Pituitary Disorders

M. Luthfi
The Endocrine System
Consists of several glands
located in various parts of the
body


Pituitary gland



The Master Gland
Primary function is to
control other glands.
Produces many hormones.
Secretion is controlled by
the hypothalamus

The Hypothalamus-Pituitary unit
most dominant portion of the entire
endocrine system
regulates the function of the thyroid,
adrenal and reproductive glands
controls somatic growth, lactation,
milk secretion and water metabolism
The Hypothalamus-Pituitary unit
Hypothalamus and anterior pituitary
Midsagital view illustrates
parvicellular neurosecretory
cells secrete releasing
factors into capillaries which
are then transported to the
anterior pituitary gland to
regulate the secretion of
pituitary hormones
Hypothalamus and posterior pituitary
Midsagital view illustrates that
magnocellular neurons nuclei
secrete oxytocin and
vasopressin directly into
capillaries in the posterior lobe
Hypothalamic releasing hormones
Hypothalamic releasing hormone

Effect on pituitary

Corticotropin releasing hormone
(CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone
(TRH)

Stimulates TSH and Prolactin
secretion

Growth hormone releasing
hormone (GHRH)

Stimulates GH secretion

Somatostatin

Inhibits GH (and other hormone)
secretion

Gonadotropin releasing hormone
(GnRH)

Stimulates LH and FSH secretion

Prolactin releasing hormone (PRH)

Stimulates PRL secretion

Prolactin inhibiting hormone
(dopamine)

Inhibits PRL secretion

Pituitary Gland
Thyroid-stimulating hormone (TSH)
Growth hormone (GH)
Adrenocorticotropin (ACTH)
Follicle-stimulating hormone (FSH)
Prolactin
Luteinizing hormone (LH)
Anterior
Pituitary
Oxytocin
ADH
Posterior
Pituitary
Anterior pituitary cells and hormones
Cell type Pituitary
population
Product Target
Corticotroph 15-20% ACTH
b-lipotropin
Adrenal gland
Adipocytes
Melanocytes
Thyrotroph 3-5% TSH Thyroid gland
Gonadotroph 10-15% LH, FSH Gonads
Somatotroph 40-50% GH All tissues, liver
Lactotroph 10-15% PRL
Breasts
gonads

ANTERIOR PITUITARY (Adenohypophysis)
SECRETES 6 HORMONES:
ACTH
controls release of cortisol
in adrenal glands
ACTH release controlled by
corticotropin-releasing
hormone (CRH)
ANTERIOR PITUITARY / Adenohypophysis
stimulates the thyroid gland to release Thyroid
hormone.
Thyroid releasing hormone; secreted by
hypothalamic neurons-control release of TSH
TSH
glucose usage
consumption of fats as an energy source GH
GH
Anterior Pituitary / Adenohypophysis
mammary gland growth
milk secretion
Prolactin
growth of ovarian follicles
spermatogenesis in males
FSH
regulates growth of gonads
reproductive activities
LH
Posterior Pituitary
stimulates gravid
uterus
causes let down of
milk from the breast
Oxytocin

causes the kidney to
retain water
ADH
(vasopressin)
Pituitary Tumors
PITUITARY TUMORS
10% OF ALL BRAIN
TUMORS
Tumors usually
cause hyper release
of hormones
Etiology of Pituitary Tumor
Non-Functioning Pituitary Adenomas

Endocrine active pituitary adenomas
Prolactinoma
Somatotropinoma
Corticotropinoma
Thyrotropinoma
Other mixed endocrine active adenomas

Malignant pituitary tumors: Functional and non-functional
pituitary carcinoma

Metastases in the pituitary (breast, lung, stomach, kidney)



Abnormal Pituitary Function
Associated with Pituitary Tumors


Hypopituitarism
Hypersecretion of Pituitary Hormones

Hypopituitarism

Pituitary adenomas most common cause
Sequence of function loss from mass effect:
Growth hormone GH deficiency
Gonadotropins hypogonadism
ACTH hypoadrenalism
TSH hypothyroidism

Hypopituitarism
GH deficiency :
decreased muscle strength and exercise tolerance,
diminished libido, increased body fat

Gonadotropin deficiency:
oligo/amenorrhea, diminished libido, infertility, hot
flashes, dypareunia, impotence, osteopenia
Hypopituitarism
ACTH deficiency :
malaise, fatigue, anorexia, hypoglycemia
mineralocorticoid secretion is preserved

TSH deficiency :
malaise, leg cramps, fatigue, dry skin,
cold intolerance
clinically similar to primary hypothroidism

Hypersecretion of Pituitary Hormones


- Hyperprolactinemia
- Acromegaly
- Cushings Disease
Hypersecretion of Pituitary Hormones
Prolactinoma :
oligo/amenorrhea, galactorrhea, infertility,
osteopenia, decreased libido, headaches, visual field
defects

Acromegaly :
ventricular hypertrophy/diastolic dysfunction, sleep
apnea, peripheral neuropathy, muscular atrophy
often insidious and may be missed
Hypersecretion of Pituitary Hormones
Cushings Disease :
central obesity, supraclavicular fat pads, proximal
myopathy, wide, purplish striae (> 1cm), skin
atrophy, spontaneous ecchymoses, hypokalemia

TSH secreting adenoma :
heat intolerance, weight loss, weakness, tremor,
sinus tachycardia, atrial fibrillation, heart failure
clinically similar to primary hyperthyroidism

Acromegaly
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm
Cushings Disease
Williams Textbook of Endocrinology. 8
th
Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Cushings Syndrome vs. Cushings Disease
Cushings syndrome is a syndrome due to
excess cortisol from pituitary, adrenal or
other sources (exogenous glucocorticoids,
ectopic ACTH, etc.)

Cushings disease
hypercortisolism due to excess pituitary
secretion of ACTH (about 70% of cases of
endogenous Cushings syndrome)
Cushings Syndrome
Moon facies
Facial plethora
Supraclavicular fat
pads
Buffalo hump
Truncal obesity
Weight gain
Purple striae
Proximal muscle
weakness
Easy bruising
Hirsutism
Hypertension
Osteopenia
Diabetes mellitus/IGT
Impaired immune
function/poor wound
healing

Central Obesity in Cushings Disease
Williams Textbook of Endocrinology. 8
th
Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Progressive Obesity of Cushings Disease
Williams Textbook of Endocrinology. 8
th
Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Age 6 Age 7 Age 8 Age 9 Age 11
Buffalo Hump in Cushings Disease
Orth, D. UpToDate
Striae in Cushings Disease
Orth, D. UpToDate
SIGNS & SYMPTOMS: Cushings
protein catabolism
muscle wasting
loss of collagen support
thin, fragile skin, bruises easily
poor wound healing
hyperglycemia
Can get diabetes-
insufficient insulin production
Polyuria
truncal obesity
buffalo hump
moon face
weight but strength
Evaluation of Pituitary Mass
Clinical Evaluation
Hormonal Evaluation
Radiologic Evaluation

Hormonal Evaluation
May include of both basal hormone measurement
and dynamic stimulation testing.

Basal hormone measurements, including:
Prolactin
TSH, FT4
ACTH, AM cortisol, midnight salivary cortisol
LH, FSH, estradiol or testosterone
Insulin-like growth factor-1 (IGF-1)

Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm
Hormonal Evaluation
Dynamic stimulation/suppression testing may be useful
in select cases to further evaluate pituitary reserve
and/or for pituitary hyperfunction

Dexamethasone suppression testing
Oral glucose GH suppression test
GHRH, L-dopa, arginine
CRH stimulation
Metyrapone
TRH stimulation
GnRH stimulation
Insulin-induced hypoglycemia
Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm
Radiological Evaluation
Preferred imaging study for the pituitary
Better visualization of soft tissues and vascular
structures than CT
MRI
Better at visualizing bony structures and
calcifications within soft tissues
Better at determining diagnosis of tumors
with calcification, such as germinomas,
craniopharyngiomas, and meningiomas
CT-scan
Diagnosis

Usually delayed non specific nature of symptoms
MRI imaging modality of choice
Tests can reveal whether adenoma is hypo- or
hyperfunctional
DIAGNOSIS -- deficiency
insulin tolerance test,
GH-RH/arginine test
IGF-1 levels
GH
sexual history
menstrual history
FSH/LH/estradiol/Prolactin/testosterone levels
Gonadotropins
AM cortisol
cosyntropin test
Insulin tolerance test
ACTH
T4 levels
TSH levels
TSH
DIAGNOSIS -- excess
prolactin level, drug history, clinical setting
(e.g. pregnancy, breast stimulation, stress,
hypoglycemia), Prl < 200ng/ml w/ large
adenoma suggests compression as etiology
Prolactinoma
IGF-1 level, oral glucose tolerance test
Acromegaly
24 hr urine cortisol, overnight
dexamethasone suppression test
Cushings
disease
free T4, T3, TSH levels
TSH
overproduction
TREATMENT
Typically requires surgical resection of adenoma
Exception is prolactinoma in which 1
st
line treatment is
dopamine agonist therapy
Octreotide now being used for agromegaly and TSH
producing adenomas
Deficiency states require replacement of the indicated
hormone