B95. Hypo and Hyperfunction of the hypthalamic hypophysial system Flashcards
What are the major hormones lost in panhypopituitarism and what is lost first?
how much of the gland is lost before symptoms occur.
panhypopituitarism, occurs with 75% loss of adenohypophysis parenchyme
Hormones lost, in order:
- GH
- LH
- FSH
- ACTH
- TSH
What are the causes of panhypopituitarism
- Tumors
- pituitary adenoma
- craniopharyngioma - Rathke pouch embryonic rmenant tumor, seen in children.
- other CNS tumors
- Granulomatous diseases
- Irradiation
- Trauma -
- skull fractures
- birth trauma
- Surgery
- Sheehan syndrome
- Autoimmune hypophysitis
- Tumors or disorders of the hypothalamus
- Congenital agenesis, exceptionally rare.
What is the presentation of Sheehan syndrome? Why is the posterior pituitary spared?
Presentation:
- poor lactation is usually the first sign, as the woman should be lactating
- loss of pubic hair,
- fatigue - signs of hypthyroidism.
The anterior pituitary is supplied by blood from the portal veinous system of the Superior Hypophyseal artery
While the posterior neurohypophysis is supplied directly by arterial branches of the Inferior hypophyseal artery.
Quick bullet point results for deficiencies of each pituitary hormone
GH: Dwarfism
LH/FSH: amenorrhea, decreased libido, impotence, infertility loss of pubic and axillary hair
TSH: hypothyroidism
ACTH: hypoadrenalism (Addison’s syndrome)
Prolactin: no postpartum lactation
Results of GH loss
in children,
- dwarfism, nanosomia
in adults,
- muscle loss
- central obesity
- impaired attention and memory
-
Insulin resistance
- hypercholesterinemia
- hyperlipidemia, LDL and HDL
- central obesity
- loss of bone mass, fractures.
Effects of low LH/FSH
menstrual abnormalities or amenorrhea
Infertility
loss of muscle mass
loss of pubic, axillary, and facial hair
decreased libido
impotense
delayed or absent puberty
imcropenis, impaired sexual development of both sexes.
Effects of low ACTH
- Results in adrenal insufficiency, without pigmentation
- hypoglycemia
- fatigue, vomitting
- anemia
- hyponatremia
Addisonian crisis:
- sudden lower body pain
- confusion, psychosis,
- severe lethargy
- hypoglycemia
- hyponatermia
- hyperkalemia
- hypotension
- severe vomitting and diarrhea, unclear cause probably CNS
- coma, death
hypercalcemia in 10% for unclear reasons.
Effect of low TSH
- hypothyroidism
- fatigue and confusion
- mental slowing
- low BMR
- low cold tolerance
- low heart rate
- low blood pressure
- weight gain and hair loss
Effect of low prolactin
just low impaired lactation
may also cause low libido but not really tho
What causes hyperpituitarism?
Adenomas of specific cell types in the anterior lobe are by far the most frequent cause.
Less commonly there is hyperplasia or carcinomas of the anterior pituitary
Paraneoplastic syndromes
and some hypothalamic disorders.
How are pituitary adenomas classified?
What are the cell types of each called?
Based on the hormones they produce, detected by immunohistostaining
- Corticotrophs - ACTH
- Somatotrophs - GH
- Lactotrophs - Prolactin
- Mammosomatotorphs - secrete both Prolactin and GH
- Thyrotrophs - TSH
- Gonadotrophs - FSH.
- Silent - cells stain for a hormone, but it is not secreted and does not have clinical manifestations.
- Hormone negative
- Rare cases are plurihormonal
What is the size classifications of pituitary adenomas
microadenomas smaller than 1 cm
macroadenomas above 1 cm.
What is the presentation of pituitary adenomas, what causes them?
95% are sporadic
5% are familial
Secretory adenomas are discovered based on their clinical symptoms of their overexpressed hormone
Hormone-negative adenomas are usually discovered as macroadenomas, and are often discovered due to their compression effects causing hypopituitarism and bilateral temporal hemanopia.
What are the mutations associated with pituitary adenomas?
GNAS1 mutations to the GsAlpha protein, ablating its GTPase activity, and causing persistent activity of the Gs signaling. This is found in about 40% of GH adenomas and in a minority of ACTH adenomas.
TP53 mutations are not common, but if they are present, they are associated with aggressive invasion and recurrence of the adenomas.
Familial pititary adenoma syndromes have mutation in one of these four genes:
- MEN1
- CDKN1B
- PRKAR1A
- AIP
What is the gross morphology and histology of a pituitary adenoma?
Well cricumscribed, soft tumor, the color of gray matter.
microadenomas remain confined to sella turcica
Macroadenomas can extend in all directions, downward and
- erode the sella turcica bones, and invade locally into the cavernous and sphenoid sinuses.
- Can grow upwards and compress the optic chiasm bilateral temproal hemanopia
Histology:
- solid cords or sheets of uniform, polygonal cells. There is sparse connective tissue.
- nuclei may be uniform or pleomorphic with low/absent mitosis.
- the cytoplasm can be acidophilic basophilic or chromophobic based on the secretory type of cell, but its function is not predictable from its H&E stain.
- The singular cell type within the tumor and the very little stroma distinguishes it from the normal anterior pituitary tissue (which has a heterogenous mix of cells).
- p53 mutations cause adenomas with high mitotic figures, called atypical adenomas, which are more locally invasive and recurrent.
Symptoms of Prolactinomas
- appear as both micro and macroadenomas
- microadenoma form is more common
- galactorrhea
- inhibition of GnRH release
- amenorrhea
- decreased libido
- infertility
They are caught earliest in pre-menopausal women.
Symptoms are harder to see in men and post menopausal women and they are usually macroadenomas by then, causing mass effects.
What are the frequencies of the different types of secretory adenomas?
- Prolactinomas - most common. 30%
- Non-secretory 25%
- GH adenomas 15%
- ACTH Corticotroph cell adenomas 15%
- FSH, LH 10%
- TSH less than 1%
TSH, FSH, and LH adenomas are all rare.
Symptoms of GH adenomas
Adults: Acromegaly
- Jaw, brow, hands, feet, and tongue enlarged
- Excessive sweat and body hair
-
Insulin resistance
- Hyperglycemia
- Type 2 Diabetes mellitus above 11mM
- Impaired OGTT, above 7.8, below 11. mM
- Hypertension
- Cardiomegaly
- Barrel chest
- Altered vitamin D signaling
- Osteoperosis
- Hypercalcemia
- Hyperprolactinemia in some cases, as PRL and GH dual mammosomatotrophic adenomas are the most common multiple secretory type.
Children: Gigantism, all the same problems plus long bones grow very large before growth plates close.
Patients with chronic acromegaly or gigantism eventually die of heart failure from cardiomegaly.
Characteristic lab measurements of hyper GH secretion
Increased IGF-1 levels
Loss of glucose suppression of GH
loss of noctournal GH surge
Increased somatomedins/somatostatins (feedback hinibitor of GH)
Paradox dopamine stimulation of GH
What are the symptoms of Corticotroph cell adenomas?
These are usually microadenomas
Causing Cushing Disease = ACTH pituitary adenoma.
Can also be caused by corticotroph cell hyperplasia or in the most rare cases by hypthalamic CRH releasing tumor.
Symptoms
- gradual onset
- hypertension
- hyperglycemia
- hypercholesterolemia
- central obesity
- moon face
- buffalo hump
- muscle loss and limb weakness
- glucosuria and polydipsia from insulin resistance
- osteoperosis and fractures
- cutaneous stria
- immune suppression and oportunistic infections
- hirsuitism in women
- amenorrhea
- mood swings depression
- Pigmentation of skin, gums, mucous mems.
Symptoms of FSH and LH adenomas
The hormones themselves usually do not cause clinical symptoms, and the tumors present once they are large enough to cause hypopituitarism from mass effects.
What are the symptoms of TSH adenomas?
Very rare, less than 1% of all pit adenomas
Cause hyperthyroidism.
What is the etiology of pituitary carcinomas?
Exceptionally rare, and virtually always have distant metastases by the time of diagnosis.
What is the frequency of the different kinds of adenomas.
Prolactinomas are most frequent, 30%
Growth hormone next
ACTH next
TSH, LS, FSH, are very rare
TSH about 1%
