Pituitary Gland Dz Flashcards
Where is the pituitary gland located
sella turcica
under optic chasm
Hypothalamic-pituitary-target gland axis
- What does the hypothalamus release
- what is result
- Releasing hormones
- Stimulate pituitary to release stimulating hormones
- Stimulating hormones stimulate target organs to secrete their hormones
Hypothalamic-pituitary-target gland axis
- What hormone is an exception to releasing hormone = release of target organ’s hormone?
Prolactin - its secretion is under inhibitory control of dopamine secreted by the hypothalamus
What are the two major categories of endocrine disease?
- hypo (decreased hormone secretion)
- hyper (increased hormone secretion)
Hypothalamic-pituitary-target gland axis
- What are four causes of hyper states?
- primary disorder
- secondary disorder
- ectopic site production
- Overactive target hormone receptors (dt genetic mutation)
Hyper states
- primary vs. secondary disorder
- Primary: target gland over secretes due to pathology directly affecting it
- Secondary: pituitary/hypothalamus over-stimulates the target gland
What is the change in hormone production due to a primary hyper state?
- Target gland hormone concentration secretion is high
- Stimulating hormone concentration is low (from the pituitary)
- Negative feedback
What is the change in hormone production due to a secondary hyper state?
Both target gland and stimulating hormone levels are high
Ectopic site production of hormone examples
- ovarian tumor
- small cell lung cancer
- SCC of the lung
Hypothalamic-pituitary-target gland axis
- 5 causes of hypo states
- primary disorder
- secondary disorder
- tertiary disorder
- Hormone is defective
- Target organ receptors are unresponsive
Hypo state primary disorder
- congenital or acquired problem of the gland
- low target hormone level
- high stimulating hormone level
- loss of negative feedback
Hypo state secondary disorder
- pituitary doesn’t secrete enough stimulating hormoen
- low target hormone level
- low stimulating hormone level
Hypo state Tertiary disorder
- hypothalamus does not secrete enough releasing hormoen
Hypo state defective hormone
- high hormone levels
- function of hormone does not occur
- corrected by exogenous hormone injection
Hypo state unresponsive target organ receptors
- high stimulating hormone levels
- organ producing hormone is trying to get target organ to respond
- target organ will NOT respond to exogenous hormone stimulation
- ex. nephrogenic diabetes insipidus
List the 6 anterior pituitary hormones and their releasing/inhibiting hormones
- Growth hormone (GH) - somatomedins
- Thyroid stimulating hormone (TSH) - T3, T4
- Adrenocorticotropic hormone (ACTH) - cortisol
- Prolactin - milk production
- Follicle Stimulating Hormone (FSH) - estrogen
- Leutinizing Hormone (LH) - progesterone, testosterone
List the 2 posterior pituitary hormones
- antidiuretic hormone (Vasopressin)
- Oxytocin
Pituitary adenomas
- describe
- slow growing
- benign
- 3rd most frequent intracranial tumor
- over secretion of hormone
- compression can cause hypopituitarism
- F>M 3:1
- Increased incidence with age
- Seen in MEN
Pituitary adenoma
- two types
- Microadenoma <10 mm
- Macroadenoma >10mm
Pituitary adenoma
- Signs and symptoms overview
Mass effect
- superior extension
- lateral extension
- Inferior extension
Pituitary adenoma
- Superior extension mass effect
- may compromise optic pathways, leading to impaired visual acuity and visual field defects (bitemporal hemianopsia)
- may produce hypothalamic syndrome: disturbed thirst, satiety, sleep, temperature regulation
Pituitary adenoma
- lateral extension mass effect
may compress cranial nerves III, IV, V, VI (diplopia)
Pituitary adenoma
- Inferior extension mass effect
may lead to cerebrospinal fluid rhinorrhea
Pituitary adenoma
- Dx
- check levels of all hormones produced by pituitary
- check levels of all target organ products
Pituitary adenoma
- Tx
- surgical excision generally first line
- radiation
- medical therapy
- Simple observation: if tumor is small, no local mass effect, nonfunctional, not affecting quality of life
Pituitary adenoma
- Sx removal explanation
- requires neurosurgeon and ENT surgeon
- Transsphenoidal approach MC
- Endonasal submucosal transeptal approach
- septal pushover/direct sphenoidotomy
- endoscopic
Pituitary adenoma
- indications for sx
- First line if symptomatic
- Medical/radiotherapy failed
- Prompt relief from excess hormone secretion and mass effect
- Pituitary apoplexy (hemorrhage) with compressive sx
Four disorders of pituitary function
- Cushings (ACTH)
- Hyperthyroidism (TSH)
- Hyperprolactinemia
- Acromegaly
Cushings
- cause
result of excess ACTH release = increased cortisol secretion
Prolactinoma
- describe
- MC functional pituitary tumor
- usually microadenoma
- can be space occupying, often with visual field defects
- often have galactorrhea and/or amenorrhea but absence does not exclude dx
Prolactinoma hormone situation
- elevated prolactin
- GnRH release is decreased
- LH and FSH are decreased
Prolactinoma
- Female sx
- amenorrhea
- Hirtutism
- decreased libido
Prolactinoma
- Male sx
- impotence (often ignored)
- infertility
- decreased libido
- gynecomastia
- larger tumors = more mass effects
Why do females often present with prolactinomas earlier then men
amenorrhea causes them to seek medical attention
Prolactinoma
- common causes
- drugs
- inhibited dopamine outflow
- hypothyroidism
Prolactinoma
- common drug causes
- why?
- decrease dopamine stores
- phenothiazine, amitriptyline, metoclopramide
Prolactinoma
- what other factors inhibit dopamine outflow?
- estrogen
- pregnancy
- exogenous sources
What prolactin level is almost always a prolactinoma
> 200
- even in a nursing mom
What do prolactin levels correlate with?
tumor size in macroadenomas
- suspect another tumor if prolactin level is LOW and tumor is LARGE
Prolactinoma
- dx
- Assess hypersecretion (basal and fasting morning PRL levels)
- might need to measure multiple times due to pulsatile secretion
- Exclude hypothyroidism by measuring TSH and T4
Prolactinoma
- false positives
- false negatives
- false positive: aggregated from of circulating PRL which are biologically inactive (macroprolactinemia)
- false negative: markedly elevated PRL level (>1000 ug/L) due to negative feedback
Prolactinoma
- treatment
- Medical (Cabergoline and bromocriptine) to decrease prolactin and tumor size
- Sx: transsphenoidal sx
- Irradiation
Growth hormone tumor
- overall effect
- onset
- Two types
- make things big (hands, feet, ears, lips, tongue)
- usually insidious, not noticeable by pt
- Acromegaly and gigantism
Gigantism
- describe
secrete excess GH before fusion of epiphyseal growth plates
Growth hormone tumor
- signs and sx
- DM or glucose intolerance
- hypogonadism
- large hands/feet
- large head w/ lowered brow and coarse features
- HTN
- colon polyps
- multiple skin tags
Acromegaly
- describe
- rare
- excess secretion of GH
- syndrome of coarsened facial features, overgrowth of hands and feet
Acromegaly
- etiology
Excess secretion of GH stimulates liver to release insulin-like growth factor (IGF-1) = most of clinical features
Acromegaly
- pathophysiology
- > 90% will have benign GH-secreting adenoma of anterior pituitary
- 10% have ectopic GH secretion, MC from pancreatic islet cell tumors, lymphoma, or hyper secretion of growth hormone releasing hormone (GHRH)
What are common causes of hypersecretion of GHRH
- hypothalamic gangliocytomas
- peripheral neuroendocrine tumors such as carcinoid, islet cell tumors, small cell lung cancer, adrenal adenoma, medullary thyroid cancer, pheochromocytoma
Acromegaly
- MSK and neuro signs and symptoms
MSK
- enlarging shoe/ring size
- arthralgia/myalgia
Neuro
- HA
- Vision change, temporal hemianopsia
- hand numbness/carpal tunnel
- fatigue/weakness
- sleep disturbance
Acromegaly
- Derm and Endocrin signs and symptoms
Derm
- increased sweating
- oily skin
Endocrine
- deepened voice
- decreased libido
- amenhorrhea/menstrual dysfunction (women)
- erectile dysfunction (men)
- galactorrhea
Acromegaly
- PE findings: face, Neuro, MSK
- Presentation may be subtle
- Review of old photos may reveal facial coarsening
Neuro:
- bitemporal hemianopia
- other CN defects
MSK:
- hypertrophic arthropathy of spine, hips, knees, ankles
- prognathism
- gigantism (peds/adolescent)
What are features of facial coarsening
- enlarging jaw (macrognathia), nose, and frontal bones
- spreading teeth, change in bite/jaw malocclusion
- Enlarging tongue
Acromegaly
- PE findings: derm, visceromegaly
Derm:
- skin thickening
- skin tags
Visceromegaly
- prostate
- kidney
- liver
- spleen
- heart
- salivary glands
- thyroid (goiter)
- tongue
Acromegaly
- Dx w/u initial testing
Serum IGF-1
- Best single test for dx
- levels 2X upper limit suggestive of acromegaly
Acromegaly
- Dx workup fu testing
- 75g OGTT will show elevated glucose levels
Acromegaly
- imaging
MRI of sella
- will detect tumors as small as 2 mm
- won’t differentiate between functioning and nonfunctioning tumor
Acromegaly
- tx
- sx
- radiation
- bromocriptine (temporizing measure0
- Octreotide
Gigantism
- overview
- caused by excess secretion of GH prior to closure of epiphyseal plates in long bones (must occur before puberty)
- commonly caused by pituitary tumors that secrete mutant protein that eliminates need for GHRH
- tumors block gonadotropin release = amenorrhea and impotence in men
Growth plates and chondrocytes
- before puberty, first layer of growth plate cells differentiate into chrondrocytes
- second layer of plate (chondrocytes) is responsive to GH - mitosis
- after maturation of chondrocytes, they deposit calcium into bone matrix to form new bone
Growth plates and growth hormone
- osteoblasts use calcium depositions to form new tissue along long bone
- excess calcium is converted into connective tissue, bones elongate
- GH activates insulin-like growth factor (IGF1) which causes growth of muscle to keep up with bone growth
Gigantism
- how common
- effect on life
- epidemiology
- 3 in a million
- 100 cases to date in US
- 2-3 times mortality of general population
- no racial or sex predilection
- not genetic
Gigantism
- signs and symptoms
- reduced life span dt medical complications
- tall, big hands/feet, coarse facial features, excess sweating, osteoarthritis, carpal tunnel, CVD, benign tumors, DM, obesity/sleep apnea, deep voice
- pituitary tumor can cause HA and visual impairment (optic chiasm)
Gigantism
- dx/testing
- no prenatal testing bc not genetic
- initial growth not usually exaggerated, apparent over time
- Blood test for IGF1
- CT/MRI
Gigantism
- tx
- difficult bc GF continually surges…
- Can remove pituitary tumor to stop release of GH
- Octreotide, bromocriptine block GH effects
- radiation to tx tumor
Hypopituitarism
- cause
- metabolically silent pituitary tumor - doesn’t secrete anything
- damage to pituitary gland: tumor, radiation, autoimmune dz, infection, hemorrhage
Two potential causes of pituitary hemorrhage
- pituitary apoplexy: hemorrhage dt rupture of adenoma
- Sheehan’s syndrome: peri or postpartum hemorrhage
Hypopituitarism
- what causes sx
- growth of tumor
- superior growth: bitemporal hemianopsia
- compression fo pituitary gland itself can cause gland dysfunction
Hypopituitarism
- ACTH
- TSH
- LH/FSH
- ACTH: secondary adrenal insufficiency
- TSH: secondary hypothyroidism
- LH/FSH: central hypoganodism. In children = pubertal delay, in adults = impotence, menstral irregularities, infertility, decreased libido
Hypopituitarism
- GH
- during childhood = pituitary dwarfism (delayed or slowed growth)
- epiphyseal plates closer before normal height
- proportionate little person (growth of everything is decreased)
Two main causes of pituitary dwarfism
- gene mutations
- tumors (MC craniopharyngioma)
pituitary dwarfism
- sx
- HA
- vomitting
- vision problems (diplopia)
- polydipsia
- sleep disturbances
- everything is small and proportionate
pituitary dwarfism
- signs and sx
- child with slow growth rate (<2” per year)
- normal intelligence and capabillities
pituitary dwarfism
- Dx
- monitor growth rate/curve
- xray to détermine bone “age”
pituitary dwarfism
- tx
- GH injections
* ADR: fluid retention, joint and muscle aches
