Male LH-independent sexual precocity in a 3.5-year-old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor.

We describe the clinical features of severe sexual precocity in a 3.5-yr-old boy. Hormonal evaluation showed LH-independent T hypersecretion. Initial examination of the adrenals and testes revealed no evidence of congenital adrenal hyperplasia, hCG- or androgen-secreting tumors, or McCune-Albright syndrome. In the coding sequence of the LH receptor gene no activating mutation was found. Spironolactone (5.7 mg/kg x d) and testolactone (40 mg/kg x d) were unsuccessful in suppressing the elevated concentration of T. To further determine the origin of the elevated serum T, a selective venous sampling procedure was planned. However before the sampling procedure, high resolution ultrasound examination showed a small tumor in the left testis, which was removed. Histology proved the tumor to be a Leydig cell adenoma. Sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of aspartic acid at position 578 with histidine, which has been shown to be a constitutively activating mutation. These findings indicate that in male patients with gonadotropin-independent sexual precocity, the presence of small testicular Leydig cell tumors harboring a somatic mutation of the LH receptor gene should be considered.

Fatal Salmonella enteritidis sepsis acquired prenatally in a premature infant.

BACKGROUND: Before the advent of antibiotic therapy, Salmonella typhi infection during pregnancy was associated with a high incidence of fetal and neonatal death. Little information is available about the risk to the fetus or the newborn of a pregnant woman infected by non-typhoid salmonella, and treatment recommendations do not exist. CASE: We report a case of transplacental infection of a fetus by non-typhoid salmonella in a woman with gastroenteritis. Salmonella enteritidis was cultured from stool of the pregnant woman, who had diarrhea and fever before cesarean was performed at 29 weeks' gestation. The premature girl died 4 hours after birth from septic shock. Salmonella enteritidis was cultured from blood cultures and swabs of the premature infant and from the placenta and uterus. CONCLUSION: This observation argues in favor of antibiotic treatment for non-typhoid salmonella infection in pregnancy because of the risk of transplacental infection of the fetus.

[Anorexia nervosa in boys--a case report]. / Anorexia nervosa bei Knaben--ein Fallbericht.

BASIC REMARKS: In contrast to female adolescents, anorexia nervosa is rarely seen in male adolescents. In consequence, more comprehensive investigations are often carried out in the latter in a search of organic disease. CASE: A boy of thirteen-and-a-half years was referred for investigation of anorexia, loss of weight, constipation, loss of concentration and depression. Physical examination revealed bradycardia, low blood pressure, hypothermia and various endocrinological disturbances: reduced somatomedin C, tri-iodine thyronine and subnormal thyroxine levels, and delayed TSH peaking after TRH stimulation. Examination of peripheral blood revealed leukopenia with underlying hyperplastic bone marrow. A CT scan revealed widening of the ventricles of the brain, and echocardiography a mitral valve prolapse. CONCLUSIONS: Anorexia nervosa is accompanied by numerous pathological findings which, however, when weight is regained, return to normal without the need for further treatment. Before instituting invasive diagnostic measures in boys or male adolescents, consideration should be given to anorexia nervosa, and a psychiatric consultation sought.

Basal ganglia calcification in pseudohypoparathyroidism type II.

The case history of a patient with basal ganglia calcifications found by computerised tomography is presented. Calcium and phosphorus metabolism showed a pattern suggesting lack of parathyroid hormone (PTH). Further studies revealed increased endogenous PTH levels and urinary cAMP excretion. However, endogenous and exogenous PTH could not elicit the cAMP-mediated phosphaturic response, indicating pseudohypoparathyroidism type II. The responses of prolactin to TRH and chlorpromazine was impaired. Basal ganglia calcification in pseudohypoparathyroidism type II may represent the only somatic abnormality in this disease apart from the biochemical abnormalities.

[Hemodynamic and electrophysiologic effects of the new calcium antagonist Ro 11-1781 (author's transl)]. / Hämodynamische und elektrophysiologische Wirkungen des neuen Calcium-Antagonisten Ro 11-1781.

In a 3-part study the new calcium-antagonist Ro 11-1781 was investigated in respect to hemodynamic, electrophysiologic and antiarrhythmic effects. In the first part of the investigation, systolic time intervals were determined as an indicator of left ventricular performance in 10 patients without cardiac disease before and 5 min after i.v. injection of Ro 11-1781 (1 mg/kg/body weight). At the same time blood pressure was measured. There was a significant decrease in systolic and diastolic blood pressure (p < 0.01). Due to the resulting activation of the sympathetic nervous system by baroreflex, heart rate increased by 7 bpm (p < 0.01), there was a shortening of the pre-ejection period PEPc by 15 ms (p < 0.01), whereas left ventricular ejection time LVETc was not changed significantly. The ratio PEPc/LVETc decreased significantly (p < 0.01), reflecting the increase of left ventricular contractility, which results from the activation of the sympathetic nervous system. The PQ interval was increased (16 ms, p less than 0.01), an atrioventricular block however was not seen. In the second part of the investigation, sinus node function was studied in 8 patients by His-bundle electrography and programmed stimulation of the right atrium. There was no significant change in sinus-node recovery time, sinu-atrial conduction time, sinus-node rate and atrial conduction time in response to Ro 11-1781. However, in 2 patients with sinus-bradyarrhythmia a second-degree sinu-atrial block was provoked by the calcium-antagonist. The drug was shown to have a negative dromotrope effect to the AV node, reflected by an increase of the PQ interval (p < 0.01), AH interval (p < 0.01) and a decrease (p < 0.01) of the maximal 1:1 conduction of the AV node, whereas the HV interval was not changed significantly. The antiarrhythmic effects of Ro 11-1781 were studied in 13 patients with atrial flutter, atrial fibrillation or paroxysmal supraventricular tachycardia: In 10 patients the injection of the calcium-antagonist produced a marked decrease in ventricular rate for a short time reflecting a neagative dromotrope effect in the AV node. In 5 patients conversion to sinus rhythm was observed.

Prophylaxis of ventricular fibrillation after acute experimental coronary occlusion by chronic beta-adrenoceptor blockade with atenolol.

Acute occlusions of the left circumflex coronary artery were performed in open-chest dogs. A control group (n = 19) was compared with three groups (total n = 17) pretreated once daily with different doses of the cardioselective beta-blocking drug atenolol (ICI 66 082) given by mouth for 5 days. Only animals without coronary collateral vessels were examined, having a mortality rate of 100% in the control group. Arrhythmias and ventricular fibrillation during the first 30 min after coronary occlusion showed a biphasic distribution in time (phase 1a and 1b). A lower degree of beta-adrenoceptor blockade reduced the incidence of arrhythmias and ventricular fibrillation in phase 1a, but fibrillation occurred in all animals during phase 1b. A higher dose of the beta-blocking drug protected the animals from ventricular fibrillation, and arrhythmias in phase 1a were greatly reduced. At all times the ventricular fibrillation threshold in the group pretreated with atenolol was significantly higher than in the control group. In both groups a significant decrease in ventricular fibrillation threshold was found only during phase 1a. The greater sensitivity of phase 1a arrhythmias to beta-blockade and the lack of a decrease in ventricular fibrillation threshold during phase 1b might indicate differences in the genesis of arrhythmias and fibrillation in phases 1a and 1b.