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Terminology (Table 8-2) Several terms related to the experience of altered sensations and pain are Enkephalin often used interchangeably, but each has speci c Substance P Receptors meaning Hyperesthesia is a general term for heightened cutaneous sensitivity The term hyperSPINAL INTERNEURON algesia refers to an increased sensitivity and a lowered threshold to painful stimuli In ammation and burns of the skin are common causes of hyRECEPTOR NEURON peralgesia The term hypalgesia, or hypoalgesia, refers to the opposite state ie, a decreased sensitivity and a raised threshold to painful stimuli A demonstrable reduction in pain perception (ie, an elevated threshold, associated with an increased reFigure 8-4 Mechanism of action of enkephalin (endorphin) and morphine in the transmission action to the stimulus once it is perceived, is someof pain impulses from the periphery to the CNS Spinal interneurons containing enkephalin times referred to as hyperpathia (subtly different synapse with the terminals of pain bers and inhibit the release of the presumptive transmitter, from hyperalgesia) In this circumstance there is an substance P As a result, the receptor neuron in the dorsal horn receives less excitatory (pain) impulses and transmits fewer pain impulses to the brain Morphine binds to unoccupied en- excessive reaction to all stimuli, even those (such kephalin receptors, mimicking the pain-suppressing effects of the endogenous opiate enkeph- as light touch) that normally do not evoke pain, a symptom termed allodynia The elicited allodynic alin pain may have unusual features, outlasting the stimulus and being diffuse, modi able by fatigue and emotion, and often being mixed with other sensations The mechSoon after the discovery of speci c opiate receptors in the anism of these abnormalities is not clear, but both hyperpathia and central nervous system (CNS), several naturally occurring peptides, allodynia are common features of neuropathic or neurogenic pain, which proved to have a potent analgesic effect and to bind specifie, pain generated by peripheral neuropathy These features are ically to opiate receptors, were identi ed (see Hughes et al for a exempli ed by causalgia, a special type of burning pain that results summary of these substances) These endogenous, morphine-like from interruption of a peripheral nerve (see page 121) compounds are generically referred to as endorphins, meaning the morphines within The most widely studied are -endorphin, a Table 8-2 peptide sequence of the pituitary hormone -lipotropin, and two Nomenclature in the description of pain and abnormal other peptides, enkephalin and dynorphin They are found in greatsensation (see also Table 9-1) est concentration in relation to opiate receptors in the midbrain At the level of the spinal cord, exclusively enkephalin receptors are Dysesthesia: Any abnormal sensation described as unpleasant by found A theoretical construct of the roles of enkephalin (and subthe patient stance P) at the point of entry of pain bers into the spinal cord is Hyperalgesia: Exaggerated pain response from a normally illustrated in Fig 8-4 A subgroup of dorsal horn interneurons also painful stimulus; usually includes aspects of summation with contains enkephalin; they are in contact with spinothalamic tract repeated stimulus of constant intensity and aftersensation neurons Hyperpathia: Abnormally painful and exaggerated reaction to a Thus it would appear that the central effects of a painful conpainful stimulus; related to hyperalgesia dition are determined by many ascending and descending systems Hyperesthesia (hypesthesia): Exaggerated perception of touch utilizing a variety of transmitters A de ciency in a particular restimulus gion would explain persistent or excessive pain Some aspects of Allodynia: Abnormal perception of pain from a normally opiate addiction and also the discomfort that follows withdrawal nonpainful mechanical or thermal stimulus; usually has of the drug might conceivably be accounted for in this way Indeed, elements of delay in perception and of aftersensation it is known that some of these peptides not only relieve pain but Hypoalgesia (hypalgesia): Decreased sensitivity and raised suppress withdrawal symptoms threshold to painful stimuli Finally it should be noted that the descending pain-control Anesthesia: Reduced perception of all sensation, mainly touch systems contain noradrenergic and serotonergic as well as opiate Analgesia: Reduced perception of pain stimulus links A descending norepinephrine-containing pathway, as menParesthesia: Mainly spontaneous abnormal sensation that is not tioned, has been traced from the dorsolateral pons to the spinal unpleasant; usually described as pins and needles cord, and its activation blocks spinal nociceptive neurons The rosCausalgia: Buring pain in the distribution of one or more troventral medulla contains a large number of serotonergic neurons peripheral nerves Descending bers from the latter site inhibit dorsal horn cells con-.

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Males with prolactin-secreting tumors rarely have galactorrhea and usually present with a larger tumor and complaints such as headache, impotence, and visual abnormalities In normal persons, the serum prolactin rises markedly in response to the administration of chlorpromazine or thyrotropin-releasing hormone (TRH); patients with a prolactin-secreting tumor fail to show such a response With large tumors that compress normal pituitary tissue, thyroid and adrenal function will also be impaired It should be noted that large, nonfunctioning pituitary adenomas also cause modest hyperprolactinemia by distorting the pituitary stalk and reducing dopamine delivery to prolactin-producing cells Acromegaly This disorder consists of acral growth and prognathism in combination with visceromegaly, headache, and several endocrine disorders (hypermetabolism, diabetes mellitus) The highly characteristic facial and bodily appearance, well known to all physicians, is due to an overproduction of growth hormone (GH) after puberty; prior to puberty, an oversecretion of GH leads to gigantism In a small number of acromegalic patients, there is an excess secretion of both GH and prolactin, derived apparently from two distinct populations of tumor cells The diagnosis of this disorder, which is often long delayed, is made on the basis of the characteristic clinical changes, the nding of elevated serum GH values (010 ng/mL), and the failure of the serum GH concentration to rise in response to the administration of glucose or TRH The new growth hormone receptor antagonist pegvisomant has been introduced to reduce many of the manifestations of acromegaly (see the editorial by Ho) Cushing Disease Described in 1932 by Cushing, this condition is only about one-fourth as frequent as acromegaly A distinction is made between Cushing disease and Cushing syndrome, as indicated in Chap 27 The former term is reserved for cases that are caused by the excessive secretion of pituitary ACTH, which in turn causes adrenal hyperplasia; the usual basis is a pituitary adenoma Cushing syndrome refers to the effects of cortisol excess from any one of several sources excessive administration of steroids (the most common cause), adenoma of the adrenal cortex, ACTH-producing bronchial carcinoma, and very rarely other carcinomas that produce ACTH The clinical effects are the same in all of these disorders and include truncal obesity, hypertension, proximal muscle weakness, amenorrhea, hirsutism, abdominal striae, glycosuria, osteoporosis, and in some cases a characteristic mental disorder (page 978) Although Cushing originally referred to the disease as pituitary basophilism and attributed it to a basophil adenoma, the pathologic change may consist only of hyperplasia of basophilic cells or of a nonbasophilic microadenoma Seldom is the sella turcica enlarged: visual symptoms or signs due to involvement of the optic chiasm or nerves and extension to the cavernous sinus are therefore rare The diagnosis of Cushing disease is made by demonstrating increased concentration of plasma and urinary cortisol; these levels are not suppressed by the administration of relatively small doses of dexamethasone (05 mg four times daily), but they are suppressed by high doses (8 mg daily) A low level of ACTH and a high level of cortisol in the blood, increased free cortisol in the urine, and nonsuppression of adrenal function after administration of high doses of dexamethasone are evidence of an adrenal source of the Cushing syndrome usually a tumor and less often a micronodular hyperplasia of the adrenal gland Diagnosis of Pituitary Adenoma This is virtually certain when a chiasmal syndrome is combined with an endocrine syndrome of either hypopituitary or hyperpituitary type Laboratory data that are.