view the lateral parasellar and suprasellar areas. The improved sella visualization possible with the endoscope reduces carotid and hypothalamic injury and makes it possible to remove the tumour completely.


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    Fig.8 Picture shows narrow field of vision with microscope and the panaromic wide field of vision with telescope.


    Following are the Advantages of Endoscopic Pituitary Surgery:

    1. Able to have a closer view which reduces overall complications
    2. Panaromic view of sella, optic nerve & carotid artery
    3. Higher magnification & excellent illumination
    4. Angled telescopes allow a full sella view and surgery doesn't require blind dissection for tumour resection
    5. Less tissue destruction (no speculum)
    6. Less time consuming
    7. Short hospital stay

  • Our Technique & Results

    We use a purely endoscopic approach for removal of pituitary tumours. Most operations are performed using a 17 cm long, 4 mm, 00 endoscope. Additional 450 telescope can provide oblique views into the sella, facilitating complete tumour resection. The same instruments used in standard microsurgical approach as well as endoscopic sinus surgery instruments are used for the endoscopic approach to the pituitary. We use power drill whenever we come across thick bony sphenoid wall or there is pre-sellar pneumatisation of sphenoid. We usecomputer assisted surgical navigation system where the pneumatization of sphenoidis of pre-sellar / conchaltype.


    Operative Technique:

    General endotracheal intubation with general anesthesia is used. Face and nostrils are prepared using a 5% povidone iodine solution and a thigh is prepared for possible harvesting of fasia lata and muscle graft.


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    Fig.9. Endoscopic view of right nasal cavity. IT - inferior turbinate. MT - middle turbinate. S - nasal septum.

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    Fig.10. Lateralization of middle turbinate (MT) exposes superior turbinate (ST) and sphenoethmoid recess (SER).

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    Fig.11. Lateralization of superior turbinate (ST) exposes the ostium of sphenoid sinus (yellow arrow).

    Vasoconstriction of nasal mucosa, especially at sphenoethmoid recess is achieved with topical epinephrine. The middle turbinate and the superior turbinate are outfractured using Freer's elevator. This manoeuver exposes the sphenoethmoid recess and the ostium of the sphenoid sinus well. The mucosa at the sphenoethmoid recess is cauterized(Fig.9, 10 & 11).


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    Fig.12. Mucosal incision made at the junction of sphenoid keel and septum and the septum is displaced laterally (yellow arrow). This exposes contralateral sphenoid.

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    Fig.13. Entire anterior wall of sphenoid is exposed. R - right side. L - left side. White star - Keel of sphenoid.

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    Fig.14. Entire anterior wall of sphenoid is removed.

    The mucosa is incised at the level of junction of sphenoid rostrum and perpendicular plate of ethmoid, to elevate the mucoperiosteum over the contra lateral half of the anterior wall of sphenoid sinus sub-periosteally. Wide spenoidotomy done by removing the entire anterior wall of sphenoid sinus using Kerroson rongeur and drill(Fig.12, 13 & 14). Inside the sphenoid sinus there may be single or multiple septa. Sufficient amount of the septa are removed to expose the sella, carotid prominence, optic prominence and opto-carotid recess. Whenever possible attempts are made to remove the mucosa covering the sella only to avoid unwanted troublesome bleeding.


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    Fig.15. Sellotomy. Laterally upto cavernous sinus. Superiorly upto tuberculum. Inferiorly upto clivus.

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    Fig.16. Dural incision.

    The condition of the floor of the sella is subject to the type of lesion found in the sellar cavity. It is nearly always intact when the lesion is a craniopharyngioma, Rathke's cleft cyst or a pituitary microadenoma. It is often thinned and/or eroded in the presence of a pituitary macroadenoma. Depending on the condition, the sella floor can be opened using chisel or a dissector and it is enlarged with Kerrison punches. The sellotomy should be wide and it should extend from cavernous sinus to cavernous sinus laterally and from tuberculum sellae to clivus in the craniocaudal direction (Fig.15).The dura is incised using a scalpel(Fig.16).


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    Fig.17. Tumour removal. Green arrow - yellowish, firm normal pituitary. Yellow arrow - pinkish, soft tumour.

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    Fig.18. After complete removal of tumour. Green arrow - preserved normal pituitary gland. Black suction tip is inside the sella where the tumour had been removed completely.

    The tumour is removed using suction and various angled curettes and whenever possible normal pituitary gland is preserved (Fig.17 & 18). As the tumour is removed, the endoscope is advanced into the empty pituitary fossa. 450 telescope is used to visualize the entire sella and ensure complete resection and avoidance of important structures such as the internal carotid arteries. After tumour removal, haemostasis is secured. If cerebrospinal fluid (CSF) leak is seen during the operation, the sella is packed with fat or muscle graft. Nasal packing is usually not required.


    With practice, exposure of the sella can be achieved significantly faster than with standard microsurgical techniques. The decreased nasal dissection involved obviates the need for postoperative nasal packing and the associated post-operative patient discomfort. The angled endoscopes allow a full sella view, and surgery does not require blind dissection for tumour resection.


    Our Experience:

    From January 1997 to December 2015, our team at the Apollo Speciality hospital has carried out 927 endoscopic pituitary surgeries successfully. Out of 927 sellar lesions we managed, there were 892 pituitary adenomas, 19 craniopharyngiomas, 3 meningiomas, 5 Rathke's cleft cysts, 6 inflammatory lesions and 2 malignant tumours. Youngest patient we have operated so far was 8 years old and the age of the patient need not be a limiting factor.


    Complications:

    In our series of 927 cases, we didn't have any major vascular injury or injury to optic nerve or hypothalamus. We had 14 cases of temporary diabetes insipidus (DI) and none had permanent DI. Patients who were detected to have CSF leak during surgery were managed successfully and none had leak during the postoperative period. Only one patient had CSF leak 3 weeks after surgery and developed meningitis.


    Conclusion:

    Surgery for pituitary lesions has become greatly refined from the time Cushing described transsphenoidal approach. Endoscopic transsphenoidal pituitary surgery is now a proven and safe method of removing pituitary lesions and has been embraced as the preferred technique the world over.



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