Who Should Treat Tuberculosis?
closing of tuberculosis sanatoriums during recent years has placed the treatment of tuberculosis in many communities into the hands of physicians inexperienced in dealing with the disease. When this shift was originally advocated, no major problems were anticipated in view of the effective antituberculous medications available. However, many physicians, including some board-certified internists, failed to understand the basic principles involved in treating the disease. A recent study in this regard showed that more than 60% of a group of 130 tuberculosis patients were inappropriately treated by standard textbook criteria.1 The possible increasing incidence of the disease in some urban areas may relate to this inept manageThe
ment.2
recently observed high incidence of drug resistance and particularly multiple drug resistances now being seen in ghetto populations may also reflect improper treatment.3 This turn of events should probably not be surprising because most medical schools offer little instruction in this condition." Some pulmonary disease fellowships provide minimal or no experience with The
it.
this problem is to provide increased to medical practitioners. tuberculosis information regarding be the medical school level as well This should done initially at as in the medically oriented residency programs. In addition, this disease should not be ignored in the plethora of postgrad¬ uate courses offered to physicians. However, most physicians not working in a specialized setting such as the inner city are unlikely to see more than a few cases of the disease in a lifetime of practice. Since its management may prove complex, physi¬ cians, on seeing a case of suspected tuberculosis, should consider seeking consultation from an infectious or pulmonary disease physician skilled in its diagnosis and management. Those patients proving to have uncomplicated disease can then be followed up by the generalist after an initial treatment plan is developed. On the other hand, those likely to have drugresistant tuberculosis or those who have tuberculosis caused by organisms other than Mycobacterium tuberculosis should be treated under the direct supervision of a pulmonary or infec¬ tious disease specialist who is well versed in tuberculosis. The second-line drugs used in such cases are often poorly tolerated, and considerable skill is required in prescribing them in such a fashion that they are acceptable to the patient. Furthermore, some serious drug reactions may occur, again requiring expert management. Arizona has basically adopted such an approach, with tuberculosis patients referred to specific general hospitals where physicians experienced in the disease make the initial evaluation of the patient's condition.' The decision to return the care of tuberculosis to the mainstream of medicine was indeed a correct one. However, its One obvious
answer to
be casual and must be made in its management.
treatment cannot
knowledgeable
by physicians
Col Richard B. Byrd, MC, USAF US Air Force Medical Center Scott Scott Air Force Base, Ill Lee B. Reichman, MD, MPH New Jersey Medical School Newark
The views expressed herein are those of the authors and do not necessarily reflect the views of the US Air Force or the Department of Defense. 1.
Byrd RB,
Horn BR, Solomon DA,
et
al: Treatment of tuberculosis
nonpulmonary physician. Ann Intern Med 86:799-802, 1977. 2. Riley RL: Rising tuberculosis rate in Baltimore city. Am
by the
Rev Respir Dis 113:577-578, 1976. 3. Schiffman PL, Ashkar B, Bishop M, et al: Drug-resistant tuberculosis in a large southern California hospital. Am Rev Respir Dis 116:821-825, 1977. 4. Huber GL, Miller RD: Training of undergraduate medical school students in pulmonary diseases: A regional analysis of New England medical schools. Chest 70:267-273, 1976. 5. Dandoy S, Hansen R: Tuberculosis care in general hospitals: Arizona's experience. Am Rev Respir Dis 112:757-763, 1975.
Diagnostic Criteria
in Diabetes
Reflecting an impaired glucose tolerance, the abnormal glucose test has for long been considered the criterion for diagnosing diabetes. The test retained this exalted status even when an abnormal glucose tolerance was demonstrated in a variety of other disorders. These were simply dismissed as tolerance
secondary diabetes. The test remained as the criterion even after
familial studies, clinical observations, and plasma-insulin determinations disclosed that it did not differentiate between the juvenile insulin-dependent and the maturity-onset types of diabetes. Elsewhere in this issue (p 833) Turkington and Weinding reject the abnormal glucose-tolerance test as a criterion for diagnosing diabetes. They discredit it primarily because in their series of 334 diabetic patients observed for a period of 18 years, the test failed to predict what is considered to be the hallmark of diabetes, its late complications, particularly diabetic retinopathy, which is specific to diabetes. The only predictor of these complications was insulin secretion induced by glucosetolerance testing. Retinopathy, nephropathy, and sensory neuropathy occurred only in patients in whom the peak of induced plasma-insulin secretion was less than 60 jiU/ml during the years of observa¬ tion. They did not occur when the peak was above this figure, regardless of the degree of glucose intolerance. Thus, insulin reserve rather than glucose intolerance emerges as the true criterion for diagnosis of diabetes. Admittedly, glucose intolerance may provide circumstantial evidence, but a criterion is more than evidence. It is more specific, more closely linked causally or logically to the entity or phenomenon that it identifies. For instance, when we assume
Address editorial communications to the Editor, 535 N Dearborn St, Chicago, IL 60610.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
looking out the window and seeing a woman wearing a fur with an upturned collar that the outside temperature is below freezing, we rely on evidence not criteria. For all we know, the woman may be showing off her fur coat and scratching an itchy ear. On the other hand, ice on the windowsill or a mercury column in the thermometer registering on
coat
below freezing temperature would be criteria. With changes in criteria often come changes in concepts. For example, when cessation of breathing and heartbeat no longer serve as criteria of death, death itself must be redefined in some other terms, eg, flattening of the EEG. Not surprisingly then, Turkington and Weinding redefine diabetes. They limit the term to a syndrome characterized by insulin deficiency. Where insulin is secreted in adequate or excessive amounts, an abnormal glucose tolerance test is not indicative of diabetes but of insulin resistance. Although not everyone will accept this restrictive definition of diabetes, almost all will agree that it helps explain the paradox of late complications despite good control in many diabetic patients. More important, the new definition may direct efforts at diabetic control to a more sharply delineated target population where it is needed most.
Samuel Vaisrub, MD
tumor
is
found,
pathology:
a
nagging
is it the
mus?
doubt about the site of primary or the hypothala¬
adrenal, the pituitary,
Cushing gave his unequivocal answer in 1932 when he demonstrated pituitary basophil adenomas in his first reported cases of the newly discovered disease.1 However, when subse¬ quent operations failed to demonstrate pituitary tumors in the majority of such patients, attention focused on the adrenals or the hypothalamus. Currently, the focus is back on the pituitary.
Tyrrell et al2 performed transsphenoidal microsurgical explora¬ tions of the sella turcica in 20 consecutive patients with Cushing's syndrome. In 17 of these, they found sellar abnormal¬ ities, 14 of which proved to be histologically confirmed pituitary microadenomas. These were selectively resected with resulting complete correction of hypercortisolism. Unsurpris¬ ingly, the investigators concluded that the great majority of patients with Cushing's syndrome have pituitary tumors, even when the latter are not demonstrable by polytomography, and that selective removal of the tumors is the recommended method of treatment. Daughaday3 endorses this recommenda¬ tion, but he excepts children, in whom pituitary irradiation is
usually effective. Although overshadowed by
successful pituitary ablation and medical conceptual implications, therapy and its conceptual have been not spin-offs totally eclipsed. Krieger et al4'5 and others since have shown that cyproheptadine, a serotonin inhibitor, relieves symptoms and restores to normal levels plasma adrenocorticotrophic hormone and Cortisol in 60% of treated patients. Although only 40 cases have been reported and the follow-up period is relatively short, these results cannot be ignored. Nor can be disregarded the evidence that serotonin stimulates secretion of cotticotropin-releasing factor6 in the hypothalamus and that the latter may well be the site of the serotonin-inhibiting action of cyproheptadine. Clearly, the hypothalamus remains a strong contender for etiologic primacy in Cushing's syndrome. Successful surgical approaches to the pituitary do not preclude conceptual etiologic approaches that may bypass the sella. its
Cushing's Syndrome\p=m-\Stilla Conundrum Hypersecretory endocrinopathies are generally treated by surgical removal or radiation of the incriminated gland even when direct pharmacologic antagonists to its oversecreted hormone are available. Such drugs are often unsuited for prolonged use because of toxic effects or loss of effectiveness. Apart from offering a prompt cure, surgical or radiological ablation of a gland eliminates the risk of malignant change or spatial expansion. On the other hand, ablation frequently generates undesirable complications, such as uncontrolled overactivity of a modulating organ and a need for major, lifelong replacement therapy. Perplexities mount when the primary cause of the endocrinopathy is called into question. Is the the true or is it hyperactive organ culprit, merely a puppet in order the endocrine an a of manipulated by organ higher hierarchy? These sources of hesitancy and confusion are epitomized in the therapeutic and conceptual approaches to Cushing's syndrome. Adrenalectomy, which is still the most widely used treatment, necessitates lifelong replacement of cortisol. Further, the removal of negative feedback restraints exerted by adrenocortical hormones often causes an increase in body pigmenta¬ tion (Nelson's syndrome) and enlargement of the pituitary gland. Irradiation of the pituitary results in multihormonal deficiencies with their attendant problems of correction. Regardless of therapeutic results, there remains, when no pituitary adrenal or ectopic adrenocortical hormone-secreting
Samuel Vaisrub, MD 1. Feldman JM: Cushing's disease: A hypothalamic flush? N Engl J Med 293:930-931, 1975. 2. Tyrrell JB, Brooks RM, Fitzgerald PA, et al: Cushing's disease selective transsphenoidal resection of pituitary microadenomas. N Engl J Med 298:753\x=req-\ 757, 1978. 3. Daughaday WH: Cushing's disease and basophilic microadenomas. N Engl J Med 298:793-794, 1978. 4. Krieger DT, Amorosa L, Linick F: Cyproheptadine-induced remission of Cushing's disease. N Engl J Med 293:893-896, 1975. 5. Krieger DT: Cyproheptadine for pituitary disorders. N Engl J Med 295:394\x=req-\ 395, 1976. 6. Krieger DT: Sleep EEG stages and plasma growth hormone concentration in states of endogenous and exogenous hypercortisolemia and ACTH elevation. J Clin Endocrinol Metab 39:986-1000, 1974. 7. Chakrabarty AS, Pillai RV, Anand BK, et al: Effect of cyproheptadine on the electrical activity of the hypothalamic feeding centers. Brain Res 6:561-569, 1967.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
closing of tuberculosis sanatoriums during recent years has placed the treatment of tuberculosis in many communities into the hands of physicians inexperienced in dealing with the disease. When this shift was originally advocated, no major problems were anticipated in view of the effective antituberculous medications available. However, many physicians, including some board-certified internists, failed to understand the basic principles involved in treating the disease. A recent study in this regard showed that more than 60% of a group of 130 tuberculosis patients were inappropriately treated by standard textbook criteria.1 The possible increasing incidence of the disease in some urban areas may relate to this inept manageThe
ment.2
recently observed high incidence of drug resistance and particularly multiple drug resistances now being seen in ghetto populations may also reflect improper treatment.3 This turn of events should probably not be surprising because most medical schools offer little instruction in this condition." Some pulmonary disease fellowships provide minimal or no experience with The
it.
this problem is to provide increased to medical practitioners. tuberculosis information regarding be the medical school level as well This should done initially at as in the medically oriented residency programs. In addition, this disease should not be ignored in the plethora of postgrad¬ uate courses offered to physicians. However, most physicians not working in a specialized setting such as the inner city are unlikely to see more than a few cases of the disease in a lifetime of practice. Since its management may prove complex, physi¬ cians, on seeing a case of suspected tuberculosis, should consider seeking consultation from an infectious or pulmonary disease physician skilled in its diagnosis and management. Those patients proving to have uncomplicated disease can then be followed up by the generalist after an initial treatment plan is developed. On the other hand, those likely to have drugresistant tuberculosis or those who have tuberculosis caused by organisms other than Mycobacterium tuberculosis should be treated under the direct supervision of a pulmonary or infec¬ tious disease specialist who is well versed in tuberculosis. The second-line drugs used in such cases are often poorly tolerated, and considerable skill is required in prescribing them in such a fashion that they are acceptable to the patient. Furthermore, some serious drug reactions may occur, again requiring expert management. Arizona has basically adopted such an approach, with tuberculosis patients referred to specific general hospitals where physicians experienced in the disease make the initial evaluation of the patient's condition.' The decision to return the care of tuberculosis to the mainstream of medicine was indeed a correct one. However, its One obvious
answer to
be casual and must be made in its management.
treatment cannot
knowledgeable
by physicians
Col Richard B. Byrd, MC, USAF US Air Force Medical Center Scott Scott Air Force Base, Ill Lee B. Reichman, MD, MPH New Jersey Medical School Newark
The views expressed herein are those of the authors and do not necessarily reflect the views of the US Air Force or the Department of Defense. 1.
Byrd RB,
Horn BR, Solomon DA,
et
al: Treatment of tuberculosis
nonpulmonary physician. Ann Intern Med 86:799-802, 1977. 2. Riley RL: Rising tuberculosis rate in Baltimore city. Am
by the
Rev Respir Dis 113:577-578, 1976. 3. Schiffman PL, Ashkar B, Bishop M, et al: Drug-resistant tuberculosis in a large southern California hospital. Am Rev Respir Dis 116:821-825, 1977. 4. Huber GL, Miller RD: Training of undergraduate medical school students in pulmonary diseases: A regional analysis of New England medical schools. Chest 70:267-273, 1976. 5. Dandoy S, Hansen R: Tuberculosis care in general hospitals: Arizona's experience. Am Rev Respir Dis 112:757-763, 1975.
Diagnostic Criteria
in Diabetes
Reflecting an impaired glucose tolerance, the abnormal glucose test has for long been considered the criterion for diagnosing diabetes. The test retained this exalted status even when an abnormal glucose tolerance was demonstrated in a variety of other disorders. These were simply dismissed as tolerance
secondary diabetes. The test remained as the criterion even after
familial studies, clinical observations, and plasma-insulin determinations disclosed that it did not differentiate between the juvenile insulin-dependent and the maturity-onset types of diabetes. Elsewhere in this issue (p 833) Turkington and Weinding reject the abnormal glucose-tolerance test as a criterion for diagnosing diabetes. They discredit it primarily because in their series of 334 diabetic patients observed for a period of 18 years, the test failed to predict what is considered to be the hallmark of diabetes, its late complications, particularly diabetic retinopathy, which is specific to diabetes. The only predictor of these complications was insulin secretion induced by glucosetolerance testing. Retinopathy, nephropathy, and sensory neuropathy occurred only in patients in whom the peak of induced plasma-insulin secretion was less than 60 jiU/ml during the years of observa¬ tion. They did not occur when the peak was above this figure, regardless of the degree of glucose intolerance. Thus, insulin reserve rather than glucose intolerance emerges as the true criterion for diagnosis of diabetes. Admittedly, glucose intolerance may provide circumstantial evidence, but a criterion is more than evidence. It is more specific, more closely linked causally or logically to the entity or phenomenon that it identifies. For instance, when we assume
Address editorial communications to the Editor, 535 N Dearborn St, Chicago, IL 60610.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
looking out the window and seeing a woman wearing a fur with an upturned collar that the outside temperature is below freezing, we rely on evidence not criteria. For all we know, the woman may be showing off her fur coat and scratching an itchy ear. On the other hand, ice on the windowsill or a mercury column in the thermometer registering on
coat
below freezing temperature would be criteria. With changes in criteria often come changes in concepts. For example, when cessation of breathing and heartbeat no longer serve as criteria of death, death itself must be redefined in some other terms, eg, flattening of the EEG. Not surprisingly then, Turkington and Weinding redefine diabetes. They limit the term to a syndrome characterized by insulin deficiency. Where insulin is secreted in adequate or excessive amounts, an abnormal glucose tolerance test is not indicative of diabetes but of insulin resistance. Although not everyone will accept this restrictive definition of diabetes, almost all will agree that it helps explain the paradox of late complications despite good control in many diabetic patients. More important, the new definition may direct efforts at diabetic control to a more sharply delineated target population where it is needed most.
Samuel Vaisrub, MD
tumor
is
found,
pathology:
a
nagging
is it the
mus?
doubt about the site of primary or the hypothala¬
adrenal, the pituitary,
Cushing gave his unequivocal answer in 1932 when he demonstrated pituitary basophil adenomas in his first reported cases of the newly discovered disease.1 However, when subse¬ quent operations failed to demonstrate pituitary tumors in the majority of such patients, attention focused on the adrenals or the hypothalamus. Currently, the focus is back on the pituitary.
Tyrrell et al2 performed transsphenoidal microsurgical explora¬ tions of the sella turcica in 20 consecutive patients with Cushing's syndrome. In 17 of these, they found sellar abnormal¬ ities, 14 of which proved to be histologically confirmed pituitary microadenomas. These were selectively resected with resulting complete correction of hypercortisolism. Unsurpris¬ ingly, the investigators concluded that the great majority of patients with Cushing's syndrome have pituitary tumors, even when the latter are not demonstrable by polytomography, and that selective removal of the tumors is the recommended method of treatment. Daughaday3 endorses this recommenda¬ tion, but he excepts children, in whom pituitary irradiation is
usually effective. Although overshadowed by
successful pituitary ablation and medical conceptual implications, therapy and its conceptual have been not spin-offs totally eclipsed. Krieger et al4'5 and others since have shown that cyproheptadine, a serotonin inhibitor, relieves symptoms and restores to normal levels plasma adrenocorticotrophic hormone and Cortisol in 60% of treated patients. Although only 40 cases have been reported and the follow-up period is relatively short, these results cannot be ignored. Nor can be disregarded the evidence that serotonin stimulates secretion of cotticotropin-releasing factor6 in the hypothalamus and that the latter may well be the site of the serotonin-inhibiting action of cyproheptadine. Clearly, the hypothalamus remains a strong contender for etiologic primacy in Cushing's syndrome. Successful surgical approaches to the pituitary do not preclude conceptual etiologic approaches that may bypass the sella. its
Cushing's Syndrome\p=m-\Stilla Conundrum Hypersecretory endocrinopathies are generally treated by surgical removal or radiation of the incriminated gland even when direct pharmacologic antagonists to its oversecreted hormone are available. Such drugs are often unsuited for prolonged use because of toxic effects or loss of effectiveness. Apart from offering a prompt cure, surgical or radiological ablation of a gland eliminates the risk of malignant change or spatial expansion. On the other hand, ablation frequently generates undesirable complications, such as uncontrolled overactivity of a modulating organ and a need for major, lifelong replacement therapy. Perplexities mount when the primary cause of the endocrinopathy is called into question. Is the the true or is it hyperactive organ culprit, merely a puppet in order the endocrine an a of manipulated by organ higher hierarchy? These sources of hesitancy and confusion are epitomized in the therapeutic and conceptual approaches to Cushing's syndrome. Adrenalectomy, which is still the most widely used treatment, necessitates lifelong replacement of cortisol. Further, the removal of negative feedback restraints exerted by adrenocortical hormones often causes an increase in body pigmenta¬ tion (Nelson's syndrome) and enlargement of the pituitary gland. Irradiation of the pituitary results in multihormonal deficiencies with their attendant problems of correction. Regardless of therapeutic results, there remains, when no pituitary adrenal or ectopic adrenocortical hormone-secreting
Samuel Vaisrub, MD 1. Feldman JM: Cushing's disease: A hypothalamic flush? N Engl J Med 293:930-931, 1975. 2. Tyrrell JB, Brooks RM, Fitzgerald PA, et al: Cushing's disease selective transsphenoidal resection of pituitary microadenomas. N Engl J Med 298:753\x=req-\ 757, 1978. 3. Daughaday WH: Cushing's disease and basophilic microadenomas. N Engl J Med 298:793-794, 1978. 4. Krieger DT, Amorosa L, Linick F: Cyproheptadine-induced remission of Cushing's disease. N Engl J Med 293:893-896, 1975. 5. Krieger DT: Cyproheptadine for pituitary disorders. N Engl J Med 295:394\x=req-\ 395, 1976. 6. Krieger DT: Sleep EEG stages and plasma growth hormone concentration in states of endogenous and exogenous hypercortisolemia and ACTH elevation. J Clin Endocrinol Metab 39:986-1000, 1974. 7. Chakrabarty AS, Pillai RV, Anand BK, et al: Effect of cyproheptadine on the electrical activity of the hypothalamic feeding centers. Brain Res 6:561-569, 1967.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
