Pituitary adenomas are benign tumours of the hormone-producing cells of the anterior pituitary, and they are the most common cause of pituitary hypersecretion syndrome and hyposecretion in adults. Because each hormone-producing cell lineage gives its own adenoma, the cell of origin is the natural way to sort them.
The five cell types of the anterior pituitary
Pituitary adenomas are benign tumours derived from one of the five hormone-producing cell types of the anterior pituitary gland, so each lineage gives its own adenoma.
- Somatotrope adenomas produce growth hormone and make up 10-15% of pituitary adenomas.
- Lactotrope adenomas are the most common form of the functioning pituitary adenoma, with a prevalence of 50-60% of all the functioning pituitary adenomas.
- Thyrotrope adenomas produce TSH.
- Corticotroph adenomas produce ACTH.
- Gonadotrope adenomas produce FSH and LH.
A sixth clinical group, the non-functioning pituitary adenoma, does not produce a syndrome from hormone excess and accounts for 15-35% of all the cases.
Somatotrope adenomas are divided microscopically into two variants. Densely granulated somatotrope adenomas (DGSA) are the more common form. Sparsely granulated somatotrope adenomas (SGSA) are less common, but they are more prevalent in younger adults and in females, have more potential for invasion, and express less growth hormone positivity than DGSAs. Mixed-pattern somatotrope adenomas, containing both variants, are also possible (see Molecular pathogenesis of pituitary adenomas).
Classification by transcription factor, hormone and cytokeratin
Within each lineage, adenomas are further typed by the transcription factors they express (proteins that switch on a cell’s hormone genes), the hormones they contain, and the pattern of cytokeratin staining (cytokeratin is a structural protein of epithelial cells). In the table, Pit-1 marks the GH-, PRL- and TSH-producing adenomas, Tpit the ACTH-producing ones, and SF-1 the gonadotroph adenoma. GH is growth hormone, PRL is prolactin, α-SU is the alpha subunit shared by the glycoprotein hormones, and ER is the estrogen receptor.
| Adenoma type | Transcription factors | Hormones | Cytokeratin |
|---|---|---|---|
| GH-producing adenomas | |||
| Densely granulated somatotroph adenoma | Pit-1 | GH, α-SU | diffuse |
| Sparsely granulated somatotroph adenoma | Pit-1 | GH | dot-like |
| Mammosomatotroph adenoma | Pit-1, ER | GH, PRL, α-SU | diffuse |
| Mixed somatotroph and lactotroph adenoma | Pit-1, ER | GH, PRL, α-SU | diffuse |
| PRL-producing adenomas | |||
| Sparsely granulated lactotroph adenoma | Pit-1, ER | PRL (Golgi) | diffuse |
| Densely granulated lactotroph adenoma | Pit-1, ER | PRL (diffuse) | diffuse |
| Acidophil stem-cell adenoma | Pit-1, ER | PRL (diffuse), GH | rare dot-like |
| TSH-producing adenoma | |||
| Thyrotroph adenoma | Pit-1, GATA-2 | β-TSH, α-SU | diffuse |
| ACTH-producing adenomas | |||
| Densely granulated corticotroph adenoma | Tpit | ACTH | diffuse |
| Sparsely granulated corticotroph adenoma | Tpit | ACTH | diffuse |
| Crooke’s cell adenoma | Tpit | ACTH | ring-like |
| Gonadotropin-producing adenoma | |||
| Gonadotroph adenoma | SF-1, GATA-2, ER | β-FSH, β-LH, α-SU | diffuse |
| Plurihormonal adenomas | |||
| Silent type III adenoma | Pit-1 (?), ER | multiple | diffuse |
| Unusual plurihormonal adenoma (NOS) | multiple | multiple | n/a |
| Hormone negative adenoma | |||
| Null cell adenoma | none | none | diffuse |
Polyhormonal adenomas
Other than the five cell types of pituitary adenomas, polyhormonal adenomas are possible. They can be either adenomas with a mixture of different cell types or adenomas with one cell type that is able to produce different hormones at the same time.
Autonomous secretion
Hormonally active pituitary adenomas work autonomously, with a reduced feedback effect on them: the tumour does not throttle its output the way a normal cell responds to circulating hormone levels. The size of a pituitary adenoma has no correlation with the level of hormone secretion from the tumour.
Hypothalamic hormone excess and hyperplasia
Among the hypothalamic hormones, GHRH and CRH are able to cause hyperplasia (an increase in the number) of their target cells in the anterior pituitary gland. Therefore, in some rare tumours of the abdomen and chest that produce GHRH and CRH, it is possible to see hyperplasia of somatotroph and corticotroph cells in the pituitary gland.
How common pituitary adenomas are
The prevalence of pituitary adenomas is about 1:1000-1500. Autopsy studies reveal that about 15% of individuals have pituitary adenomas that are completely silent and asymptomatic. They are more common in women during the fertile ages.
Pituitary adenomas account for about 15% of all cases of intracranial neoplasm, and in about 1/4 of all autopsies a microadenoma of the pituitary gland is found.
Pituitary carcinoma
Pituitary carcinoma is very rare. It is a pituitary tumour that has spread beyond the sella to the cranium, the spine or the rest of the body; a malignant tumour involving the pituitary is far more often a metastasis that travelled there from elsewhere.