What Are Pituitary Tumours?

Introduction

The pituitary gland is a small, pea-sized gland located at the base of the brain (just behind the eyes). It is multifunctional and responsible for producing and releasing several hormones into the bloodstream. Pituitary gland tumours are usually benign tumours, but they can sometimes metastasise (spread) to other organs. In these cases, the cancer is called a pituitary carcinoma.

It’s important to note that the term ‘pituitary carcinoma’ only refers to metastatic cancer originating in the pituitary gland, and not cancer that spreads to it. However, tumours can spread to the pituitary gland from the breast, lung, prostate, colon, or kidneys. 

Pituitary tumours are also known as pituitary adenomas or pituitary neuroendocrine tumours, especially in Europe. There are functioning pituitary tumours which secrete hormones and non-functioning pituitary tumours that do not secrete hormones.

Pituitary tumours (PTs) and pituitary carcinomas (PCs) can vary significantly in their clinical presentation (symptoms), clinical course (progression and spread) and response to therapy between patients. Consequently, medical professionals will need to consider multiple factors when treating pituitary tumours, including the tumour’s size and biology and the patient’s age and general health.^1-4

What causes pituitary tumours?

The exact underlying aetiology (causes) of pituitary tumours is still unclear, but most tumours develop due to genetic alterations, or mutations. There are ongoing studies investigating the molecular mechanisms influencing the development and nature of pituitary tumours.

These mechanisms include regulating the expression of specific genes via methylation or histone regulation, and modifying the expression of long non-coding ribonucleic acids (RNAs), which has been linked to malignant (spreading) tumours in a few studies. Pituitary tumours that are linked to certain germline (inheritable) mutations are seemingly more likely to be invasive and resistant to treatment.⁴ 

Moreover, some hereditary conditions are associated with an increased risk of developing pituitary tumours, such as multiple endocrine neoplasias (MEN)-1 syndrome. In contrast, there are no real steps you can take to prevent pituitary tumours, as no environmental or lifestyle factors have been directly correlated to them.⁴ 

Furthermore, aggressive pituitary tumour (APT) can be suspected in the following cases:²

• Cases not responding to high doses of cabergoline in macro prolactinomas, or those who lose sensitivity to dopamine agonists
• Tumours progressing after radiotherapy (RT)
• Somatotroph invasive macroadenomas that fail to respond to somatostatin analogues treatment
• Tumours that show rapid progression or relapse after surgical removal
• Tumours that have high proliferative markers
• Corticotroph invasive macroadenomas (particularly in men)

Your medical professional will be able to discuss these conditions with you.

Epidemiology

• The prevalence of pituitary carcinoma is extremely low, estimated at 1/1,000,000. Pituitary carcinomas originate from functioning pituitary gland tumours, which secrete hormones. These tumours include lactotroph and corticotroph carcinomas, which each representing one third of the cases
• The median age at diagnosis of pituitary carcinoma is 44 to 45
• The median latency period (the time between tumour diagnosis and first metastasis) is approximately 5 to 7.5 years⁴

Symptoms of pituitary tumours

The clinical presentation (symptoms) of pituitary tumours depend on their type, which can be either functional (hormone secreting) and non-functional (not hormonesecreting). Generally, functional tumours can be detected early through the symptoms and physiological changes caused by the excess secretion of hormones.

However, non-functional pituitary tumours are usually only detected when they are large enough to press against the pituitary gland (or other brain structures) and cause neurologic deficits. Pituitary carcinomas are suspected if neck or back pain are present, which could be due to spine metastasis. 

If the pituitary tumour presses on the cranial nerves (12 major nerves which control your senses and movement), it may result in facial pain, ptosis, or diplopia. However, if the third ventricle of the brain is involved, patients may experience obstructive hydrocephalus - a condition where fluid builds up in the brain. Non-specific symptoms can be present in larger pituitary tumours (macroadenomas) such as headaches.⁴

Functional pituitary tumours may cause other symptoms depending on the type and quantity of hormones they secrete. According to the World Health Organisation (WHO), pituitary gland tumours are classified by the pituitary hormone content, histopathological features, and ultrastructural features of the tumour cells.⁵

Symptoms linked to the oversecretion of certain hormones by pituitary tumours include:⁴

• Growth hormone (GH): The oversecretion of GH in adults causes acromegaly where body tissues and bones grow faster, leading to abnormalities in their structure. This includes larger hands and feet
• Prolactin: The oversecretion of prolactin in females can cause amenorrhea-galactorrhea syndrome. However, in males it causes impotence
• Follicle-stimulating hormone (FSH) and/or luteinising hormone (LH): The oversecretion of FSH in reproductive-age women may result in hyperstimulation associated with ovarian cysts, amenorrhea and galactorrhea
• Thyrotropic (TSH): TSH is a form of secondary hyperthyroidism, which causes common symptoms of hyperthyroidism such as weight loss, sweating, diarrhoea, and intolerance to heat
• Adrenocorticotropic hormone (ACTH): Excessive production of ACTH results in Cushing’s syndrome. This is a condition that occurs when there is excessive amounts of cortisol in the body. Common symptoms of Cushing’s syndrome are a red and puffy face, high blood pressure, high blood sugar (that could develop into diabetes), overgrowth of facial hair, a lump on the back of neck, and rapid weight gain

Diagnosis and evaluation of pituitary tumours

Laboratory tests

The common laboratory tests used to diagnose pituitary tumours are urine and blood tests. This may include specific hormonal level testing to explain your symptoms; however, hormonal tests are also conducted in patients suspected to have non-functioning tumours.

In order to rule out hypersecretory tumours, endocrine tests are conducted to check the levels of certain hormones. Mainly, these tests will assess the levels of the hormones insulin-like growth factor (IGF-1) and prolactin. In patients with clinical manifestations of Cushing’s syndrome, early morning cortisol levels will also be evaluated. 

Hypo-secreting tumours, which are characterised by the low production of one or more hormones, are detected by measuring the levels of several hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone in men, T4, and cortisol. Each hormone of interest has a specific test that is performed as a confirmatory test following basic laboratory testing.⁴

Imaging

Magnetic resonance imaging (MRI) is often required to assess the pituitary gland and check for tumours. Pituitary tumours can be classified via imaging according to their size: tumours greater than 1 centimetre in diameter are classified as macroadenomas, whilst smaller tumours are classified as microadenomas. 

A computed tomography angiography (CTA) scan of the head plays an important role in pre-operative plans to investigate the adjacent vascular structures to the tumour mass.

Pituitary carcinomas can be identified in the absence of histopathologic features through radiographic techniques, particularly spinal MRI.⁴

Treatment and management

Surgery

Surgery is often used to treat patients with pituitary carcinoma and is a recommended option for patients with tumours pressing on structures adjacent to the pituitary, such as the third ventricle or optic pathway.

Radiotherapy

Radiotherapy is another treatment option that aims to prevent further hormone secretion and tumour growth. Due to its potential side effects, radiotherapy is only used on rapidly growing tumours, aggressive pituitary tumours, and pituitary carcinoma. 

Chemotherapy

The first line chemotherapy drug used to treat pituitary tumours is Temozolomide, which is an oral alkylating agent that exerts irreversible damage to deoxyribonucleic acid (DNA). Temozolomide has shown great promise in patients with pituitary tumours, improving 5-year survival rates and significantly reducing tumour progression.

However, Temozolomide only reduced tumour mass in ~6% of patients and is not always completely effective. At the moment, Temozolomide is the only fully tested and available drug for pituitary tumours. As such, it is highly recommended that Temozolomide is used early, in the hopes of limiting tumour growth.

Antisecretory Medications

In patients with functional pituitary carcinoma, it is extremely important to control (or stop) the oversecretion of hormones. 

• Patients with hypercortisolism are given steroidogenesis inhibitors such as ketoconazole to reduce the risk of mortality and morbidity from excess cortisol
• Patients with lactotroph tumours can be given dopamine agonists, such as cabergoline
• Patients with somatotrophic tumours, There are several therapeutic agents available for patients with somatotrophic tumours, including dopamine agonists, somatostatin analogues (octreotide), or growth hormone receptor antagonists (pegvisomant)⁴

Research and Future Therapies

There are currently several treatment options being investigated for use against pituitary tumours, including immunotherapy, drugs that target specific molecules (such as bevacizumab and everolimus), and several tyrosine kinase inhibitors (TKIs).⁴

Prognosis

On average, patients with metastatic pituitary tumours survive 4 years once the tumour begins to spread. The prognosis for benign tumours is much more positive, with 82% of patients surviving past 5 years. THe prognosis of pituitary carcinomas is much less positive.⁴

Summary

Pituitary tumours are a form of brain tumour. Whilst mostly benign, pituitary tumours can spread to other organs, but this is rare. There are functioning pituitary tumours that secrete certain hormones and non-functioning pituitary tumours which are non-secreting hormone tumours.

The aetiology of pituitary tumours is currently unknown, but there are ongoing studies to investigate it further. Generally, the symptoms of these tumours depend on their type and the types and amounts of hormones they secrete.

However, pituitary carcinoma symptoms can be detected from neck or back pain due to the pressing of tumour mass on adjacent structures. Diagnosis involves using urine and blood tests, in addition to MRI and CT scans. Treatment and management strategies include surgery, radiotherapy, chemotherapy and antisecretory medications for functioning pituitary tumours which secrete specific hormones.