Pituitary disorders - Endo Flashcards
Pathophysiology Overview
Anatomical Disease Classification
- Anterior Pituitary (Adenohypophysis)
- Posterior Pituitary (Neurohypophysis)
Functional Disease Classification
- Hyperpituitarism: ↑ trophic hormones
- Hypopituitarism: ↓ trophic hormones
Local Mass Effects
- viz field defects (bitemporal hemianopia), and other CN palsies
- possible decreased pituitary hormones
- elevated intracranial pressure (HA+N+V)
- seizures
- obstructive hydrocephalus
melatonin
- made in the pineal gland, not the pituitary gland
- production is stimulated by dark and inhibited by light
- tryptophan is its precursor
- function not entirely known, but best thoughts are:
- sleep regulation
- anti-aging antioxidant
Hypothalamus - hormones
-makes Releasing or Inhibitory hormones which increase or decrease pituitary release of hormones:
-TRH thyrotropin releasing hormone
-PIF prolactin inhibitory factor (Dopamine)
-CRH corticotropin releasing hormone
-GHRH growth hormone releasing hormone
-GIH growth hormone inhibitory hormone (Somatostatin)
GnRH gonadotropin releasing hormone
Pituitary - hormones
-makes many trophic hormones, some of which are:
- TSH thyroid stimulating hormone
- PRL prolactin
- ACTH adrenocorticotrophic hormone
- GH growth hormone
- FSH follicle stimulating hormone
- LH lutenizing hormone
- Oxytocin
- MSH Melanocyte Stimulating Hormone
- ADH Anti-diuretic hormone
Posterior pit also secretes which hormone that regulates total body water:
-ADH, aka vasopressin, by increasing water reabsorption in renal collecting ducts, which puts more water back into the blood
Pituitary Adenoma
Pathophys
- functional 60%: excessive hormones -> clinical manifestations
- silent 40%: no hormone excess or clinical manifestations, but since it is a mass, it may give symptoms of mass effect
usually solitary
-however, 3% of pit adenomas are part of the Multiple Endocrine Neoplasia Type 1 (MEN-1) Syndrome
classified based on which hormone they secrete
- usually just one hormone
- combos are possible; mc combo is GH + PRL producing pit adenoma
S/S
-syndromes due to hormone overproduction
+/- mass effect (HA, N/V, viz changes, CN palsies, possible decreased, instead of increased, hormones)
W/U
-brain MRI, serum hormone levels, visual field testing, CN exam
Hyperprolactinemia
Etio
- Prolactinoma (50% of all pit adenomas)
- anything that stops hypothal’s Prolactin Inhibitory Factor (DA) action on the pit, like a stalk mass, which blocks hypothalamus DA from getting to the pituitary gland -> no inhibition = ↑ PRL - many meds which are DA-antagonists
- hypothyroidism (see elsewhere)
PRL action
- lactation
- inhibits GnRH = ↓ FSH + LH
Pathophys
- ↑ PRL = too much lactation and ↓↓ FSH + LH
- galactorrhea
- hypogonadal symptoms
S/S
- galactorrhea: spontaneous breast milk discharge unrelated to childbirth or nursing
- hypogonadal sxs: amenorrhea, infertility, impotence, decreased libido
W/U
- elevated serum PRL
- but is also common in many situations
- R/o preg, estrogen therapy, hypothy, psych meds (Dopamine antagonists like risperidone), H2 antagonists like cimetidine/Tagamet, liver or renal dz
- brain MRI
Hyperprolactinemia - tx
remove meds which increase PRL
correct hypothyroidism
serial MRIs
if asymptomatic:
- just monitor (MRIs and monitor for osteoporosis if no meds used with serial bone densitometry)
- DA agonists + Estrogens if pt desires pregnancy AND adenoma is small (<10mm)
if symptomatic:
-DA agonists (more DA = more PRL inhibition)
-cabergoline/Dostinex
-bromocriptine/Parlodel
+/- Surgery (transsphenoidal excision of adenoma)
-especially if there are viz field defects, or if meds fail
+/- Radiation (if meds fail)
Acromegaly
Etio
-GH producing adenoma (10% of all pit adenomas)
Physio
-GH ↑ liver release of insulin-like growth factor (IGF-1)
Pathophys
↑ GH = ↑↑ IGF-1 +/- ↑ PRL
↑ childhood GH (before closure of the epiphyses)= gigantism
-continued ↑ GH into adulthood = acromegaly
S/S
- excessive growth (↑ soft tissue mass)
- large jaws, tongue, tall stature, thick brows, huge hands (“moist, doughy handshake”), wide feet, separated teeth
- ↑ internal organ growth
- arthralgias, carpal tunnel syndrome
- HAs, HTN (cardiomegaly), OSA (macroglossia), DM
- if concurrent hyperPRL, then amenorrhea, galactorrhea, infertility, decreased libido
W/U
- serum IGF-1
- if nl for age, then acromegaly is ruled-out
- looking for serum GH levels is futile (due to its natural pulsatile release)
- check serum PRL (make sure it is not a Mixed-Adenoma)
- brain MRI for pituitary tumor
- screen for DM
Acromegaly - tx
- transsphenoidal surgical excision (80% success)
- if surgery fails, then meds : cabergoline/Dostinex (DA agonist)
- best if patient shows s/s of hyperPRL and hyperGH, but also effective for pts with nl PRL levels
- octreotide/Sandostatin (a somatostatin analogue = dec GH release): not too helpful if GH levels are very high (>20ng/mL)
- pegvisomant/Somavert (GH receptor antagonist): doesn’t shrink tumor size, so must monitor viz field exams, GH levels and serial MRIs
-if above fails, then stereotactic radiation therapy
Hypopituitarism
Etio
-caused by a mass lesion: hypothal, stalk, pituitary lesions
not caused by a mass lesion
- congenital, surgery, radiation, tumor, infection, trauma, ischemia (Sheehan’s Syndrome = intrapartum pituitary infarction)
- hypothalamic damage (infection, tumor, surgery, radiation, trauma)
S/S
- dependent on which hormone or hormones are deficient
- could just be mass effect symptoms without hormone deficiencies
- Headache/N/V, visual field changes, other CN palsies, seizures, obstructive hydrocephalus
- hyperprolactinemia (hypothalamic damage = ↓ DA (PIF) = ↑ PRL)
- hypogonadism: infertility; associated with Prader-Willi Syndrome and Kallman Syndrome, failure to enter puberty
- hypothyroidism (see elsewhere)
- Adrenal Insufficiency (see elsewhere, d/t decreased ACTH)
- combined pituitary hormone deficiencies (Panhypopituitarism, or Panhypopit): genetic mutations are causative
Hypopituitarism - w/u and tx
W/U
- brain MRI
- labs: pituitary hormones will be ↓, hypothalamic releasing hormones may be ↓ or normal or ↑ based on where the problem is
Tx
- transsphenoidal excision
- replace deficient hormones, especially to treat adrenal insufficiency and hypothyroidism
- give corticosteroids first, then thyroid hormone/levothyroxine/Synthroid (so as to not precipitate adrenal crisis)
- androgen and estrogen replacement
Dwarfism
-pt is short: adult height < 4’10”
~200 different etiologies
70% Achondroplasia
- very short limbs, nl sized abdomen, large head
- autosomal dominant mutation of Fibroblast Growth Factor Receptor 3 on chromosome 4
“Pituitary Dwarfism” = a GH Deficiency
-mainly due to genetic mutations and pituitary or hypothalamic lesions
GH Deficiency
S/S depend on timing
- infant: hypoglycemia and micropenis
- child: absent growth, delayed puberty
- adult: rare but osteopenia, decreased strength and muscle bulk, slowed mentation, depression
Tx
- recombinant human growth hormone SQ injections 3-4x qwk or depot route 2x qmonth (Nutropin Depot)
- usually titrated up to side effects or normalized IGF-1 levels: must monitor for both
- SEs = edema, headache, arthralgias/myalgias, carpal and tarsal tunnel syndrome, HTN, retinopathy
