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Hypothalamic & Pituitary Hormones
Kaukab Azim, MBBS, PhD
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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
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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
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Growth hormone releasing hormone (GHRH)
GHRH analog: Sermorelin Used rarely as a diagnostic test for GH responsiveness
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IGF-1 as Peripheral effector
Growth Hormone Secretion of GH is stimulated by GHRH and inhibited by GIH (somatostatin) GH preparations for therapeutic use: Somatropin: Recombinant human GH Somatrem: Recombinant human GH IGF-1 as Peripheral effector
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Molecular and Cellular Basis of GH Action
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Growth hormone (Somatotropin)
Most of the actions of GH are mediated by IGF-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. Gluconeogenesis
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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
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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
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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
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Somatostatin analogs: Therapeutic uses
Acromegaly To prevent gigantism Carcinoid syndrome VIPoma, gastrinoma Ruptured esophageal varices
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Somatostatin analogs: Adverse drug reactions
GIT problems: abdominal cramps, diarrhea, malabsorption, steatorrhea Gall stones Vitamin B12 deficiency Cardiovascular problems: Sinus bradycardia, conduction disturbances
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GH antagonist Pegvisomant Decreases IGF-1; GH remains high
Also effective in those who do not/stop responding to octreotide
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Prolactin Secretion of prolactin is under the control of dopamine (prolactin inhibiting hormone) secreted by hypothalamus
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Prolactin
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Hyperprolactinemia Prolactin secreting pituitary adenoma
Drug induced hyperprolactinemia Antipsychotics Metochlopramide Drugs to manage hyperprolactinemia: Bromocriptine Cabergoline (ka-BER-goe-leen)
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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
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Oxytocin : Adverse reactions
Cardiac arrhythmia, CNS stimulation, excessive uterine contractions, and hyponatremia. Contraindications: Fetal distress Abnormal fetal presentation Prematurity CPD (cephalo-pelvic disproportion)
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Vasopressin (arginine-vasopressin)
Vasopressin has: Antidiuretic activity Vasopressor activity (Vasoconstriction) Decreased secretion/response to ADH causes Diabetes insipidus Excessive secretion of ADH causes: SIADH
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Vasopressin receptors
V1 receptors: On vascular smooth muscles Pressor effect: meditated through IP3/DAG ↑Ca+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
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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
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SIADH Due to excessive secretion of ADH Drug induced SIADH:
Carbamazepine, vinca alkaloids, Chlorpropamide Drugs to manage SIADH Demeclocycline Conivaptan (vasopressin antagonist)
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