By Dr. Zahoor
1
Objectives
 We will study
1. Pituitary gland and Hypothalamus
2. Increased Secretion of Pituitary Hormone
causing disorders
3. Hyposecretion of Pituitary hormones
2
Pituitary gland and Hypothalamus
 Hypothalamus and anterior pituitary are connected by
hypophyseal – pituitary portal blood supply
 Hypothalamus and posterior pituitary are connected
by neural tissue
 Pituitary gland, size of pea, is enclosed in Sella turcica
and bridged over by a fold of duramater, has
sphenoidal air sinuses below, optic chiasma above,
cavernous sinus laterally.
3
Pituitary gland and Hypothalamus
 Tumor of pituitary can produce visual field defect by
pressure on the optic chiasma which lies above the
pituitary fossa
4
Hypothalamus - Pituitary
 Hypothalamic neuron secrete pituitary releasing and
inhibiting factors and hormones
 There are five major anterior pituitary axis
- Growth hormone axis
- Thyroid axis
- Adrenal axis
- Gonadotropins axis
- Prolactin axis
5
Hormones
of Anterior
and
Posterior
Pituitary
6
Hypothalamus - Pituitary
 Majority of anterior pituitary hormones are under
positive control by hypothalamic releasing hormones,
except Prolactin which is under tonic inhibition of
dopamine
 Applied – in hypothalamic disease, there is deficiency
of anterior pituitary hormones but over secretion of
Prolactin
7
Hypothalamus - Pituitary
 Posterior pituitary is Neuro anatomically connected to
hypothalamic nuclei
 ADH and Oxytocin are synthesized in supraoptic and
paraventricular nuclei in anterior hypothalamus
 They are transported along the axon and stored in
posterior pituitary
8
Pituitary Gland
 Excessive secretion of anterior pituitary causes
1. Acromegly or Gigantism – due to increased growth
hormone (GH)
2. Hyperprolactinimia
3. Cushing disease and nelson’s syndrome – due to
increased ACTH secretion
9
Pituitary Gland
 Decreased secretion of anterior pituitary causes
1. Short stature in child due to growth hormone
deficiency
2. Hypothyroidism – due to decrease TSH
10
Pituitary Hyper secretion
Syndrome
- Acromegly
- Gigantism
 Increased growth hormone secretion in adults causes
Acromegly
 Increased growth hormone secretion in children
(before epiphyseal fusion) causes Gigantism
 Both Acromegly and Gigantism occur due to pituitary
growth hormone secreting tumor
11
Symptoms and Signs of Acromegly
12
Symptoms and Signs of Acromegly
13
Symptoms and Signs of Acromegly
Compare hands
Ring Finger
14
Acromegly
Investigations
 GH levels – high in Acromegly
(not diagnostic alone as GH increases during stress or
GH pulse)
 Growth hormone suppression test- Glucose tolerance
test (GTT) and GH levels – it is diagnostic if there is
no suppression of growth hormone after glucose load
 IGF – 1 levels are increased
15
Acromegly
Investigations (cont)
 Visual field examination – by temporal hemianopia
occurs commonly
 MRI scan of pituitary reveals pituitary adenoma
16
Acromegly
Management and Treatment
1. Surgery
 Pituitary micro adenoma
- Surgery via trans - Sphenoidal route, remission
occurs in 60-90% cases
 Pituitary macro adenoma
- Surgery for large tumors open transcranial usually
transfrontal route
17
Acromegly
Management and Treatment
2. Radiotherapy
 External radiotherapy is used when surgery is
impracticable or surgery fails to normalize growth
hormone ( GH) levels
18
Acromegly
Management and Treatment
3. Medical therapy
 Somatostatin receptor agonist e.g. octreotide ,They
decrease GH and IGH level
 Dopamine agonist – Bromocriptine
Most effective in mixed GH and Prolactin producing
tumor
 GH receptor antagonist – Pegvisomant (Somavert) is
GH receptor antagonist, by blocking the action of GH ,
it controls disease activity.
19
Hyperprolactinaemia
20
Hyperprolactinaemia
 Prolactin is secreted by anterior pituitary and is under
tonic dopamine inhibition
 Prolactin stimulates milk secretion from breast
 Prolactin inhibits gonadal activity and decreases
GnRH pulsatility at hypothalamic level
 Prolactin blocks action of LH on ovary and testis
producing hypogonadism
21
Control and
Action of
Prolactin
22
Range of Serum
Prolactin seen in
common causes of
Hyperprolactinae
mia
23
Hyperprolactinaemia
Physiological causes of Hyperprolactinaemia
 Pregnancy
 Lactation
 Severe stress
 Sleep
24
Hyperprolactinaemia
Pathological causes of Hyperprolactinaemia
 Prolactinoma (tumor of pituitary gland)
 Polycystic ovary syndrome
 Primary hypothyroidism (as TRH increases Prolactin)
Rare causes
 Estrogen therapy
 Renal failure
 Liver failure
 Post-ictal state
 Chest wall injury
25
Hyperprolactinaemia
Drugs causing Hyperprolactinaemia
 Dopamine antagonist
-Metaclopramide
-Domperidone
-Antipsychotic
26
Hyperprolactinaemia
Clinical features
 Hyperprolactinaemia stimulates milk production in the
breast and inhibits GnRH and gonadotropins secretion
 It usually presents with
- Galctorrrhoea
- Oligomenorrhoea
- Amenorrhoea
- Decreased libido in both sexes
- Decreased potency in men
- Sub fertility
27
Hyperprolactinaemia
Clinical features (cont)
- Estrogen or Androgen deficiency (in long term
osteoporosis specially in women)
- Delayed puberty
- Mild gynaecomastia in men
28
Hyperprolactinaemia
Investigation
 Prolactin level – are increased
- Mild increase in Prolactin level 400-600mU/L may be
physiological, level above 5000mU/L always imply
Prolactin secreting pituitary tumor
 Visual field
 Exclude primary hypothyroidism
 Radiology for pituitary tumor
 MRI of pituitary (when Prolactin level above
1000mU/L)
29
Treatment
1.
Medical Treatment
-Dopamine agonist
-Bromocriptine, Carbergoline
2. Trans Sphenoidal surgery
3. Radiotherapy
30
Hypopituitarism
31
Hypopituitarism
 Deficiency of pituitary hormones may be selective or
multiple
 Isolated deficiency of GH, LH/FSH, ACTH or TSH can
occur
 Cause may be genetic and congenital, autoimmune or
idiopathic
 Multiple deficiency can be due to tumor – usually GH
and gonadotropins are affected first
32
33
Hypopituitarism
Clinical features
 Symptoms and signs depend upon the extent of
hypothalamic and/or pituitary deficiencies
 There may be
- GH deficiency
- Secondary hypothyroidism
- Hypoadrenalism
- Gonadal deficiencies
- Hyperprolactaenimia
- Panhypopituitarism – causes classic picture of pallor
with hairlessness (‘alabaster skin’)
34
Syndromes related to
Hypopituitarism
35
Syndromes related to
Hypopituitarism
Kallmann’s Syndrome
 This syndrome is isolated gonadotropins (GnRH)
deficiency
 There is Anosmia (decreased or absent sense of smell)
 Color blindness
 Cleft palate (some times)
 It is familial, sex linked disorder caused by mutation of
KAL1 gene
36
Syndromes related to
Hypopituitarism
Sheehan’s Syndrome
 It occurs due to pituitary infarction following
postpartum hemorrhage. It is rare in developed
countries.
Pituitary Apoplexy
 Sometimes a pituitary tumor enlarges rapidly due to
hemorrhage
 It may produce severe headache, double vision, and
sudden visual lose
37
Syndromes related to
Hypopituitarism
Empty Sella syndrome
 An (empty Sella) is reported some times on pituitary
imaging
 It may follow spontaneous infarction or regression of
pituitary tumor
 Despite this, pituitary function is usually normal.
Why?
 Because pituitary is eccentrically placed and flattened
against the floor of roof of fossa
38
Posterior Pituitary
Vasopressin (ADH) hormone disorder
 There may be
1. SIADH (Syndrome of Inappropriate ADH secretion)
overproduction of ADH
2. Cranial Diabetes Insipidus (due to deficiency of
ADH)
NOTE – There is nephrogenic Diabetes Insipidus as
V2 receptors are resistant to the effect of hormone
ADH in the kidney.
39
Case History
A 50 year old woman is referred to the hospital
with history of sweating and joint pains. She has 10
year history of hypertension and more recently has
been discovered to have impaired glucose tolerance.
The striking feature on examination is her deep voice
and oily skin. A medical student notices increase interdental space and macroglossia, and suggests a possible
diagnosis of Acromegly. Further questioning elicits
increased shoe size, and the need to enlarge her
wedding ring 3 times over the last 15 years.
40
Questions:
1.
What test would be more helpful in the diagnosis?
a. Growth hormone
b. Oral glucose tolerance test (OGTT)
c. OGTT and growth hormone combined
d. Calcium
2.
What further investigation should be performed?
a. Dexamethasone test
b. Inferior petrosal sinus sampling
c. MRI of Pituitary
d. None
3.
Best treatment choice in Acromegly is
a. Somatostatin receptor agonist
b. Dopamine agonist
c. Radiotherapy alone
d. Pituitary surgery
41
Answers:
Answer to Question 1:
c. OGTT and growth hormone combined
Answer to Question 2:
c. MRI of Pituitary
Answer to Question 3:
d. Pituitary Surgery
42
Thank you
43