Download Overview of Pituitary Syndromes

Overview of Pituitary Syndromes
& Hypopituitarism
General characteristic of Hormones
They have specific rates and patterns of secretion (diurnal, pulsatile, cyclic
patterns)
Their secretion depends on feedback mechanism, either positive(rare) or
negative
They affect only cells with appropriate receptors
Trophic Hormones: hormones that control the secretion of other endocrine
glands eg. TRH, TSH, ACTH etc.
Effector Hormones: produce an effect directly on target organs eg. ADH,
T3, T4 etc.
Pituitary gland
Anatomy
Histology
Physiology
Diseases of pituitary gland
Anatomy of pituitary gland
Pituitary gland lies in the base of the skull in a portion of sphenoid bone
called sella turcica
Master gland (controls the activity of many other endocrine glands)
Controlled by the hypothalamus
Consists of two lobes
Anterior lobe (adenohypophysis)
Posterior lobe (neurohypophysis)
Measures 15X10X6 mm wt 500-900 mg
It may double in size during pregnancy
Normal Pituitary Anatomy
Anatomy of pituitary gland
Anterior lobe
glandular tissue, accounts for 75% of total weight
Hormones produced by this lobe are controlled by regulating
hormones from the hypothalamus
Posterior lobe
More of a terminus of axons of neurons in the supraoptic and
paraventricular nuclei of the hypothalamus
does not produce hormones but stores those produced by the
neurosecretory cells in the hypothalamus
Release of hormones is triggered by receptors in the hypothalamus
Histology of the Pituitary Gland
Anterior pituitary cells were originally classified as
Acidophilic cells
Basophilic cells
Chromophopic cells
With immunocytochemical and electron microscopic techniques, classified
by their secretary products
Somatotrophs
GH secreting cells
Account about 50% of anterior P.G
Acidophilic stained
Lactotrophs
Prl secreting cells
acidophilic stained
10-15% of anterior PG
Corticotrophs
ACTH secretary cells
basophilic cells
15-20% of anterior PG
Gonadotrophs
LH,FSH secretary cells
basophilic staining
10-15% of anterior PG
Thyrotrophs
TSH secreting cells
basophilic cells
< 10% of anterior PG
Anterior Pituitary Hormones
Posterior Pituitary Hormones
Antidiuretic hormone (ADH) or Vasopressin: vasoconstricts arterioles to
increase arterial pressure; increases water reabsorption in distal tubules
Oxytocin: stimulates uterus to contract at childbirth; stimulates mammary
ducts to contract (milk ejection in lactation)
Anterior Pituitary Disorders
Hormone
Increased
level
Decreased level
GH
Gigantism
(child)
Acromegaly
(adult)
Dwarfism (child)
Lethargy, premature
aging
ACTH
Cushing’s
Disease
Addison’s Disease
TSH
Secondary
Hyperthyroidsm
Secondary
Hypothyroidsm
Prolactin
Galactorrhoea
amenorrhea
Failure to Lactate
Late puberty,
infertility
FSH
LH
Menstrual cycle
disturbance
Amenorrhea,
impotence
Posterior Pituitary Disorders
Hormone
Increased
Decreased
Oxytocin
Precipitates
childbirth,
excess milk
Prolonged
childbirth,
diminished
milk
ADH
(vassopressin)
SIADH
Diabetes
Insipidus
Anterior Pituitary Disorders
Hypopituitarism:
commonly caused by infarction, removal, or destruction of the gland
by disease process
Hyperpituitarism:
almost always caused by pituitary adenoma
Hypopituitarism
Hypopituitrism is manifested by diminished or absent secretion of one or
more PH
Deficiency of all the pituitary hormones is called panhypopituitarism
The development of signs and symptoms is often slow and insidious
Hypopituitrism is either primary event caused by diseases of the pituitary
gland or secondary to diseases of the hypothalamus (due to diminished
secretion of hypothalamic releasing hormones)
Treatment and prognosis depend on the extent of hypofunction and the
underlying cause
Causes of Hypopituitarism
1. Pituitary diseases
Infarction
postpartum necrosis (Sheehan syndrome)
vascular disease
head trauma
Infections
tuberculosis , fungi
pyogenic , syphilis
toxoplasmosis
Pituitary Apoplexy
Empty Sella syndrome
Granulomatous disease
Sarcoidosis
Histiocytosis
Infiltrative disease
Autoimmune lymphocytic hypophysitis
Hemochromatosis
Neoplasm's involving pituitary
Pituitary adenoma
Craniopharyngioma
Metastasis or primary carcinoma (rare)
Aneurysm of internal carotid artery
Idiopathic or genetic
deficient production of pituitary hormone
synthesis of abnormal hormone
Iatrogenic
stalk section
radiation
removal of pituitary adenoma
Causes of hypopituitarism
2. Hypothalamic diseases
Mass lesions
benign (craniopharyngiomas)
malignant tumors (metastatic from lung, breast, etc.)
Infiltrative lesions –
sarcoidosis
Langerhans cell histiocytosis
Radiation - for CNS and nasopharyngeal malignancies
Infections - Tuberculous meningitis
Developmental and genetic causes
Septo-Optic dysplasia
Kallman Syndrome
Laurence-Moon-Bardet-Biedl Syndrome
Frohlich Syndrome
Head trauma
Structural anomalies of hypothalamus
Clinical Features of Hypopituitarism


Can present with features of deficiency of one or more or all the
pituitary hormones (called panhypopituitarism)
Clinical presentation depends on:




Age at onset
Hormone effected
Speed of onset
Duration of the deficiency
GH deficiency
Deficiency in children lead to short stature
Deficiency in adult may be asymptomatic or may present with nonspecific
symptoms like fatigue, decreased muscle mass, loss of libido decreased
bone mineral density, and increased risk of cardiovascular disease
Insulin-like growth factor-I (IGF-I) is the major mediator of growth hormone
(GH)-stimulated somatic growth
IGF-I is synthesized in liver and secreted into the blood under the control of
growth hormone
Gonadotrophin deficiency (hypogonadism)
In women
Before Puberty - primary amenorrhea and failure of puberty
development
After Puberty - secondary amenorrhea and regression of secondary
sexual characteristic, infertility
In men
Before Puberty - failure of puberty development
After Puberty - decrease libido or impotence, loss of secondary
sexual characteristic, infertility
TSH deficiency
Leads to Secondary Hypothyroidism
Child – Cretinism
Adult - Myxedema
Clinical features
cold intolerance
dry skin
loss of hair
mental dullness
Constipation
increase in wt
Bradycardia
slow reflexes
Hoarseness
puffiness of the face
ACTH deficiency
Leads to secondary adrenocortical insufficiency
(Addison’s Disease)
Clinical features
Weakness
Nausea and vomiting
Anorexia
Wt loss
Postural hypotension
Hypoglycemia
Hyponatremia
Prolactin Deficiency
Inability to lactate postpartum
Often the 1st manifestation of Sheehan syndrome
Sheehan's syndrome (postpartum hypopituitarism)
a rare, but potentially life threatening, complication of severe post
partum hemorrhage
The pituitary gland is enlarged in pregnancy and prone to infarction
from hypovolemic shock
common presentation is failure to lactate and
amenorrhea/oligomenorrhea,
but any of the manifestations of hypopituitarism (eg, hypotension,
hyponatremia, hypothyroidism) can occur anytime from the
immediate postpartum period to years after delivery
Diagnosis of Hypopituitarism
Biochemical diagnosis of pituitary insufficiency
Demonstrating low levels of trophic hormones in the setting of low target
hormone levels
Provocative/ stimulation tests may be required to assess pituitary reserve
Tests Of Pituitary Sufficiency
Hormone
Test
Normal response
GH
Insulin tolerance test: Regular
insulin 0.1 uint/kg IV
L-dopa 250-500
Arginine 0.5 gm
Glucose <40 mg/dL; GH
should be >3µg/L
GH should be >3µg/L
Prolactin
TRH test: 200–500 µg IV
Normal prolactin is >2
µg/L and increase
>200% of
baseline
TSH
Basal thyroid function tests:
T4, T3, TSH
TRH test: 200–500 µg IV
Low free thyroid
hormone
levels in the setting of
low TSH
5-10 fold increase in
TSH
Tests of Pituitary Sufficiency
Hormone
Test
Normal response
LH &
FSH
Basal LH, FSH,
testosterone, estrogen
levels
GnRH test: GnRH (100
µg) IV
Basal LH and FSH should be
increased in postmenopausal
women Low testosterone levels
in the setting of low LH and FSH.
LH should increase by 10 IU/L
and FSH by 2 IU/L
ACTH
Insulin tolerance test:
Regular insulin 0.1 uint/kg
IV
CRH test: 1ug/kg IV
ACTH stimulation test:
ACTH (Cosyntropin), 0.25
mg IM or IV
Glucose <40 mg/dL
Cortisol should increase by
>7µg/dL or to >20 µg/dL.
Basal ACTH increases two- to
fourfold and peaks at
20–100 pg/mL.
Normal response is cortisol >21
µg/dL
Treatment of Hypopituitrism
Deficient
hormone
Therapy
TSH
L-thyroxine 0.075–0.15
mg daily
ACTH
Hydrocortisone (10–20
mg A.M.; 5–10 mg P.M.)
Cortisone acetate (25 mg
A.M.; 12.5 mg P.M.)
Prednisone (5 mg A.M.;
2.5 mg P.M.)
LH &
FSH
Men :testosterone
Women :cyclic estrogen
and progesterone
GH
Adults: Somatotropin
(0.1–1.25 mg SC qd)
Children: Somatotropin
(0.02–0.05 mg/kg per d)
Growth Hormone Excess
Mostly due to GH secreting pituitary adenoma
Gigantism
GH excess before closure of epipheseal growth plates of long bones
Acromegaly
GH excess after closure of epipheseal growth plates of long bones
Insidious onset
Usually diagnosed late
Growth Hormone Excess
May have DM or glucose intolerance
Hypogonadism
Large hands and feet
Large head with a lowering brow and coarsening features
Hypertensive – 25%
Colon polyps
3-6 more likely than general population
Multiple skin tags
GIGANTISM
ACROMEGALY
Growth Hormone Excess
 Diagnosis
 Screen:
 Check for high IGF-I levels (>3 U/ml)
 Remember, levels very high during puberty
 Confirm:
 100gm glucose load
 GH levels do not fall to <5ng/ml
 MRI or CT & visual field tests to determine size and position of the
pituitary adenoma
 Treatment
 Surgical resection of adenoma
 Radiation
 Bromocriptine - temporary measure
 May decrease GH by 50%
 Somatostatin (Octreotide)
 For suboptimal response to other treatment
Posterior Pituitary Disorders
SIADH & Diabetes Insipidus are major disorders of the posterior
pituitary……however
Even if posterior lobe becomes damaged, hormonal deficiencies usually do
not develop because……??
SIADH (Syndrome of Inappropriate Anti-Diuretic Hormone)
Too much ADH produced or secreted.
SIADH commonly results from malignancies, CHF, & CVA - resulting in
damage to the hypothalamus or pituitary which causes failure of the
feedback loop that regulates ADH.
Patient retains water causing dilutional hyponaetremia & decreased
osmolality.
Decreased serum osmolality cause water to move into cells
Signs and Symptoms
Lethargy & weakness
Confusion or changes in neurological status
Cerebral edema
Muscle cramps
Decreased urine output
Weight gain without edema
Hypertension
Assessment
Serum sodium low
Serum osmolality low
Urine osmolality disproportionately elevated in relation to the serum
osmolality
Urine specific gravity elevated
Plasma ADH elevated
Treatment of SIADH
Treat underlying cause
Hypertonic or isotonic IV saline solution
Monitor for signs of fluid and electrolyte imbalance
Monitor for neurological effects
Monitor intake and output
Weigh
Restrict fluid intake
Lithium inhibits action of ADH to promote water excretion.
Diabetes Insipidus (DI)
Etiology
 Deficiency in secretion of ADH
 Agenesis or irreversible destruction of the neurohypophysis
 Malformation or destruction of the neurohypophysis by a variety of
diseases or toxins
 Neurohypophyseal DI, Pituitary DI, or Central DI
 Deficiency in action of ADH
 Can be genetic, acquired, or caused by exposure to various drugs
 Nephrogenic DI
Clinical Manifestations
Polyuria of more than 3 litres per 24 hours in adults (may be up to 20!)
Urine specific gravity low
Polydipsia (excessive drinking)
Weight loss
Dry skin & mucous membranes
Possible hypovolemia, hypotension, electrolyte imbalance
Diagnostic Tests
Serum sodium may be high
Urine specific gravity low
Urine osmolality low
Water deprivation test
In DI water deprivation does not result in urine concentration
Differentiating b/w Neurogenic vs Nephrogenic DI
Administer Desmopressin (DDAVP)
Measure urine osmolality at 30,60,120 min
An increase of >50% indicates severe pituitary DI
Smaller or absent response is strongly suggestive of nephrogenic DI
Treatment of Diabetes Insipidus





Neurogenic DI
DDAVP
Chlorpropamide (Diabinese)
Nephrogenic DI
Not affected by treatment with DDAVP or chlorpropamide
 May be reduced by treatment with a thiazide diuretic and/or amiloride
in conjunction with a low-sodium diet
 Inhibitors of prostaglandin synthesis (e.g., indomethacin) are also
effective in some patients
Thank You