The Pituitary Gland
The pituitary gland is a very small gland located in the brain, below the hypothalamus and behind the bridge of the nose. The pituitary plays a major role in the overall health of the
human being. It maintains a connection between the endocrine and the nervous system. One of its most important role is to release many hormones which affects human reproduction, sexual development, metabolism and growth.
The pituitary gland is stimulated by negative feedback. When necessary, the hypothalamus releases its hormones, such as Gonadotropin realizing hormone, and thyrotropin releasing hormone. These hormones target specific area in the pituitary, allowing the release of hormones from the same.
The gland is divided into anterior and posterior pituitary. Different parts of the pituitary gland secrete different types of hormones. The anterior pituitary gland consists of glandular epithelium and releases the following hormones:
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Human growth hormone (hGH)
• Luteinizing hormone (LH)
• Melanocyte-stimulating hormone (MSH)
• Thyroid-stimulating hormone (TSH)
• Prolactin (PRL)
The posterior pituitary is an extension of the nervous tissue and it releases:
• Antiduiretic Hormone (ADH).
The pituitary gland is of the size of a pea, yet, its job to is essential to the well-being of the body. The goal of the pituitary gland, also known as the “Master Gland” is to release its hormones designed to reach specific receptors in the body. Once the hormones reach their target, it will stimulate other glands and tissues in the body. Some of the targets of the hormones release by pituitary, are the ovaries, testes, thyroid, adrenal and the mammary glands. Inhibiting the release or binding of the hormones to its target glands, can have serious adverse effect in the body.
Majority of Pituitary tumors are classified as benign neoplasm of pituitary because they don’t spread to other areas of the body. These tumors usually stay in the Stella Turcica (the area in the brain where the pituitary gland lays). These tumors do not grow very large, yet their presence can press on nerves, vessels that release hormones and/or suppress the pituitary gland, leading to abnormal clinical manifestations.
Pituitary tumors are classified by their size and function and these classifications are important for treatment and diagnosis. Depending on the size of the tumor, they are called; Microadonoma (small tumor) or Macroadenoma (large tumor). Microadenomas are less than 1 cm in size. Many times, these tumors are not treated because they are so small that do not manifest any symptoms or cause threat to the patient. Macroadonomas are greater than 1 cm. and because they are larger in size, these can manifest with symptoms. Macroadenomas are usually associated with prolactin levels 3000 mU/L (3) The function of the tumor is important for its diagnosis. Some of these tumor do not secrete hormones and they are known as Non-Functional Adenomas. However, there are pituitary tumors that do secrete excess hormones, and they are known as Functional Adenomas.
Prolactinomas are the most common type of benign pituitary tumors. This tumor produces excessive prolactin. They are more common in women than in men. Prolactin is a hormone whose function is to produce breast milk in the women, specially after childbirth, however its normal levels in men it is not well understood.
Clinical Presentation of hyperprolactinemia, due to Prolactinoma
There are some similarities in the clinical presentation for men and women. Patients whom are found to have a Prolactinoma may present with pressure headaches, vision changes (typically decreases in peripheral vision) and hypogonadism. One of the most common symptoms for men with hyperprolactinemia are gynecomastia, erectile dysfunction, and decreased libido.
The Endocrine Institute in Petah Tikva, Israel (1) conducted a study with a group of men found to have a Prolactinoma and how the tumor affected their Testosterone levels. They found that those men whom had testosterone levels lower than the normal range, were more symptomatic than those men that had testosterone levels within the normal range. The study showed that although some men had testosterone levels within the normal range, they would still have (minimal) symptoms of hypogonadism. Concluding that normal levels of testosterone, does not exclude the presence of a Prolactinoma. They also learned there was a correlation in tumor size and testosterone levels. The larger the Prolactinoma, the lower the level of testosterone. The men that participated in the study, were treated with Cabergoline, with an end result of improved testosterone levels and improve hypogonadism symptoms (1).
Premenopausal women with hyperprolactinemia, also experience hypogonadism, including infertility, oligomenorrhea, or amenorrhea and in some cases galactorrhea. In women, the levels of hyperprolactinemia correlate with the severity of the of the symptoms. Female patients whose serum prolactin levels are 100 ng/mL are found to have abnormal estradiol levels, leading to amenorrhea, vaginal dryness and hot flashes. Female patients with moderate serum prolactin in levels of the 50-100 ng/mL experiences oligomenorrhea or amenorrhea. Those with mild levels of serum prolactin usually between 20-50 ng/mL, may have shorter Luteal phase during menstrual cycle due to low levels of progesterone. Among the patients with mild hyperprolactinemia who were evaluated for infertility, 20% had normal menstrual cycle (2). Those women with amenorrhea due to high levels of serum prolactin, can also experience lower bone density in the lower spine and forearm. However, the bone density can be improved by restoring menstruation. (2)
Diagnosis of Prolactinoma
When a patient presents with symptoms of hyperprolactinemia, it is important to start by ruling out secondary causes of the high levels of prolactin. As medical providers, we should ensure that a good clinical history is taken, assess the medications that the patient is currently taking, check for TSH, Free T4 levels, pregnancy test, biochemical tests and physical examination, along with neurological imagining, before the diagnosis of Prolactinoma is concluded(4). Once secondary causes for hyperprolactinemia have been ruled out, all patients with suspected Prolactinoma must obtain imaging of the head. A Magnetic Resonance Imaging (MRI) of the head using pituitary sellar protocol is the prefer imaging test (3). An MRI can help rule out differential diagnosis of pituitary lesions. Only pituitary adenoma can cause hypersecretion of the pituitary gland,but lesions in the sella turcica, can cause hyposecretion of the gland (2) . Once the diagnosis of Prolactinoma is made, it is important to assess the function of the pituitary gland to identify other hormonal imbalances (3).
Management of Prolactinoma
The goal in treatment of a Prolactinoma is to eliminate the effects of the tumor in the patient, to obtain and maintain normal levels of serum prolactin and to preserve the function of the pituitary gland. Pharmacological treatment, surgery and radiotherapy are the different types of managements for Prolactinoma to achieve these goals.
Pharmacological treatment is the first line treatment recommended for the management of Prolactinoma. The prefer drugs consist of dopamine agonist such as Carbergoline, Bromocriptine, Pergolide or Quinagolide. These drugs shrink the tumor in size and suppress prolactin, usually in the first 2-3 weeks of starting medical treatment, it does this by stimulating G-proteins coupled dopaminergic type 2 receptors in Prolactinoma(3) . In a retrospective study of 455 participants, cabergoline resulted in normoprolactinaemia in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 patients with macroadenomas(5).
Transsphenoidal surgery (Figure 1) is indicated after months of usage of pharmacological treatment and failure in decreasing serum prolactin levels in symptomatic patients. Another indication for surgery is if there is pituitary apoplexy with persistent neurological signs or symptoms (3) (Table 1).
Radiotherapy is recommended for patients that have undergone surgery and are still found to have residues of the tumor. Radiotherapy is also recommended for those found to have malignant Prolactinoma. Patients that undergo radiotherapy will required anterior pituitary function test for 10 years due to increased risk of hypopituitarism (3).