HYPOPITUITARISM

Dr. Rasikapriya
First year paediatrics
 OBJECTIVES
• Introduction
• Classification
• Pathophysiology
• Clinical features
• Investigation
• Management
 PITUITARY GLAND
The pituitary is located
at the base of the brain,
in a small depression of
the sphenoid bone
(sella turcica).
• Purpose: control the
activity of many other
endocrine glands.
“ Master gland”
• Has two lobes,
the anterior & posterior lobes.
 HYPOPITUITARISM
• Hypopituitarism- denotes
1. Underproduction of GH alone
2. In combination with deficiencies of other
pituitary hormones.
• Incidence – 1 in 4000- 1 in 10000 live births
( as per Nelson).
 Contd…
• Hypopituitarism occurs when the anterior
(front) and posterior lobes of the pituitary
gland loses its ability to make hormones,
resulting in multiple pituitary hormone
deficiencies. Physical symptoms depend on
which hormones are no longer being
produced by the gland.
GH Dwarfism, Lethargy,
Premature aging
ACTH Addison’s disease
TSH Decrease in BMR,HR,CO,BP.
Cretinism
PROLACTIN Too little milk
FSH Late puberty, Infertility
LH Amenorrhea, Impotence

OXYTOCIN Prolonged labour, Diminished

milk
ADH(VASSOPRESSIN) Diabetes insipidus, Dilute
urine and Increased urine
output.
 ETIOLOGY
HYPOPITUITARISM

1. CONGENITAL
2. ACQUIRED
 CONGENITAL
• Perinatal insults (eg, traumatic delivery, birth
asphyxia)
• Interrupted pituitary stalk
• Absent or ectopic neurohypophysis
 CONTD..
Genetic disorders:
• Isolated GH deficiency types IA, IB, II, III
• MPHD (eg, from PIT1 and PROP1 mutations)
• Septo-optic dysplasia
• Isolated gonadotropin deficiency (eg,
fromKAL and KISS1R mutations)
 CONTD..
Developmental central nervous system (CNS)
defects:
• Anencephaly
• Holoprosencephaly
• Pituitary aplasia or hypoplasia

IDIOPATHIC
 ACQUIRED CAUSES
• Any lesion that damages hypothalamus,
pituitary stalk or anterior pituitary hormone
deficiency .
• Most common lesion- craniopharyngioma
• Diabetes insipidus- most frequently seen.
BRAIN DAMAGE Traumatic brain injury
Subarachnoid hemorrhage
Neurosurgery
Irradiation
Stroke
PITUITARY TUMORS Adenomas

NON PITUITARY TUMORS Craniopharyngioma

Meningiomas
Gliomas
Chordomas
Metastases

INFECTION Abscess, Hypophysitis, Meningitis,

Encephalitis.
INFARCTION Apoplexy, sheehan syndrome
AUTOIMMUNE DISORDER Lymphocytic hypophysitis
OTHERS Hemochromatosis, Histiocytosis,
Empty sella, Perinatal insults
 Clinical features
Congenital :
Growth and development:
• Birthweight: near-normal
• Birth length: may be slightly decreased
• Postnatal growth: severe growth failure
• Bone age: delayed, but may be advanced relative
to height age
• Genitalia: micropenis in childhood; normal for
body size in adults
• Puberty: delayed 3-7 yr
• Sexual function and fertility: normal
• Craniofacies
• Hair: sparse before the age of 7 yr
• Forehead: prominent; frontal bossing
• Skull: normal head circumference; craniofacial
disproportion due to small facies
• Facies: small
• Nasal bridge: hypoplastic
• Orbits: shallow
• Dentition: delayed eruption
• Sclerae: blue
• Voice: high pitched
• Musculoskeletal/metabolic/miscellaneous
• Hypoglycemia: in infants and children; fasting
symptoms in some
• adults
• Walking and motor milestones: delayed
• Hips: dysplasia; avascular necrosis of femoral
head
• Elbow: limited extensibility
• Skin: thin, prematurely aged
• Osteopenia
• Common presentation- Hypoglycemia.
• Jaundice
• Electrolyte disturbances
 ACQUIRED
• TUMORS- headache, vomiting, visual
disturbance, pathologic sleep patterns,
decreased school performance, seizures,
polyuria and growth failure.

• Craniopharyngioma- visual field defects, optic

atrophy, papilledema and cranial nerve palsy.

• Loss of weight, asthenia, sensitivity to cold,

mental torpor and absence of sweating.
 Contd..
• Sexual maturation fails or regression
• Atropy of gonads with amenorrhea and loss of
pubic hair.
• Growth slows dramatically.
 INVESTIGATION
• CRITERIA FOR GROWTH FAILURE:
1. Height < 1 percentile for age and sex
2. Height > 2 SD below sex adjusted mid parent
height.
 Evaluation
Growth related history and patient Growth failure
physical exam Short stature

Imaging CT and MRI

Laboratory Measurement of GH, IGF-1 and IGF-1

binding protein levels.
Determination of peak GH levels after
stimulation test

Special testing Family history and genetic analyses

Other functions Levels TSH, free thyroxin, ACTH, Cortisol,

Gonadotropines, Gonadal steriods.
GH stimulation test
 Contd..
TEST PROTOCOL LEVELS SPECIFICITY
Exercise 10 mins 0,10,20, mins 50%
Insulin 0.05-0.1 U/kg 0,30,60,90 mins 85%
Clonidine 0.15mg/m2 0,30,60,90 mins 80%
GHRH 1mcg/kg -30,0,30,45 mins 95%

PREREQUISITES FOR GH STIMULATION:

1. Normal thyroid profile
2. Priming in childern with bone age <10 yrs and delayed puberty
BOYS- Testosterone enanthate 100mcg IM 5 days prior to test
GIRLS- Ethinyl estradiol 100mcg/day -3 days.
INTERPRETATION:
<5 ng/ml-Growth hormone deficiency
5-10ng/ml- Indeterminate
>10ng.ml- Growth hormone deficiency excluded.
MRI

MPHD
Triad- small anterior
pituitary, missing or
attenuated pituitary stalk
and ectopic posterior
pituitary bright spot at base
of hypothalamus
 TREATMENT
• Recombinant h GH- 0.18-0.3 mg/kg/week
• Higher dose – puberty.
• Subcutaneously 6 to 7 divided doses.
• Maximum response- 1st year treatment.
 Contd..
• Recombinant IGF-1 – SC , 2 divided doses.
• In MPHD- other hormonal deficiencies
• TSH deficiencies- thyroxin
• ACTH deficiencies- hydrocortisone
• Infant with micropenis- 1 -2 (3 months course)
25 mg testosterone cypionate or testosterone
enanthate.
 FOLLOW UP
• CLINICAL- Height velocity and Z score for
height.
• Blood sugar, TSH, bone age- yearly
• After puberty- bone age 6 monthly

• DISCONTINUATION OF TREATMENT:
Target height is achieved
Bone age- boys-16years, girls- 14 years.
 Diabetes Insipitus
• DI is usually insidious but can occur with
damage to the hypothalamus or the pituitary.
(neurogenic DI)
• May be a result of defect in renal tubules, do
not respond to ADH (nephrogenic DI)
• Decreased production or release of ADH
results in massive water loss
• Leads to hypovolemic & dehydration
 CLINICAL FEATURES
Polyuria
Urine specific gravity low
Polydipsia (excessive drinking)
Weight loss
Dry skin & mucous membranes
Possible hypervolemia, hypotension,
electrolyte imbalance
 DIAGNOSTIC TESTS
• Serum sodium
• Urine specific gravity
• Serum osmolality
• Urine osmolality
• Serum ADH levels
• Vasopressin test and water deprivation test:
increased hyperosmolality is diagnostic for DI.
 TREATMENT
Medical management includes
• Rehydration IV fluids (hypotonic)
• Symptom management
• ADH replacement (vasopressin)
• For nephrogenic DI: thiazide diuretics,
mild salt depletion, prostaglandin
inhibitors (i.e. ibuprophen)
THANK YOU