Pituitary Adenoma

What is Pituitary Adenoma?

Pituitary adenomas are a type of lump that can crop up in the front part of your pituitary gland, located at the base of your brain. These tumors typically grow slowly and are usually harmless. They’re categorized based on how big they are or the particular type of cell they come from.

Pituitary adenomas can be classed as microadenomas, macroadenomas, or giant tumors. A microadenoma is pretty small, less than 10 mm. A macroadenoma, on the other hand, is a tumor larger than 10mm. And then you have giant pituitary tumors, which are bigger than 40 mm.

Some pituitary adenomas are “functioning”, meaning the cells that make them up release one or more hormones from the front part of the pituitary. But there are also “nonfunctioning” adenomas which don’t release any hormones. These, however, can still cause other problems by squashing the surrounding area of the pituitary, which can lead to a deficiency in some hormones.

People with pituitary adenoma need their condition reviewed by a team of different specialists from areas such as hormone medicine (endocrinology), eye health (ophthalmology), and brain surgery (neurosurgery).

What Causes Pituitary Adenoma?

The exact cause of pituitary adenomas, a type of tumor in the pituitary gland, is not known. Most pituitary adenomas occur randomly, without any known cause. According to a study done in Iceland that looked at 410 cases of pituitary adenomas, 43% of these adenomas did not function (meaning they did not release any hormones), 40% released prolactin, 11% released growth hormone, and 6% released Adrenocorticotropic hormone. It is rare for genetic mutations to occur in pituitary adenoma, and only around 5% of all pituitary tumors are passed down through families.

Certain genetic mutations have been discovered to play a role in the development of pituitary adenomas. Some of these include:

Multiple endocrine neoplasia type 1 (MEN1): This is a gene that usually helps to suppress the formation of tumors. A mutation that reduces the gene’s function can lead to tumor formation in the parathyroid, pancreatic, and pituitary glands.

Multiple endocrine neoplasia type 4 (MEN4): This condition involves a mutation in the CDKN1B gene. It presents with pituitary tumors, and can also result in overactive parathyroid glands, and tumors in the testes and cervix.

Carney complex (CNC): In this condition, there is a mutation in the gene PRKAR1A, normally a tumor suppressor gene. This leads to a number of conditions including one where the adrenal glands produce too many nodules (primary pigmented nodular adrenocortical disease), testicular tumors, lumps in the thyroid, skin that has too much color in some spots, and overgrowth of certain body parts (acromegaly).

Familial isolated pituitary adenomas (FIPA): About 15% of FIPA cases in adolescence or early adulthood have been linked to a mutation in the AIP gene. The tumors found in these cases are often aggressive and usually produce too much growth hormone, leading to acromegaly, a condition where the hands, feet and face are larger than normal.

Risk Factors and Frequency for Pituitary Adenoma

Pituitary adenomas are usually discovered by chance through medical imaging performed for unrelated reasons. Because these tumors are often small and do not show obvious symptoms, it’s hard to determine how common they are in the general population. The estimated prevalence of pituitary adenomas has been calculated from autopsy reports and radiological data.

• There’s significant variation in the reported prevalence of pituitary adenomas based on different studies and sources.
• In a meta-analysis study, on average, about 16.7% of the instances were pituitary adenomas; 14.4% found in autopsies and 22.5% identified in radiology tests.
• Several studies conducted across different geographic areas over many years help us understand the incidence of pituitary adenomas. For instance, a well-known study from Iceland showed a prevalence rate of 115 per 100,000 people.

Signs and Symptoms of Pituitary Adenoma

A pituitary adenoma is a tumor that can vary in size and function. Small tumors, or pituitary microadenomas, are typically discovered by chance during a brain MRI. They typically don’t cause symptoms unless they’re releasing hormones. Larger tumors, or pituitary macroadenomas, can cause various symptoms due to their size and the pressure they exert on the surrounding areas. These could include hormone imbalances and symptoms associated with the tumor’s mass effect. Rarely, these tumors can suddenly bleed, causing a condition known as pituitary apoplexy. This can result in sudden headaches, vision changes, and hormone imbalances.

Regarding symptoms arising due to the mass effect of the tumor, here are some common ones:

• Visual impairment: Disruptions in vision occur in about 40% to 60% of patients due to the tumor putting pressure on the optic nerve. This can lead to visual field defects, double vision, and nerve-related issues.
• Headache: This is a common but non-specific symptom.
• Hormone deficiencies: These might occur, particularly in cases of large tumors, leading to various symptoms resulting from the deficiency of certain pituitary hormones:
• Gonadotropin: causes irregular menstrual cycle in women and issues with sexual performance in men.
• Growth hormone (GH): can cause fatigue and weight gain in adults.
• Thyroid-stimulating hormone (TSH): symptoms include weight gain, fatigue, sensitivity to cold, and constipation.
• Adrenal corticotropic hormone (ACTH): symptoms can include fatigue, arthritis, weight loss, low blood pressure, dizziness, nausea, vomiting, and abdominal pain.

If the adenoma is also releasing hormones (secreting adenoma), symptoms can vary based on the specific hormone it’s releasing:

• Prolactin-secreting: High prolactin levels can lead to infertility, lower libido, and osteoporosis in both men and women. Women may experience irregular menstrual cycle and abundant milk production, while men can experience issues with sexual performance and abnormal breast tissue growth.
• Growth hormone (GH) secreting: Symptoms can be headaches, vision changes, increase in ring or shoe size, arthritis, carpal tunnel syndrome, and excessive sweating. Patients often have visibly altered facial features, enlarged tongue, and skin tags. They might also have other health conditions like high blood pressure, heart disease, sleep apnea, and polyps in the colon.
• ACTH-secreting: Symptoms include weight gain, muscle weakness, mood disorders, easy bruising, and a tendency to fracture easily. Physical features might include a round face, red cheeks, fat accumulation above the collarbone, easy bruising, and purple stretch marks on the abdomen and underarms.
• TSH-secreting: Symptoms can include palpitations, irregular heart rhythms, and weight loss. Physical examination may reveal shaking hands and an enlarged thyroid gland.

Testing for Pituitary Adenoma

Pituitary adenomas, which are a type of tumor, are usually discovered accidentally during routine CT scans. To better identify and analyze the tumor and check for any bleeding into the tumor, an MRI with a special contrast agent called gadolinium is necessary.

Doctors will screen for two situations. The first is hypopituitarism, a condition where your pituitary gland doesn’t produce enough hormones. The second is hypersecretion, where too many hormones are released. Even if a patient shows no symptoms, The Endocrine Society suggests a detailed biochemical assessment, which involves testing for numerous hormones.

The levels of prolactin, a hormone that can stimulate milk production among other functions, often reflect the size of the adenoma. If the prolactin level is below 200 ng/ml, it might indicate a small adenoma or due to certain medicines. A level above 200 ng/ml suggests a large adenoma that releases prolactin. Prolactin levels can be increased due to pregnancy, breastfeeding, nipple stimulation, chest trauma, underactive thyroid, kidney failure, and certain types of medications. It’s important to identify “big-prolactin,” an inactive form of prolactin, to prevent unnecessary treatment.

IGF-1/GH: A screening test for a condition called acromegaly, marked by enlarged hands and/ or feet, and GH deficiency, can be done by assessing the serum IGF-1 levels. Poorly controlled diabetes, malnutrition, sepsis, underactive thyroid, liver and kidney failure can affect IGF-1 and GH levels. If IGF-1 level isn’t high as expected in acromegaly patients or is unclear, a 75 gm oral glucose challenge test can be done. If the GH level stays above 1 ng/dl even when blood sugar is high, it confirms acromegaly.

Cortisol Examination: A morning fasting cortisol level assessment can help evaluate pituitary-adrenal insufficiency. If morning cortisol is unclear or low, the clinician should perform a cosyntropin stim test.

Tests for Cushing’s disease, caused by overexposure to cortisol for a prolonged period, involve checking late-night salivary cortisol, 24-hour urine free cortisol, or a dexamethasone suppression test. It’s important to cautiously interpret these tests as factors like external steroids, depression, excess alcohol intake, and oral contraceptives affect cortisol levels.

Once hypercortisolemia, a condition characterized by an excess of cortisol in the blood, is confirmed, the next step is to check the ACTH hormone to identify the cause. Hypercortisolemia with elevated ACTH suggests an ACTH producing adenoma. In this case, inferior petrosal sinus sampling (IPSS), an invasive procedure, is recommended to differentiate between ectopic vs. pituitary Cushing.

A low free T4 thyroid hormone with normal or low TSH (thyroid-stimulating hormone) could mean secondary hypothyroidism (a condition where your thyroid doesn’t produce enough hormones typically due to pituitary or hypothalamic disease). An adenoma that produces TSH will present with high T4 and T3 thyroid hormones.

Gonadotropin levels (LH/FSH): If estradiol or testosterone levels are low but LH/FSH levels are normal or low, hypogonadotropic hypogonadism might be diagnosed. This condition entails decreased function of the male testes or female ovaries.

Treatment Options for Pituitary Adenoma

Managing pituitary adenomas, which are tumors that develop in the pituitary gland located at the base of the brain, requires a collaboration between an endocrinologist (a doctor who specializes in hormone-related conditions) and a neurosurgeon (a surgeon who operates on the brain and other parts of the nervous system). Their aim is to develop a personalized treatment plan focused on the patient’s specific needs.

If the pituitary adenoma isn’t causing any hormonal changes (i.e., it’s non-functioning), it may need to be surgically removed if it’s particularly large (a macroadenoma) and causing issues such as vision problems, significant growth over time, or a loss of endocrine function. This is usually done through a process known as transsphenoidal resection, where the surgeon accesses the tumor through the nose and sinuses. After surgery, there’s usually an improvement in visual symptoms and hormonal function. If there is any remaining tumor, radiotherapy (treatment using radiation) may be recommended. For those who don’t need surgery, regular check-ups with an endocrinologist and yearly MRI scans are important to monitor the size of the tumor and to check for any hormonal disruptions.

For adenomas that secrete prolactin hormone (prolactin-secreting adenomas), treatment may involve medication like dopamine agonists (DA), including cabergoline and bromocriptine. DAs can help lower prolactin levels and reduce the size of the tumor. However, surgery might be needed in cases where the tumor isn’t responding to medication, or if the side effects are intolerable. Radiotherapy is only used in rare situations where the tumor is aggressive, continues to grow despite other treatments.

For tumors that secrete growth hormone (GH-secreting adenomas), the main goal of treatment is to lower growth hormone levels. Surgery is usually the first recommended treatment. However, if surgery doesn’t wholly remove the tumor, or the patient can’t have surgery, medication such as somatostatin analogs (SSA) may be prescribed. In some cases, radiotherapy might also be used as additional treatment.

Tumors that secrete adrenocorticotropic hormone (ACTH-secreting adenomas), causing high cortisol levels, are primarily treated with surgery. Medical therapy can also be an option, which may include drugs to lower ACTH production or adrenal cortisol production. In severe cases, removal of both adrenal glands might be necessary. Again, radiotherapy might be used as well.

Finally, for tumors that secrete thyroid-stimulating hormone (TSH-secreting adenomas), surgery is typically the first treatment option. Before surgery, it is crucial to control high thyroid hormone levels to avoid a thyroid storm, a potentially life-threatening condition. This can be achieved by using certain medications. If surgery doesn’t completely resolve the issue, SSA may be used to decrease TSH levels and reduce the tumor size.

What else can Pituitary Adenoma be?

When a doctor is considering a diagnosis, there are many other conditions related to the brain and central nervous system that must also be considered. Some of these possibilities include:

• Arachnoid cyst: a fluid-filled sac that can form between the brain and the arachnoid membrane that surrounds it
• Basilar artery thrombosis: a blood clot in the main artery that supplies blood to the brain
• Brainstem glioma: a type of tumor found in the brain stem
• Cavernous sinus syndrome: a condition that involves the veins of the brain, often associated with a tumor or an infection
• Cerebral venous thrombosis: a blood clot in the brain’s venous sinuses
• Craniopharyngioma: a type of non-cancerous brain tumor
• Dermoid cyst: a type of tumor that’s present at birth and includes skin and other tissues
• Ependymoma: a type of tumor that develops in the brain and spinal cord
• Glioblastoma multiforme: an aggressive type of cancer that occurs in the brain or spinal cord
• Leptomeningeal carcinomatosis: a rare complication of cancer in which the disease spreads to the membranes surrounding the brain and spinal cord
• Low-grade astrocytoma: a type of brain tumor that grows relatively slowly
• Meningioma: a generally noncancerous tumor that arises from the meninges, the membranes that surround your brain and spinal cord
• Primary CNS lymphoma: a rare form of non-Hodgkin lymphoma that occurs in the brain
• Rathke cleft cyst: a noncancerous fluid-filled growth that develops between parts of the brain and the pituitary gland
• Tuberculous meningitis: an infection of the meninges, the protective membranes covering the brain and spinal cord, caused by tuberculosis bacteria

What to expect with Pituitary Adenoma

The outcome for patients with pituitary adenomas (tumors in your pituitary gland, a small gland at the base of the brain) depends on whether these tumors are functioning or non-functioning. Non-functioning adenomas and prolactinomas (tumors that make an excess of a hormone called prolactin) generally have excellent outcomes if treated quickly with surgery or medication.

However, functioning adenomas, such as those causing Cushing’s disease (a condition caused by high corticosteroid levels in the body for a longer period) and acromegaly (a disorder that results from excess growth hormone after the growth plates have closed), are associated with other health problems and complications. If treatment is delayed, especially in patients with Cushing’s disease, the mortality rate tends to be higher.

Preventing Pituitary Adenoma

Pituitary adenomas, or non-cancerous tumors in the pituitary gland, are quite common. These tumors can cause symptoms either from their size, which might press against other parts of the brain, or by altering the levels of certain hormones in the body.

Treatment of pituitary adenomas requires a thorough evaluation by a team of specialists. This team includes an endocrinologist, who specializes in hormonal disorders, a neurosurgeon, who performs brain surgeries, a neuro-ophthalmologist for any eye or vision-related issues, and sometimes a radiation oncologist, who specializes in cancer treatment using radiation. Together, they aim to address and manage pituitary gland diseases.

Education for patients diagnosed with a pituitary adenoma is crucial. Understanding when to seek medical attention is necessary for managing this condition effectively.

Also, there are potential side effects of the treatments for pituitary adenomas, and understanding these adverse effects will help patients anticipate and prevent potential complications. It can also reduce risk of death from complications related to pituitary adenomas and its treatments.