Classification of Pituitary Adenomas

Question 1

Pituitary Cell Type: Lactotroph

Hormone:

Adenoma Subtypes

Associated Syndrome

Answer 1

Pituitary Cell Type: Lactotroph

Hormone: prolactin

Adenoma Subtypes: lactotroph adenoma, silent lactotroph adenoma

Associated Syndrome: Galactorrhea and amenorrhea (in females), Sexual dysfunction, infertility

Question 2

Pituitary Cell Type: somatotroph

Hormone

Adenoma Subtypes

Associated Syndrome

Answer 2

Pituitary Cell Type: somatrotroph

Hormone: GH

Adenoma Subtypes:

1. Densely granulated somatotroph adenoma
2. Sparsely granulated somatotroph adenoma
3. Silent somatotroph adenoma

Associated Syndrome:

1. Gigantism (children)
2. Acromegaly (adults)

Question 3

Pituitary Cell Type: Mammosomatotroph

Hormone:

Adenoma Subtypes

Associated Syndrome

Answer 3

Pituitary Cell Type: Mammosomatotroph

Hormone: Prolactin, GH

Adenoma Subtypes: Mammosomatotroph adenomas

Associated Syndrome: Combined features of GH and prolactin excess

Question 4

Pituitary Cell Type:Corticotroph

Hormone

Adenoma Subtypes

Associated Syndrome

Answer 4

Pituitary Cell Type: Corticotroph

Hormone: ACTH and other POMC-derived peptides

Adenoma Subtypes:

1. Densely granulated corticotroph adenoma
2. Sparsely granulated corticotroph adenoma
3. Silent corticotroph adenoma

Associated Syndrome:

1. Cushing syndrome
2. Nelson syndrome

Question 5

Pituitary Cell Type:

Hormone

Adenoma Subtypes

Associated Syndrome

Question 6

Pituitary Cell Type: Thyrotroph

Hormone

Adenoma Subtypes

Associated Syndrome

Answer 6

Pituitary Cell Type: Thyrotroph

Hormone: TSH

Adenoma Subtypes:

1. Thyrotroph adenomas
2. Silent thyrotroph adenomas

Associated Syndrome:

1. Hyperthyroidism

Question 7

Pituitary Cell Type: Gonadotroph

Hormone:

Adenoma Subtypes:

Associated Syndrome:

Answer 7

Pituitary Cell Type: Gonadotroph

Hormone: FSH, LH

Adenoma Subtypes:

1. Gonadotroph adenomas
2. Silent gonadotroph adenomas (“null cell,” oncocytic adenomas)

Associated Syndrome:

1. Hypogonadism
2. mass effects
3. hypopituitarism

Question 8

MEN1 mutations

Answer 8

1. LOF
2. MEN1 encodes for menin, a protein with protean roles in tumor suppression, including repression of oncogenic transcription factor JunD, and in histone modification.
3. Germline inactivating mutations of MEN1 (multiple endocrine neoplasia, type 1)
4. GH, prolactin, and ACTH adenomas

Question 9

GNAS

Answer 9

1. GOF
2. GNAS encodes for alpha subunit of stimulatory G-protein, Gsα. Oncogenic mutation of GNAS constitutively activates Gsα, leading to upregulation of intracellular cyclic AMP (cAMP) activity
3. Activating mutation
4. GH adenomas

Question 10

PRKAR1A

Answer 10

1. GOF
2. PRKAR1A encodes for a negative regulator of protein kinase A (PKA), a downstream mediator of cAMP signaling. Loss of PKA regulation leads to inappropriate cAMP activity
3. Germline inactivating mutations of PRKARIA are present in autosomal dominant Carney complex
4. GH and prolactin adenomas

Question 11

Cyclin D1

Answer 11

1. GOF
2. Cell cycle regulatory protein; promotes G1-S transition
3. Overexpression
4. Aggressive adenomas

Question 13

CDKN1B

Answer 13

1. LOF
2. The p27 protein is a negative regulator of the cell cycle
3. Germline inactivating mutations of CDKN1B (“MEN-1-like” syndrome)
4. ACTH adenomas

Question 14

Aryl hydrocarbon receptor interacting protein (AIP)

Answer 14

1. LOF
2. Receptor for aryl hydrocarbons and a ligand-activated transcription factor
3. Germline mutations of AIP cause pituitary adenoma predisposition [PAP] syndrome
4. GH adenomas (especially in patients younger than 35 years of age)

Question 15

Retinoblastoma (RB)

Answer 15

1. LOF
2. Retinoblastoma protein is a negative regulator of the cell cycle
3. Methylation of RB gene promoter
4. Aggressive adenomas