Anterior pituitary disorders Flashcards
Causes of increased prolactin
Stalk compression
hypothalamic injury
prolactinoma, cosecretion with pituitary adenoma
hypothyroid
Effects of increased prolactin
amenorrhea
infertility
impotence
galactorrhea
Causes of decreased prolactin
pregnancy: progesterone inhibits lactation
GH increase cause
tumour (acremegaly, adult)
ACTH increase causes
pituitary adenoma
ectopic ACTH tumours
–> Cushing’s disease/syndrome
Addison’s disease will increase ACTH but a decrease in cortisol
ACTH decrease reasons
autosomal cortisol secreting tumours –> secondary adrenal insufficiency
LH increase reasons
gonadotroph cell adenoma (rare)
FSH decrease causes
pituitary failure
–> secondary hypogonadism, infertility
TSH increase causes
primary hypothyroidism (TSH > 10)
TSH decrease causes
Primary hyperthyroidism (TSH < 0.1) --> secondary hypothyroidism
Usual order of loss of pituitary function
GH LH FSH TSH ACTH PRL
Causes of hypopituitarism
Vascular: aneurysm, arteriosclerosis
I: sarcoidosis, histiocytosis, AI
N: pituitary carcinoma, craniopharyngioma, pituitary tumour, metastatic carcinoma, pinealoma
Drug-related
Radiation
CV, autoimmune/allergic
Head truma, post-partum pituitary necrosis
ENdocrine: DM, hemoglobinopathies, Fe overload, hypothalamic disease, isolated hormone deficiency
Genetic - familial hypopituitaris
Testing GH axis
measure IGF1
stimulation test: insulin-induced hypoglycemia, glucagon + arginine
suppression test: gluose suppression test
Testing gonadotropic axis
measure LH FSH testosterone estradiol
stimulation test: GnRH
suppression test: excess LH/FSH extremely rare
Testing thyroid axis
TSH, free T4
stimulation test: administer TRH
Testing adrenocortical axis
measure ACTH, am cortisol, urine cortisol
Stimulation test: insulin-induced hypoglycemia, ACTH stress test
suppression test: dexamethasone
Testing prolactin axis
measure prolactin
stimulation test: TRH
Triple bolus test
insulin, TRH, GnRH
Clomiphene stimulation test
interrupts negative feedback loop –> stimulates gonadotropin release from pituitary
GH secreting tumou frequency
8-10%
Prolactinoma frequency
30%, most common
Mixed GH-prolactin adenoma frequency
4.5%
ACTH-secreting tumour frequency
14%
Thyrotroph tumour frequency
rare <1%
Gonadotropic tumour freq
rare: 2.5%
Granular cell tumour frequency
1-2% of unselected biopsies, most frequent of posterior ptiuitary
Craniopharyngioma
sella turcica epithelial tumour
disturbance of HPA axis, vision, CSF flow
heavily calcified and hard to operate on
3-5% of all intracranial neopaslms
Consequences of GH excess
before closure of epiphyseal plate: gigantism
after closure of epiphyseal plates: acromegaly
- thickened sweat skin, large feet, hands, skull and jaw, cardiomegaly, organomegaly, hypertension, arthritis, carpal tunnel syndrome, paresthesias, fatigue, glucose intolerance
may have mass effects of pituitary adenoma
Consequences of TSH excess
secreting tumours are rare
causes goiter and hyperthyroidism
weight loss, nervousness, rapid heartbeat, difficulty sleeping, frequent bowel movements
women: amenorrhea
Consequences of excess sex hormones
precocious puberty
Initiation of sexual maturation before puberty (8 girls 9 boys)
Pituitary mass effect
hypothalamus
compress optic chiasma
compres normal pituitary tissue
compress pituitary stalk - block GnRH, dopamine transport
Management of small pituitary tumours
<10 mm and no hormonal hypersecretions
- 2-4 mm: no further testing
- 5-9 mm: MRI 1-2x over next 2 years, if lesion stable, reduce frequncy
Pit tumour pharmacotherapy
Most useful in prolactinomas
May use in other tumours as an adjunct to surgery/radiotherapy
Options:
Dopamine agonists –> prolactinomas, less useful for GH
Somatostatin analogue –> acromegaly
Pegvisomant (GH receptor blocker) –> acromegaly refractory to octreotide
Ketoconazole, metyrapone, mitotane –> cushing’s disease
Pituitary surgery
for large tumours and other hyperfunctional tumours
Transphenoidal : used in 95% cases
Indications:
1st line for symptomatic pituitary adenomas
used when medical/radiotherapy fails
provides prompt relief
indictaed in pituitary apoplexy with compressive symptoms
Pituitary radiotherapy
reserved for patients with large tumours and/or persistent hormonal hyperfunction despite surgical intervention
2 types:
1)conventional: slow response, 80% success in acromegaly, 50% cushing’s
- high rate of hypopituitarism and other complications possible
2) gamma knife radiosurgery: stereotactic CT guided cobalt 60 gammar adiation to narrowly focused area
success: 70% acromegaly, 70% cushings
- lower complication rate, still high for hypopituitarism
Acromegaly therapy
1) surger
2) octreotide - shrinks tumour
3) GH receptor antagonist - pegvisomat
Prolactinoma therapy
1) dopamine agonist
2) surgery
3) radiation
Hypogonadotropic hypogonadism
Low LH and FSH
Congenital or acquired
Acquired more common
Congenital causes of hypogonadotropinism
Idiopathic - most often
Familial hypogonadotropic hypogonadism - can be tarnsmitted as X-linked, autosomal recessive, or dominant
- mutations in GnRH receptor, LH/FSH mutation, etc
Acquired causes of low LH and FSH
1) severe illness, stress, malnutrition, exercise - reversible
2) dopamine antagonists/serotonin agonists –> increased prolactin inhibits GnRH
3) Hyperprolactinemia - as above, or may destroy surrounding gonadotropes
4) Sellar Mass lesions: should be distinguished from prolactinomas
5) hemochromatosis
Pituitary investigations
structural imaging –> CT/ MRI (best)
Functional evaluation –> PET-FDG
MACROadenomas usually nonfunctional
MICROadenomas usually functional
Complete androgen insensitivity
X-linked recessive normal female external genitalia absent vagina/short vagina with blind end testes in abdomen, inguinal canals, or labia majora normal Leydig cells + no spermatogenesis Normal breast development reduced/absent pubic hair normal female psychological development testosterone normal or Increased LH increased increased estrogen
