Pituitary adenoma

Description

Pituitary adenoma is a benign tumor arising from the pituitary gland.

Anatomy and physiology 

Pituitary gland is located in the middle of the skull base under the brain. It is a nested in the “sella turcica” (Turkish saddle) at the top part of the nasal cavity in the sphenoid sinus. Therefore, pituitary gland is located at the border of the brain and the nasal cavity.

 

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It is controlling other endocrine glands and therefore called an “orchestra conductor” of endocrine system. 

Pituitary gland has two parts which have different functions. Front part or adenohypophysis produces and releases several hormones:

 

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TSH (thyroid stimulating hormone) is a single hormone controlling function of thyroid gland. It direct action on the gland is to stimulate it to produce more thyroid hormones.

ACTH (adrenocorticotropic hormone) is a hormone stimulating adrenal glands to make more steroid hormones like cortisol. 

LH (luteinizing hormone) and FSH (follicle stimulating hormone) — in both women and men these hormones are necessary for proper function of the reproductive system.  

Prolactin is a hormone stimulating milk production by breast tissue during breastfeeding period. 

Back part or neurohypophysis stores and releases vasopressin (AKA antidiuretic hormone —controls water balance) and oxytocin (controls uterus contraction during delivery). Oxytocin is also known as a “cuddle hormone” or “love hormone” since it is released when people make social bonds.

Pituitary gland itself is controlled by the part of the brain called hypothalamus, located just above the gland. The anatomical relationship between pituitary gland and hypothalamus is unique. Pituitary stalk is an anatomical connection between the hypothalamus and pituitary. Hormones of neurohypophysis like oxytocin and vasopressin are produced in the hypothalamus and delivered to pituitary via the stalk. Also venous blood escaping from hypothalamus does not enter systemic circulation. Rather it flows to pituitary gland through the pituitary stalk. Therefore, control hormones released by hypothalamus can directly reach pituitary. Integrity of pituitary stalk is essential for normal pituitary function.

 

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Classification

Pituitary adenomas are classified either on basis of their size or hormone status. 

Based on the size of adenoma:

    Microadenoma is a tumor with size less than 1 cm

    Macroadenoma is a tumor more than 1 cm

Based on the hormonal status of adenoma:

   Hormone active adenoma:

     Prolactinoma

     Tireotropinoma

     Corticotropinoma

     Gonadotropinoma

     Somatotropinoma

   Hormone inactive adenoma.

Symptoms

Pituitary adenoma clinically presents with endocrine disturbance and/or compressive effect on nearly structures. 

 

Endocrine disturbances depend on hormonal status of the adenoma. If tumor is producing extra amount of hormone (hormone active adenoma) usually symptoms are related to excess of particular hormone:

 

Prolactinoma - usually presents with galactorrhea — i.e. abnormal milk or milk-like substance discharge from the nipples. In women, menstrual cycle usually is irregular. In men, libido and erection are diminished. 

Galactorrhea illustration

Thyreotropinoma - excess of TSH stimulates thyroid gland to produce and secrete more thyroid hormones. The patient develops typical symptoms of hyperthyroidism. 

 

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Corticotropinoma - increased ACDH stimulated adrenals to synthesize and release excessive amounts of steroid hormones. This usually leads to Cushing’s disease. On typical presentation, the patients develop obesity, hypertension (high blood pressure) and hyperglycemia (increased sugar in blood).

Cushing's disease symptoms

Gonadotropinoma is a type of pituitary adenoma producing either FSH or LH. Despite increased level of these hormones ovaries and testes are not stimulated. This type of hormonal excess may not be symptomatic at all. If there are symptoms usually they are related to reproductive function suppression. Infertility, loss of libido, menstrual disturbances are usual symptoms.

A couple suffering from infertility

Somatotropinoma presentation is different in children and adults. Since children are capable of growing increased amount of growth hormone produces abnormal growth — a condition is knows as gigantism. In adults, only small bones are growing. Usually hands, legs and face is affected  leading to acromegalia.  

In addition to hormonal hyper-secretion symptoms, pituitary adenoma may cause compression of the normal pituitary gland and lead to hypopituitarism — ie loss of normal pituitary function.

Another group of symptoms related to pituitary adenoma is caused by  its mass effect. In other terms growing tumor may compress nearby structures and cause neurological deficit.

Optic nerves pass just above pituitary gland and are most commonly affected that leads to loss of vision. Typically optic chiasm is compromised causing loss of vision on sides. These patients usually complain of narrowing of their visual fields. Presence of loss of vision is very important since it is considered as one of the most important indications for surgery. 

If tumor extends sideways it may invade cavernous sinus. Fine nerves passing inside the cavernous sinus may become compressed and compromised leading to double vision. 

In rare cases tumor may reach gigantic size invading the brain. Usually seizures and/or hydrocephalus can be seen in these cases.

Sometimes tumor grows downward toward nasal cavity. It may remain silent for a long time because nasal cavity is big enough to accommodate growing tumor. But eventually nasal cavity may become obstructed leading to apnea.

Pituitary tumor is slow growing allowing nearby structures to adapt to compression by the tumor. Yet there in some cases pituitary apoplexy may develop leading to rapid tumor expansion. This condition is caused either by bleeding into the adenoma or ischemic event causing tumor swelling. In any case expanding tumor mass compresses optic nerve and normal pituitary causing loss of vision and hypopituitarism. Pituitary apoplexy is an emergent condition requiring prompt removal of the tumor to relieve the pressure from the optic nerves and preserve vision. Delays in surgical procedure may lead to permanent loss of vision. 

Treatment 

There are endocrinological and neurosurgical perspectives involved in the treatment of pituitary adenomas. From the endocrinological perspective, it is important to restore the body’s hormonal balance. Neurosurgeons on the other hand focus on relieving the pressure from the neural structures. Therefore, usually these patients are treated with team of endocrinologists and neurosurgeons. 

Prolactinomas can be initially treated with medical treatment. Dopamine agonist drugs can suppress the tumor growth and relieve mass effect. However there are several handicaps of medical treatment. First, in some instances this therapy fails to control tumor growth. Second, patients may not tolerate side effects of the medication. Third, dopamine agonist therapy makes tumor fibrotic and difficult to remove surgically. Another handicap of the medical treatment is a significantly increased risk of pituitary apoplexy. All patients receiving dopamine agonist therapy should be instructed about this complication and they should immediately seek neurosurgical intervention in cases of sudden vision loss. 

Somatotropinomas are usually treated with surgery since complete removal leads to cure. Residual tumors or adenomas not suitable for surgical removal are treated with somatostatin therapy. This synthetic hormone inhibits the secretion of growth hormone from the tumor. 

Cortictotropinomas are challenging tumors since they may be too small  to be detected by MRI. Additional tests and even explorative surgery may be required to identify location of these tumors. Another aspect of corticotropinoma surgery is stormy post-operative period. These patients have increases level of steroid hormones which drops significantly after surgery. Therefore, these patients may experience significant steroid withdrawal symptoms post-operatively. 

Gonadotropinomas and hormonally hormonally inactive tumors are not treated unless there is a mass effect. There is no conservative treatment available for these types of pituitary adenoma and the surgery is the only choice. 

Surgery for pituitary adenomas is usually performed from the nasal cavity and is considered as one of the most difficult neurosurgical procedures. The surgeon may use either microscope or endoscope for approaching and removing the tumor. In recent years, growing number of neurosurgeons use endoscope for this pituitary surgery. Nasal cavity is very narrow and has irregular shape making surgical manipulation difficult. Additionally, pituitary gland is located at the deepest part of the nasal cavity, inside the sphenoid sinus. During surgery the sphenoid sinus is exposed from the nasal cavity. Afterwards, by opening the floor of the sella the tumor is visulized and removed.

There are several hurdles of pituitary surgery.  Carotid arteries pass on each side of the piutary gland and posess significant problem for the surgeon. Another important aspect is possibility of cerebrospinal fluid leakage. Normally pituitary gland and adenoma are separated from the brain by a thin membrane called diaphragma sellae. This membrane may be damaged during surgery leading to cerebrospinal fluid leakage from the nose — rhinorrhea. Since nasal cavity is infected area the CSF leakage may cause meningitis which is a potentially life threatening condition.