What is pituitary surgery?
Pituitary tumors are a diverse group of benign and malignant neoplasms accounting for 16.7% of brain tumors and the third most common intracranial tumor.Surgical resection is the primary method preferred in interventional therapy that has led a hormonal resolution in more than 80% of the tumor subtypes, accounting for reduced rates of complications and mortality. As pituitary tumors present both endocrine and neuro-oncological issues, hence a multidisciplinary approach is required involving neurological, ophthalmological and endocrinological interventions.
Causes of pituitary tumors
- Molecular genetics: Majority of the pituitary tumors are monoclonal, which implies that genetic insult to a single cell results in spontaneous or acquired somatic change (initiation) and subsequently grow by clonal expansion (promotion), in relation to intrinsic mutation or extrinsic promoting factors. The gene strongly implicated in tumorigenesis is gsp oncogene and subsequent development of somatotroph adenomas. This pattern is exhibited by 40% of Growth Hormone (GH) - secreting tumors (somatotropinomas). Approximately 15% of Familial Isolated pituitary adenoma (FIPA) patients show mutations involving AIP gene and these patients were found to be younger at diagnosis with larger pituitary adenomas.
- Multiple Endocrine Neoplasia (MEN) type 1: Approximately 5% of patients exhibit a familial genetic background associated with MEN type 1. There is a germline mutation in MEN 1 gene encoding for protein menin; that brings about inactivation of tumor suppressor genes.
Signs and symptoms of pituitary tumors
- Impairment of visual functions manifested as visual field defects, decreased visual acuity, and decreased color vision, Ophthalmoplegia
- Neurological symptoms such as sudden onset severe headache, vomiting, dizziness, and diplopia or double vision
- Excessive prolactin secretion in premenopausal women causes amenorrhea, oligomenorrhea, or regular menses with infertility; galactorrhea
- Men develop loss of libido and erectile dysfunction, gynecomastia and galactorrhea
- Development of diabetes insipidus (DI), polyuria, and polydipsia (Diabetes insipidus is characterized by frequent urination (often hourly), especially at night; hypernatremia occurs if the patient does not ingest enough fluid to compensate for the urinary loss)
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH), causing hyponatremia with symptoms of fatigue, nausea, vomiting, and headache
- Excessive GH production causes acromegaly in adults and gigantism if it occurs before epiphyseal closure. Acromegaly is usually identified because of acral and facial enlargement.
- Pituitary hypersecretion of ACTH results in excessive stimulation of the adrenal glands, resulting in hypercortisolism and Cushing’s syndrome. Symptoms and signs of Cushing’s include weight gain (central, abdominal obesity, supraclavicular, posterior cervical), difficulty losing weight despite strict dieting, mood changes (most commonly depression), hirsutism, frontal and temporal hair loss, acne, oligomenorrhea or amenorrhea, muscle weakness (usually proximal), hypertension, diabetes, osteopenia, osteoporosis, bone fractures, skin infections (tineaversicolor, furuncles), vaginal candidiasis, facial plethora, and thin skin with ecchymoses
- TSH-secreting tumor is the rarest type of adenoma and causes hyperthyroidism with symptoms of tachycardia, tremor, weight loss, difficulty sleeping, heat intolerance, and hyperdefecation.
- Lymphocytic hypophysitis, pituitary apoplexy, and evidence of more extensive disease such as cranial nerve palsies, temporallobe epilepsy, hydrocephalus, and cerebrospinal fluid (CSF) rhinorrhoea are rarely seen.
Diagnosis of pituitary tumors
The diagnosis of pituitary tumorsrequires both, biochemical (endocrine studies) and anatomic (imaging studies) evaluation to provide maximal information and to direct appropriate therapy.
- Glucocorticoid deficiency: Provided the patient has not taken exogenous glucocorticoids for at least 24 hours, a single plasma cortisol of, 495nmol/l measured one hour after a 250 mg intramuscular or intravenous bolus of adrenocorticotrophic hormone (ACTH, synacthen) indicates deficiency.
- Thyroid hormone deficiency: Free thyroxine (FT4) at or below the bottom of the normal range indicates deficiency: thyrotrophin values (TSH) are frequently within the ‘‘normal’’ range. A patient who is listless and gaining weight and whose FT4 and TSH are both near the lower limit of the normal ranges is likely to have secondary hypothyroidism and may benefit from a trial of thyroxine replacement.
- Sex hormone deficiency: Amenorrhoea in women and tiredness and loss of libido in men. Erectile function is often impaired and both sexes become infertile with suppressed or low normal concentrations of gonadotrophins (FSH and LH). In women, no confirmatory tests are usually necessary. In men, low circulating testosterone concentrations indicate deficiency.
- Growth hormone deficiency: The peak GH secretory response to a bolus of GH releasing hormone (1 mg/kg) given at the beginning of a 30 minute infusion of arginine (0.5 g/kg) is a safer and more potent GH secretogogue than insulin induced hypoglycaemia.11 Measured every 15 minutes for 2 hours from time zero, failure to reach 20 mU/l (in our practice) indicates deficiency.
- Dynamic tests to evaluate pituitary hormone hypersecretion: in patients suspected with Acromegaly (GH)- oral glucose tolerance test is indicated, in patients suspected with Cushing’s syndrome- low dose dexamethasone test is indicated, while in Cushing’s disease- low dose dexamethasone test along with CRHa test, inferior petrosal sinus sampling and high-dose dexamethasone test is indicated;(aCRH: corticotropin-releasing hormone)
- Dynamic tests to evaluate pituitary hormone hyposecretion: in cases of ACTH deficiency- Insulin tolerance test and Metyrapone test, are indicated. In cases of GH deficiency- Insulin tolerance test, L-DOPA test, Arginine test, GHRHa test, and GHRPbtest.In cases of antidiuretic hormone (ADH) deficiency- water deprivation test is recommended. In cases of Gonadotropin (LH, FSH) deficiency- GnRHc test is recommended;(aGHRH: growth hormone-releasing hormone, bGHRP: growth hormone-releasing peptide, cGnRH: gonadotropin-releasing hormone)
- Vasopressin deficiency: Transient polyuria, nocturia, and thirst following pituitary surgery isusually sufficient to make the diagnosis of diabetes insipidus. Formal water deprivation testing is rarely required
- Imaging: Magnetic resonance imaging (MRI) scanning of the pituitary region, involving fine cuts and saggital and coronal reconstruction, which is the gold standard imaging method for pituitary disease. Computed tomography (CT) is referred for detection of calcified lesions like craniopharyngiomas. MRI enhancement by gadolinium,can be helpful for small microadenomas.
- Visual fields: in most of the cases progressive deterioration of visual fields is the main neurological criterion guiding the surgical intervention. Computerised visual fields are benficial even in cases where contact between the optic pathways and pituitary mass is absent, as this could be due to previous impingement or potential vascular shunting. Esterman fields are important to objectively assess fitness to drive.
Types of pituitary tumors
- Prolactinoma: It is the most common pituitary tumor accounting for 40–60% of clinically recognizable hyperfunctioning pituitary tumors and 6% to 23% in unselected autopsy series. Generally present as sparsely granulated, monohormonal, lactotroph adenomas. Estrogens cause hypertrophy and hyperplasia of normal and neoplastic lactotrophs. Rising levels of estrogen in normal pregnancy are responsible for lactotroph hypertrophy and hyperplasia, and the progressive increase in prolactin secretion, as well as the increase in size of the pituitary gland. 20–40% of women presenting with symptoms of oligo/amenorrhea, whether primary or secondary, have hyperprolactinemia, with prolactinomas being the most frequent cause of the hyperprolactinemic state. The incidence rises to 70–80% of women in whom the amenorrhea is associated with galactorrhea.
- Somatotroph adenoma: Associated with acromegaly and gigantism. The prevalence of acromegaly is approx 40–70 patients/1 million, and the incidence 3–4/yr/million. In most of the cases the disease onsets early in life but the diagnosis is delayed till adulthood. The diagnosis of acromegaly is based on the unmistakable clinical picture and the demonstration of inability of glucose to suppress growth hormone (GH) production. Release of GH is pulsatile, characterized by a succession of peaks and troughs throughout the 24-h day.Peak concentrations of approx 30 µg/L is observed in young women, that decrease with advancing age, are lower in obesity, and increase during prolonged fasting.Usually a space-occupying lesion can also be identified in the sellaturcica.If a GH-secreting pituitary adenoma develops before or during puberty, i.e., before the epiphyseal growth plates are fused, children may grow in excess before the correct diagnosis of pituitary gigantism is made. These tumors grow invasively owing to their large size, thus compromising the secretion of gonadotropins, this leads to hypogonadism. Therefore, these adolescents continue to grow long after the age of normal growth arrest and develop eunuchoid body proportions. Studies have found that one out of every five patients with gigantism are associated with McCune-Albright syndrome. Because of their large body weight combined with muscular weakness, neuropathy, and osteoarthropathy, such patients often have foot problems and a risk of foot ulcerations.
- Corticotroph adenoma: Associated with Cushing’s disease and Nelson disease. Cushing’s syndrome refers to the clinical manifestations of excess glucocorticoidsirrespective of specific etiology, while Cushing’s disease is often insidious in nature and refers to those cases of Cushing’s syndrome secondary to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, leading to glucocorticoid and androgen excess. Cushing’s disease accounts for 70% of patients with endogenous Cushing’s syndrome, and 30% attributable to the ectopic ACTH syndrome and primary adrenal tumors. A female predominance of 4:1has been observed. The characteristic finding is obesity, with a central distribution, leading to fat accumulation in the face (moon faces), neck, trunk, and abdomen, with relative sparing of the limbs. Dorsocervical (buffalo hump) and supraclavicular fat pad enlargement are also seen. Centripetal obesity can be documented by an elevated waist-to-hip circumference or central obesity index. Nelson disease refers to the rapid enlargement of ACTH-secreting pituitary adenomas after bilateral adrenalectomy for Cushing’s disease. It presents with aggressive and rapidly growing tumors, hyperpigmentation, and elevated ACTH levels, often accompanied by headaches and visual fields defects.
- Thyrotroph adenomas: Thyrotroph adenomas are rare pituitary tumors that eitherarise from a de novo somatic mutation of a thyrotroph cell or bythyrotroph hyperplasia following hypothyroidism.Initial complaints are of goiter and clinical signs of hyperthyroidism like fatigue, heart palpitations and heat intolerance. The TSH level is not completely suppressed, although circulating levels of T3 and T4 are elevated. Hypothyroidism may occur either due to congenital aplasia of the thyroid gland, or induced by iatrogenic thyroid ablation, antithyroid drugs, or following X-ray exposure of the thyroid. Most commonly occur due to autoimmune thyroiditis hence thyroid antibodies are commonly found in the serum. A femalepreponderance is seen. Hypothyroidism is mostly symptomatic once it causes thyrotroph hyperplasia of the pituitary. Unexplained weight gain, cold intolerance, fatigue, and headache are the common presenting symptoms. They almost uniquely show an exaggerated response of TSH. Measurements of free T4, TSH, and prolactin are recommended as associated hyperprolactinemia was found in approximately 78% of cases.
- Pituitary tumors in children: The adenohypophysis is derived from the anterior wall of Rathke’s pouch, an epithelial outgrowth of the primitive buccal cavity or the stomodeum, that forms at 24th day of intrauterine life. It meets the neurohypophysis, which extends inferiorly as an outgrowth of the hypothalamus. The cleft between the anterior and posterior wall usually regresses, but on rare occasions, it can expand and cause symptoms. Higher levels of most pituitary hormones are produced in the last two trimesters of fetal development and during the first two months postnatally. Pituitary adenomas account for approximately 2% of all pediatric brain tumors.
- Pituitary carcinoma: Approximately 0.2% of primary adenohypophyseal tumors eventually undergo either or both craniospinal/brain metastasis, or systemic spread. Such rare behavior is the sine qua non of “pituitary carcinomas.” Over 75% of pituitary carcinomas are hormone-producing and endocrine-active. PRL cell carcinoma is the most common subtype.
Grades of pituitary tumors
As proposed by Hardy, microadenomas are less than 1cm in diameter, while macroadenomasare greater than 1 cm in diameter. Microadenomas are designated as grade 0 if the sellar appearance is, and grade I if minor sellar changes are present. Macroadenomas, causing diffuse enlargement are grade II, showing focal destruction are grade III, and with extensive destruction of sella are grade IV tumors. Macroadenomas are further subclassified on the degree and direction of extrasellar extension.
- Grade 0: Intra-pituitary microadenoma; normal sellar appearance.
- Grade I: Intra-pituitary microadenoma; focal bulging of sellar wall.
- Grade II: Intrasellarmacroadenoma; diffusely enlarged sella; no invasion.
- Grade III: Macroadenoma; localized sellar invasion and/or destruction.
- Grade IV: Macroadenoma; extensive sellar invasion and/or destruction.
Pituitary surgery procedures
- Transphenoidal approach: It is the most physiologic and minimally traumatic technique of surgical access to the sella, as it provides a direct and superior visualization of the pituitary gland and adjacent pathology. Due to its effectiveness and safety, this approach is indicated in more than 95% of pituitary tumors.
- Transcranial approach: In case of tumors that have extended beyond the sella, and have spilled into the anterior, middle, or posterior cranial fossae, a transcranial approach offers superior access.
- Extracranial approach: When the standard transsphenoidal corridor proves too restrictive for tumors that extend widely beyond the confines of the sella, an extracranial approach can be utilized.
Complications of pituitary surgery
- Damage to the HT may result from direct surgical injury, and also from hemorrhage or ischemia provoked by the procedure
- Damage to the optic nerves and chiasm can also occur from direct surgical trauma, hemorrhage, or ischemia
- Arterial injury is one of the chief sources of operative mortality accompanying the procedure
- CSF rhinorrhea and meningitis are caused by disruption of the sellar diaphragm
- In the process of stripping the tumor from the medial dura, injury to the cavernous sinus and its contents can occur
- Iatrogenic Hypopituitarism
- Diastasis or fracture of the hard palate, optic canals, or the cribiform plate
Am I a good candidate for pituitary surgery?
Patient entails a pituitary surgical intervention if in addition to the mentioned signs and symptoms, they experience apoplexy i.e. hemorrhage into an existing pituitary tumor or acute necrosis of the tumor with subsequent swelling. If there is a progressive mass and systemic involvement of the disease with hyperfunctioning of hormones or a failure of prior therapy then surgery is advised.
Recovery time and aftercare
Following surgery, monitoring of water and electrolyte balance is mandatory. Exogenous stress level steroids (hydrocortisone 20 mg/d) are rapidly tapered, beginning on the first p/o day. Prophylactic antibiotics are continued until the nasal packing is removed, usually till the second p/o day. In uncomplicated cases, the patient can be discharged from hospital by the fourth day. The first follow-up visit occurs about 6 wk after surgery, follow-up gadolinium enhanced MRI of the sella is usually performed at approx 3 mo postoperatively, formal visual field examinations are also performed at the 3-mo visit for patients who presented with any preoperative visual deficits.
Success rate of pituitary surgery:
Transsphenoidal surgical interventions have been highly successful over the years, with only 0.5% mortality and 2.2% morbidity rates noted.
Benefits of pituitary treatment:
Surgical intervention of microadenoma of Acromegaly has shown a remission rate of 72%, prolactinoma 87%, and Cushing’s disease 91%., while macroadenomas have shown a remission of 50 to 56%. Recurrence after surgery in case of Acromegaly is 8%, prolactinoma is 13%, and Cushing’s disease is 12% in adults and 42% in children.
Cost of pituitary surgery:
Cost of the surgery including the non-surgical parts like the investigative procedures and hospitalization may range approximately at $72,000.
Why choose Medcureindia?
Pituitary tumors are a heterogeneous group of tumors both clinically and pathologically, which is a challenge for the patient, their family and the consultant physician. We provide extensive assistance for patient as well as their accompanying family members, and reinforce adequate care. Our advanced technology and diverse expertise in the field are handy for felicitous surgical interventions.