2/10 Hypothal Pit Disorders - Meininger Flashcards
ANATOMY
hypothal and pituitary
both sit at base of brain
pituitary aka “master gland” → control many other endocrine organs (thyroid, adrenals, testes/ovaries)
- sits in sella turcica (‘Turkish saddle’) → surrounded by bone on all sides except superiorly
pituitary parts
- pars nervosa (post pit)
- connected to hypothal via pituitary stalk → post pit is a storage area for hypothal hormones
- pars intermedia
- pars tuberalis
- pars distalis (ant pit)
pituitary adenomas
most common to least common
- prolactinoma
- PRIMARY TX: medical tx with dopamine agonist! (decreases prolactin and shrinks tumor)
- gonadotroph/non-secr adenoma
- GH-secreting adenoma → acromegaly
- ACTH-secreting adenoma → Cushing’s disease
- TSH-secreting adenoma
2-5: primary tx is SURGERY, radiation, then med tx
consequences of pituitary tumors
- hypopituitarism → not enough space for actual fxal cells to grow into and operate in
- optic nerve/chiasm compression → visual field abnormalities
- pituitary stalk compression → central DI
- CSF leak / meningitis
- cavernous sinus invasion → CN palsy
visual field issues
- optic nerve compression
- optic chiasm compression
- optic tract compression
optic nerve comp
optic chiasm comp: bitemporal hemianopsia
optic tract comp
pituitary fx abnormalities
hypersecretion & hyposecretion
hormone terminology
- “levels”
- organs
- produce…
- tertiary/central: hypothalamus → RELEASING HORMONES
- TRH, GnRH, CRH
- secondary/central: pituitary → TROPHIC HORMONES
- primary/end-organ: endocrine organ →
anterior pituitary hormones
-
somatotrophs
- growth hormone (GH)
-
gonadotrophs
- follicle stim hormone (FSH)
- luteinizing hormone (LH)
-
corticotrophs
- adrenocorticotrophic hormone (ACTH)
-
thyrotrophs
- thyroid stim hormone (TSH)
-
lactotrophs
- prolactin (PRL)
posterior pituitary hormones
- antidiuretic hormone (ADH) aka vasopressin
- lesions affecting these neurons → central DI
- oxytocin
*both made in hypothalamus, stored and released from post pit
hypersecretion
excess hormone secretion from ant pituitary cells
- GH → gigantism, acromegaly
- LH/FSH → precocious puberty, central hypergonadism
- ACTH → Cushing’s disease
- TSH → central hyperthyroidism
or…
release of tonic dopamine inhibition (PRL)
- PRL → hyperprolactinemia → decr gonadotropins
hyposecretion
result of anatomic lesions affecting anterior pit
- GH → pit dwarfism, adult GH def
- LH/FSH → secondary hypogonadism
- ACTH → secondary adrenal insuff
- TSH → secondary hypothyroidism
- PRL → failure to lactate
acromegaly
what is it
signs/sx
normal axis
GH excess
- enlargement at periphery → hands, feet
GH axis: normal
- interplay of GHRH and somatostatin
- hypothal releases GHRH → stim GH release
- hypothal releases somatostain → inhib GH release
- GH stimulates liver to release IGF1
negative feedback:
- GH on hypothal and pituitary
- IGF1 on hypothal and pituitary
endocrine testing principle
hypo and hyper secretion
to rule out hyposecretion…
- stimulate that endocrine axis
to rule out hypersecretion…
- suppress that endocrine axis (ex. dexamethasone suppression test → neg feedback on pituitary to decr ACTH secretion)
acromegaly
dx/tx
dx:
- elevated IGF1
- GH NOT suppressed 1hr post oral glucose tolerance test
tx:
- surgical
- rad
- pharma
- octreotice (somatostain analog)
- pegvisomant (GH receptor antagonist)
GH deficiency
deficiency of something along the axis:
- GHRH from hypothal
- GH form pituitary
- IGF1 from liver
clinical signs/sx
- children: short stature, frontal bossing, central obesity, high pitched voice
- adult: decr bone density, abnl lipid profile, dep/decr well being, central obesity
etiology
- NEUROENDOCRINE
- congenital/inherited
- septo-optic dysplasia
- acquired
- anatomic lesions (pituitary, hypothal, craniopharyngioma)
- fx/idiopathic (starvation, child abuse, failure to thrive)
- congenital/inherited
GH deficiency
dx
tx
dx
- stimulation test
- insulin tolerance test
- arginine
- GHRH
- exercise
tx
- pharmacological
- GH
- GHRH
hypothal-pit-gonadal axis
GNRH from hypothal is released in PULSATILE fashion
-
LH from pituitary is released in PULSATILE fashion
- testosterone production from Leydig cells
- ovarian steroidogenesis
-
FSH is non-pulsatile
- spermatogenesis
- growth of ovarian follicular granulosa cell
abnormalities of HPG axis
4 categories
- congenital/inherited
- Kallman’s syndrome (isolated gonadotropin def w anosmia or hypoosmia)
- acquired
- anatomic lesions (hypothal, pit)
- functional/idiopathic
- starvation/low body weight
- delayed puberty
- precocious puberty
- ectopic
- ectopic hCG, nonseminoma gernm cell tumors, lung carcinomas, hepatomas
HPG axis abnormalities
clinical manifestations
- hypogonadism
- amenorrhea
- gynecomastia
- infertility
- decr libido
- absence or decr in secondary sexual chars
- osteoporosis
- hypergonadism
- premature secondary sex chars
HPG axis abnormalities
tx
congenital/inherited
- Kallman’s syndrome
- pulsatile GnRH
- use of hCG and hMGs (FSH)
acquired
- pit surgery
fxal/idiopathic
- incr body weight (anorexia nervosa, rigorous exercise)
- precocious puberty (long acting GnRH agonists)
miscellaneous (might not hit all aspects of disease…ex. fertility)
- estrogen/progesterone replacement
- testosterone replacement
Cushing’s disease
what axis?
HPA
hypothal-pit-adrenal axis
hypothalamus-pituitary-adrenal axis
normal
- hypothal releases CRH
- pituitary releases corticotropin
- adrenals release cortisol
negative feedback
- cortisol exercises negative feedback on hypothal and pituitary
Cushing’s SYNDROME
(and where Cushing’s disease falls within that)
excess cortisol in body
causes can be…
-
ACTH-dependent
- Cushing’s disease: incr in pit ACTH
- ectopic ACTH
-
ACTH-indep
- adrenal adenoma or carcinoma
- iatrogenic (MOST COMMON)
clinical manifestations of Cushing’s Disease
Cushing’s Disease
dx/tx
dx
- 1mg overnight dexamethasone suppression test
- 24h urine free cortisol
tx
- surgical
- pituitary
- adrenal (rare) → can result in Nelson’s Syndrome
- radiation
- pharmacological
- ketoconazole, metyrapone, aminoglutethimide → inhibit adrenal steroid enzymes
secondary adrenocortical insufficiency
causes
most common type of adrenal insuff (often iatrogenic)
- acquired
- anatomic lesions (pituitary, hypothal)
- pharma
- withdrawal of prescribed glucocorticoids
- withdrawal of medications with glucocorticoid-like effect (ex. megesterol)
2 adrenal insuff
clinical manifestations
- n/v
- fatigue/weakness
- lightheadedness/confusion
- hypotension
- fever
- hypoglycemia
- hypoNa (bc glucocorticoid def, NOT mineralocorticoid def)
- NOT hyperpig
2 adrenal insuff
dx/tx
dx
- stimulation tests
- ACTH (cortrosyn) stim test
- insulin tolerance test
- adrenal insufficiency with decr ACTH
tx
- pharma
- clucocorticoid replacement
HTP axis
normal
hypothalamus-pituitary-thyroid axis
- hypothalamus releases TRH (+), somatostatin (-)
- pituitary releases thyrotropin
- thyroid releases T3 and T4
negative feedback:
- T3 and T4 exert neg feedback on hypothal and pit
neuroendo causes of thyroid disease
secondary hyper/hypothyroidism
note both involve TSH/T4/T3 going in SAME DIRECTION
secondary hyperthyroidism
- RAREST secretory pit tumor
- incr TSH, T4, T3
- tx: pit surgery/rad/pharma
secondary hypothyroidism
- usually pit lesion
- decr TSH, T4, T3
- labs similar to sick euthyroid symdrome
- tx depends on cause…pit surg and thyroid hormone replacement
- ***before relacing thyroid, want to make sure pt doesnt have BOTH thyroid def and adrenal insufficiency!
- thyroid hormone controls metabolism BUT in context of person with adrenal insuff…if you restore thyroid hormone, the remaining cortisol is goign to be metabolized faster! could make adrenal insuff worse! → adrenal crisis
prolactin axis
prolactin is not stimulated - it is CONSTITUTIVELY INHIBITED via DA secretion from hypothal
sooo, block DA → prolactin released
causes of hyperprolactinemia
- microprolactinoma (<200)
- macroprolactinoma (>200)
- pit stalk compression
- meds which interfere with DA pathways (antipsychs)
- primary hypothyroidism
- TRH → TSH and prolactin secretion
- pregnancy
hyperprolactinemia
clinical manifestations
tx
elevated PRL → inhibited GnRH release → decr gonadotropins
- similar clinical manifestations as hypogonadism
- galactorrhea
- oligomenorrhea/amenorrhea
- infertility
- gynecomastia
- osteoporosis
tx
- PRL-secreting adenomas → first line tx = PHARMA
- bromocriptine (short acting DA agonist)
- cabergoline (long acting DA agonist)
PRL deficiency
inability to lactate
consider/evaluate…
- panhypopituitarism
- eval other pit axes
