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Chapter 59

Drugs Related to Hypothalamic and Pituitary Function

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Hypothalamus and Pituitary Related anatomically and functionally Regulate all bodily processes 15 hormones and regulatory factors

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Overview of Hypothalamic and Pituitary Endocrinology

Hormones of the anterior pituitary Growth hormone (GH) Corticotropin Thyrotropin Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin

Hormones of the posterior pituitary Oxytocin Antidiuretic hormone

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Fig. 59–2. Negative feedback regulation of the hypothalamus and anterior pituitary.

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Growth Hormone Biologic effects

Promotes growth Promotes protein synthesis Carbohydrate metabolism

Physiology Regulation of release Biologic effects Promotion of protein synthesis Effect on carbohydrate metabolism

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Growth Hormone Pathophysiology

Deficiency• Pediatric: short stature• Adult: reduced muscle mass

Excess• Pediatric: gigantism• Adult: acromegaly• Treatment overview

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Growth Hormone Therapeutic uses

Pediatric growth hormone deficiency Pediatric non–growth-hormone-deficient short

stature Pediatric short stature associated with Prader-Willi

syndrome (PWS) Adult growth hormone deficiency

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Growth Hormone Adverse effects and interactions

Hyperglycemia Neutralizing antibodies Carpal tunnel syndrome Fatality in patients with Prader-Willi syndrome Interaction with glucocorticoids

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Fig. 59–3. Regulation of growth hormone release.

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Acromegaly Growth hormone excess Pituitary adenoma Clinical manifestations Treatment

Surgery Radiation Somatostatin

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Somatropin (Humatrope) 10 preparations available Identical to human GH IM or subQ administration

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Insulin-Like Growth Factor-1 Mecasermin (Increlex)

Synthetic of natural insulin-like growth factor-1 (IGF-1)

Used in GH deficiency that is not responsive to GH treatment

Adverse effects• Hypoglycemia, hypertrophy of tonsils, intracranial

hypertension, vomiting, arthralgia, otitis media, elevation of serum aminotransferases and lipids, overgrowth of fat, facial bones, and kidneys

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Prolactin Produced by the anterior pituitary Stimulation of milk production after parturition Effects of hypersecretion (excessive

secretion) Females: amenorrhea, galactorrhea, infertility,

possible delay of puberty in girls Males: reduced libido and potency, galactorrhea,

possible delay of puberty in boys

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Prolactin Treatment for hypersecretion

Suppression of prolactin release • Cabergoline (Dostinex)• Bromocriptine (Parlodel)

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Other Anterior Pituitary Hormones

Thyrotropin Thyroid-stimulating hormone (TSH)

Corticotropin Adrenocorticotropic hormone (ACTH)

Gonadotropins Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)

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Antidiuretic Hormone ADH: also known as vasopressin

Promotes renal conservation of water Works on the collecting ducts of the kidney to

increase their permeability to water Produced in the hypothalamus

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Antidiuretic Hormone Therapeutic uses

Diabetes insipidus Cardiac arrest Postoperative abdominal distention Preparation for abdominal radiography Desmopressin for nocturnal enuresis (bedwetting) Hemophilia A Von Willebrand’s disease

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ADH Use with Diabetes Insipidus Diabetes insipidus

Deficiency of ADH• Polydipsia (excessive thirst)• Excretion of large volumes of dilute urine

Treatment: ADH replacement• Desmopressin (agent of choice)• Vasopressin

Adverse effects• Water intoxication• Excessive vasoconstriction

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Antidiuretic Hormone Antagonist Conivaptan (Vaprisol)

ADH antagonist Used in short-term IV therapy for hyponatremia in

hospitalized patients with euvolemia and/or hypervolemia

Monitor serum sodium closely owing to risk of hypernatremia

Tolvaptan Oral vasopressin antagonist Used to reduce hyponatremia in euvolemic or

hypervolemic patients

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Oxytocin Produced by hypothalamus Stored in posterior pituitary Two physiologic roles

Promotion of uterine contractions during labor Stimulation of milk ejection during breast-feeding

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Drugs for Acromegaly Somatostatin analogs

Octreotide and lanreotide GH receptor antagonist

Pegvisomant (Somavert)

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Drugs Related to Hypothalamic Function

Seven regulatory factors in the hypothalamus Have only three clinical applications GnRH and its synthetic analogs: to treat prostate

cancer and endometriosis and to induce ovulation CRH: diagnose adrenal disorders Somatostatin: acromegaly

Gonadotropin-releasing hormones Leuprolide Goserelin Nafarelin Gonadorelin