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Pituitary Neoplasm

Pituitary neoplasms are benign adenomas in the vast majority of cases and can secrete pituitary hormones such as prolactin and growth hormone. Symptoms include a headache and bitemporal hemianopsia in larger tumors, while hormone-induced effects such as acromegaly, galactorrhea, and Cushing's disease may be observed. The diagnosis is made by thin-sliced MRI and treatment usually involves surgery. In the case of prolactinoma, dopamine agonists are efficiently used.


Presentation

Patients may present with diverse complaints that significantly depend on which pituitary cells are affected and whether the tumor is secreting or not. Smaller, nonsecreting adenomas may be asymptomatic, but the majority of patients report at least one or two symptoms. A headache is rather common, while visual complaints are often present in larger tumors due to compression of the optic chiasm. Bitemporal hemianopsia is highly specific for a pituitary neoplasm, while decreased visual acuity and abnormal pupillary light reflex may be noted as well. Tumor-dependent symptoms seen in pituitary adenomas include:

In larger tumors, increased production of more than one hormone may be seen [11]. On the other hand, craniopharyngiomas are often accompanied by some form of hormone insufficiency. In approximately 80% of cases, hormonal dysfunction is encountered, most commonly GH, FSH, and LH, but a deficiency of any pituitary hormone may occur [3].

Camping
  • Certain molecular changes of G-proteins lead to a persistent generation of important second messenger cAMP, with resultant uncontrolled cellular proliferation.[symptoma.com]
Buffalo Hump
  • Features of Cushing's disease, such as central obesity, moon facies, hypertension and development of a "buffalo hump", may be seen in ACTH-secreting tumors. In larger tumors, increased production of more than one hormone may be seen.[symptoma.com]
Loss of Peripheral Vision
  • […] of peripheral vision), drooping eyelids or changes in color vision Headache Lack of energy Nasal drainage of clear fluid Nausea and vomiting Problems with the sense of smell In rare cases, these symptoms occur suddenly and can be severe ( pituitary apoplexy[medlineplus.gov]
  • Large tumors put pressure on the area around the pituitary gland and cause: Headaches Problems with eyesight, especially loss of peripheral vision (what you can see off to the side even as you look straight ahead) and double vision They can also press[webmd.com]
  • This can lead to symptoms such as: Eye muscle weakness so the eyes don't move in the same direction at the same time Blurred or double vision Loss of peripheral vision Sudden blindness Headaches Facial numbness or pain Dizziness Loss of consciousness[cancer.org]
  • Loss of peripheral vision may occur first and be undetected. This may progress to eventual blindness if the pressure is not removed from the nerve. Almost any kind of visual problem can be seen with large pituitary tumors.[houstonmethodist.org]
Hemianopsia
  • Cushing-like effects, diplopia, bitemporal hemianopsia and diabetes insipidus are some of many symptoms that can be encountered.[symptoma.com]
  • The most common problem is to lose vision in the outer fields (peripheral vision), called a bitemporal hemianopsia. Often patients do not notice this, as they correct for the problem by moving their head back and forth.[houstonmethodist.org]
  • This type of pituitary adenoma results in: • Blurry vision • Loss of peripheral vision, called bitemporal hemianopsia • Loss of color perception, the ability to distinguish colors • Headache Pituitary apoplexy can be a severe result of any type of pituitary[texasspineandneurosurgerycenter.com]
  • Learn More Neurological problems Larger pituitary macroadenomas often cause loss of visual acuity or peripheral vision (termed bitemporal hemianopsia) from pressure on the optic nerves and optic chiasm which is directly above the pituitary gland.[pacificneuroscienceinstitute.org]
  • Visual studies are important for evaluating any possible or existing visual field defects caused by large tumors that compress the optic pathways; bitemporal hemianopsia (loss of peripheral visual field) is the classic finding when a pituitary tumor compresses[skullbaseinstitute.com]
Diplopia
  • Cushing-like effects, diplopia, bitemporal hemianopsia and diabetes insipidus are some of many symptoms that can be encountered.[symptoma.com]
  • […] muscle weakness exertional intolerance and shortness of breath oligomehnorrhea (decreased menstrual flow) nervousness and irritability other mental disturbances sleep disturbances (including insomnia) changes in vision, photophobia, eye irritation, diplopia[pituitary.mgh.harvard.edu]
  • However, the physical signs that are typically present with large pituitary tumors such as bitemporal hemianopsia, diplopia or often signs of III, IV, VI nerve palsies are not present.[clinicaladvisor.com]
Blurred Vision
  • Patients with involvement of one optic nerve may notice dim, dark, or blurred vision in one eye. Occasionally this may be noted when one happens to cover one eye and notes that they can't see out of the opposite eye.[willseye.org]
  • Their growth can compress nearby cranial nerves, causing blind spots, blurred vision, or double vision. Pituitary tumors also can cause symptoms through the overproduction of hormones.[neurosurgery.wustl.edu]
  • Pressure from these tumors on nearby structures can cause of wide range of symptoms, including: Body hair loss Change in the amount and frequency of urination Decrease in sexual libido, usually in men Dizziness Double vision, blurred vision or peripheral[loyolamedicine.org]
Headache
  • The clinical presentation mainly depends on hormone-secreting effects, but a headache may often be the only symptom.[symptoma.com]
  • CONSUMERS: Click here for the Consumer Version Patients with hypothalamic-pituitary lesions generally present with some combination of Symptoms and signs of a mass lesion: headaches, altered appetite, thirst, visual field defects—particularly bitemporal[merckmanuals.com]
  • Headache Patients with macroadenomas often have frontal, forehead and temporal area headaches. Pituitary adenoma removal often results in headache resolution.[pacificneuroscienceinstitute.org]
  • These tumors may grow large enough to cause symptoms such as headaches and vision problems before they are found. (See the symptoms for large tumors above.)[cancer.org]
  • […] in a woman who is not pregnant or breast-feeding Too much ACTH may cause: Headache Some loss of vision Weight gain in the face, neck and trunk of the body, and thin arms and legs A lump of fat on the back of the neck Thin skin that may have purple or[cancer.osu.edu]
Bitemporal Hemianopsia
  • Cushing-like effects, diplopia, bitemporal hemianopsia and diabetes insipidus are some of many symptoms that can be encountered.[symptoma.com]
  • The most common problem is to lose vision in the outer fields (peripheral vision), called a bitemporal hemianopsia. Often patients do not notice this, as they correct for the problem by moving their head back and forth.[houstonmethodist.org]
  • This type of pituitary adenoma results in: • Blurry vision • Loss of peripheral vision, called bitemporal hemianopsia • Loss of color perception, the ability to distinguish colors • Headache Pituitary apoplexy can be a severe result of any type of pituitary[texasspineandneurosurgerycenter.com]
  • Learn More Neurological problems Larger pituitary macroadenomas often cause loss of visual acuity or peripheral vision (termed bitemporal hemianopsia) from pressure on the optic nerves and optic chiasm which is directly above the pituitary gland.[pacificneuroscienceinstitute.org]
  • Visual studies are important for evaluating any possible or existing visual field defects caused by large tumors that compress the optic pathways; bitemporal hemianopsia (loss of peripheral visual field) is the classic finding when a pituitary tumor compresses[skullbaseinstitute.com]
Sexual Dysfunction
  • Hyperprolactinemia symptoms could include menstruation irregularities and other menstrual problems, breast discharge in women, loss of libido, sexual dysfunction and headaches.[uwhealth.org]
  • Some common symptoms include: Vision problems Headaches Nausea and vomiting Unexplained weight change Menstrual cycle changes in women Sexual dysfunction Please note that the presence of these symptoms alone do not mean that you have a pituitary tumor[barrowneuro.org]
  • Compression of the pituitary gland by a hormone-inactive tumor can result some form of pituitary failure with one or more of the following pituitary tumor symptoms : • Low blood pressure • Fatigue • Inability to handle stress • Sexual dysfunction Compression[texasspineandneurosurgerycenter.com]
  • Manifestations may include hypogonadism (sexual dysfunction, loss of libido, and impotence), hypothyroidism (fatigue, weakness, weight gain, coarse dry hair and dry skin, cold intolerance, depression), adrenal insufficiency (fatigue, weakness, loss of[pacificneuroscienceinstitute.org]
Amenorrhea
  • In the case of prolactinoma amenorrhea, galactorrhea and infertility may be encountered, while acromegaly and gigantism are usually the result of GH-secreting pituitary adenoma.[symptoma.com]
  • Prolactinoma and nonfunctioning pituitary adenoma: infertility amenorrhea (absence of menses or menstrual periods) oligomenorrhea (irregular/sparse menstruation) decreased libido (interest in sex) galactorrhea (breast milk production / leakage / nipple[pituitary.mgh.harvard.edu]
  • They may cause discharge from breasts (galactorrhea), irregular periods (oligomenorrhea) or loss of normal menstrual function (amenorrhea) in females and impotence in men.[my.clevelandclinic.org]
  • In women, this can cause loss of menstrual periods (amenorrhea) and fluid discharge from the breasts (galactorrhea).[willseye.org]
  • Panhypopituitarism - Refers to deficiency of several anterior pituitary hormones; may occur in a slowly progressive fashion (eg, pituitary adenomas) Hormonal overproduction - Clinical effects Prolactin Hypogonadism, if hyperprolactinemia sustained Women - Amenorrhea[emedicine.medscape.com]

Workup

A detailed patient history and a thorough physical examination may provide sufficient information to suspect a pituitary neoplasm. Obvious signs such as acromegaly and galactorrhea, strongly suggest the presence of the pituitary tumor, after which appropriate laboratory and imaging studies need to be done. Levels of PRL, insulin-like growth factor 1 (IGF-1), LH, FSH, TSH, and ACTH should be obtained. The diagnosis of prolactinoma can be made solely on laboratory findings [12]. MRI is used to confirm the presence of a pituitary tumor and identify its exact location, but because tumors may be very small, 1-mm thick slices are recommended [4]. If patients report a family history of other endocrine tumors, a detailed diagnostic workup toward identifying potential familial syndromes such as MEN 1 should be conducted.

Enlarged Sella
  • A pituitary tumor tends to produce an enlarged sella (sella turcica). Alternatively, an enlarged sella may represent empty sella syndrome.[merckmanuals.com]

Treatment

After the diagnosis of a pituitary neoplasm is made by MRI, treatment depends on various factors, such as the size, location, and a presence of symptoms. Large, symptomatic tumors are often surgically handled as soon as possible, most likely via the transsphenoidal approach. Not all tumors have to be surgically handled, as some respond to pharmacologic therapy quite well. Dopamine agonists, such as bromocriptine, are shown to be very effective against prolactinomas and often cause sufficient tumor shrinkage with marked reduction of prolactin synthesis [12]. Growth hormone receptor antagonists and somatostatin analogs are used in the case of GH-secreting adenoma, while steroidogenesis inhibitors are often used as adjunctive therapy in ACTH-secreting tumors [8]. Radiotherapy is often used as first or second-line therapy in managing pituitary neoplasms, as they are shown to be very sensitive to radiation and their main use is in the post-operative setting [8]. Studies have shown that adjunctive radiation therapy, especially when complete excision of the tumor is not possible, is significantly better over surgery alone [13].

When it comes to surgery, indications include symptomatic patients, both secretory and nonsecretory tumors of a large size that cause local tissue destruction. Microadenomas that are discovered incidentally may not require surgical therapy but should be followed up instead. The transsphenoidal approach, although shown to be one of the most favored approaches in managing pituitary neoplasms, carries several risks. Olfactory injury and pituitary apoplexy are some of the most important [14] , which is why all attempts to manage these tumors conventionally should be made. However, with the introduction of intraoperative MRI examination [15], higher complete excision rates have been observed.

Prognosis

An early diagnosed neoplasm carries a very good prognosis. These tumors are almost universally benign, as cases of malignant pituitary tumors are extremely rare. However, in the case of large adenomas which cause significant damage to the optic chiasm and surrounding structures, patients could have a serious clinical picture. Additionally, numerous complications may arise during surgical therapy, especially in the setting of a large pituitary neoplasm, which is why an early diagnosis significantly improves chances of a successful treatment.

Etiology

The pituitary gland is composed of two lobes: the anterior (adenohypophysis) and posterior (neurohypophysis), with each region containing cells that create specific hormones. In the anterior lobe, there are several cell types, each having distinct physiological function [3]:

  • Thyrotroph cells synthesize thyroid-stimulating hormone (TSH).
  • Somatotroph cells produce growth hormone (GH).
  • Gonadotroph cells secrete luteinizing (LH) and follicle-stimulating hormone (FSH).
  • Corticotroph cells secrete adrenocorticotropic hormone (ACTH)
  • Lactotroph cells produce prolactin (PRL).

Oxytocin and vasopressin (antidiuretic hormone or ADH), on the other hand, are produced in the posterior hypophysis from magnocellular neurons. Each of these cellular types can be a source of neoplastic growth, resulting in the development of adenoma. These tumors can be described as secretory or nonsecretory and their clinical presentation directly depends on presence or absence of the hormone production [2]. Craniopharyngiomas, however, arise from squamous rest cells that are located between the two pituitary lobes. Several gene mutations have been discovered in patients with pituitary neoplasms and are thought to be the main causative factors. In the case of adenoma PTTG [9] and several other genes are involved. Galectin-3, a beta-galactoside-binding protein, is a significant factor in pituitary tumor formation [10]. Genetic processes in craniopharyngiomas remain incompletely resolved, but mutations in the β-catenin gene are confirmed in these neoplasms [2].

Epidemiology

Approximately 10-15% of all intracranial tumors are pituitary neoplasms and numerous studies have established that these lesions are not uncommon in the general population. Prevalence rates are estimated to range from 10-16.7% in some larger samples, while macroadenomas are seen in 1 in 600 individuals [4] [5]. Other studies report much higher rates of these tumors, up to 38% [5], implying that many individuals with microadenomas are undiagnosed, presumably because a significant percentage of these tumors are nonsecretory and very small. The majority of pituitary tumors are adenomas (approximately 90%) [1]. Craniopharyngiomas, however, comprise between 80-90% of pituitary tumors seen in childhood and their peak incidence is shown to be between 5-14 years [3]. Apart from a family history of pituitary tumors or MEN 1, no other risk factors have been identified so far.

Sex distribution
Age distribution

Pathophysiology

The pathogenesis model invariably includes genetic factors and various protein molecular changes have been identified. In the case of secreting adenomas, the cascade starts with alterations in G-proteins as a result of gene mutations. G proteins are a basic component of signal transduction, and they are responsible for transmission of signals from cell surface receptors to intracellular effectors, which are responsible for a generation of second messengers. Certain molecular changes of G-proteins lead to a persistent generation of important second messenger cAMP, with resultant uncontrolled cellular proliferation [2]. In addition, various genes, such as those which encode for galectin-3 protein and PTTG, exhibit mutations. In craniopharyngiomas, β-catenin gene mutations have been observed in about 20% of patients.

Prevention

Although the pathogenesis of pituitary neoplasms is mainly well understood, no preventive measures exist. An early diagnosis that can be achieved through detailed evaluation of patients with unexplained headaches and other accompanying symptoms, can undoubtedly lead to better outcomes.

Summary

Pituitary neoplasms comprise 10-15% of all intracranial tumors and are almost universally benign [1]. Pituitary adenomas and craniopharyngiomas are the two most common types, with somewhat different prevalence rates among age groups. Adenomas are divided based on the presence or absence of hormone production. Prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are all synthesized in the pituitary gland and depending on the location of the tumor, one or more hormones may be secreted [2]. Adenomas comprise almost 90% of pituitary tumors in adults [1], while craniopharyngiomas constitute 80-90% of pituitary fossa tumors found in children [3]. Estimated prevalence rate between 10-16.7% suggest that this tumor is rather often in the general population (although not all of them cause symptoms), while very large adenomas ( > 1cm, or macroadenomas) are thought to develop in approximately 1 in 600 individuals [4] [5]. These tumors may also appear as constituents of familial syndromes such as multiple endocrine neoplasia type 1 (MEN 1), in which concomitant development of pituitary, pancreatic and parathyroid neoplasms are observed. Various gene mutations have been established in the pathogenesis of pituitary neoplasms. Molecular changes of various genes, such as PRKAR1A and pituitary tumor transforming gene (PTTG) are seen in pituitary adenomas [6] [7]. On the other hand, β-catenin gene mutations are seen in craniopharyngiomas, along with various cytogenetic abnormalities [2]. The clinical presentation mainly depends on hormone-secreting effects, but a headache may often be the only symptom. In the case of prolactinoma amenorrhea, galactorrhea and infertility may be encountered, while acromegaly and gigantism are usually the result of GH-secreting pituitary adenoma. Cushing-like effects, diplopia, bitemporal hemianopsia and diabetes insipidus are some of many symptoms that can be encountered. To make the diagnosis, magnetic resonance imaging (MRI) is the gold standard, together with an evaluation of hormone levels that are suspected to be abnormal based on clinical findings [8]. Treatment principles depend on the location, size and secretory properties of the tumor. Surgical excision of the tumor via the transsphenoidal approach is often indicated as the first-line therapy, but some tumors may be handled without surgery. Prolactinomas are effectively treated by dopamine agonists, such as bromocriptine, while somatostatin analogs and GH-receptor antagonists together with radiotherapy are being used in GH-secreting tumors [8].

Patient Information

Pituitary neoplasms arise from the pituitary gland, one of the most important glands in our body, since it secretes various hormones that regulate a vast number of important functions in the body. In general, tumors of the pituitary are divided into two major groups: adenomas (constitute approximately 90% of all pituitary tumors in adults ) and craniopharyngiomas (80-90% of pituitary tumors in children). Additionally, adenomas can be classified into a secreting and nonsecreting group, meaning that the cells affected by neoplastic growth may secrete abnormal amounts of hormones or remain inactive. Growth hormone, prolactin, adrenocorticotropic hormone (ACTH), gonadal hormones and thyroid-stimulating hormone (TSH) are all synthesized and secreted inside the pituitary gland and tumors may arise from each of the cells that are responsible for their production. Consequently, overproduction of hormones is often encountered in adenomas and result in characteristic symptoms. Tumors of cells that create prolactin (prolactinomas) cause symptoms such as gynecomastia (enlarged breasts), galactorrhea (milk discharge from the breasts) and infertility, while neoplasia of growth hormone secreting cells will cause a profound growth of hands, feet and the jaw (acromegaly). Various other symptoms may be seen, including headaches, visual problems, hypertension, central obesity, but hypopituitarism (reduced secretion of hormones) may be encountered as well, especially in craniopharyngiomas. To make the diagnosis, establishing levels of pituitary hormones and magnetic resonance imaging of the head (MRI) is imperative. Once the tumor is confirmed, treatment depends on the tumor type. Prolactinomas are treated only by drugs, specifically dopamine agonists such as bromocriptine, which suppress prolactin production and tumor growth, but surgical excision is usually the preferred method for all other tumors. Surgery is performed through the nose and the sinus that is below the pituitary gland (the sphenoid sinus), which is why it is called "transsphenoidal" surgery. Radiation and adjunctive drugs may be used to facilitate better outcomes. This tumor has a very good prognosis if caught and treated early so that minimal damage to adjacent tissues is made. In larger tumors that have caused local tissue destruction, however, persistent neurological symptoms such as visual changes may ensue, which is why early recognition is the key.

References

Article

  1. Villwock JA, Villwock M, Deshaies E, Goyal P. Significant increases of pituitary tumors and resections from 1993 to 2011. Int Forum Allergy Rhsinol. 2014;4(9):767-770.
  2. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
  3. Keil MF, Stratakis CA. Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics. Expert Rev Neurother. 2008;8(4):563-574.
  4. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  5. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101(3):613–619.
  6. Zhang X, Horwitz GA, Heaney AP, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999;84(2):761-767.
  7. Yu R, Melmed S. Pathogenesis of pituitary tumors. Prog Brain Res. 2010;182:207-227.
  8. Chanson P, Salenave S. Diagnosis and treatment of pituitary adenomas. Minerva Endocrinol. 2004;29(4):241-275.
  9. Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev. 2007;28(2):165-186.
  10. Riss D, Jin L, Qian X, et al. Differential expression of galectin-3 in pituitary tumors. Cancer Res. 2003;63(9):2251-2255.
  11. Chahal HS, Stals K, Unterländer M, et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med. 2011;364(1):43-50.
  12. Colao A. Pituitary tumours: the prolactinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(5):575-596.
  13. Kreutzer J, Fahlbusch R. Diagnosis and treatment of pituitary tumors. Curr Opin Neurol. 2004;17(6):693-703.
  14. Rotenberg BW, Saunders S, Duggal N. Olfactory outcomes after endoscopic transsphenoidal pituitary surgery. Laryngoscope. 2011;121(8):1611-1613.
  15. Paterno' V, Fahlbusch R. High-Field iMRI in transsphenoidal pituitary adenoma surgery with special respect to typical localization of residual tumor. Acta Neurochir (Wien). 2014;156(3):463-474.

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Last updated: 2018-06-22 05:48