Main syndromes

A compilation of the main syndromes in medical practice.
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Astrid M. Libman, Julio Libman

Pituitary tumor syndrome is defined as the set of symptoms and signs that occur as a consequence of the development of an expansive lesion, generally an adenoma, in relation to the pituitary.

Pathophysiology

The pituitary is located at the base of the skull in a cavity of the sphenoid, the sella turcica. Above it is separated from the cerebrospinal fluid of the suprasellar cistern by a portion of the dura that is called the sellar diaphragm. The diaphragm is below the optic chiasm and is crossed by the pituitary stalk and blood vessels. On both sides of the sella turcica are the cavernous sinuses, through which the carotids and some oculomotor nerves pass.

The etiology of pituitary adenomas is not completely clear. They represent approximately 10% of all intracranial tumors and are a frequent finding at autopsies. They are benign monoclonal adenomas that can express and secrete hormones autonomously, causing hyperprolactinemia, acromegaly, or Cushing's disease, or they can be functionally silent and initially diagnosed as a sellar mass. The formation of these adenomas is related to multiple pathogenic processes, including initial chromosomal mutations that cause mutated pituitary stem cells. These transformed cells are subject to multiple signals that facilitate clonal expansion and to various permissive factors, including signals from receptors for hypothalamic hormones (excessive production of hypothalamic hormone releasing somatotrophin or adrenocorticotropin?), intrapituitary growth factors (epidermal growth factor, fibroblast growth factor, etc.), activation of oncogenes or loss of function of tumor suppressor genes. These alterations would ultimately result in cell proliferation and the autonomous production and secretion of different hormones.

In transgenic animals that overexpress the somatotrophin-releasing hypothalamic hormone gene, pituitary enlargement occurs due to a marked hyperplasia of the somatotropes and eventual development of somatotrophin-producing adenomas. Similarly, thyrotrophin (TSH) -producing tumors have occurred in untreated long-standing hypothyroid animals.

Notwithstanding these observations, hormone secretion by an adenoma is usually independent of hypothalamic physiologic control, and surgical resection of well-defined adenomas results in definitive cure of excessive hormone production.

Symptoms and signs

The clinical manifestations of pituitary tumors depend on their size, location, and the presence or absence of hormonal secretion.

Due to their size, they are classified into macroadenomas and microadenomas, depending on whether their diameter is greater or less than 10 millimeters. Due to their location, they can be intrasellar or suprasellar. Symptoms and signs derived from the compression of neighboring structures are greater in suprasellar tumors such as craniopharyngioma or in those of intrasellar origin that are larger and expand outside the sella turcica, such as somatotropin producers or so-called “adenomas. chromophobes ”.

If the existence of hormonal secretion is considered, the tumors are classified as non-secreting and secreting. Among the former are craniopharyngiomas and chromophobic adenomas, which produce a picture of hypopituitarism due to compression or destruction of extratumoral tissues.

Craniopharyngiomas, more frequent in children and young people, originate in embryonic remains of Rathke's bursa, presenting their highest incidence in the second decade of life. They can however go unnoticed for a long time. More than half are cystic, the rest are solid or mixed. Chromophobic adenomas can grow to a considerable size. They accumulate few secretory granules and for this reason appear as “chromophobic” in light microscopy, whether or not they produce hormones. Even when they are the cause of pituitary functional deficit, plasma prolactin is elevated in more than 50% of patients; this is generally due to the production of this hormone by the adenoma, increase that can also be caused by interference by the tumor mass with the inhibition of secretion by compromising the hypothalamic-pituitary portal circulation and preventing the arrival of dopamine. Many "chromophobic" adenomas, not associated with a clinically detectable hormonal hypersecretion state, contain and secrete intact gonadotrophins or their subunits.

The hypopituitarism that appears as a consequence of the presence of these tumors is more often partial than total. For unclear reasons, the secretory capacity of somatotrophin and gonadotropins is the first to be affected, whereas the clinical manifestations of TSH and ACTH deficiency are observed later.

Secreting adenomas include those listed below:

Somatotrophin producers . In general at the time of diagnosis they are macroadenomas. They lead to gigantism or acromegaly, depending on whether they appear before or after ossification of the diaphyse-epiphyseal cartilages of the long bones. Approximately 20% produce prolactin simultaneously.

Producers of ACTH . They are microadenomas, so local manifestations cannot be expected. They produce Cushing's disease, through hyperplasia and hyperfunction of the adrenals, especially the reticular and fascicular areas of the cortex. When this condition is sometimes treated with bilateral adrenalectomy without having previously irradiated the pituitary, about 20% of patients present with rapid and aggressive tumor growth with intense pigmentation due to the production of large amounts of ACTH and -melanocyte hormone. stimulant, derived from a common precursor, proopiomelanocortin.

Producers of prolactin . They can be microadenomas or macroadenomas. In females they give rise to galactorrhea syndrome - amenorrhea, oligohypomenorrhea and anovulation. In men, in those who grow larger for unclear reasons, they cause erectile dysfunction and sterility due to oligospermia.

Producers of TSH and gonadotropins . TSH-producing adenomas are very rare, comprising less than 2% of pituitary tumors. The patients present a picture of hyperthyroidism with detectable or elevated levels of TSH, a fact that is striking given that hyperthyroidism in any of its forms is accompanied by suppressed TSH.

In recent years it has been recognized that a significant number of clinically nonfunctioning adenomas produce gonadotropins or their alpha and beta subunits. In most cases they are macroadenomas.

Functioning adenomas may influence hormone production in the non-tumor pituitary by mechanisms other than direct compression or destruction. The inhibition of gonadotropin production due to the effect of hyperprolactinemia, and the suppression of gonadotropins to varying degrees is known. somatotropin, prolactin and TSH due to an excess of cortisol.

In the presence of a pituitary adenoma, mainly a macroadenoma, the symptoms and signs of a tumor mass are associated with general endocrine manifestations, the former or the latter may predominate. Microadenomas do not usually manifest tumor-dependent symptoms and signs. Headache is a frequent reason for consultation. It does not have a characteristic distribution, being able to be frontal, inter or retro-orbital, or diffuse. It can be continuous or intermittent and of variable intensity. It is produced by the compression of neighboring structures, such as the sellar diaphragm and vascular walls.

Visual defects, expression of the suprasellar extension of the lesion and compression of the optic pathway, may or may not be associated with headache. The patient may not be aware of this alteration that is revealed, if it is rude, in a confrontational campimetry, comparing the visual field of the patient with that of the observing doctor, or by performing a visual field. Damage to the optic nerve is revealed by pale papilla on examination of the fundus. However, papilledema and total blindness are not very common.

Lateral extension to the cavernous sinus can produce ptosis, diplopia, or ophthalmoplegia due to involvement of the oculomotor nerves.

Pituitary apoplexy, the result of a spontaneous bleeding in an adenoma, constitutes a true endocrinological emergency. The picture can evolve in a period of 24 to 48 hours with severe headache, stiff neck, ocular paralysis, loss of vision, cardiovascular collapse, hypoglycemia and coma. Diagnostic imaging, CT or MRI, without contrast, usually shows the presence of bleeding, stem deviation, compression of normal pituitary tissue, and, in severe cases, signs of parasellar hemorrhage.

Eventually the discovery of an adenoma can be a chance finding when obtaining an X-ray, CT, or MRI of the skull or cervical spine for other reasons.

Study methodology

Diagnostic studies in a patient suspected of harboring a pituitary tumor include diagnostic imaging, neuro-ophthalmological and endocrine evaluation. The latter is considered in the sections corresponding to adenohypophyseal hyper and hypofunction.

MRI is the procedure of choice for the diagnosis of pituitary tumors due to its greater resolving power to identify changes in soft tissues.

When a pituitary adenoma or parasellar abnormalities are suspected, MRI should focus specifically on the gland, since the brain gland is often not optimal for visualizing the pituitary gland. This procedure allows detailed identification of the tumor and its effect on neighboring soft structures, including the optic pathway and cavernous sinuses. High-resolution coronal and sagittal views before and after contrast gadolinium administration identify most adenomas.

After the administration of gadolinium, microadenomas are usually hypodense when compared with the normal gland, a fact attributable to compromised vascularization. They can also cause glandular asymmetry and stem deviation. Macroadenomas, which are more vascular, have a greater affinity for gadolinium and frequently produce alterations and enlargement of the sella turcica.

They can grow upward, compromising the optic pathway, or may extend to the sphenoid sinus or cavernous sinuses. The pituitary gland may transiently increase in size in adolescence, during pregnancy, or after multiple pregnancies, and as a consequence of untreated primary hypothyroidism or long-standing primary hypogonadism.

CT allows the visualization of bone structures, including the sellar floor and the clinoid processes, and determine their invasion. It also recognizes the calcifications that characterize craniopharyngioma.

The neuro-ophthalmological evaluation is carried out by means of campimetry, which allows determining the involvement of the optical pathway. The classic homonymous bilateral hemianopia or upper quadrant defects can occur in the presence of a macroadenoma that extends upward and compresses the optic chiasm. In practice, it is possible to observe from a normal visual field to combinations of unilateral or bilateral defects in all quadrants. The reasons for these variations include the different positions of the chiasm above the saddle and in relation to the growth of the adenoma and variable compromises of the chiasmatic circulation. Craniopharyngiomas, due to their position, are more likely to produce optic atrophy and amaurosis.