Drug therapy for pituitary and hypothalamic dysfunction

Anterior Pituitary Hormones

• Anterior pituitary produces seven hormones.

  • GH and prolactin act directly on target tissues.

  • Other five act indirectly by stimulating target tissues to produce other hormones.

7 Anterior Pituitary Hormones

• Corticotropin (ACTH)

• GH (somatotropin)

• Thyrotropin (TSH)

• Follicle-stimulating hormone (FSH)

• Luteinizing hormone (LH)

• Prolactin

• Melanocyte-stimulating hormone (MSH)

Posterior Pituitary Hormones

• Antidiuretic hormone

  • Makes renal tubules more permeable to water

  • Reabsorb more water- less urine

  • Secreted when blood more concentrated or when blood volume is low

• Oxytocin

  • Functions in childbirth to initiate contractions

  • Causes milk to “let down”

Hormones

chemical messengers with specific regulatory effects on cells

Hypothalamic Hormones

• to stimulate or inhibit secretion of specific hormones

• to regulate anterior pituitary hormones

  • Anterior pituitary synthesizes/secretes hormones.

  • Posterior pituitary mainly nerve fibers.

types of Hypothalamic Hormones

• Corticotropin-releasing hormone (CRH)

• Growth hormone–releasing hormone (GHRH)

• Somatostatin- releasing inhibitor factor

• Thyrotropin-releasing hormone (TRH)

• Gonadotropin-releasing hormone (GnRH)

• Prolactin-releasing factor; prolactin-inhibiting factor (PIF)

Select Pituitary Disease processes

• Acromegaly

  • excessive secretion of GH

• Growth hormone deficiency

• Diabetes Insipidus

  • dysfunction in the posterior pituitary lobe secretion of ADH

• Precocious puberty

  • early maturation of the hypothalamic–pituitary–gonadal axis

Growth Hormone Treatment for Acromegaly

• Surgery removal of pituitary or adenoma

• Radiation

• Drugs

Growth Hormone Treatment Pegvisomant (Somavert)

• GH receptor antagonist

• Monitor GH and IGF-1 levels

Growth Hormone Treatment for Growth Hormone Deficiency

Administration of Growth Hormone Somatropin

Growth Hormone Treatment Adverse effects GH administration

• Hyperglycemia (diabetogenic)

• Antibodies to GH

• Carpal tunnel syndrome w/ Serostim

• Fatal in Prader-Willi syndrome (PWS) patients r/t obesity, OSA

• Glucocorticoids oppose GH effects

Somatropin Pharmacodynamics/ Action

• Stimulates skeletal, linear, muscle and organ growth

• Stimulation of cartilage growth at epiphyseal plate

Somatropin Uses/ Indications

• Deficiency of endogenous Growth Hormone

• Growth failure associated with Prader-Willi syndrome, Noonan’s syndrome

Somatropin Contraindications

• Closed epiphyses

• Severe non-proliferative diabetes retinopathy

• Acute critical illness

• Underlying intracranial lesions

Somatropin Adverse Effects

• Mild edema, headache, localized muscle pain, weakness, hyperglycemia

• Certain patients at risk for increased ICP

Diabetes Insipidus versus SIADH

• Secretion of Antidiuretic Hormone

• Hyposecretion

• SIADH= Hypersecretion

Diabetes Insipidus

• Three forms: neurogenic, nephrongenic, psychogenic

• Patho: Dec ADH>inability to concentrate urine>polyuria>inc plasma osmolality> thirst>polydipsia

• Sx: gross polyuria, nocturia, thirst, polydipsia, low urine SG, low urine osmolarity, high serum osmolarity

• Tx: DDAVP (desmopressin) ie Vasopressin

  • IV orr intranasally

  • Adverse Effects: water intoxication, CV effects

Desmopressin acetate (DDAVP) Pharmacodynamics/Action

• Increases cyclic adenophosine monophosphate (cAMP)

• Increase water permeability

• Decrease urine volume

Desmopressin acetate (DDAVP) Uses/Indications

Neurogenic diabetes insipidus

Desmopressin acetate (DDAVP) Adverse Effects

• Erythema, swelling of injection site

• Drowsiness, headache, lethargy, shortness of breath

• Gastric irritation, abdominal cramping

• Black Box: hyponatremia leading to seizures

Hypersecretion: Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• Incidence increases in presence of malignant tumors

  • lung cancers, leukemia, lymphomas, Hodgkin’s disease

• Secondary to surgical procedures

• Patho:

  • inc> ADH >inc renal water retention >water intoxication >hyponatremia, hypo-osmolarity >suppression of renin / aldosterone

Precocious Puberty

Development of secondary sexual characteristics at young age (8-9)

Leuprolide acetate (Lupron) Pharmacodynamics/Action

• LH- releasing hormone agonist

• Suppresses production of ovarian and testicular steroids

Leuprolide acetate (Lupron) Uses/Indications

• Central precocious puberty

• Administer until age 11 in girls and age 12 in boys

Leuprolide acetate (Lupron) Adverse Effects

• Pain at injection site

• May affect antidiabetic drugs