Pituitary and Hypothalamus

Question 1

Pituitary-Hypothalamus Axis

Answer 1

Production of most hormones in the anterior
pituitary is controlled by factors secreted by the
hypothalamus.
• These are carried to the anterior pituitary by a
portal vascular system
• The posterior pituitary secretes 2 peptide
hormones, first synthesized in the hypothalamus
and then stored within axon terminals.
• These are released in response to appropriate
stimuli.

Question 2

5 cell types – based on specific Abs against pituitary hormones

Answer 2

Somatotrophs – GH (50% of cells)
Lactotrophs (mammotrophs) – prolactin
Corticotrophs – ACTH, POMC, MSH
Thyrotrophs – TSH
Gonadotrophs – LH and FSH

Question 3

Hyperpituitarism

Answer 3

adenomas, hyperplasia, carcinomas, secretion of hormones by non-pituitary tumors, certain hypothalamic disorders

Question 4

Hypopituitarism

Answer 4

ischemic injury/surgery/radiation, inflammatory reactions, nonfunctional pituitary adenomas

Question 5

Local mass effects

Answer 5

radiographic abnormalities of sella turcica, visual field abnormalities, elevated intracranial pressure, pituitary apoplexy

Question 6

Pituitary adenoma

Answer 6

Most common cause of hyperpituitarism, anterior lobe, may be functional/nonfunctional, peak incidence from 35-60 years
Microadenomas or macroadenomas
Classified on the basis of hormone(s) produced by neoplastic cells, detected by immunohistochemical stains
Composed of sheets/cords of uniform polygonal cells with absent reticulin network (in contrast to normal pituitary); reticulin stain important

Question 7

genetics of pituitary adenomas

Answer 7

Sporadic (95%) – G-protein mutations in alpha subunits that interferes with its intrinsic GTPase activity
Familial – MEN1, CDKN1B, PRKAR1A, AIP

Question 8

Molecular abnormalities associated with aggressive behavior –

Answer 8

overexpression of cyclin D1, mutations of p53, and epigenetic silencing of RB1

Question 9

Prolactinomas

Answer 9

Most common adenoma type, 30% of cases
Increased prolactin secretion
Amenorrhea/galactorrhea/decreased libido/infertility
Other causes such as physiological/drugs/estrogens/renal failure
Treatment – surgery or bromocriptine

Question 10

Somatotropinoma

Answer 10

2nd most common type
Excessive GH
Children – gigantism; adults – acromegaly

Question 11

ACTH cell (corticotroph) adenomas

Answer 11

Excess production of ACTH
Hypercortisolism (Cushing disease)

Question 12

Hypopituitarism

Answer 12

Causes – ischemic injury/surgery/radiation, inflammatory reactions, nonfunctional pituitary adenomas
At least 75% of parenchyma is lost, mostly because of a destructive process
Tumors or other mass lesions, traumatic brain injury, surgery/radiation, pituitary apoplexy (sudden hemorrhage), ischemic necrosis (DIC, sickle cell anemia, Sheehan syndrome), empty sella syndrome, inflammatory disorders/infections, hypothalamic lesions

Question 13

GH deficiency –
LH and FSH deficiency –
TSH deficiency –
ACTH deficiency –

Answer 13

dwarfism
amenorrhea (absence of menstruation), infertility, etc
hypothyroidism
hypoadrenalism
Prolactin deficiency

Question 14

Posterior pituitary syndromes

Answer 14

Involve ADH – ADH binds to receptors on cells in collecting ducts of kidney and promotes reabsorption of water back into circulation
Diabetes insipidus – ADH deficiency, central or nephrogenic, loss of large volumes of dilute urine, hypernatremia, polydipsia (inc thirst)
Syndrome of inappropriate ADH secretion: water retention

Question 15

Lesions of the hypothalamus

Answer 15

Disruption of function of hypothalamic/pituitary axis – hypopituitarism, hyperprolactinemia
Neurologic – visual field defects
Hypothalamic suprasellar tumors
Clinically significant because they may cause:
Hypofunction or hyperfunction of anterior pituitary
Diabetes insipidus
Includes: gliomas and craniopharyngiomas

Question 16

Craniopharyngioma

Answer 16

Slow-growing, accounts for 1-5% of intracranial tumors
Bimodal age distribution
Commonly cystic and multiloculated
Arises from remnants of the craniopharyngeal duct and/or Rathke cleft
2 distinct histologic types
Adamantinomatous – children, squamous epi, wet keratin and calcification, cysts contain “machine oil”
Papillary – adults, lack keratin, calcification and cysts

Question 17

Pineal Gland

Answer 17

center of the brain, between 2 hemispheres
Pineal gland is a midline structure, and is often seen in plain skull x-rays as it is often calcified

Question 18

Effects of pineal lesions

Answer 18

precocious puberty due to melatonin deficiency
Precocious puberty- early onset of puberty
Neurologic – increased intracranial pressure due to mass effect (non-neoplastic cysts, germ cell neoplasms, pineal parenchymal tumors)