Chapter 19

Chapter 19: Introduction to
Hormones and Pituitary Function

By Robert E. Jones
Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
Introduction
Pituitary
Master gland: secretes hormones that regulate other glands
Needed for metabolism & gonadal, thyroidal, & adrenal function
A transponder that translates neural input into a hormonal or

endocrinologic product
Distinguishing features of pituitary function

Feedback loops
Pulsatile secretions
Diurnal rhythms
Environmental or external modification of its performance
Embryology and Anatomy

Three distinct parts of pituitary:
1. Anterior pituitary or adenohypophysis

Largest portion of gland; originates from Rathkes pouch
2. Intermediate lobe or pars intermedialis

Poorly developed in humans; has little functional capacity
3. Posterior pituitary or neurohypophysis

Arises from diencephalon; responsible for storage & release of
oxytocin & vasopressin
Pituitary resides in a pocket of sphenoid & is surrounded by

dura mater.
Embryology and Anatomy (contd)

Relational anatomy of pituitary and hypothalamus
Functional Aspects of the HypothalamicHypophysial Unit

Afferent pathways (inputs) to hypothalamus are
integrated in various specialized nuclei, processed, &
resolved into specific patterned responses.
Characteristics of hypothalamic response patterns
Similar for each specific pituitary hormone
Open-loop negative feedback mechanisms (like thermostat)
Pulsatility
Cyclicity
Functional Aspects of the HypothalamicHypophysial Unit (contd)

Simple feedback loop
Hypophysiotropic or Hypothalamic
Hormones
Peptides & bioactive amines are most common products
of hypothalamus.
Hypothalamic hormones often have multiple actions:
TRH stimulates secretion of both TSH & prolactin.
GnRH stimulates both LH & FSH production.
Somatostatin inhibits GH & TSH release from pituitary.
Vasopressin stimulates water metabolism & ACTH secretion.
Hypophysiotropic hormones are found throughout central

nervous system, gut, pancreas, & other endocrine glands.
Anterior Pituitary Hormones

Larger & more complex than those from hypothalamus
Two types
Tropic: actions are specific for another endocrine gland

GH: affects substrate metabolism & stimulates liver to produce growth
factors
Direct effectors: act directly on peripheral tissue

LH: directs testosterone production from Leydig cells
FSH: ovarian recruitment; folliculogenesis, spermatogenesis
TSH: directs thyroid hormone production from thyroid
ACTH: regulates adrenal steroidogenesis
Pituitary Tumors
According to autopsy studies, up to 20% of people harbor
clinically silent pituitary adenomas.
Findings consistent with pituitary tumors are observed in
1030% of normal individuals undergoing MRI exams.
Pituitary tumors account for 91% of lesions from patients
who have undergone transsphenoidal surgery.
Physiologic enlargement of pituitary can be seen during
puberty & pregnancy.
Growth Hormone
Actions of Growth Hormone
Amphibolic: influences both anabolic & catabolic processes
Allows effective transition from a fed state to a fasting state

without shortage of substrates
Directly antagonizes effect of insulin on glucose metabolism
Provides hepatic gluconeogenesis
Stimulates lipolysis
Enhances protein synthesis in skeletal muscle & other tissues
Stimulates production of insulin-like growth factors
Growth Hormone (contd)

Testing
Based on dynamic physiology of growth hormone axis
Testing for autonomous production of growth hormone relies on

normal suppressibility of growth hormone by oral glucose
loading.
Strategies to stimulate growth hormone

Insulin-induced hypoglycemia (outdated method)
Combination infusions of GHRH & amino acid L-arginine
Infusion of L-arginine coupled with oral L-DOPA

Acromegaly
Results from pathologic or autonomous growth hormone excess;

in most cases, a pituitary tumor
Causes the following:

Gigantism
Bony & soft tissue overgrowth
Progressive enlargement of hands, feet, mandible, & skull
Arthritis, diabetes, hypertension, atherosclerosis, muscle
weakness, sleep apnea; shortened life expectancy

Growth Hormone Deficiency
Occurs in both children & adults

Children: genetic or due to tumors
Adults: result of structural/functional pituitary abnormalities
Results in growth failure in children
Various genetic defects are associated:

Recessive mutation in GHRH gene, failure of GH secretion
Loss of GH gene
GH insensitivity
Structural lesions of pituitary or hypothalamus
Prolactin
Characteristics
Structurally related to GH & placental lactogen
Considered a stress hormone; has vital functions in reproduction
Classified as a direct effector hormone
Regulates via tonic inhibition, not intermittent stimulation
Its secretion is inhibited by dopamine.
Its physiologic effect is lactation.
Excess prolactin usually leads to hypogonadism.
Prolactin (contd)
Prolactinoma
A pituitary tumor that directly secretes prolactin
Most common type of functional pituitary tumor
Clinical presentation depends on patient age/gender, tumor size:

Premenopausal women: menstrual irregularity/amenorrhea,
infertility, galactorrhea
Men/postmenopausal women: headaches or visual complaints
Other Causes of Hyperprolactinemia
Pituitary stalk interruption, dopaminergic antagonist medications,

thyroidal failure, renal failure, polycystic ovary syndrome
Prolactin (contd)
Clinical Evaluation of Hyperprolactinemia
Careful history & physical examination
Obtain TSH & free T4 levels.
If pituitary tumor is suspected, careful assessment of other

anterior pituitary function & evaluation of sellar anatomy w/ MRI
Prolactin (contd)
Management of Prolactinoma
Therapeutic goals
Reduce tumor mass
Restore normal gonadal function & fertility
Prevent osteoporosis
Preserve normal pituitary function
Therapeutic options: simple observation, surgery, radiotherapy,

medical management with dopamine
Idiopathic Galactorrhea: lactation in women with normal

prolactin levels
Hypopituitarism
Failure of either pituitary or hypothalamus results in loss
of anterior pituitary function:
Panhypopituitarism: complete loss of function
Monotropic hormone deficiency: loss of only a single hormone
Associated with low or normal levels of tropic hormone

Both tropic & target hormone levels should be measured
when there is any suspicion of pituitary failure.
If one secondary deficiency is documented, search for
other deficiency states & cause for pituitary failure.
Hypopituitarism (contd)
Etiology of Hypopituitarism
Pituitary, parasellar, metastatic, & hypothalamic tumors
Postpartum ischemic necrosis of pituitary
Infiltrative diseases: hemochromatosis, sarcoidosis, histiocytosis
Fungal infections, tuberculosis, syphilis
Lymphocytic hypophysitis
Severe head trauma, pituitary surgery, radiotherapy
Treatment of Panhypopituitarism
Thyroxine, glucocorticoids, gender-specific sex steroids
Posterior Pituitary Hormones

Posterior pituitary is an extension of forebrain & represents
storage region for oxytocin & vasopressin.
Oxytocin
A cyclic nonapeptide, with a disulfide bridge connecting amino acid

residues 1 & 6
Has a critical role in lactation
Likely plays a major role in labor & parturition
Synthetic oxytocin, Pitocin, is used in obstetrics to induce labor.
Has been shown to have effects on pituitary, renal, cardiac, &

immune functions
Posterior Pituitary Hormones (contd)

Vasopressin
A cyclic nonapeptide, structurally similar to oxytocin, with an

identical disulfide bridge; differs by only 2 amino acids
Major action is to regulate renal free water excretion & water

balance.
A potent pressor agent & affects blood clotting
Hypothalamic osmoreceptors & vascular baroceptors regulate

release of vasopressin from posterior pituitary.
Deficiency can lead to diabetes insipidus, characterized by

excessive urine production (polyuria) & intense thirst
(polydipsia).

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Chapter 19: Introduction to

Hormones and Pituitary Function

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Master gland: secretes hormones that regulate other glands

Needed for metabolism & gonadal, thyroidal, & adrenal function

A transponder that translates neural input into a hormonal or

Distinguishing features of pituitary function

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Embryology and Anatomy

1. Anterior pituitary or adenohypophysis

2. Intermediate lobe or pars intermedialis

3. Posterior pituitary or neurohypophysis

Pituitary resides in a pocket of sphenoid & is surrounded by

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Embryology and Anatomy (contd)

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Functional Aspects of the HypothalamicHypophysial Unit

Similar for each specific pituitary hormone

Open-loop negative feedback mechanisms (like thermostat)

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Functional Aspects of the HypothalamicHypophysial Unit (contd)

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

TRH stimulates secretion of both TSH & prolactin.

GnRH stimulates both LH & FSH production.

Somatostatin inhibits GH & TSH release from pituitary.

Vasopressin stimulates water metabolism & ACTH secretion.

Hypophysiotropic hormones are found throughout central

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Anterior Pituitary Hormones

Tropic: actions are specific for another endocrine gland

Direct effectors: act directly on peripheral tissue

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Amphibolic: influences both anabolic & catabolic processes

Allows effective transition from a fed state to a fasting state

Directly antagonizes effect of insulin on glucose metabolism

Provides hepatic gluconeogenesis

Enhances protein synthesis in skeletal muscle & other tissues

Stimulates production of insulin-like growth factors

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Growth Hormone (contd)

Based on dynamic physiology of growth hormone axis

Testing for autonomous production of growth hormone relies on

Strategies to stimulate growth hormone

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Growth Hormone (contd)

Results from pathologic or autonomous growth hormone excess;

Causes the following:

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Growth Hormone (contd)

Occurs in both children & adults

Results in growth failure in children

Various genetic defects are associated:

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

Structurally related to GH & placental lactogen

Considered a stress hormone; has vital functions in reproduction

Classified as a direct effector hormone

Regulates via tonic inhibition, not intermittent stimulation

Its secretion is inhibited by dopamine.

Its physiologic effect is lactation.

Excess prolactin usually leads to hypogonadism.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

A pituitary tumor that directly secretes prolactin

Most common type of functional pituitary tumor