Pituitary Tumor Neurogram
Pituitary adenomas represent the third most common primary intracranial neoplasm encountered in neurosurgical practice, with a reported annual incidence ranging from 1-14.7 per 100,000 persons. The clinical presentation of pituitary tumors varies significantly depending on the underlying pathological subtype of adenoma involved. Broadly, categories of pituitary adenoma can be characterized as being either clinically functioning or nonfunctioning depending on whether the tumor produces biologically active hormones or not.
Nonfunctional pituitary adenomas present in general as a consequence of local mass effect. Patients often initially present to their primary physicians with complaints of headache from irritation of the dura mater or fatigue from panhypopituitarism, and as the tumor extends to involve the optic chiasm, they will present with varying degrees of visual loss. The classic presentation of the visual deficit is a bitemporal hemianopsia, but central scotomas and generalized blurring of vision are sometimes the complaint. Panhypopituitarism as a consequence of mass effect on the normal pituitary gland can result in fatigue and sexual dysfunction ranging from decreased libido to lack of erectile function, and often requires direct questioning of the patient to elicit.
Hyperfunctioning pituitary tumors arise from neoplastic transformation of secretory hormone cells and present with syndromes associated with excess production of their respective hormone. These syndromes include growth hormone excess resulting in the classic presentation of acromegaly in adults and gigantism in children, ACTH hypersecretion resulting in Cushing's disease, and hyperprolactinemia from prolactin adenomas.
AcromegalyPatients with acromegaly most often present in the third to fifth decade of life with focal enlargement of bones and soft tissues. These manifest as coarse facial features, frontal bossing, prognathism, dental malocclusion, macroglossia, spade-like enlargement of the hands and feet, spinal stenosis and degenerative joint disease, paresthesias from nerve entrapment, cardiac enlargement and subsequent heart failure, and impaired glucose tolerance. By the time patients are diagnosed with acromegaly they have already had multiple medical diagnoses made such as diabetes mellitus, congestive heart failure, and sleep apnea. Surgical procedures like carpal tunnel releases and lumbar decompressions are also not uncommonly done prior to the underlying diagnosis being made.
Although serum elevation of growth hormone is the hallmark of acromegaly, it is important to exclude other conditions associated with random elevations of GH such as diabetes, renal failure, cirrhosis, malnutrition, and stress. Acromegaly and gigantism have the following endocrinologic profile:
1. Demonstration of lack of suppression of GH levels following
2. Elevations of somatomedin-C (Insulin-like Growth Factor -1) level
Another subset of functional pituitary adenomas, corticotroph adenomas, may present clinically with a constellation of symptoms known as Cushing's disease. Cushing's disease refers specifically to a hypercortisolemic state generated in response to excess production of ACTH by a pituitary adenoma. Women constitute more than 75% of affected patients, with presentation of classic features being most common in the fourth and fifth decades of life.
The Cushingoid features of patients with ACTH secreting adenomas include moon facies, centripetal obesity, 'buffalo hump', supraclavicular fat deposition, hirsutism, hyperpigmentation, plethora, vascular fragility, and abdominal striae. Systemic symptoms include generalized weakness, fatigue, myopathy, and metabolic effects including hypertension, glucose intolerance, osteoporosis, menstrual abnormalities, and immunosuppression. Psychiatric disturbances are also common complications of a hyperadrenocorticotrophic state.
It is important to distinguish Cushing's disease as a subset of
Cushing's syndrome, which represents the general description of any
iatrogenic or endogenous hypercortisolemic state. Cushing's disease has
the following endocrinologic profile:
1. Hypercortisolism as demonstrated by elevations of serum cortisol and 24 hour urinary free cortisol
2. Loss of diurnal serum cortisol variation
3. Moderately elevated ACTH levels
4. Suppression of serum cortisol levels with high dose dexamethasone testing, but not with low dose dexamethasone testing
It is also important to realize that although 80-90% of patients with Cushing's disease fit this profile, 15% percent of patients may not show suppressibility of cortisol levels with high dose dexamethasone (8mg /day). Recent improvements in inferior petrosal sinus sampling have increased the accuracy of localizing disease in the pituitary gland, including lateralization of non-visualized microadenomas to either hemisphere of the gland by evaluation of ACTH gradients in both inferior petrosal sinuses.
Prolactin secreting pituitary adenomas present four times as frequently in women as in men. It should be noted that both the age of presentation and symptomatology at presentation are markedly different in the sexes. Women classically present in the second or third decade of life with symptoms related to increased prolactin levels such as amenorrhea and galactorrhea (Forbes-Albright syndrome), infertility, and decreased libido. In contrast, men usually present in the fourth or fifth decades of life and have sexual dysfunction and symptoms related to mass effect attributable to an enlarging sellar mass. This may partly explain the reason why pituitary adenomas in males are often found at more advanced stages whereas the majority of women are identified with microadenomas.
The elevated prolactin associated with these tumors must be distinguished from elevations of prolactin due to 'stalk section effect' - inhibited transport of prolactin inhibiting factor (dopamine), medications, hypothyroidism, cirrhosis, and renal failure. These conditions generally cause an elevation of serum prolactin above 21 ng/ml, but generally lower than 200 ng/ml. Large prolactinomas usually secrete PRL (prolactin) at levels greater than 200 ng/ml. Invasive disease is suggested when PRL levels exceed 1000 ng/ml.
The unique aspect of prolactin secreting tumors is the ability to control disease with pharmaceutical intervention. Bromocriptine and other dopamine agonists (pergolide, cabergoline) have been shown to normalize PRL levels, restore reproductive function, and reduce tumor mass with reasonable efficacy. Common indications for surgical intervention include symptoms associated with mass effect, apoplexy, intolerance of medications, and tumor resistance to medical therapy. Radiation therapy may be appropriate in those patients with recurrent disease refractory to surgical and medical therapy.
GENERAL PRINCIPLES OF DIAGNOSIS AND TREATMENT
Patients presenting with signs and symptoms suggestive of a pituitary adenoma require a comprehensive workup and treatment plan reflecting a strong interdisciplinary effort with endocrinologists, neurosurgeons, neuroophthalmologists, and neurooncologists working in concert with referring physicians. At this institution, a pituitary clinic is held weekly with endocrinology and neurosurgery together seeing the approximately 520 new pituitary patients referred each year.
When a new patient is assessed, following a thorough history and physical examination, an endocrine diagnosis is reached by testing pituitary and end organ function in basal and provoked states. A useful initial screening includes basal measurements of PRL, IGF-1, plasma cortisol, ACTH, LH/FSH, alpha subunit, thyroxine, and TSH. This initial survey estimates the integrity of the various hypothalamic-pituitary-end organ axes and their relative excesses and deficiencies. Further provocative, dynamic and special hormonal assays may be required to precisely define an endocrinopathy. It is imperative that, in the diagnosis and evaluation of the patient with visual symptoms or extension of tumor outside the sella, a complete neuro-ophthalmologic evaluation be performed in order to document disease progression and responses to therapeutic intervention. The greatest advance in diagnosis and evaluation has been the advent of magnetic resonance imaging. In the case of ACTH-secreting adenomas that are too small to be visualized by MRI, inferior petrosal sinus sampling of ACTH levels has been helpful in localizing the lesion to the pituitary gland and in some instances is able to lateralize the lesion to either hemisphere of the pituitary gland, thereby enabling more precise resection and preservation of remaining normal pituitary function.
Once the diagnosis of pituitary adenoma has been established by clinical, laboratory, and radiological means, an assessment of therapeutic options is made. Therapy for pituitary tumors should always seek to reverse the endocrinopathy if it is present, restore normal pituitary function, and remove the tumor mass with restoration of normal neuro-ophthalmologic function.
Although there is emerging latitude for pharmacologic care of pituitary tumors, as in the treatment of PRL-secreting adenomas, the majority of pituitary lesions require surgical intervention. The increased safety and efficacy of transsphenoidal pituitary microneurosurgery has afforded a less traumatic, minimally invasive, corridor to the pituitary gland with increased efficacy of surgical resection as compared to trans-cranial approaches. At this institution, we operate upon approximately 150-175 pituitary adenomas every year and the vast majority (>90%) are performed via an endonasal transphenoidal technique.
The combined efforts of primary care physicians, endocrinologists, neuro-ophthalmologists, neurosurgeons, and radiation oncologists have ensured that technologic advances in medicine have resulted in better outcomes for patients presenting with either an endocrinopathy and/or mass effect from pituitary adenomas.
Edward R. Laws, Jr., M.D., FACS
Dilantha B. Ellegala, M.D.
Ashok Asthagiri, M.D.
Nicholas F. Maartens, M.D., FRCS
AH Kaye, ER Laws Jr., K Thapar. Brain Tumors. Chapter 39: Pituitary Tumors. Pp 759 - 76. Churchill Livingstone. NY. © 1995
JH Stein, S Melmed, GD Braunstein. Internal Medicine. Fifth Edition. Chapter 295: Disorders of the Hypothalamus and Anterior Pituitary. Pp. 1773 - 87. Mosby. St Louis, MO. © 1998
ER Laws Jr., Pituitary surgery. Endocrinol Metab Clin North Am - 01-Mar-1999; 28(1): 119-31