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TESTOSTERONE PROPIONATE,THE ANTERIOR PITUITARY, AND HYPERTHYROIDISM
1134
CORRESPONDENCE BLOOD PRESSURE IN SCARLATINAL NEPHRITIS To the Editor of THE LANCET
SiR,—In his paper in your issue of April 30th (p. 999) Dr. R. Workman Carslaw, from his experience of 50 cases of scarlet fever, came to the conclusion that it was impossible to diagnose early postscarlatinal nephritis by daily blood-pressure readings. This conclusion is confirmed by my observations many years agowhen I published a paper on blood pressure in scarlet fever based on the study of 122 Of the 33 cases in this series which developed cases. nephritis only 12 showed any hypertension, which was never extreme or of long duration, while in the remaining 21, whose ages ranged from three to twelve years, the systolic blood pressure did not rise above 110. The absence of any rise of blood pressure in many cases of post-scarlatinal nephritis and the large number in which only a slight and transient rise was noted are in keeping with the fact that scarlatinal nephritis is as a rule a benign affection, the great majority of such cases ending in complete In the early days of clinical sphygmorecovery. manometry T. Janeway,2 like most physicians interested in the subject, hoped that it would furnish most important indications in acute infectious disease. Some years later,3 however, he had to confess that that hope had been disappointed. I think," he "that most of us must now wrote, agree with the conclusions of Kurt Weigert from his extensive studies of the acute infections, and which have been confirmed for scarlet fever by Rolleston, that the value of the blood-pressure measurement for prognosis in the acute infectious diseases is slight. It is an additional factor which is occasionally useful, as in typhoid patients with haemorrhage, but for the most part the simpler observations made by our predecessors in clinical medicine of the facies, the tongue, the pulse, and the heart sounds, and the state of the nervous system, make the prognosis equally well without a knowledge of the blood-pressure curve." T am. Sir. voilrs faithfullv. J. D. ROLLESTON. "
TESTOSTERONE PROPIONATE,THE ANTERIOR PITUITARY, AND HYPERTHYROIDISM To the Editor
of
THE
LANCET
SiR,-In your issue of Feb. 12th I reported that the male hormone, testosterone propionate, if given in adequate doses, renders the endometrium atrophic. But it remained doubtful whether it acts on the endometrium itself, on the ovarian follicle (antagonising the female hormone), or on the sexual motor, the anterior pituitary. To answer this question I ascertained the amount of gonadotropic hormone in the urine in women receiving testosterone for haemorrhage at the menopause, and found that under treatment it either disappeared or diminished, according to the dosage. This demonstrates that testosterone acts through the pituitary-a conclusion supported by the observation of J. B. Hamilton and J. M. Wolfe (Endocrinology, March, 1938,) that in rats it suppresses production of gonadotropic substances by the pituitary. If, indeed, the male hormone blocks the production of gonadotropic hormone by the anterior pituitary 1
Brit. J. Child. Dis. 1912, 9, 444 ; Acute Infectious p. 271. 2 Clinical Study of Blood. Pressure, 1904. 3 Bull. Johns Hopk. Hosp. 1915, 26, 348.
2ED, 1929,
Diseases,
it may also interfere with the action of the other anterior pituitary hormones, such as the thyrotropic, adrenotropic, and growth factors. Accordingly, on the assumption that hyperthyroidism may be caused by excessive secretion of thyrotropic hormone, testosterone has been tried in Graves’s disease, and I am able to report the first success with this remedy. The patient, a girl of 14, is being treated by Dr. S. F.
Seelig in St. John’s Hospital, Lewisham, London, according to my suggestions. She had conspicuous exophthalmos, a diffusely enlarged thyroid, excitability, tremor, and a pulse-rate of 150. She had lost weight during the last few months and was rest in bed with suffering from insomnia ; administration of bromide and phenobarbitone failed to bring the slightest improvement. Under the influence of 850 mg. of testosterone propionate, given a over period of two months, the thyrotoxic symptoms diminished considerably. Although the patient was not kept in bed, and received no drugs, her weight increased, the pulse-rate dropped to 84, the tremor became hardly visible, and the exophthalmos lessened. Excessive perspiration vanished and she became much calmer. The treatment began on March lst and improvement has continued from that time onwards. Though it is too early to judge of the permanence of the cure, the evidence of this case suggests that testosterone propionate can be used to reduce
excessive
thyrotropic activity on the part of the pituitary gland. The effect of the treatment was to perform a partial temporary functional hypophysectomy. In my latest cases I have found that this effect can be attained not only by injecting the male hormone, but also by rubbing it into the skin. The percutaneous dose corresponds to the dose given intramuscularly. The results of the above investigations were reported by me to the International Congress of Obstetrics and Gynxcology held in Amsterdam last week. I am,
Sir,
yours
faithfully, ALFRED A. LOESER.
PYLORIC STENOSIS IN TWINS
of THE LANCET interesting paper in
To the Editor
SIR,-Dr. Sheldon’s your last issue illustrates two common fallacies in twin research, which tend to bring the method into disrepute. Under the title " Hypertrophic pyloric stenosis in one of uniovular twins " he mentions that 22 out of 23 twin pairs were discordant for this disease, and that the number of twins in his material was unduly large. Since roughly one-third of all twins are monovular, and since on the basis of a single Mendelian recessive a quarter of the binovular male pairs ought to be concordant, the obvious deduction is that even in this tiny sample some 7 twins with faulty genes have failed to develop the disease. The case report which is given supports this deduction and the general impression left by the article is that in the aetiology of pyloric stenosis important environmental factors are involved which, since we are dealing with twins, must be extra-uterine. Such a conclusion is quite unjustified on the evidence presented. Assuming for the purpose of simplification that pyloric stenosis occurs only in male infants, and making one or two other minor adjustments, the following calculation is sufficiently accurate. In 2000 births there will be 25 twin births producing 4 pairs of uniovular males, the same number of binovular male pairs, 8 pairs of unlike sex, and 8 female pairs. Among 1000 male infants selected
CORRESPONDENCE BLOOD PRESSURE IN SCARLATINAL NEPHRITIS To the Editor of THE LANCET
SiR,—In his paper in your issue of April 30th (p. 999) Dr. R. Workman Carslaw, from his experience of 50 cases of scarlet fever, came to the conclusion that it was impossible to diagnose early postscarlatinal nephritis by daily blood-pressure readings. This conclusion is confirmed by my observations many years agowhen I published a paper on blood pressure in scarlet fever based on the study of 122 Of the 33 cases in this series which developed cases. nephritis only 12 showed any hypertension, which was never extreme or of long duration, while in the remaining 21, whose ages ranged from three to twelve years, the systolic blood pressure did not rise above 110. The absence of any rise of blood pressure in many cases of post-scarlatinal nephritis and the large number in which only a slight and transient rise was noted are in keeping with the fact that scarlatinal nephritis is as a rule a benign affection, the great majority of such cases ending in complete In the early days of clinical sphygmorecovery. manometry T. Janeway,2 like most physicians interested in the subject, hoped that it would furnish most important indications in acute infectious disease. Some years later,3 however, he had to confess that that hope had been disappointed. I think," he "that most of us must now wrote, agree with the conclusions of Kurt Weigert from his extensive studies of the acute infections, and which have been confirmed for scarlet fever by Rolleston, that the value of the blood-pressure measurement for prognosis in the acute infectious diseases is slight. It is an additional factor which is occasionally useful, as in typhoid patients with haemorrhage, but for the most part the simpler observations made by our predecessors in clinical medicine of the facies, the tongue, the pulse, and the heart sounds, and the state of the nervous system, make the prognosis equally well without a knowledge of the blood-pressure curve." T am. Sir. voilrs faithfullv. J. D. ROLLESTON. "
TESTOSTERONE PROPIONATE,THE ANTERIOR PITUITARY, AND HYPERTHYROIDISM To the Editor
of
THE
LANCET
SiR,-In your issue of Feb. 12th I reported that the male hormone, testosterone propionate, if given in adequate doses, renders the endometrium atrophic. But it remained doubtful whether it acts on the endometrium itself, on the ovarian follicle (antagonising the female hormone), or on the sexual motor, the anterior pituitary. To answer this question I ascertained the amount of gonadotropic hormone in the urine in women receiving testosterone for haemorrhage at the menopause, and found that under treatment it either disappeared or diminished, according to the dosage. This demonstrates that testosterone acts through the pituitary-a conclusion supported by the observation of J. B. Hamilton and J. M. Wolfe (Endocrinology, March, 1938,) that in rats it suppresses production of gonadotropic substances by the pituitary. If, indeed, the male hormone blocks the production of gonadotropic hormone by the anterior pituitary 1
Brit. J. Child. Dis. 1912, 9, 444 ; Acute Infectious p. 271. 2 Clinical Study of Blood. Pressure, 1904. 3 Bull. Johns Hopk. Hosp. 1915, 26, 348.
2ED, 1929,
Diseases,
it may also interfere with the action of the other anterior pituitary hormones, such as the thyrotropic, adrenotropic, and growth factors. Accordingly, on the assumption that hyperthyroidism may be caused by excessive secretion of thyrotropic hormone, testosterone has been tried in Graves’s disease, and I am able to report the first success with this remedy. The patient, a girl of 14, is being treated by Dr. S. F.
Seelig in St. John’s Hospital, Lewisham, London, according to my suggestions. She had conspicuous exophthalmos, a diffusely enlarged thyroid, excitability, tremor, and a pulse-rate of 150. She had lost weight during the last few months and was rest in bed with suffering from insomnia ; administration of bromide and phenobarbitone failed to bring the slightest improvement. Under the influence of 850 mg. of testosterone propionate, given a over period of two months, the thyrotoxic symptoms diminished considerably. Although the patient was not kept in bed, and received no drugs, her weight increased, the pulse-rate dropped to 84, the tremor became hardly visible, and the exophthalmos lessened. Excessive perspiration vanished and she became much calmer. The treatment began on March lst and improvement has continued from that time onwards. Though it is too early to judge of the permanence of the cure, the evidence of this case suggests that testosterone propionate can be used to reduce
excessive
thyrotropic activity on the part of the pituitary gland. The effect of the treatment was to perform a partial temporary functional hypophysectomy. In my latest cases I have found that this effect can be attained not only by injecting the male hormone, but also by rubbing it into the skin. The percutaneous dose corresponds to the dose given intramuscularly. The results of the above investigations were reported by me to the International Congress of Obstetrics and Gynxcology held in Amsterdam last week. I am,
Sir,
yours
faithfully, ALFRED A. LOESER.
PYLORIC STENOSIS IN TWINS
of THE LANCET interesting paper in
To the Editor
SIR,-Dr. Sheldon’s your last issue illustrates two common fallacies in twin research, which tend to bring the method into disrepute. Under the title " Hypertrophic pyloric stenosis in one of uniovular twins " he mentions that 22 out of 23 twin pairs were discordant for this disease, and that the number of twins in his material was unduly large. Since roughly one-third of all twins are monovular, and since on the basis of a single Mendelian recessive a quarter of the binovular male pairs ought to be concordant, the obvious deduction is that even in this tiny sample some 7 twins with faulty genes have failed to develop the disease. The case report which is given supports this deduction and the general impression left by the article is that in the aetiology of pyloric stenosis important environmental factors are involved which, since we are dealing with twins, must be extra-uterine. Such a conclusion is quite unjustified on the evidence presented. Assuming for the purpose of simplification that pyloric stenosis occurs only in male infants, and making one or two other minor adjustments, the following calculation is sufficiently accurate. In 2000 births there will be 25 twin births producing 4 pairs of uniovular males, the same number of binovular male pairs, 8 pairs of unlike sex, and 8 female pairs. Among 1000 male infants selected