Pituitary Disorders
Kaset Chimplee M.D.
HYPOTHALAMUS
ANTERIOR PITUITARY
TARGET GLAND
Peripheral Hormones
+ Trophic Hormones
- Inhibitory Hormones
Releasing Factors +
HypothalamicAnteriorPituitary
Target GlandPeripheral Hormones
TRH
TSH
Thyroid
T3, T4
GHRH+Somatostatin-
GH
Liver
IGF-1
GnRH
LH, FSH
OvaryTestisSex steroidhormones
CRH
ACTH
AdrenalGlandCortisol
Hypothalamic
AnteriorPituitary
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 dyspla
- sia, Prader Willi S.• Tumors: - Pituitary secretory or
nonsecretory adenoma -Hypothalamus Cranioph
aryngioma, pinealoma etc• Immunological - Lymphocytichypophysitis• Infiltrative - Hemochromatsis,
Histiocytosis, Sarcoidosis Metastasis CA(breast and
bronchus)• Infectious - TB, Mycoses, Syphilis• Physical trauma - Head traum
a, Surgery, Radiation• Vascular - Sheehan’s 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 pube
rty, eunuchoid proportions Girl- delayed breast developm
ent, pubic&axillary hair Boy- phallus and testis remain
small, sparse body hair Adult: Women- breast atrophy, l
oss pubic&axillary hair,
secondary amenorrhea Men- testicular atrophy, d
ecreased libido,
impotence, loss of body hair• ADH Deficiency: DI with polyur
ia, 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 disorderOthers- 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
fa t s ta in
fo llow yearlyP R L , G H (if in d ica ted )
n orm a l
trea tas in d icated
n orm a l p ro lac tinab n orm a l TS H
M ac road en om ap ro lac tin > 2 0 0 n g /m l
M ic road en om aN on sec re to ry p itu ita ry
ad en om ap ro lac tin < 1 0 0 n g /m l
N orm a l TS HP ro lac t in e leva te
M R I
G alac to rrh each eck :p ro lac t in ,TS H , h C G
N on g a lac to rrh ea l d isc h arg e
N ip p le d isch arg e
GAP VIPTRH
PRLrp
Sucking
Serotonin(+)
Prolactinoma• Prolactin secreting pituitary adenoma
(lactrotrophs)– microadenoma ( < 10 mm in tumor size )– macroadenoma ( > 1 0 mm in tumor si
ze )
• Most common secreting pituitary tumor
Complication
• 1. Mass effects of the tumor• 2. Hormonal effects
Mass effects of the tumor
• 1. Microadenoma :– nn nnnnnn nnnnnnnnnnnnn– nnnnnnnn nnnnn nnnn nnnnn nnnn nnnnnn nnnnnn
nnnnn• 2. Macroadenoma :
– n nnnnn nnnnnn nnnnnnnnnnn n()– homonemous hemianopia (optic tract comp
n)– nn nnnnn n nnnnnnnnn nnnnn nnnnnnnnn n,,, 1,2( )– nnnn nnnnnnnnn n()– n nnn n nnn nnnnnnnnnn n nnnnnnnnnnn nn nnn,, ,, (
mal pituitary tissue )
Hormonal Effects
G on ad al in su ffic ien cy
d im in is h p u lsa tile L H , F S H re lease
a lte ra t ion inp itu ita ry L H R H sec re tion
in c rease en d og en ou s op ia te ton e
P ro lac t in om a
Hormonal Effects
• Chronic hyperprolactinmia decrease bon e density in both men and women
• Menopause with hyperprolactinemia dec rease bone deasity than menopause wit
h 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 than200 n ----- g / l +l ar ge pi t ui t ar y t umor : >m
echanical effects from stalk compression
• Prolactin level less than200 n ------- g /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
Cushing’s disease - * 2540women > men , age years * solitary monoclonal corticotroph adenoma * 1usually intracellular microadenoma (< cm) - *macroadenoma extrasellar extension/invasion *midlife, gradual progress * hypokalemia, virilization, extremely high cortisol
10excretion (> fold normal) : very uncommon * invasive pituitary adenoma : slightly younger age * Nelson’s syndrome : hyperpigmentation + high A
CCC CCCCCC CCCCC CCCCCCCCC CCCCCCCCCCCC C
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 ) ArginineVasopressin
Peptide hormone
CHROMOSOME 20
MAGNOCELLULAR NEURON
Actions of ADH• Increase water reabsorption in collecting du
ct• Stimulate ACTH secretion• Physiologic Antipyretics : lower core body t
emperature• Improve memory by hippocampal action• Modulating baroreceptor mediated controlle
d 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
p rim ary p o lyd ip s ia C D I o r N D I
S tan d ard wa te r d ep riva tion tes t
p u re wa ter d iu res isC osm < 3 .0 m l/m in
F E osm < 3 %
m ix so lu te -wa terC osm > 3 .3 m l/m in
F E osm > 3 %
U osm /P osm < 0 .9 U osm /P osm > 0 .9P u re so lu te d iu res is
Y esP O L Y U R E A
N O- U R G E N C Y O F U R IN A TIO N
- IN C O N TIN E N C E
> 3 0 0 0 m l /2 4 H r
Approach to solute or mix diuresis
Typ e o f s o lu te
g lu cose d iu res is u rea,m an n ito l d iu res is
2 (U N a+ U K )/U osm < 0 .4org an ic s o lu te
U N a+ U K > > U C ld ru g an ionke ton u ria
b ica rb on a tu ria
U N a+ U K < U C ld iu re tic
N aC l loadrecovery from A R F ob s tru c tion
2 (U n a+ U K )/U osm > 0 .6e lec tro lyte d iu res is
S o lu te d iu res is
Questions in Diabetes Insipidus• Question : What is osmolal clearance and how can we ca
lculate ?• Answer : conceptsurine volume
= free water volume + specific volume with solute excretion= CH2O + Cosm
if Uosm = Posm ----> no free waterurine volume = Cosm
ifUosm > Posm ----> negative free water clearance (total water reabsorbtion)
urine volume = Cosm - CH2O
Questions in Diabetes Insipidus
• Answer : (continue)If
Posm > Uosm ----> positive free water clearance
urine volume = Cosm + CH2OUosm 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 Vif > 3% ----> mixif < 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 trau
ma 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 posm pre pNa post uosm/posm post uos
m/posm+ ADH post pADH
Normal NL NL 1> 1 10
PPD/DDI 1 1 10> (< %)
CCDI 1 1 50> (> %) -
PCDI 1 -1 1050> ( %)
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 SIADHPattern Characteristics Frequency
Type A Erratic ADH secretion20% Type B Reset osmostat 3 5 % Type C ADH leak with selective 35%
loss of ADH suppression Type D - ADH dissociated diuresis1 0 %
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 con’t 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 <1 0 0 mOsm/kgH2 O• 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: craniopha
ryngioma, pinealoma, dermoid , epidermoid tumor
• Symptoms: Hypothalamic distur- bances disorders of
- Thirst Polyuria, Polydipsia
- Appetite Hyperphagia and Obesity
Temperature regulationsBehaviorsConsciousness