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Rare But Curable Disease
Rare But Curable Disease LEWIS M. HURXTHAL, M.D.
or disorders that are commonly encountered in the daily practice of medicine rarely lend themselves to an absolute cure or a complete correction of the varied manifestations. More often treatment results in a significant amelioration of disease. It is with this connotation that the word curable will be used herein. Physicians are frequently confronted with ever new combinations of symptoms and signs from which they must try to piece together a pattern suggesting one of the established syndromes. Familiarity with rarer diseases, especially through long experience, and a dash of intuitive suspicion, are valuable assets in recognizing potentially curable diseases. The list of rare but curable diseases met with in the practice of internal medicine is not long. The symptoms and signs of such diseases, however, are frequently seen in the more common diseases so that one has to look through or beyond that which does not appear to be unusual. This subject could be arranged and discussed under several headings, such as nutrition, electrolytes, enzymes, endocrinology, infection and hematology, but since clinical syndromes frequently overlap the boundaries of classification no attempt will be made to separate and present these diseases on such a basis. Let us con5ider the problem of hypertension, especially diastolic hypertension. The following should be considered and systematically excluded: (1) coarctation of the aorta, (2) pheochromocytoma, (3) primary aldosteronism, (4) unilateral occlusive arterial renal disease, and (5) Cushing's disease. To be sure, these are relatively rare causes of hypertension but they should always be considered; they take. 'precedence _. because they are, in the main, curable. Recurrent convulsive seizures, even in children, do not always stem from idiopathic epilepsy, brain injury or tumor. Idiopathic or postoperative hypoparathyroidism with tetany may cause seizures as well as choked optic disks. Seizures may result from hyperinsulinism caused by islet cell tumor of the pancreas; when hypoglycemia is demonstrated, especially in young females, factitious insulin hypoglycemia is always a considera"tion. Factitious systemic diseases are only rarely seen, but those most commonly encountered are the result of surreptitious consumption of such SYSTEMIC DISEASES
255
256
LEWIS
M.
HURXTHAL
medications as insulin, thyroid preparations, laxatives, barbiturates, bromides and other sedatives, and acetanilid. In addition, deception is occasionally accomplished by not taking the prescribed diet or medication, such as thyroid, or if it is taken, secretly vomiting it. Cure begins with detection, which is often difficult. The possibility of iatrogenic disease is always worth considering. It is important to distinguish hypopituitary dwarfism, which can be somewhat ameliorated but is not as yet curable, from other causes of dwarfism. Clinical features indistinguishable from hypopituitary dwarfism may be encountered in children with malabsorption syndromes. The dwarfism that results from the malabsorption syndrome of gluten enteropathy is usually curable. Dwarfism resulting from thyroid deficiency in children is not always accompanied by the characteristic cretinoid appearance or the classical physical findings. Thyroid replacement therapy affords a cure when diagnosis is established early. Precociou8 genital development in the newborn male, or enlargement of the clitoris in the newborn female, or either one discovered at a later time, results in most instances from the congenital adrenogenital syndrome. This condition is the result of an adrenocortical enzymic defect, the effects of which are readily corrected by cortisone. Postpuberal onset of this type of adrenogenital syndrome has been reported and the metabolic defect may be halted by cortisone although certain residual stigmata may be expected in this as well as the former type described. Masculinization of the female at any age or of the prepuberal male may be the result of tumor and if it is not malignant, it is surely curable. Adult male eunuchoidism resulting from a selective pituitary gonadotropic deficiency is characterized by normal stature but by increased span, normal thyroid function and clinically normal adrenocortical function, and responds well to chorionic gonadotropin with regard to genital development, sexual function and occasionally spermatogenesis. Testosterone may do the same, with less likelihood of producing fertility. If no response is obtained to chorionic gonadotropins, the actual lesion may be in the testes. When eunuchoidism is the result of primary testicular disease, testosterone is the drug of choice since there is no hope of fertility. Acromegaly is a rare disease which is often overlooked in the incipient stage before facial and other characteristic changes become apparent. Although bony changes are not reversible, progression of the disease can be arrested by pituitary radiotherapy or, if necessary, surgery. Perhaps the rare but curable disease most often considered in clinical practice is Addison's disease because of the common presenting complaints of weakness and fatigue. Patients with Addison's disease almost always show at least some of the characteristic physical signs. In addition, with the newer methods for laboratory assessment of adrenocortical function, the diagnosis of Addison's disease may be documented with
Rare But Curable Disease
257
relative ease. Addison's disease responds dramatically to cortisone replacement therapy. There are rare but curable types of anemia. Primary pernicious anemia may simulate malignant disease with anorexia and weight loss, but the correct diagnosis can be made by appropriate hematologic and auxiliary studies. The anemia, of course, is corrected by monthly injections of vitamin B12 • A diagnosis of pernicious anemia is sometimes made in hypothyroid patients who occasionally have macrocytic anemia. These patients may have been treated with B12 for years without success, whereas thyroid replacement results in a cure of the anemia. Pyridoxine deficiency anemia is a rare anemia of the hypochromic type; it does not respond to iron, but may be cured by administration of pyridoxine. Osteoporosis which affects probably 75 per cent of women and 15 per cent of men over 55 years of age may be caused by rare but curable diseases. The most common skeletal manifestation of hyperparathyroidism is osteoporosis. Osteoporosis also may be encountered in Cushing's disease and long-standing hyperthyroidism. These three endocrinopathies are considered curable diseases provided definitive therapy is instituted before irreparable complications occur. Malabsorption syndromes usually cause osteoporosis and osteomalacia. Both processes may be ameliorated by treatment, but this type of osteomalacia can be cured by appropriate therapy. Weakness may be the result of a variety of causes but one which may be overlooked is myasthenia gravis. Leg weakness during repetitive effort is not an unusual complaint but initially more characteristic symptoms are transient double vision, weakening of the voice, and drooping of one or both eyelids. These manifestations tend to become more pronounced as the day goes on. Except in severe cases and in the later stages of the disorder, neostigmine produces a satisfactory restoration of muscle function. Patients may complain of tiredness but actually mean they have a desire to sleep. Often thyroid deficiency is suspected, but in reality these patients have narcolepsy. Patients with this disorder have great difficulty keeping awake and characteristically fall asleep at inappropriate times, for example in theaters, streetcars, or at dinner, in spite of the presence of other persons. The amphetamines, properly administered, allow a fairly normal existence. Spontaneous myxedema may also be considered a rare disease, especially when compared to the incidence of hyperthyroidism. The classical case with puffy periorbital edema, dry skin, slow speech, and fine scalp hair in women is rarely overlooked. The diagnosis may be very elusive, however, when the hypothyroidism is of less severe degree. When the latter is suspected, laboratory tests of thyroid function and sometimes a trial of therapy usually permit the correct diagnosis. Thyroid therapy
258
LEWIS
M.
HURXTHAL
affords a cure except in the presence of angina pectoris, in which case optimum replacement may be impossible. There are other systemic diseases which frequently but not invariably are curable. For example, in temporal arteritis, steroid therapy affords symptomatic relief and there is presumptive evidence that it halts the progression of the disease. Eventually the steroid therapy may be gradually withdrawn. Lupus erythematosus cannot be cured by steroids but can be held in abeyance for long periods of time, during which "normal health" may be enjoyed. Subacute bacterial endocarditis is rare, frequently smoldering and undiagnosed, and the disease process can be cured, although the heart valves may be permanently damaged. Occult malignant disease is difficult to diagnose, but a thorough investigation may in some cases reveal a potentially fatal disease which may be curable. The diseases discussed have been drawn from my personal experience and are not intended to represent a complete list of rare and curable diseases. The diseases were selected on the basis of infrequent occurrence, diagnostic elusiveness and dramatic therapeutic response. Nothing is more rewarding in the practice of medicine than to uncover one of the above rare but curable diseases. Constant vigilance, therefore, is the necessary ingredient of successful diagnosis.
or disorders that are commonly encountered in the daily practice of medicine rarely lend themselves to an absolute cure or a complete correction of the varied manifestations. More often treatment results in a significant amelioration of disease. It is with this connotation that the word curable will be used herein. Physicians are frequently confronted with ever new combinations of symptoms and signs from which they must try to piece together a pattern suggesting one of the established syndromes. Familiarity with rarer diseases, especially through long experience, and a dash of intuitive suspicion, are valuable assets in recognizing potentially curable diseases. The list of rare but curable diseases met with in the practice of internal medicine is not long. The symptoms and signs of such diseases, however, are frequently seen in the more common diseases so that one has to look through or beyond that which does not appear to be unusual. This subject could be arranged and discussed under several headings, such as nutrition, electrolytes, enzymes, endocrinology, infection and hematology, but since clinical syndromes frequently overlap the boundaries of classification no attempt will be made to separate and present these diseases on such a basis. Let us con5ider the problem of hypertension, especially diastolic hypertension. The following should be considered and systematically excluded: (1) coarctation of the aorta, (2) pheochromocytoma, (3) primary aldosteronism, (4) unilateral occlusive arterial renal disease, and (5) Cushing's disease. To be sure, these are relatively rare causes of hypertension but they should always be considered; they take. 'precedence _. because they are, in the main, curable. Recurrent convulsive seizures, even in children, do not always stem from idiopathic epilepsy, brain injury or tumor. Idiopathic or postoperative hypoparathyroidism with tetany may cause seizures as well as choked optic disks. Seizures may result from hyperinsulinism caused by islet cell tumor of the pancreas; when hypoglycemia is demonstrated, especially in young females, factitious insulin hypoglycemia is always a considera"tion. Factitious systemic diseases are only rarely seen, but those most commonly encountered are the result of surreptitious consumption of such SYSTEMIC DISEASES
255
256
LEWIS
M.
HURXTHAL
medications as insulin, thyroid preparations, laxatives, barbiturates, bromides and other sedatives, and acetanilid. In addition, deception is occasionally accomplished by not taking the prescribed diet or medication, such as thyroid, or if it is taken, secretly vomiting it. Cure begins with detection, which is often difficult. The possibility of iatrogenic disease is always worth considering. It is important to distinguish hypopituitary dwarfism, which can be somewhat ameliorated but is not as yet curable, from other causes of dwarfism. Clinical features indistinguishable from hypopituitary dwarfism may be encountered in children with malabsorption syndromes. The dwarfism that results from the malabsorption syndrome of gluten enteropathy is usually curable. Dwarfism resulting from thyroid deficiency in children is not always accompanied by the characteristic cretinoid appearance or the classical physical findings. Thyroid replacement therapy affords a cure when diagnosis is established early. Precociou8 genital development in the newborn male, or enlargement of the clitoris in the newborn female, or either one discovered at a later time, results in most instances from the congenital adrenogenital syndrome. This condition is the result of an adrenocortical enzymic defect, the effects of which are readily corrected by cortisone. Postpuberal onset of this type of adrenogenital syndrome has been reported and the metabolic defect may be halted by cortisone although certain residual stigmata may be expected in this as well as the former type described. Masculinization of the female at any age or of the prepuberal male may be the result of tumor and if it is not malignant, it is surely curable. Adult male eunuchoidism resulting from a selective pituitary gonadotropic deficiency is characterized by normal stature but by increased span, normal thyroid function and clinically normal adrenocortical function, and responds well to chorionic gonadotropin with regard to genital development, sexual function and occasionally spermatogenesis. Testosterone may do the same, with less likelihood of producing fertility. If no response is obtained to chorionic gonadotropins, the actual lesion may be in the testes. When eunuchoidism is the result of primary testicular disease, testosterone is the drug of choice since there is no hope of fertility. Acromegaly is a rare disease which is often overlooked in the incipient stage before facial and other characteristic changes become apparent. Although bony changes are not reversible, progression of the disease can be arrested by pituitary radiotherapy or, if necessary, surgery. Perhaps the rare but curable disease most often considered in clinical practice is Addison's disease because of the common presenting complaints of weakness and fatigue. Patients with Addison's disease almost always show at least some of the characteristic physical signs. In addition, with the newer methods for laboratory assessment of adrenocortical function, the diagnosis of Addison's disease may be documented with
Rare But Curable Disease
257
relative ease. Addison's disease responds dramatically to cortisone replacement therapy. There are rare but curable types of anemia. Primary pernicious anemia may simulate malignant disease with anorexia and weight loss, but the correct diagnosis can be made by appropriate hematologic and auxiliary studies. The anemia, of course, is corrected by monthly injections of vitamin B12 • A diagnosis of pernicious anemia is sometimes made in hypothyroid patients who occasionally have macrocytic anemia. These patients may have been treated with B12 for years without success, whereas thyroid replacement results in a cure of the anemia. Pyridoxine deficiency anemia is a rare anemia of the hypochromic type; it does not respond to iron, but may be cured by administration of pyridoxine. Osteoporosis which affects probably 75 per cent of women and 15 per cent of men over 55 years of age may be caused by rare but curable diseases. The most common skeletal manifestation of hyperparathyroidism is osteoporosis. Osteoporosis also may be encountered in Cushing's disease and long-standing hyperthyroidism. These three endocrinopathies are considered curable diseases provided definitive therapy is instituted before irreparable complications occur. Malabsorption syndromes usually cause osteoporosis and osteomalacia. Both processes may be ameliorated by treatment, but this type of osteomalacia can be cured by appropriate therapy. Weakness may be the result of a variety of causes but one which may be overlooked is myasthenia gravis. Leg weakness during repetitive effort is not an unusual complaint but initially more characteristic symptoms are transient double vision, weakening of the voice, and drooping of one or both eyelids. These manifestations tend to become more pronounced as the day goes on. Except in severe cases and in the later stages of the disorder, neostigmine produces a satisfactory restoration of muscle function. Patients may complain of tiredness but actually mean they have a desire to sleep. Often thyroid deficiency is suspected, but in reality these patients have narcolepsy. Patients with this disorder have great difficulty keeping awake and characteristically fall asleep at inappropriate times, for example in theaters, streetcars, or at dinner, in spite of the presence of other persons. The amphetamines, properly administered, allow a fairly normal existence. Spontaneous myxedema may also be considered a rare disease, especially when compared to the incidence of hyperthyroidism. The classical case with puffy periorbital edema, dry skin, slow speech, and fine scalp hair in women is rarely overlooked. The diagnosis may be very elusive, however, when the hypothyroidism is of less severe degree. When the latter is suspected, laboratory tests of thyroid function and sometimes a trial of therapy usually permit the correct diagnosis. Thyroid therapy
258
LEWIS
M.
HURXTHAL
affords a cure except in the presence of angina pectoris, in which case optimum replacement may be impossible. There are other systemic diseases which frequently but not invariably are curable. For example, in temporal arteritis, steroid therapy affords symptomatic relief and there is presumptive evidence that it halts the progression of the disease. Eventually the steroid therapy may be gradually withdrawn. Lupus erythematosus cannot be cured by steroids but can be held in abeyance for long periods of time, during which "normal health" may be enjoyed. Subacute bacterial endocarditis is rare, frequently smoldering and undiagnosed, and the disease process can be cured, although the heart valves may be permanently damaged. Occult malignant disease is difficult to diagnose, but a thorough investigation may in some cases reveal a potentially fatal disease which may be curable. The diseases discussed have been drawn from my personal experience and are not intended to represent a complete list of rare and curable diseases. The diseases were selected on the basis of infrequent occurrence, diagnostic elusiveness and dramatic therapeutic response. Nothing is more rewarding in the practice of medicine than to uncover one of the above rare but curable diseases. Constant vigilance, therefore, is the necessary ingredient of successful diagnosis.