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Copstead-Kirkhorn: Pathophysiology, 4thEdition

Chapter 40: Disorders of Endocrine Function

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Endocrine disorders occur because of hypersecretion, hyposecretion, or nonresponsivenessby target cells.

Hypersecretion is usually due to secreting tumors, autoimmune disease, or excessive

stimulation of the gland by trophic signals.Hyposecretion may be due to failure or congenitalabsence of glandular tissue, autoimmune destruction, surgical removal of the gland, or lack

of normal trophic signals.

Hyporesponsiveness is clinically similar to hyposecretion and is due to hormone receptor

dysfunction. This phenomenon is called tissue resistance. Endocrine disorders involving the hypothalamic-pituitary system are often classified as

primary or secondary.

Primary endocrine disorders result from intrinsic defects within the hormone-secreting gland. econdary disorders result from abnormal pituitary secretion of trophic signals.

!anifestations of an endocrine disorder are due to abnormal target gland function and are

therefore similar whether the etiologic classification is primary or secondary.

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"yposecretion of #" results in decreased linear growth in children. $n some cases decreased

linear growth occurs despite normal #" levels, and abnormalities of $#%-& generation orresponsiveness are suspected.

#" deficiency may be idiopathic or related to tumors, radiation, or trauma. The diagnosis is

confirmed by a finding of decreased #" levels in the blood and deficient #" release inresponse to hypoglycemia or other stimulants.

Excessive #" production is usually due to pituitary adenoma. Excess #" during childhood

results in increased linear growth and giantism. Excess #" secretion after closure of boneepiphyses results in increased bulk and acromegaly.

%eatures of acromegaly include a protruding 'aw, increased bone density, increased growth of

soft tissues (e.g., nose, ears), and large hands and feet. Excessive #" secretion causespersistent hyperglycemia and increased insulin production in some individuals.

erum $#%-& measurement is used to assess for acromegaly. "igh $#%-& and an elevated #"

level that is not suppressed by administration of oral glucose aids in the diagnosis. Treatment

entails surgical removal or pharmacologic palliation of the pituitary tumor.

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Thyroid hormone (T*, T+) is produced in follicular cells of the thyroid gland. The synthesisand secretion of thyroid hormone are stimulated by T" from the pituitary gland. Thyroid

hormone is an important stimulator of growth and cellular metabolism.

"ypothyroidism may be primary (due to congenital agenesis, autoimmune destruction,irradiation, trauma, surgical removal of the gland, or iodine deficiency) or secondary to

pituitary hyposecretion of T".

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T" level is helpful in differentiating between primary (high T") and secondary (low T")

causes of hypothyroidism. 5ow serum T*and T+levels confirm the diagnosis of

hypothyroidism. !anifestations of hypothyroidism are attributable to a generali6ed decrease in metabolism.

7ntreated congenital hypothyroidism results in profound mental and physical retardation

(cretinism). !anifestations of hypothyroidism include nonpitting edema (myxedema), slowed mentation,

weight gain, dry skin, constipation, decreased heart rate, decreased pulse pressure, lethargy,

and loss of the outer third of the eyebrow. evere hypothyroidism may lead to myxedemacoma, characteri6ed by bradycardia, hypothermia, hypotension, and decreased level of

consciousness. Treatment centers on hormone replacement therapy.

"yperthyroidism may be primary (#raves disease, autoimmune, tumor related,

inflammatory) or secondary to pituitary hypersecretion of T". The blood level of T" ishelpful in differentiating primary (low T") from secondary (high T") hyperthyroidism.

"igh levels of T*and T+confirm the diagnosis of hyperthyroidism.

The manifestations of hyperthyroidism result from a generali6ed increase in metabolism.

"yperactivity, irritability, insomnia, weight loss, increased appetite, heat intolerance,diarrhea, and palpitations are common. !ost individuals have a detectably enlarged thyroid

gland. Exophthalmos is immune-mediated and occurs with #raves disease. Thyroid storm may be precipitated by stress or manipulation of the gland. $t is characteri6ed

by tachycardia, hypertension, high temperature, and cardiac dysrhythmias. Treatment

includes 8-blockers to control cardiovascular symptoms, antithyroid drugs to reduce thyroidproduction, radioactive iodine to ablate the gland, and surgical removal of tumors.

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The adrenal cortex produces three classes of steroid hormones9 (&) glucocorticoids, ()mineralocorticoids, and (*) sex steroids. #lucocorticoid synthesis is regulated by the pituitary

secretion of :T". !ineralocorticoid synthesis is regulated by the renin-angiotensin system.

The glucocorticoid cortisol provides the primary negative-feedback mechanism to inhibit:T" release.

:drenocortical insufficiency may be primary (:ddison disease), in which case it is

characteri6ed by high :T" levels in the blood and hyperpigmentation of skin related toexcessive pituitary secretion, or it may be secondary, in which case it is characteri6ed by low

:T" levels.

Primary adrenal insufficiency may follow autoimmune destruction of, surgical removal of, or

trauma to the gland. Exogenous administration of steroids suppresses :T", resulting inadrenocortical atrophy. udden withdrawal of exogenous steroids may result in adrenal

insufficiency.

$nherited defects in biosynthetic en6ymes necessary for cortisol production may affect one ormore of the steroid hormone synthesis pathways. ortisol deficiency results in pituitary

release of :T", stimulating the adrenal gland to enlarge (congenital adrenal hyperplasia).

Excess androgens may be synthesi6ed, leading to masculini6ation of females and precociouspuberty in males.

!anifestations of primary adrenocortical insufficiency include weight loss, salt wasting,

volume depletion, low blood pressure, hypoglycemia, and hyperkalemia. tress may lead to

severe symptoms (:ddisonian crisis), including circulatory collapse (hypotension).

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Treatment includes hormone replacement therapy. ;osages are generally increased during

periods of stress (e.g., surgery).

Excess cortisol production due to pituitary hyperstimulation of the adrenal cortex is termedCushing disease. "ypercortisolism of any other cause is termed Cushing syndrome. :T"

excess may be due to pituitary adenoma or exogenous production by nonpituitary tumors.

ushing syndrome is commonly due to administration of exogenous steroids. linical manifestations of ushing disease and ushing syndrome include moon facies,

cervical fat pad, central obesity, thin extremities, weight gain, thin skin, striae, hypertension,

and hyperglycemia. Plasma cortisol levels and the urinary excretion of cortisol metabolitesare increased. urgical removal of :T"-producing tumors or removal of the adrenal gland

is the usual treatment.

Primary hyperaldosteronism (onn syndrome) is usually due to adrenal tumor. :ldosterone

enhances sodium and water reabsorption and potassium excretion from the kidney, leading tohypervolemia, hypertension, and hypokalemia.

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The adrenal medulla releases catecholamines into the bloodstream when stimulated by thesympathetic nervous system. atecholamines increase heart rate, blood pressure, and glucose

release from the liver. : pheochromocytoma is a catecholamine-secreting tumor that is usually located in the

adrenal medulla. Excessive catecholamine release from the tumor causes intermittent or

persistent hypertension, headache, tachycardia, tremor, and irritability. !ost tumors arebenign, and surgical removal relieves the disorder. :drenergic blocking agents may be used

to manage the hypertension until surgical treatment is accomplished.

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PT" is an important regulator of serum calcium levels. 5ow serum levels of ioni6ed calcium

are a potent stimulus for PT" release. PT" increases calcium absorption from the #$ tract in

concert with uate hydration may help prevent the formation of kidney stones.

"ypoparathyroidism may be idiopathic, autoimmune, or secondary to surgical removal of theparathyroid gland. The manifestations result from low serum calcium levels, which increase

neuromuscular excitability. Paresthesias, cramps, spasms, tetany, and sei6ures may result.

Elicitation of hvostek and Trousseau signs indicates neuromuscular hyperexcitability.Treatment entails calcium (and vitamin ;) supplementation rather than PT" replacement.

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:;" secretion is primarily regulated by osmoreceptors in the hypothalamus that respond to

changes in extracellular osmolality. :n increase in osmolality stimulates secretion of :;".?enal distal and collecting tubules respond to :;" by becoming more permeable to water.

$n the presence of :;", water is reabsorbed from the urine filtrate, resulting in a

concentrated urine. entral ;$ is due to lack of production of :;" by the hypothalamus or release by the

posterior pituitary gland. entral ;$ may be idiopathic or related to brain surgery, trauma, or

tumor. 4ephrogenic ;$ is caused by lack of renal collecting tubule responsiveness to :;".

4ephrogenic ;$ may be caused by receptor abnormalities, renal disease, medications, or

electrolyte imbalance.

!ost commonly, ;$ causes polydipsia accompanied by thirst, polyuria, and increased serumsodium and osmolality. $ncreased osmolality may cause cellular shrinkage with neurologic

signs and symptoms. The diagnosis is confirmed when dilute urine is formed during water

deprivation, which is promptly corrected with administration of vasopressin.

;$ is treated with :;" hormone replacement therapy (;;: