Clinical significance of associated nodular lesions of the adrenal in patients with aldosteronoma

Thirty-seven patients with primary aldosteronism were treated by unilateral total adrenalectomy during a 7-year period (1981–1987). The 37 patients were classified into 3 groups on the basis of adrenal pathology: unilateral solitary adenoma, 23 cases (group 1); unilateral adenomas, 3 cases (group 2); and adenoma with multiple macro- or microscopic nodules, 11 cases (group 3). The preoperative conditions of the patients (age, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and serum potassium concentration), postoperative sequential changes of hormone levels, and outcome of hypertension were compared among the groups in order to determine whether the differences of adrenal pathology would affect the postoperative course. The preoperative parameters excluding age at surgery did not differ significantly among the 3 groups. The mean age in group 3, however, was slightly higher than in groups 1 and 2 (47.8 versus 42.8 versus 42.7 years). Postoperative hormonal changes were also similar, particularly in groups 1 and 3, staying within the normal range throughout the follow-up period (mean, 31 months; range, 3–86 months). However, postoperative improvement of hypertension showed marked differences, being significantl retarded in patients with multinodular lesions (group 3), about half of whom remained hypertensive even after 1 year. Nodular lesions other than adenoma(s) were, therefore, thought not to contribute to hormonal excess but to result from intractable hypertension.

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Resumen Treinta y siete pacientes con aldosteronismo primario fueron tratados mediante adrenalectomía total unilateral en un período de 7 años (1981–1987). Los 37 pacientes fueron clasificados en 3 grupos con base en la patología adrenal: adenoma solitario unilateral, 23 casos (grupo I); adenomas unilaterales, 3 casos (grupo 2); y adenoma con múltiples macro-o micronódulos, 11 casos (grupo 3). Las condiciones preoperatorias de los pacientes (edad, duración de la hipertensión, actividad de renina plasmática, concentración plasmática de aldosterona, y concentración sérica de potasio), los cambios postoperatorios secuenciales en los niveles hormonales, y el resultado de la hipertensión fueron comparados en los 3 grupos, con el objeto de determinar si las diferencias en la patología adrenal podrían afectar la evolución postoperatoria. Los parámetros preoperatorios, excluyendo la edad en el momento de la cirugía, no diferieron significativamente en los 3 grupos. La edad promedio en el grupo 3, sin embargo, fue ligeramente superior en los grupos 1 y 2 (47.8 versus 42.8 versus 42.7 años).Los cambios hormonales postoperatorios también fueron similares, particularmente en los grupos 1 y 3, manteniéndose dentro del rango normal a través del seguimiento (promedio, 31 meses; rango, 3–86). Sin embargo, la mejoría postoperatoria de la hipertensión exhibió diferencias marcadas, con aparación significativamente tardía en pacientes con lesiones nodulares (grupo 3); aproximadamente la mitad de éstos permanecieron hipertensos aún después de un año. Por consiguiente, se piensa que las lesiones nodulares diferentes del adenoma(s) no contribuyen al exceso hormonal sino que resultan de la hipertensión intratable.

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Résumé Trente-sept patients ayant un hyperaldostéronisme primaire ont eu une surrénalectomie totale unilatérale entre 1981 et 1987. Ces 37 patients ont été classés en 3 groupes selon la pathologie surrénalienne: adénome solitaire unilatéral, 23 cas (groupe 1); adénome unilatéral, 3 cas (groupe 2); et adénome avec nodules micro ou macroscopiques multiples, 11 cas (groupe 3). On a comparé les données préopératoires (âge, durée de l'hypertension, activité rénine plasmatique, concentration d'aldostérone plasmatique et kaliémie), les changements hormonaux postopératoires, et l'évolution de l'hypertension afin de déterminer si des différences de pathologie surrénalienne peuvent influencer l'évolution postopératoire. Les paramètres préopératoires (excepté l'âge) ne différaient pas de façon significative parmi les 3 groupes. L'âge moyen était plus élevé dans le groupe 3 que dans les groupes 1 et 2 (47.8 versus 42.8 versus 42.7 ans).Les variations hormonales postopératoires étaient également similaires, surtout dans les groupes 1 et 3, restant dans les limites de la normale pendant la période de suivi (moyenne, 31 mois; extrêmes, 3 à 86 mois). Cependant l'amélioration de l'hypertension postopératoire était différente, retardée de façon significative chez les patients ayant des lésions multinodulaires (groupe 3), la moitié d'entre eux restant hypertendus après un an. Les lésions nodulaires, étant donné que les adénomes ne donnent pas d'hypersécrétion hormonale, peuvent traduire plutôt une hypertension prolongée.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Dorsal fracture of the hamate: distinctive radiographic appearance

Six patients who injured their wrists had radiographs documenting a dorsal, 5- to 10-mm oblong fragment of bone immediately proximal to the base of the fourth and/or fifth metacarpal bones. The fragment was seen on the pronation oblique and/or lateral projections, but not on the posteroanterior projection. The radiographic appearance of the fragment was remarkably similar in all cases. In the one patient in which it was performed, pluridirectional tomography demonstrated that the fragment originated from the dorsal surface of the hamate. Five of the six patients also had associated posterior dislocation of the fourth and/or fifth metacarpals. We conclude that this fragment represents a coronal fracture through the body of the hamate resulting from posterior dislocation or subluxation of the fourth and/or fifth metacarpal.     

Hemodynamic shifts during physical exercise in patients with ischemic heart disease

In 82 CHD male patients aged 35-54 years with well-preserved working capacity (threshold load, 600-750 kgm/min) who had underwent bicycle ergometer test, the time course of changes in the major hemodynamic parameters was found to be significantly similar to that of healthy individuals. The cases who stopped performing bicycle ergometer tests because of anginal attacks, and ST segment depression or either showed a more significant elevation in systolic and diastolic blood pressure at the maximum load rate and lower increase in heart rate than in healthy subjects, which may be regarded as a compensatory mechanism that prevents a further decrease in coronary flow. Diminished increase in stroke index and cardiac index suggests reduced myocardial contractility.     

Accessory left-ventricular chorda and the early ventricular repolarization syndrome

Electrocardiographic symptoms were evaluated in 53 patients with an additional left-ventricular chorda (ALVC), detected by two-dimensional echocardiography. Signs of early ventricular repolarization (EVR) were identified in 45 (84.9%) patients. A transverse ALVC was more common in EVR-free patients (87.5%), as compared to patients with ALVC + EVR combinations (51.1%; p less than 0.05).     

Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species differences

The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption was prolonged and incomplete in the cynomolgus monkey. The bioavailability of abecarnil was 20-30% in all the species investigated. The terminal half-life of the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h). Abecarnil was able to pass the blood-brain barrier achieving concentrations in the brain similar to those in plasma. Tissue distribution of labeled compounds was rapid with highest concentrations in the liver, adrenals, kidneys and pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the feces of the rat, the rabbit and the cynomolgus monkey.     

Stimulus-secretion coupling of arginine-induced insulin release. Resistance of arginine- and ornithine-stimulated glucagon and insulin release to D,L-alpha-difluoromethylornithine

In the isolated perfused rat pancreas, D,L-difluoromethylornithine, tested at a concentration of 3 mmol/L, failed to affect the release of glucagon and insulin caused, over 15 min stimulation, by either L-arginine or L-ornithine (2.0, 5.0 or 10.0 mmol/L) in the presence of either 3.3 or 5.6 mmol/L D-glucose. The inhibition of ornithine decarboxylase also failed to affect the release of glucagon provoked by either L-leucine (2 or 3 mmol/L) or L-glutamine (2 mmol/L) and the secretion of insulin stimulated by a rise in glucose concentration from 5.6 to 10.6 mmol/L. These data are interpreted to suggest that the rapid generation of polyamines from either L-arginine or L-ornithine does not play any significant role in the immediate glucagonotropic and insulinotropic action of these cationic amino acids.     

Both alpha- and beta-adrenoreceptors contribute to the central depressor effect of catecholamines

We compared the effects of alpha 2- and beta-adrenoreceptor blockade on the central actions of catecholamines and metabolites of alpha-methyldihydroxyphenylalanine, epinephrine, alpha-methylnorepinephrine, and alpha-methylepinephrine were studied. I.c.v. and nucleus tractus solitarii (NTS) injections were carried out under anesthesia. Following i.c.v. injection, both epinephrine and methylepinephrine rapidly reduced blood pressure and heart rate, but the effects of methylnorepinephrine occurred somewhat later. Following microinjection into the nucleus of the solitary tract, epinephrine, methylepinephrine, and methylnorepinephrine all caused hypotension and bradycardia. The hypotensive effects of all 3 amines in the NTS were attenuated in additive fashion by yohimbine, an alpha 2 adrenoreceptor antagonist, and timolol, a beta-adrenoreceptor antagonist, whereas only yohimbine attenuated the bradycardia. The combination of yohimbine and timolol abolished the effects of the amines. These data suggest that in the NTS both alpha 2 and beta adrenoreceptor stimulation contribute to the hypotensive effects of these amines, but that only alpha 2 adrenoreceptors are principally involved in the heart rate response.     

The difference in blood pressure between upper arm and finger during physical exercise

Summary. A new apparatus which measures the blood pressure in the finger continuously and yet not invasively was tested for its usefulness during exercise. It was compared with upper arm measurements in 23 volunteers during prolonged bicycle ergometry. Simultaneously, a pulse plethysmogram was recorded from another finger of the same arm, whereas in six additional volunteers Doppler measurements were carried out on the radial artery. The results show that finger systolic pressure ceased to rise at about 40% of maximal exercise; the difference with the continuously rising systolic pressure in the upper arm becoming significant at 140 W. At the same time the amplitude of the finger plethysmogram became significantly higher than its initial value, indicating distinct cutaneous vasodilation, whereas the volunteers also became hot and started to perspire. However, the radial artery ‘flow’, deduced from the Doppler measurements, did not change significantly during exercise. It increased sharply and markedly in the cooling down period. Simultaneously with this increase in flow, HR and both systolic blood pressures fell drastically whereas the plethysmography amplitude remained about stable at its raised level. The results fit in with the idea that a compromise is achieved between the need for muscle activity and the need for temperature regulation. It is concluded that the Finapres functions well during exercise, but that the systolic pressure in the finger is not representative for its more central counterpart during cutaneous vasodilation. It is argued that opening up of AVAs may contribute to this pressure effect.