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Transcript
Hypothalamic
&
Pituitary Hormones
Kaukab Azim, MBBS, PhD
Uses of Hypothalamic & Pituitary Hormones
• Short stature due to hypopituitarism (Pituitary dwarfism)
• Acromegaly and gigantism
• Carcinoid syndrome, VIPoma, and ruptured esophageal
varices
• Hyperprolactinemia
• Induction of labor
• Diabetes insipidus
• SIADH
2
Concepts in Endocrinology
• Primary, secondary and tertiary endocrine disorders
• Feedback regulation
• Endocrine disorders:
– Deficiency, or
– Excess
• Mechanisms of action
• Uses of hormones /analogs:
– Diagnostic use
– Therapeutic use
3
Growth hormone releasing hormone
(GHRH)
• GHRH analog: Sermorelin
• Used rarely as a diagnostic test for GH responsiveness
4
Growth Hormone
• Secretion of GH is stimulated
by GHRH and inhibited by GIH
(somatostatin)
• GH preparations for
therapeutic use:
– Somatropin: Recombinant
human GH
IGF-1 as
Peripheral
effector
– Somatrem: Recombinant
human GH
5
Growth hormone (Somatotropin)
• Most of the actions of GH are
mediated by IGF-1 ( insulinlike growth factor 1)
“somatomedins” - the
peptides produced in the
liver and cartilage.
• The somatomedins stimulate
skeletal growth, amino acid
transport, protein synthesis,
nucleic acid synthesis and
cell proliferation.
6
Therapeutic uses of GH
• Short stature due to
Congenital/acquired GH
deficiency (Pituitary Dwarfism)
• GH deficiency in adults
• Turner’s syndrome
• AIDS related muscle wasting
7
GH preparations: Adverse effects
In children
• Increased Intracranial
tension
• Headache
• Papilledema
• Scoliosis
• Diabetes mellitus
In adults
•
•
•
•
•
•
Peripheral edema
Arthritis
Arthralgia
Myalgia
Carpal tunnel syndrome
Diabetes mellitus
8
Growth hormone inhibiting hormone
(Somatostatin)
Somatostatin analogs:
• Octreotide – S/C, daily
• Sandostatin-LAR - (Slow release preparation of
octreotide) once every 4 weeks
• Administration of somatostatin analogs result in
decrease in GH and IGF-1 levels
9
Somatostatin analogs: Therapeutic uses
• Acromegaly
• To prevent gigantism
• Carcinoid syndrome
• VIPoma, gastrinoma
• Ruptured esophageal
varices
10
Somatostatin analogs:
Adverse drug reactions
• GIT problems:
– Abdominal cramps, diarrhea, malabsorption,
steatorrhea
– Gall stones
– Vitamin B12 deficiency
• Cardiovascular problems:
– Sinus bradycardia, conduction disturbances
11
GH antagonist
Pegvisomant
• Decreases IGF-1; GH remains high
• Effective in those who do not/stop responding
to octreotide
12
Molecular and Cellular Basis of GH Action
13
Prolactin
Secretion of prolactin is under
the control of DOPAMINE
(prolactin inhibiting hormone)
secreted by hypothalamus
14
Hyperprolactinemia
• Prolactin secreting pituitary adenoma
• Drug induced hyperprolactinemia
– Antipsychotics
– Metochlopramide
Drugs to manage hyperprolactinemia:
• Bromocriptine
• Cabergoline (ka-BER-goe-leen)
16
Oxytocin
Actions meditated through
IP3/DAG
↑ Ca+2
Therapeutic uses
• To induce and augment labor after cervix has
ripened
• To control post-partum hemorrhage
• To improve milk ejection – nasal oxytocin
17
Oxytocin : Adverse reactions
• Cardiac arrhythmia, CNS stimulation, excessive
uterine contractions, and hyponatremia.
Contraindications:
•
•
•
•
Fetal distress
Abnormal fetal presentation
Prematurity
CPD (cephalo-pelvic disproportion)
18
Vasopressin
(arginine-vasopressin)
Vasopressin has:
– Antidiuretic activity
– Vasopressor activity (Vasoconstriction)
• Decreased secretion/response to ADH causes
Diabetes insipidus
• Excessive secretion of ADH causes: SIADH
19
Vasopressin receptors
1. V1 receptors:
– On vascular smooth muscles
– Pressor effect: meditated through IP3/DAG
↑Ca+2
2. V2 receptors
– Renal: On distal and collecting duct cells of nephron
• Antidiuretic effect: mediated through ↑cAMP
– Extrarenal:
• Release of coagulation factors VIIIc and Von
willebrand factor
20
Therapeutic uses of vasopressin/analogs
• Vasopressin (Pitressin)
 Therapeutic uses
• Advanced Cardiac life support
• Bleeding esophageal varices
• Desmopressin
 Long-acting synthetic analog of vasopressin
 Antidiuretic : vasopressor activity = 3000:1
 Therapeutic uses:
• Neurogenic diabetes insipidus
• Von Willebrand disease and hemophillia
• Enuresis
21
SIADH
• Due to excessive secretion of ADH
Drug induced SIADH:
– Carbamazepine, vinca alkaloids, Chlorpropamide
Drugs to manage SIADH
– Demeclocycline
– Conivaptan (vasopressin antagonist)
22
Questions…
23