Pituitary Disorders

Kaset Chimplee M.D.

HYPOTHALAMUS
ANTERIOR PITUITARY
TARGET GLAND
Peripheral Hormones
+ Trophic Hormones
- Inhibitory Hormones Releasing Factors +
Hypothalamic
Anterior
Pituitary
Target Gland
Peripheral
Hormones
TRH
TSH
Thyroid
T3, T4
GHRH+
Somatostatin-
GH
Liver
IGF-1
GnRH
LH, FSH
Ovary
Testis
Sex steroid
hormones
CRH
ACTH
Adrenal
Gland
Cortisol
Hypothalamic
Anterior
Pituitary
Target tissue
Prolactin
Dopamine
Breast
TSH
Hypothalamic
Posterior Pituitary
Peripheral
Target Gland
Vasopressin
Vasopressin
Kidney,
Blood vessels
Oxytocin
Oxytocin
Uterus,
Breast
PITUITARY DISORDERS
Hypopituitarism
Pituitary Tumors
Empty Sella Syndromes
Disease of Posterior Pituitary- DI, SIADH
Clinical Manifestations of
Pituitary Disorders
Hormone Hypersecretions
Hypopituitarisms
Local Mass Effects
Hypopituitarism
Definition: Diminished secretion of one or more
pituitary hormones
Can be caused by either anterior pituitary gland
destruction or secondary to hypothalamic disorders
Usually slow and insidious disorder
Pituitary lesion may result in single or multiple
hormone losses
Etiology of Hypopituitarism
Congenital: Septo-optic dysplasia, Prader-Willi S.
Tumors: Pituitary- secretory or nonsecretory adenoma
Hypothalamus-Craniopharyngioma, pinealoma etc
Immunological - Lymphocytic hypophysitis
Infiltrative - Hemochromatsis, Histiocytosis, Sarcoidosis
Metastasis CA(breast and bronchus)
Infectious - TB, Mycoses, Syphilis
Physical trauma - Head trauma, Surgery, Radiation
Vascular - Sheehans syndrome, apoplexy, carotid aneurysm
Symptoms of Hypopituitarism
TSH Deficiency: lethargy, constipation, cold intolerance
bradycardia, wt. gain, poor appetite, dry skin,
delayed reflex relaxation
ACTH Deficiency: lethargy, weakness, nausia, vomitting
dehydration, orthostatic hypotension, coma if untreated
GH Deficiency: Infancy&Childhood- growth retardation
short stature and fasting hypoglycemia
: Adult- increased abdominal adiposity, reduced strength&
exercise capacity, impaired psychosocial well-being
Symptoms of Hypopituitarism cont
Gonadotropin Deficiency:
Childhood: failure to enter puberty, eunuchoid proportions
Girl- delayed breast development, pubic&axillary hair
Boy- phallus and testis remain small, sparse body hair
Adult: Women- breast atrophy, loss pubic&axillary hair,
secondary amenorrhea
Men- testicular atrophy, decreased libido,
impotence, loss of body hair
ADH Deficiency: DI with polyuria, polydipsia and nocturia
Diagnosis
Clinical: depend on specific hormones that are lacking
Hormonal reserve evaluation:
TSH: TFT: FT4 and/or FT3, TSH (may be WNL or )
ACTH: ACTH stimulation test
Insulin-induced hypoglycemic test
GH: Insulin-induced hypoglycemic test
Stimulation tests: arginine, clonidine, prpanolol,
L-dopa, GHRH
IGF-BP3

Diagnosis
Hormonal reserve evaluation cont:
Gonadotropins (LH and FSH):
Female- serum LH, FSH and estradiol(+HCG, prolactin)
Male- serum LH, FSH and testosterone
Prolactin: serum prolactin
ADH: Water deprivation test, vasopressin test


Treatment of hypopituitarism
Correct causes:
Adequate replacement of hormones:
TSH deficiency: Levothyroxine- 0.05-0.15 mg/d
ACTH deficiency: Prednisolone- 5-7.5mg/d
Cortisone acetate- 20-37.5 mg/d
Gonadotropins deficiency: Male: Testosterone IM
Female: Estrogen, progesterone
HMG IM or GHRH infusion for infertility
Treatment of hypopituitarism cont
Adequate replacement of hormones cont:
GH deficiency: hGH 0.3-1 mg/d
Prolactin deficiency: replacement not necessary
ADH deficiency: DDAVP intanasal 1-3 times/d
Chlorpropamde, clorfribrate, carbamazepine
(some residual releasible ADH)
Pituitary Tumors
Incidence: 1.85 / 1000,000 / year
Autopsy: 20-25%
Prolactinoma 30-40%
Gonadotropinoma 10-20%
GH secreting adenoma 2-17%
ACTH secreting adenoma 10%
TSH secreting adenoma <1%
Clinical manifestations of pituitary tumors
Endocrine manifestations: - Hypersecretion
- Hypopituitarism
Mass effects:
Optic nerve- bitemporal hemianopia, central scotoma
Carvernous sinus- opthalmoplegia, ptosis, diplopia
Hypothalamus- DI, ANS dysfunction, sleep disorder
appetite and thirst disorder
Others- headache, hydrocephalous, dementia, psychosis

Prolactinoma
Most common secretory pituitary tumor
Clinical manifestations:
Female- amennorhea, galactorrhea, infertility
- estrogen deficiency: hot flushes, vaginal dryness
- weight gain, hirsutism
Male- loss of libido, impotence
- often delayed diagnosis macro-prolactinoma
visual impairment, headache, hypopituitarism
Approach to nipple discharge
fat stain
follow yearly
PRL , GH (if indicated )
normal
treat
as indicated
normal prolactin
abnormal TSH
Macroadenoma
prolactin>200ng/ml
Microadenoma
Nonsecretory pituitary
adenoma
prolactin<100ng/ml
Normal TSH
Prolactin elevate
MRI
Galactorrhea
check :prolactin ,TSH , hCG
Nongalactorrheal discharge
Nipple discharge

GAP
VIP
TRH
PRLrp
Sucking
Serotonin (+)
Prolactinoma
Prolactin secreting pituitary adenoma
(lactrotrophs)
microadenoma ( < 10 mm in tumor size )
macroadenoma ( > 10 mm in tumor size )

Most common secreting pituitary tumor
Complication
1. Mass effects of the tumor
2. Hormonal effects
Mass effects of the tumor
1. Microadenoma :
no visual abnormalities
headache occur more offen than normal
individuals
2. Macroadenoma :
bitemporal hemianopia ( optic chiasm compression
)
homonemous hemianopia (optic tract compression )
CN II , IV, VI , V1 , V2 palsy ( cavernous
sinus extension )
seizure (temporal lobe extension )
GH , corticotropin , LH , FSH , TSH deficiency (
compression of normal pituitary tissue )
Hormonal Effects
Gonadal insufficiency
diminish pulsatile LH , FSH release
alteration in
pituitary LHRH secretion
increase endogenous opiate tone
Prolactinoma
Hormonal Effects
Chronic hyperprolactinmia decrease bone
density in both men and women

Menopause with hyperprolactinemia
decrease bone deasity than menopause
with normal prolactin level
Diagnosis of prolactinoma
1. Prolactin level more than 200 ng
/l
2. Presence of macroadenoma
more than 10 mm in tumor size
1.+2. : most likely a prolactinoma
Diagnosis of prolactinoma
Prolactin level less than 200 ng / l + large
pituitary tumor : -----> mechanical effects
from stalk compression

Prolactin level less than 200 ng /l +
microadenoma : -------> prolactin
secreting microadenoma
Diagnosis of prolactinoma

Microadenoma

Macroadenoma

Pituitary Apoplexy

Pituitary Apoplexy

Treatment of prolactinoma
Medical: bromocriptine 2.5-15 mg/d orally
: other dopamine agonists- eg. Pergolide,
carbergolide, lisulide
Transphenoidal surgery: rarely curative
indicated in: persistent VF defects despite bromocriptine
: intolerant of dopamine agonists
: relieve symptom in tumor with large
cystic or hemorrhge
Radiotherapy: peristent tumor after surgery or med.Rx
Cushings disease
* women > men , age 25-40 years
* solitary monoclonal corticotroph adenoma
* usually intracellular microadenoma (< 1 cm)
* macroadenoma- extrasellar extension/invasion
* midlife, gradual progress
* hypokalemia, virilization, extremely high cortisol
excretion (>10 fold normal) : very uncommon
* invasive pituitary adenoma : slightly younger age
* Nelsons syndrome : hyperpigmentation + high
ACTH levels after bilateral adrenalectomy
Acromegaly
GH excess: children- gigantism
adult- acromegaly
Insidious and chronic debilitating
Shortened life expectancy: increased death from
cardiovascular disease, cerebrovascular disease,
respiratory disease, malignancy
Almost always due to GH-secreting pituitary adenoma
Others: Ectopic GH- pncreatic, breast, lung tumors
Ectopic GHRH- pancreatic tumors, carcinoids

Clinical Features of Acromegaly
Somatic: Acral change- enlarged hand and feet
Musculoskeletal- arthralgia, prognathism,
malocclusion of teeth, poximal myopathy
Skin changes- sweationg, oily skin
GI- polyps, carcinoma,
CVS- cardiomegaly, HT
Viseromegaly- thyroid, liver, tongue
Clinical Features of Acromegaly cont
Endocrine-metabolic:
Reproductive- menstrual abnormalities,
galactorrhea, decreased libido
CHO metabolisms- IGT, diabetes mellitus
Lipid changes- hypertriglyceridemia
Others- hypercaciuria, elevation of serum P
Diagnosis of Acromegaly
Clinical features:old pictures may be helpful
Thickness of heel pad(M:>21,F:>18mm)
Glucose suppressed GH concentrations:
normal <2ug/L, acromegaly usually >10ug/L
Increased IGF-1 level
CT or MRT: 90% of tumor size>1cm.
If no pituitary mass is detected, extrapituitary sauce
of GH or GHRH should be sought
Treatment of Acromegaly
Objectives: return GH/IGF-1 to normal, decreased tumor
size, preserve pituitary functions
GH < 2 ug/L representing cure
Transhenoidal surgery: initial therapy of choice
Medical Rx: Octrotide-effective, requires chronic therapy
Bromocriptine- less effective
Radiotherapy: effective but need time,high incidence of
hypopituitarism
Gonadotropin-Secreting pituitary tumors
Rare and reported mainly in men
Majority are large at presentation, mostly secrete FSH
Usually presents with S/S of mass effects
Men may present with low or normal testosterone and
sperm count
Should be DDx from menopause or 1 hypogonadism
Surgical removal usually 1 treatment, may required
subsequent radiotherapy
Thyrotropin-Secreting pituitary tumors
Extremely rare
Presenting with hyperthyroidism, goiter, and
in appropriate elevate TSH
Usually plurihormonal: co secrete GH, PRL, alpha-
subunit
Treatment by surgery with or without radiotherapy
Octreotide has been found to be useful
May required I131 to control thyrotoxicosis
Empty Sella Syndrome
Occurs when the arachnoid membranes herniate
through incompetent diaphragmatic sella, partially
filling with CSF and copressing pituitary gland
Etiology:Primary- usually obese women, HT, ICP
Secondary- following surgery or XRT,
post pituitary infarction
usually asymptomatic, endocrine function usually WNL
Diagnosis is confirmed by CT or MRI
Adenohypophysis: Anterior
pituitary gland
Neurohypophysis : Posterior
pituitary gland
ADH ( Arginine
Vasopressin )
Arginine
Vasopressin

Peptide hormone
CHROMOSOME 20
MAGNOCELLULAR NEURON
Actions of ADH
Increase water reabsorption in collecting
duct
Stimulate ACTH secretion
Physiologic Antipyretics : lower core body
temperature
Improve memory by hippocampal action
Modulating baroreceptor mediated
controlled of blood pressure

ADH acts on V2 receptors
AQP2
AQP3-4
Regulations of ADH secretion


Regulations of ADH secretion
Neurogenic, also known as central, hypothalamic, pituitary or
neurohypophyseal is caused by a deficiency of the
antidiuretic hormone, vasopressin.


Nephrogenic, also known as vasopressin-resistant is caused
by insensitivity of the kidneys to the effect of the
antidiuretic hormone, vasopressin.

Dipsogenic, a form of primary polydipsia is caused by
abnormal thirst and the excessive intake of water or other
liquids

Water Diuresis
Clinical Approach to Polyurea
primary polydipsia CDI or NDI
Standard water deprivation test
pure water diuresis
Cosm<3.0 ml/min
FEosm<3%
mix solute-water
Cosm>3.3 ml/min
FEosm>3%
Uosm/Posm < 0.9 Uosm/Posm >0.9
Pure solute diuresis
Yes
POLYUREA
NO
- URGENCY OF URINATION
- INCONTINENCE
> 3000 ml /24 Hr
Approach to solute or mix
diuresis
Type of solute
glucose diuresis urea,mannitol diuresis
2(UNa+UK)/Uosm <0.4
organic solute
U Na+U K>> U Cl
drug anion
ketonuria
bicarbonaturia
U Na+U K < U Cl
diuretic
NaCl load
recovery from ARF obstruction
2(Una+UK)/Uosm >0.6
electrolyte diuresis
Solute diuresis
Questions in Diabetes Insipidus
Question : What is osmolal clearance and how can we
calculate ?
Answer : concepts
urine volume = free water volume + specific volume with
solute excretion
= CH
2
O + Cosm
if Uosm = Posm ----> no free water
urine volume = Cosm
if Uosm > Posm ----> negative free water clearance (total
water reabsorbtion)
urine volume = Cosm - CH
2
O
Questions in Diabetes
Insipidus
Answer : (continue)
If Posm > Uosm ----> positive free water
clearance
urine volume = Cosm + CH
2
O
Uosm x Uvol = Posm x Cosm
Cosm = Uosm x Uvol
Posm
Questions in Diabetes Insipidus
Question : How can we calculate FEosm ?
Answer : FE osm = (Cosm / GFR) x 100 , GFR =
(Ucr/Pcr) x V
if > 3% ----> mix
if < 3% ----> pure

Question : Mention drugs that caused Nephrogenic DI ?
Answer : Lithium , Amphotericin B , domeclocycline
, Streptozocin , Methoxyflurane

Questions in Diabetes Insipidus
Question : Describe phase after Hypothalamic
trauma or injury ?

Answer : phase I ----> polyurea (1-2 day after
event)
phase II ----> antidiuresis (5-7 day)
phase III ----> polyurea (permanent
or recovery as long as 6
month
phase IV ----> recovery
Questions in Diabetes Insipidus
Question : In water deprivation test why we
stop the process when bodyweight decrease
from 3-5% of baseline ?
Answer : To eliminate the effect of
hypovolemia on ADH secretion.
Questions in Diabetes
Insipidus
pre p
osm
pre p
Na
post u
osm
/p
osm
post u
osm
/p
osm
+ADH post p
ADH
Normal NL NL >1 >1 (<10%)
PPD/DDI >1 >1 (<10%)
CCDI <1 >1 (>50%) -
PCDI >1 > 1 (10-50%)
CNDI <1 <1(<10%)
PNDI >1 >1 (<10%)
Questions in Diabetes
Insipidus
Question 21 : How can we initiate therapy with
desmopressin ?

Answer : Start with low dose such as 1 puff or
0.1 ml (10 ug) at bed time
The second dose can prescribed for the
morning or the noon.
Patients with volume depletion : isotonic saline
infusion until hemodynamically stable
Syndrome of Inappropriate ADH secretion
(SIADH)
Definition : sustained endogenous production of ADH
resulted in excess water conservation
- Hyponatremia,Volume expansion
- Increased GFR
- Tubular sodium wasting
- decreased tubular absorption of creatinine and
uric acid
- No edema
Patterns of ADH secretion in SIADH
Pattern Characteristics Frequency

Type A Erratic ADH secretion 20%
Type B Reset osmostat 35%
Type C ADH leak with selective 35%
loss of ADH suppression
Type D ADH-dissociated diuresis 10%
Major causes of SIADH
Malignant neoplasia carcinoma: bronchogenic, pancreatic
lymphoma and leukemia, thymoma and mesothelioma
Central nervous system disordrers:
Trauma, Tumors, Infection, Porphyria
Pulmonary disorders:
TB, pneumonia, abscess, fungal infections,
positive pressure ventilator
Drugs:
chlorfribate, carbarmazepine, chlorpropamide,
cyclophosphamide, morphine, amitryptylline

Diagnosis of SIADH
Essential reuirements
decreased effective osmolality- Posm<275mOsm/kgH2O
Inappropriate urinary concentrations- Uosm>100
Euvolemia- absence clinical signs of hypovolemia
Elevated urinary sodium excretion with normal salt
and water intake
Absence of other potential causes of euvolemic hypoosmolality;
hypothyroidism, hypocortisolism
and recent antidiuretic use
Diagnosis of SIADH cont
Supplemental criteria
Abnormal water load test(inability to excrete at least 90% of
a 20ml/kg water load within 1 hr and or failure to dilute
Uosm to <100mOsm/kgH2O
Inappropriately elevated AVP relative to Posm
No significant correction of plasma osmolality with volume
expansion but improvement after fluid restriction

Clinical manifestations of SIADH
Symptoms and signs of the disease that causes SIADH
Hyponatremic encephalopathy
- headache, nausea
- disorientation, confusion
- obtundation, seizure
- cerebral edema, respiratory arrest
Treatment of SIADH
Correct the ethiologic causes
Fluid restriction: depend on urine out put and
insensible loss , generally < U output-500cc/d with
relatively high NaCl intake
Pharmacologic therapy:
- demeclocycline
- lithium carbonate
- AVP V2 receptor antagonist
HYPOTHALAMIC DYSFUNCTION
Common etiology: craniopharyngioma, pinealoma,
dermoid, epidermoid tumor
Symptoms: Hypothalamic disturbances- disorders of
Thirst- Polyuria, Polydipsia
Appetite- Hyperphagia and Obesity
Temperature regulations
Behaviors
Consciousness