PITUITARY DISORDERS

HYPOTHALAMUS

receives autonomic nervous system input from different areas of the brain

neurons lead to production of: vasopressin, oxytocin, GHRH, Somatostatin

Median eminence = inferior boundary of pituitary gland that connects hypothalamus to the pituitary

What does it regulate?

limbic functions (emotion,memory,arousal)

food and water intake

body temp

CV function/Resp function

Diurnal rhythms (circadian rhythm)

PITUITARY GLAND
"hypophysis"

hormones synthesized in the hypothalamus reach the
anterior pituitary via the hypothalamic-hypophyseal portal
vessels

ANTERIOR PITUITARY
"Adenohypophysis"
"Master Gland"

controlled by specific hypothalamic releasing
and inhibitory hormones (not by direct nerve stimulation
like the PP)

hormones produced

GH (somatotropin)

stimulates protein synthesis and overall growth in all body tissues

Prolactin

promotes lactation and inhibits gonadal function

in women (in the ovary) can block follicular genesis and lead to decreased estrogen & an-ovulation

ACTH
(adrenocorticotropic hormone)

stimulates synthesis and secretion of adrenocortical hormones

TSH
(thyroid stimulating hormone)

iodine uptake and thyroid hormone systhesis

FSH
(follicle stimulating hormone)

sperm maturation- testes
follicle growth- ovaries

LH
(lutenizing hormone)

stimulates testosterone synthesis in testes and ovulation, corpus luteum formation, estrogen and progesterone synthesis in the ovaries

POSTERIOR PITUITARY
"Neurohypophysis"

extension of neurons of the periventricular
and super optic nuclei of the hypothalamus. Cell
bodies rest in the hypothalamus and end in the
axon terminals that comprise the PP

secretes hormones through direct nerve stimulation

2 main hormones produced: vasopressin & oxytocin

Vasopressin

main function

antidiuretic hormone, acts on the
renal collecting ducts to conserve
water

Oxytocin

main function

contracts smooth muscle in breast during lactation
uterine contractions

growth hormone

anabolic peptide that directly stimulates cell proliferation and growth

secretion

daytime pulses after: meals, exercise, stress

peak = during first 1-2 hours of sleep

growth hormone patho

growth promoting effects of GH are mediated by IGF-1 (before and after birth) and IGF-2 (in utero)

GH stimulates formation of IGF-1 in the liver and pripheral tissues

GH is secreted by ANTERIOR pituitary in a pulsatile fashion

several short bursts- mostly at night

concentration highest- night
concentration lowest- waking hours

MAIN CAUSE

GH-secreting pituitary adenoma

Acromegaly

caused by excess GH

Gigantism

excess secretion of GH PRIOR TO EPIPHYSEAL CLOSURE IN CHILDREN

short stature = patients who are > 2 SD below population mean

6 months-3 years

conginital disorder

genetic abnormalities: GHRH
deficiency, GH gene deletion

developmental disorders: pituitary
aplasia, hypoplasia

any age during growth development

acquired condition

hypothalamic/pituitary disorders

head trauma

pituitary infarction

various CNS infections

psychosocial deprivation

hypothyroidism

poorly controlled T2DM

drugs (transient): glucocorticoids, methylphenidate,
dextroamphetamine

New Growth Hormone Dificiency Test

Macimorelin (Macrilen)

Prolactin

secreted by ANTERIOR pituitary in a pulsatile manner

concentrations peak during sleep

regulated by hypothalamic inhibitory effects of dopamine

transient elevations: sleep, exercise, coitus, eating, stress

measure levels when pt is at rest in supine position or in
a chair for > 2 hours

Prolactinomas produce prolactin

microadenomas: < 10 mm in diameter; no increase in size

macroadenomas: > 10 mm in diameter; continue to grow and may invade other issues

Feedback Loop

coarsening of facial features

increased hand volume, ring size, shoe, size

enlarged tongue

various dermatologic conditions

local effects of GH-secreting tumor: HA, visual disturbances

elevated GH and IGF-1 concentrations: excessive sweating, neuropathies, joint pain, parasthesis

following oral glucose tolerance test (OGTT): elevated GH > 1mcg/L and elevated IFG-1 levels

HTN

CAD

cardiomyopathy

left ventricular hypertrophy

esophageal

colon

stomach

radiation therapy

for poor surgical candidates and those who refuse
or dont respond to surgical or medical interventions

Who gets it?

poor surgical candidates

inadequate response to surgery

preference for medical therapy

preferred in
pregnancy

formulations

Immediate Release (IR)- SQ injection

Long Acting Release (LAR)- IM injection
*use for adherence

Drug-Drug interactions

cyclosporine

BB and CCB

ADE

N/V/D/GI cramps
(subsides 2 weeks after tx)

injection site reaction

hyper OR hypoglycemia

cholelithiasis

hypothyroidism

Drug-Drug interactions

cyclosporine

ADE: same as octreotide

most effective

ADE: higher incidence
of hyperglycemia

Drug-Drug Interactions

- concominant cispride
- dronedar
- pimozide
- thioridazine

use if high IGF-1 levels and refractory
to somatostatin analogs

DOES NOT INHIBIT GH PRODUCTION BECAUSE IT BLOCKS GH RECEPTORS (DOES NOT DECREASE TUMOR SIZE)

USE OF GH VALUES FOR TITRATION IS NOT HELPFUL!!

ADE

diarrhea

increased LFTs (check monthly for 6 months then q6 months)
*dc if transaminases > 3x ULN

reduced growth velocity

delayed skeletal maturation

average birth rate

central obesity, prominence
of forehead, immaturity of
face

peak GH concentrations < 10 mcg/L
during a 2 hour period following a GH
provocation test (subnormal response)

provocative stimuli to induce GH secretion: insulin, clonidine,
L-dopa, arginine, glucagon, GHRH

+/- reduced IFG-1 and binding protein

+/- loss of other pituitary hormones
(hypoglycemia or hypothyroidism)

provocation test

bone age

growth velocity

percentile of anthropometric
measurements

pubertal stage: Tanner Scale

mainstay of therapy

SC or IM injections

dosing is WEIGHT BASED

potency is expressed as
international units/mg

1 mg contains 2.6 IU of GH

children: achieve normal adult height

adults: increase muscle mass and reduce adiposity

ONLY INDICATED FOR TREATMENT OF SHORT
STATURE DUE TO SEVERE PRIMARY IGF-1 DEFICIENCY

increase growth velocity in children with short stature
who have low IGF-1 AND resistance to GH

WEIGHT BASED DOSING

pregnancy category C

ADE: hypoglycemia

if growth rate < 2-2.5 in 1 year

DOUBLE DOSE FOR 6 MONTHS

if still no satisfactory response, dc therapy

continue tx until satisfactory adult
height or growth velocity has decreased
< 2-2.5 cm/year after pubertal growth suprt

prolactin secreting benign pituitary tumors (prolactinomas)

drug induced

Dopamine antagonists

Antipsychotics

Phenothiazine

Metoclopramide

Domperidone

Verapamil

Prolactin Stimulators

Methyldopa, Reserpine, SSRIs, 5-HT1 receptor
agonists (triptans), Estrogens, Progestins, Protease
inhibitors, GnRH analogs, Benzodiazepines, TCAs,
MAOI, opioids, cocaine

CNS lesions physically compress pituitary stalk
and interrupt tonic hypothalamic dopamine
secretion

increased TRH in hypothyroidism

renal or hepatic impairment causing
decreased clearance of prolactin

unable to determine cause: idiopathic hyperprolactinemia

sx related to local effects of prolactin-secreting
tumor (HA, visual disturbances) resulting from
tumor compression of optic chiasm

females: oligomenorrhea, amenorrhea,
galactorrhea (nipple discharge), infertility

males: decreased libido, infertility
visual loss

fasting prolactin serum concentrations
at rest > 25 mcg/L (elevated)

normal values

levels do not typically rise to > 150 mcg/L in drug induced disease

if > 150 probably due to tumor

significant risk for development of osteoporosis

increased risk of ischemic heart disease if left untreated

check multiple serum prolactin levels in pts w/ modest elevations

obtain med history

presence of hypothyroidism, renal failure, hepatic dysfunction

CT or MRI to determine presence of tumor

normalize serum prolactin

re-establish gonadotropin secretion

restore fertility, and reduce risk of osteoporosis

tumor shrinkage (macroadenomas)

correction of visual defects (macroadenomas)

*less affective than medical therapy with dopamine
agonist for sx control!!

reserved for patients who are refractory to or cannot
tolerate dopamine agonists, or large tumor that could
cause severe compression of adjacent tissues

ONLY IN CONJUNCTION WITH SURGERY

DOC for fertility or pregnancy

superior efficacy, besster GI ADE, less frequent dosing

CANT BE USED IN PREGNANCY

DOC for management of prolactinomas