7 Indications for Surgery on Pituitary Tumors: A Neurosurgeon’s Perspective

Rudolf Fahlbusch and Vincenzo Paternó

Historical Development

Historically, the development of indications for surgery in pituitary tumors can be divided into three phases. The first phase started around 1900 with the development of the surgical approaches. The transcranial approach appeared first and was favored by Victor Horsley (1889) and Fedor Krause (1900), followed by the transsphenoidal approach, favored by Hermann Schloffer (1907) and Harvey Cushing (1909).¹

The second phase was mainly concerned with clinical findings. The indications for surgery were the patient’s symptoms, especially ophthalmologic deterioration. The endocrinological classification and indications for surgery were developed much later, in the 1960s, when assessment of hormone levels became possible. At the same time, the introduction of the microscope into the neurosurgical operating room made selective adenomectomy possible, as defined by Jules Hardy for the transsphenoidal approach,² and further fostered by the subsequent development of computed to-mography (CT) and magnetic resonance imaging (MRI).^3,4

The third phase was characterized by improvements in surgical accuracy starting in the 1990s with the introduction of the endoscope and later the introduction of neuronavigation^5–7 and intraoperative MRI.^7–9 In parallel, alternative endocrinologic medical treatment was developed, especially antiproliferative treatment, first with a dopamine agonist for prolactinomas and later with somatostatin analogues for acromegaly.^10–12

Indications for Surgery

Assessing the patient’s appropriateness for surgery for pituitary tumors begins with a multidisciplinary evaluation of the symptoms, conducted by the primary care physician, a neurosurgeon, an endocrinologist or neuroendocrinologist, a neuroradiologist, an ophthalmologist, and radiologist. The pituitary gland’s anatomy and function are assessed. The surgeon and endocrinologist evaluate the pituitary lesion. Indications for surgery for pituitary tumors, such as pituitary adenomas, depend on the functional symptoms and the imaging results. It is mandatory to assess the patient’s endocrinologic function before recommending surgery.

A pituitary adenoma originates from the pituitary gland and first causes endocrine symptoms, such as hormonal excess or a partial pituitary insufficiency.

Ophthalmologic symptoms develop when the optic chiasm is contacted and compressed by the tumor. Oculomotor nerve disturbance occurs when the tumor is growing into the cavernous sinus. In addition to the endocrinologic and ophthalmologic indications for surgery, an important indication occurs in cases of suprasellar development when obstruction of the foramen of Monro in turn obstructs the hydrocephalus.

Initial symptoms may be subclinical and thus must be elucidated with sophisticated endocrine function tests, and ophthalmologic and neuroradiologic examinations.

Surgery for a primary adenoma has to be weighed against other treatment options, mainly medical antiproliferating treatment and, more rarely, x-knife/radiotherapy (RT). Surgery may be selected as an alternative treatment when primary medical treatment for a hormonally active adenoma has failed. Surgery may also be indicated for tumor recurrences or progressive growth of residual tumor.

Patient Symptoms

Many patients with a pituitary lesion appear healthy on physical examination. The pituitary adenoma is discovered only as an incidental finding when an MRI is performed (see Incidentaloma, below).

Headache is not a typical presenting symptom for a pituitary adenoma, but it is one of the main reasons why patients undergo a screening MRI. The sellar space is quite small and a lesion of any size may produce or exacerbate headaches. Acute headache occurs in pituitary apoplexy, and chronic headache occurs in transitory acromegaly or is due to an obstructive hydrocephalus (tumor blockage of the foramen of Monro). Periorbital headache occurs when the cavernous sinus is compressed or invaded by pituitary tumors. There is only one indication for surgery to relieve an isolated headache that is not necessarily accompanied by other symptoms: Rathke’s pouch cyst can cause frontal or midline headache, and thus it is the only indication for surgery in patients with no endocrinologic deficit or ophthalmologic indication.¹³

Ophthalmologic disturbance of the optic nerves, optic chiasm, or oculomotor nerves is an indication for surgery. Evidence of an ophthalmologic or visual defect is a cause for concern and may require urgent tumor resection to decompress the involved structures. Compression of the optic chiasm may cause a mild deficit or complete bitemporal hemianopia. Tumor invasion into the cavernous sinus may generate a clinical picture that suggests involvement of one or more of the associated cranial nerves.14–16

Chiasma compression syndrome is characterized by a visual field defect followed by loss of visual acuity and then optic nerve atrophy. The visual field defect starts with central or paracentral scotomas followed by upper temporal defects and finally nasal field defects. The differential diagnosis for primary optic diseases includes glaucoma. The diagnosis may be difficult to make in the early stage of the tumor.

Homonymous hemianopia occurs in lateralized suprasellar tumor development when the optic tract is compressed; temporal hemianopia develops in symmetric suprasellar extension. Double vision occurs when the abducent and oculomotor nerves that are localized in the lateral part of the cavernous sinus are damaged acutely or chronically.¹⁷

Endocrinologic Deterioration

Two endocrinologic scenarios should been evaluated in cases of a pituitary tumor, pituitary insufficiency, or pituitary hyperfunction. The patient’s signs and symptoms guide physicians in choosing which laboratory tests should been performed to determine the correct diagnosis by assessing the pituitary and target gland hormones in both the basal and dynamic states.^4,14,15

As an initial endocrine screen, done in the morning under fasting conditions, basal serum measurements should be performed for the following hormones: prolactin (PRL), growth hormone (GH), insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and estrogen, thyroid-stimulating hormone (TSH), free triiodothyronine (FT₃) and free thyroxine (FT₄), and cortisol. Then, additional provocative, dynamic, and special hormonal assays may be indicated to define precisely a specific endocrinopathy.

If no local facility exists to perform these studies, the blood can be sampled and stored at 4°C in the refrigerator and sent later that day or the next day to a specialized laboratory.

Pituitary insufficiency is usually a chronic process, associated with both large and small tumors. A macroadenoma contained within a normal-sized sella can cause hypogonadism, and if the tumor grows within the sella compartmeant it will cause total anterior pituitary insufficiency. In cases of intra- and suprasellar growth, sometimes moderate anterior pituitary (AP) insufficiency can occur, depending on the compressive effect of the tumor on the pituitary body and its stalk. Hypothalamic compression can lead to tertiary AP insufficiency.

Secondary hypogonadotropic hypogonadism (HH) is defined by absent or decreased functions of the male testes or the female ovaries. HH is caused by a lack of the gonad-stimulating pituitary hormones FSH and LH, which is associated with a decrease in the gonadal hormones testosterone and estrogen.

In addition to hyposomatotropism (GH deficiency can be assessed by insulin-induced hypoglycemia), secondary hypogonadism is the most sensitive indicator of early partial pituitary insufficiency.

The majority of patients with HH secondary to such tumors have multiple pituitary hormone deficiencies in addition to gonadotropin deficiency. In adults, prolactinomas are the most frequent cause of HH and may do so by either interfering with gonadotropin-releasing hormone (GnRH) secretion, or, in the case of macroadenomas, by local destruction and compression of the gonadotrophs. Hyperprolactinemia causes altered dopaminergic function, which has been shown to reduce GnRH messenger RNA (mRNA) levels and decrease serum levels of LH, FSH, and testosterone. Although men with hyperprolactinemia may develop galactorrhea, it occurs less frequently than in women, presumably due to the lack of stimulation by estrogen and progesterone. Clinically, men with hypogonadism may experience a loss of libido or impotence and may have soft and small testes. Loss of secondary sexual hair development starts in the pubic area, followed by thinning in the axilla and facial beard. Fine wrinkling of the facial skin is characteristic and is likely to be a result of both a testosterone and GH deficiency. In children, craniopharyngioma is the most common tumor resulting in HH and is often associated with growth retardation, visual field defects, and diabetes insipidus.

Secondary hypothyroidism occurs in about half of the patients with AP insufficiency. Clinically, the patients complain of fatigue, weakness, weight gain or increased difficulty losing weight, dry hair, rough pale skin, hair loss, cold intolerance, muscle cramps and frequent muscle aches, constipation, depression, irritability, memory loss, and decreased libido. The patient may have any number of these symptoms, and they will vary with the severity of the thyroid hormone deficiency and the length of time the body has been deprived of the proper amount of hormone.

Secondary adrenal insufficiency is caused by lack of production of adrenocorticotropic hormone (ACTH) in the pituitary gland. Patients may show symptoms of hypoglycemia, dehydration, weight loss, and disorientation. They may also experience adynamia, weakness, tiredness, dizziness, low blood pressure with orthostatic hypotension, muscle aches, nausea, vomiting, and diarrhea. These symptoms may develop gradually and insidiously. Addison’s can present with tanning of the skin, which may be patchy or evenly distributed all over the body. In some cases a person with normally light skin may be mistaken for another race with darker pigmentation. Characteristic sites of tanning are skin creases (e.g., of the hands) and the inside of the cheek (buccal mucosa). Goiter and vitiligo may also be present.

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