Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. The Pituitary gland (P) is located in the Sella turcica (S) at the base of the skull. It measures less than 10 millimeters in diameter. Its importance can be judged by the fact that it is known as the ‘master’ gland of the endocrine ‘orchestra’ in view of the control it exerts on majority of endocrine glands in the body.
The Pituitary gland is an amalgam of two tissues consisting of the Anterior and Posterior components which are distinctly different in structure, reflecting their differing embryological origins.
The hormone predominantly affected in Acromegaly is the Growth Hormone with the following features:
- Produced by the Adenohypophysis (Anterior Pituitary)
- Target tissue (Primary site of action): Liver, Adipose tissue
- Action: Promotes growth
In plurihormonal Pituitary adenomas the commonest combination is the secretion of Growth Hormone (GH) with Prolactin (PRL).
Like most tumors the exact cause of pituitary adenomas is not known. In the majority of cases these may occur as isolated tumors or as components of a syndrome like Multiple Endocrine Neoplasia type 1 and Carney complex. Few genetic predictors of Pituitary adenoma development exist.
A clinical condition of Familial Isolated Pituitary Adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like Multiple Endocrine Neoplasia Type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas. The aryl hydrocarbon receptor interacting protein (AIP) gene has been implicated in 20% of FIPA families.
Most GH secreting Pituitary adenomas usually form from a genetic mutation in one a single, pituitary cell called a ‘Somatotrope’ cell. This mutation causes uncontrolled growth and reproduction of these cells. The genetic mutation is not present at birth, is not inherited and happens later during life (acquired mutation). The exact reason this mutation occurs is unknown.
Acromegaly is a rare, slowly progressive, acquired disorder that affects adults. When the disease affects children prior to the end of puberty, the excess GH results in ‘Gigantism’ due to accelerated growth and tall stature.
Acral enlargement is the cardinal feature of Acromegaly (Adapted from The Free Dictionary from Farlex). This pertains to the face, hand and feet. Facial features gradually become coarse because of the overgrowth of soft tissues and cartilage. Facial bones gradually become prominent, the lower jaw protrudes (prognathism), and an underbite may cause a wide separation and misalignment between the teeth (malocclusion). Affected individuals may also have an abnormally large tongue and unusually thick, full lips. People with acromegaly eventually develop a deep and husky voice due to thickening of the vocal cords and enlargement of the sinuses. Acromegaly also results in a gradual enlargement of the hands and feet.
One-third of Acromegalic patients harbour microadenomas; at diagnosis,whereas most patients have pituitary macroadenomas (more than 10 mm), many of which extend beyond the confines of sella turcica resulting in visual loss and neurological deficits.
Two critical factors of importance in patient prognosis and chance for postoperative remission are adenoma size (more than 20 mm) and preoperative GH level (more than 50 ng/ml).
Acromegaly is a rare disorder that affects males and females in equal numbers. This disorder occurs in approximately 50 to 70 people per million. Diagnosis of Acromegaly may be difficult to make as the symptoms develop almost imperceptibly over several years. The diagnosis is made based on:
- Clinical features of Acral enlargement or Gigantism
- Hormone profile: Acromegaly should be diagnosed in the presence of a random GH of more than 0.4 μg/L and an elevated IGF-1 level and confirmed by GH that is unable to be suppressed to less than 1 μg/L after oral glucose tolerance test.
- Magnetic Resonance Imaging of Brain including Sella Physicians may test the blood for elevated levels of
- Additional tests may be performed to assess the extent of acromegaly in an individual including echocardiography to evaluate whether the heart is enlarged.
- Biochemistry: Hyperglycemia
The desire for surgical cure of Acromegaly, is greater because sustained secretion of Growth Hormone is physically deforming and eventually life threatening.
Acromegaly is often treated by a combination of surgery, medications and radiation therapy. No single therapeutic option is effective for everyone. An individual’s specific treatment plan will based on several factors including the size and location of the pituitary tumor; the presence or absence of certain ocular or neurological symptoms; an individual’s age and general health; and/or other elements. The goals of treatment in Acromegaly are:
- To return growth hormone levels to normal,
- To decrease the size of a pituitary adenoma (if present) thereby relieving pressure on the surrounding tissue,
- To maintain normal pituitary function, and reverse or improve associated symptom.
Acromegaly is usually treated by transsphenoidal surgery; a procedure in which all or part of a pituitary tumor is removed. Surgery often results in a rapid therapeutic response, immediately relieving pressure on surrounding brain structures and lowering growth hormone levels. When surgery is successful, soft tissue swelling may decrease in just a few days. Surgery is more effective in individuals with small tumors (microadenomas) than in those with large tumors (macroadenomas). Surgery may not successfully improve all symptoms (e.g., headaches may persist) and, in some cases, removal of the entire tumor may not be possible, resulting in growth hormone levels that remain too high.
Medical therapy is recommended in individuals in whom:
- Surgery in contraindicated,
- Surgery did not work or failed to return hormone levels to normal or
- Large tumors may require shrinkage before tumor decompression
Medications are often used to treat individuals with Acromegaly. These include:
- Somatostatin analogues including Octreotide and Lanreotide
- Growth hormone receptor antagonists such as Pegvisomant, and
- Dopamine antagonists like Cabergoline