Pituitary Disorders

The Endocrine System

Consists of several glands

located in various parts of the
Pituitary gland
body

The Master Gland

Primary function is to
control other glands.
Produces many hormones.
Secretion is controlled by
the hypothalamus
 Hypothalamus and Pituitary

The hypothalamus-pituitary unit :

the most dominant portion of the entire endocrine

system
regulates the function of the thyroid, adrenal and
reproductive glands
also controls lactation, milk secretion and water
metabolism
Anatomy
 Hypothalamus-functions

Hypothalamus- integrative center for endocrine and autonomic nervous system

Control of some endocrine glands by neural and hormonal pathways

Two major groups of hormones secreted: inhibiting and releasing

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 Stimulates ACTH secretion

(CRH)
Thyrotropin releasing hormone Stimulates TSH and Prolactin
(TRH) secretion
Growth hormone releasing Stimulates GH secretion
hormone (GHRH)
Somatostatin Inhibits GH (and other hormone)
secretion
Gonadotropin releasing hormone Stimulates LH and FSH secretion
(GnRH)
Prolactin releasing hormone (PRH) Stimulates PRL secretion

Prolactin inhibiting hormone Inhibits PRL secretion

(dopamine)
 Pituitary Gland

Posterior oxytocin
Pituitary ADH

Thyroid-stimulating hormone (TSH)

Growth hormone (GH)
Anterior Adrenocorticotropin (ACTH)
Pituitary Follicle-stimulating hormone (FSH)
Prolactin
Luteinizing hormone (LH)
 Anterior pituitary cells and hormones

Cell type Pituitary Product Target

population
Corticotroph 15-20% ACTH Adrenal gland
b-lipotropin 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)

ACTH
 ANTERIOR PITUITARY(adenohypophysis)
- TSH
Stimulates the thyroid gland
metabolic rate

- GH (Growth Hormone)
stimulates growth of
bone/tissue
glucose usage
consumption of fats as an
energy source
 Anterior pituitary

promotes mammary gland growth

Prolactin and milk secretion

stimulates growth of ovarian

FSH follicles & spermatogenesis in males

regulates growth of gonads &

LH reproductive activities
 Posterior Pituitary

Oxytocin
stimulates gravid uterus
causes let down of milk from the breast

ADH (vasopressin)
causes the kidney to retain water.
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

decreased muscle strength

decreased exercise tolerance
GH deficiency diminished libido
increased body fat

oligo/amenorrhea
diminished libido
Gonadotropin Infertility
deficiency dypareunia
impotence
osteopenia
 Hypopituitarism
malaise
fatigue
ACTH anorexia
deficiency hypoglycemia
mineralocorticoid secretion is preserved

malaise
leg cramps
fatigue
TSH deficiency dry skin,
cold intolerance
clinically similar to primary hypothroidism
Hypersecretion of Pituitary Hormones

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

ventricular hypertrophy/diastolic
dysfunction
sleep apnea
Acromegaly peripheral neuropathy
muscular atrophy
often insidious and may be missed
 Hypersecretion of Pituitary Hormones

central obesity
supraclavicular fat pads,
Cushings proximal myopathy, wide
purplish striae (> 1cm)
Disease skin atrophy
spotaneous ecchymoses,
hypokalemia

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

http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm
 Cushings Disease

Williams Textbook of Endocrinology. 8th 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)
Hypercorticolism

tertier

secunder

primer
 Cushings Syndrome

Moon facies Proximal muscle

Facial plethora weakness
Supraclavicular fat Easy bruising
pads Hirsutism
Hypertension
Buffalo hump Osteopenia
Truncal obesity Diabetes mellitus/IGT
Weight gain Impaired immune
Purple striae function/poor wound
healing
 Central Obesity in Cushings Disease

Williams Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
 Progressive Obesity of Cushings Disease

Age 6 Age 7 Age 8 Age 9 Age 11

Williams Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
 Buffalo Hump in Cushings Disease

Orth, D. UpToDate
 Striae in Cushings Disease

Orth, D. UpToDate
SIGNS & SYMPTOMS: Cushings
Evaluation of Pituitary Mass

Clinical Evaluation
Hormonal Evaluation
Radiologic Evaluation
 Clinical Evaluation

examined for clinical signs suspicious for pituitary

hyperfunction or hypofunction
 Hormonal Evaluation

Basal hormone measurement and dynamic

stimulation testing.

Screening basal hormone measurements :

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
CRH stimulation
TRH stimulation
GnRH stimulation
Insulin-induced hypoglycemia

Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

Dexametason test
Low dose : 2 mg
High dose : 8 mg
Glucosa GH suppression test
75 g Glucosa
GHRH
TRH Stimulating
N

N/

CRH Stimulating
Inf Petrosal Sinus Sampling
GnRH stimulation
 Radiologic Evaluation

MRI
Preferred imaging study for the pituitary
Better visualization of soft tissues and vascular structures
than CT
Structures such as fatty marrow and orbital fat show up as
bright images.
high-intensity signals of structures with high water content,
such as cerebrospinal fluid and cystic lesions

Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

 Radiologic Evaluation

CT-scan
Better at visualizing bony structures and calcifications within
soft tissues
Better at determining diagnosis of tumors with calcification,
such as germinomas, craniopharyngiomas, and meningiomas
May be useful when MRI is contraindicated, such as in patients
with pacemakers or metallic implants in the brain or eyes
Disadvantages include:
less optimal soft tissue imaging compared to MRI
use of intravenous contrast media
exposure to radiation
 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,
GH IGF-1 levels

sexual history
menstrual history
Gonadotropins FSH/LH/estradiol/Prolactin/testosterone
levels

AM cortisol, cosyntropin test

ACTH insulin tolerance test

T4
TSH TSH levels
 DIAGNOSIS - excess
prolactin level, drug history, clinical setting (e.g.
Prolactinoma pregnancy, breast stimulation, stress, hypoglycemia

IGF-1 level
Acromegaly oral glucose tolerance test

Cushings 24 hr urine cortisol

disease overnight dexamethasone suppression test

TSH free T4, T3, TSH levels

overproduction
Dexametason test
 TREATMENT

surgical resection

dopamine agonist
prolactinoma
therapy

Octreotide , grwth agromegaly

h receptr antag TSH producing adenomas

require replacement of the indicated

Deficiency states hormone
 DIABETES INSIPIDUS
Diabetes insipidus is a disorder of the
posterior lobe of the pituitary gland
characterized by a deficiency of antidiuretic
hormone (ADH), or vasopressin. Great
thirst (polydipsia) and large volumes of
dilute urine characterize the disorder.
A) Central diabetes insipidus
Head trauma or surgery
T
Pituitary or hypothalamic tumor
Intracerebral occlusion or infection
Y
B) Nephrogenic diabetes insipidus
Systemic diseases involving the
kidney
Multiple myeloma
P
E
sickle cell anemia
Polycystic kidney disease
Pyelonephritis
Medications such as lithium
Pathophysiology
Central DI :
Loss of vasopressin-
producing cells,
Causing deficiency in
antidiuretic hormone
(ADH) synthesis or
release;
Deficiency in ADH,
resulting in an inability
to conserve water,
leading to extreme
polyuria and polydipsia
Pathophysiology
Nefrogenic DI

Depression of
aldosterone release
or inability of the
nephrons to respond
to ADH,
causing extreme
polyuria and
polydipsia
 Signs and symptoms
Polyuria with urine output of 5 to 15 L daily
Polydipsia, especially a desire for cold fluids
Marked dehydration, as evidenced by dry
mucous membranes, dry skin, and weight loss
Anorexia and epigastric fullness
Nocturia and related fatigue from interrupted
sleep
 Diagnostic test results
High serum osmolality, usually above 300
mOsm/kg of water
Low urine osmolarity, usually 50 to 200 mOsm/kg
of water;
low urine-specifi c gravity of less than 1.005
Increased creatinine and blood urea nitrogen
(BUN) levels resulting from dehydration
Positive response to water deprivation test: Urine
output decreases and specific gravity increases
Water deprivation test
 Goals of management
The objectives of therapy are
(1) to replace ADH (which is usually a long-term
therapeutic program),
(2) to ensure adequate fluid replacement, and
(3) to identify and correct the underlying cause
 Treatments

Replacement vasopressin therapy with

intranasal or I.V. DDAVP (desmopressin
acetate)
Correction of dehydration and electrolyte
imbalances
 Treatment
A thiazide diuretic to deplete sodium and
increase renal water reabsorption
Restriction of salt and protein intake