SECTION VI1I THE ENDCRINE SYSTEM Acromegaly A 48-year-old man complaining of impotence sought medical attention.Over the years,he experienced increasing difficulty with maintaining and,more recently, achieving an erection Further that heas als frequently.The patient's shoe size had increased from a 9-C to 11-EEE over the past 5 years,and his dental plate had to be altered three times in 6 years.Recently, friends have remarked on changes in his appearance.The patientals adnitted to tingling of his fingers and joint pains. On physical examination,he had coarse facial features with a bulbous nose and a beetlebroed look.The tonge as enlarged and teeth erewide spaced.Testing of visual fields showed a loss of both lateral (temporal)fields.The hands and feet were enlarged with spadelike fingers.The liver was enlarged.Laboratory studies showed a fasting plasma glucose level of1 mg/dl.Fasting gowth hormone (GH)was 40 ng/l.and it did not decrease after administration of an oral glucose load.On agnetic resonance imging a mss protruded upard from the sel 1.Why did the physicia measure the 2.The concentration of what other peptide is certainly elevated in this patient's plasma,and what is the source of this peptide? 3.hat has caused the changes in the patient's facial features,tongue,hands feet,and liver? 4.What has caused the neurologic and joint symptoas? 5.hat is the normal effeet of glucose administration on the plasm leve and why did it not change in this patient? 6.Why is the fasting plasma glucose level elevated,and what changes in the plasma insulin level ould you expect to find?
SECTION VIII THE ENDOCRINE SYSTEM Acromegaly A 48-year-old man complaining of impotence sought medical attention. Over the years, he experienced increasing difficulty with maintaining and, more recently, achieving an erection. Further questioning revealed that he was also shaving less frequently. The patient's shoe size had increased from a 9-C to 11-EEE over the past 5 years, and his dental plate had to be altered three times in 6 years. Recently, friends have remarked on changes in his appearance. The patient also admitted to tingling of his fingers and joint pains. On physical examination, he had coarse facial features with a bulbous nose and a beetle-browed look. The tongue was enlarged and teeth were wide spaced. Testing of visual fields showed a loss of both lateral (temporal) fields. The hands and feet were enlarged with spadelike fingers. The liver was enlarged. Laboratory studies showed a fasting plasma glucose level of 150 mg/dl. Fasting growth hormone (GH) was 40 ng/ml, and it did not decrease after administration of an oral glucose load. On magnetic resonance imaging, a large pituitary mass protruded upward from the sella turcica. l. Why did the physician measure the GH? 2. The concentration of what other peptide is certainly elevated in this patient's plasma, and what is the source of this peptide? 3. What has caused the changes in the patient's facial features, tongue, hands, feet, and liver? 4. What has caused the neurologic and joint symptoms? 5. What is the normal effect of glucose administration on the plasma GH level, and why did it not change in this patient? 6. Why is the fasting plasma glucose level elevated, and what changes in the plasma insulin level would you expect to find?
7.What is the most likely cause of the patient's impotence,and what hormonal abnornalities explain it? 8.What effects might this pituitary tuor mass have on other anterior and posterior pituitary functions,and by what mechanisms? 9.What has caused the impairment of visual fields? this patient? 11.If the tunor mass were removed surgically,what physical changes would you 12.If the normal anterior pituitary gland were removed surgically along with the tor,hat would be the consequences for the patient?How ould you correc the situation? 13.If the patient wished to restore gonadal function,what hormonal replacement ANSWER 1.The features of this patient and the history of the changes in his appearance and shoe size strongly suggest an excess of growth hormone ()This is usually 2.GH stimulates the synthesis of a peptide mediator called somatonedin or insulin-like growth factor-1 (IGF-1).This is produced in the liver,but also in many other tissues that contain G target cells.Plasma sonatomedin levelsill be high in patients with Gll-secreting tumors. 3.cl via somatomedin (and its plasma membrane receptor)stimlates proliferation of chondrocytes(cartilage cells).osteblasts and tissue cells.This causes excess linear growth in children and giantism results.In adults Thiscauses widening of digits thickened vertebrae,ribs,skull bones,and ndble with resultant alteration in facial features and position of the teeth
7. What is the most likely cause of the patient's impotence, and what hormonal abnormalities explain it? 8. What effects might this pituitary tumor mass have on other anterior and posterior pituitary functions, and by what mechanisms? 9. What has caused the impairment of visual fields? 10. What molecule made in the hypothalamus might be therapeutically useful in this patient? 11. If the tumor mass were removed surgically, what physical changes would you expect to see in the patient? 12. If the normal anterior pituitary gland were removed surgically along with the tumor, what would be the consequences for the patient? How would you correct the situation? 13. If the patient wished to restore gonadal function, what hormonal replacement therapy would be needed? ANSWER 1. The features of this patient and the history of the changes in his appearance and shoe size strongly suggest an excess of growth hormone (GH). This is usually caused by a tumor of pituitary somatotrophs, and this disease is called acromegaly. 2. GH stimulates the synthesis of a peptide mediator called somatomedin or insulin-like growth factor-l (IGF-l). This is produced in the liver, but also in many other tissues that contain GH target cells. Plasma somatomedin levels will be high in patients with GH-secreting tumors. 3. GH via somatomedin (and its plasma membrane receptor) stimulates proliferation of chondrocytes (cartilage cells), osteoblasts and connective tissue cells. This causes excess linear growth in children and giantism results. In adults whose bone growth centers are already closed, appositional bone growth is stimulated. This causes widening of digits, thickened vertebrae, ribs, skull bones, and mandible, with resultant alteration in facial features and position of the teeth
Proliferation of muscle cells increases lean body mass.as exemplified by enlargement of the muscular tongue.The visceral parenchymal cell growth is stimlated,which causes enlargenent of organs such as the liver and kidneys. causes osteorthritis.Also.nerves can be compressed by the growing bone at points where the nerves pass through grooves in the bone. 5.Glucose normally suppresses GH release.When GH is created autonomously by a somatotrophic tumor,there is usually no response to glucose administration. 6.Gll is an insulin antagonistic hormone that inhibits insulin-stimlated glucose uptake by muscle cells as well as the insulin effects on the liver.Thus the fasting plasma glucose level rises.In response to the high glucose levels, plasma In addition, growth of pancreatic islet beta cells. 7.There are three possible causes of the patient's impotence,which reflect First,the pituitary to y have destroved gonadotropin-producing cells by exerting pressure on them.The resultant loss of luteinizing hormone (and follicle-stimlating hormone (FSH)decreases the testosterone by the the testes.Second,the have compressed the hypophyseal stalk and cut off transport of gomadotropin-releasinghoroe(GnRH)dow the pituitary portal veins from the Lll and FSll secretions.Third,such tumors may secrete prolactin,a hormone structurally related toH High prolactin levels inhibit GnRH release fron the hypothalamus and thus would decrease L and FSH secretion. 8.Similarly.ACTH and/or TSH secretion might be impaired by the same two mechanisns described above for and FSH.This would in turn cause cortisol and thyroxine deficiencies. 9.The optic nerves cross just above the pituitary gland on their route to the occipital cortex.Pressure from a tumor on this crossing point causes a characteristic defect in the visual ficlds
Proliferation of muscle cells increases lean body mass, as exemplified by enlargement of the muscular tongue. The visceral parenchymal cell growth is stimulated, which causes enlargement of organs such as the liver and kidneys. 4. Stimulation of the growth of connective tissue and synovium and cartilage causes osteoarthritis. Also, nerves can be compressed by the growing bone at points where the nerves pass through grooves in the bone. 5. Glucose normally suppresses GH release. When GH is created autonomously by a somatotrophic tumor, there is usually no response to glucose administration. 6. GH is an insulin antagonistic hormone that inhibits insulin-stimulated glucose uptake by muscle cells as well as the insulin effects on the liver. Thus the fasting plasma glucose level rises. In response to the high glucose levels, plasma insulin levels will also be elevated. In addition, GH directly stimulates growth of pancreatic islet beta cells. 7. There are three possible causes of the patient's impotence, which reflect a low plasma testosterone level. First, the pituitary tumor may have destroyed gonadotropin-producing cells by exerting pressure on them. The resultant loss of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreases the secretion of testosterone by the Leydig cells of the testes. Second, the tumor may have compressed the hypophyseal stalk and cut off transport of gonadotropin-releasing hormone (GnRH) down the pituitary portal veins from the median eminence to the anterior pituitary gonadotrophs; this process would decrease LH and FSH secretions. Third, such tumors may secrete prolactin, a hormone structurally related to GH. High prolactin levels inhibit GnRH release from the hypothalamus and thus would decrease LH and FSH secretion. 8. Similarly, ACTH and/or TSH secretion might be impaired by the same two mechanisms described above for LH and FSH. This would in turn cause cortisol and thyroxine deficiencies. 9. The optic nerves cross just above the pituitary gland on their route to the occipital cortex. Pressure from a tumor on this crossing point causes a characteristic defect in the visual fields
10.Growth hormone secretion is normally under dual regulation from the hypothalams.It is stmlated by Gn and inhibited by somatostatin.The latter, in a long-acting analog form,can reduce the elevated CH levels in patients with acromegaly because their tumors contain plasna menbrane receptors for the 11.The swelling of soft tissues would resolve promptly.However,the bone changes caused by excess G uld resolve veryslow(and perhaps not at all)because of the relatively slow rate of normal bone turnover 12.Inadvertent removal of the anterior pituitary gland would cause permanent deficiencies of TSH.ACTH,FSH,LH,MSH,and prolactin.Replacement therapy with its secretion would be maintained by the reninangiotensin systen Lack ofaction might cause pale skin and the inability to geta tan upon exposure toultraviolet light.There are no knom of prolactin deficiency in mles.Reoval of the posterior pituitary gland would not ordinarily cause deficiency as o as the suprahypophyseal portion of the axons from the hypothalamic neurons tha svnthesize ADH remained intact. 13.If the patient still wished to father a child,and his gonadotrophic cells of GnRH would be effective.If his gomadotrophic cells were destroyed,he would require regular administration of LH and FS If the patient only wished to restore sexual potency.therapy
10. Growth hormone secretion is normally under dual regulation from the hypothalamus. It is stimulated by GnRH and inhibited by somatostatin. The latter, in a long-acting analog form, can reduce the elevated GH levels in patients with acromegaly because their tumors contain plasma membrane receptors for the hypothalamic inhibitory peptide. 11. The swelling of soft tissues would resolve promptly. However, the bone changes caused by excess GH would resolve very slowly (and perhaps not at all) because of the relatively slow rate of normal bone turnover. 12. Inadvertent removal of the anterior pituitary gland would cause permanent deficiencies of TSH, ACTH, FSH, LH, MSH, and prolactin. Replacement therapy with thyroxine and cortisol would be necessary. Aldosterone would not be needed because its secretion would be maintained by the reninangiotensin system. Lack of MSH action might cause pale skin and the inability to get a tan upon exposure to ultraviolet light. There are no known consequences of prolactin deficiency in males. Removal of the posterior pituitary gland would not ordinarily cause ADH deficiency as long as the suprahypophyseal portion of the axons from the hypothalamic neurons that synthesize ADH remained intact. 13.If the patient still wished to father a child, and his gonadotrophic cells were not significantly damaged, then treatment with daily pulsatile administration of GnRH would be effective. If his gonadotrophic cells were destroyed, he would require regular administration of LH and FSH. If the patient only wished to restore sexual potency, he would require only testosterone replacement therapy