THE DEFINITION OF TRUE RECURRENCE OF PITUITARY-DEPENDENT CUSHING''S SYNDROME AFTER TRANSSPHENOIDAL OPERATION

Two patients are described with pituitary-dependent Cushing's syndrome who had successful transsphenoidal selective removal of basophil microadenomas. After a period of adrenal insufficiency the clinical signs and the cortisol secretion rate became normal after 12-18 months, together with the return of a normal feedback response to glucocorticoids (dexamethasone suppression), a normal diurnal rhythm of plasma cortisol, and a normal response to stress (increase of plasma cortisol to insulin-induced hypoglycaemia). However, pituitary-dependent Cushing's syndrome recurred 38 and 56 months after operation. This was preceded by gradual changes of the results of the dexamethasone tests, disappearance of the diurnal rhythm of cortisol, and of the responses of plasma cortisol to hypoglycaemia. 'True recurrence' should be defined as the return of the clinical and biochemical characteristics of Cushing's syndrome after a successful transsphenoidal operation, with a normal hypothalamic-pituitary-adrenal axis as evidenced by a normal response to dexamethasone, a normal diurnal rhythm of cortisol and a normal increase of plasma cortisol with insulin-induced hypoglycaemia.     

AMBULATORY BLOOD PRESSURE MONITORING AND CLINICAL CHARACTERISTICS OF THE TRUE AND WHITE-COAT RESISTANT HYPERTENSION

The resistant hypertension has been differentiated in true resistant hypertension and white-coat resistant hypertension by using ambulatory blood pressure monitoring. White-coat resistant hypertension was defined as high clinic blood pressure, despite triple treatment for at least 3 months, but day-time blood pressure values < 135/85 mmHg. The aim of this study was to evaluate the presence of different clinical characteristics between two types of resistant hypertension.

The study group consisted of 49 patients with essential hypertension, resistant to an adequate and appropriate triple-drug therapy, that included a diuretic, with all 3 drugs prescribed in near maximal doses and that had persistently elevated clinic blood pressure (>140/90 mm Hg), for at least 3 months. They represented the 2% of 2500 hypertensive outpatients that referred at our Hypertension Unit. Patients with white-coat resistant hypertension (n=19) were older (p<0.05) than those with true resistant hypertension (n=30). The sodium intake (p<0.05) and alcohol intake (p<0.05) were significantly higher in patients with true resistant hypertension than in those with white-coat resistant hypertension. The renin plasma activity and plasma aldosterone were higher (p<0.05) in patients with true resistant hypertension than in those with white-coat resistant hypertension with normal plasma electrolyte balance. There were no significant differences in mean values of office systolic and diastolic blood pressures between white coat resistant hypertensives and true resistant hypertensives (165+17 vs 172+28 and 98+12 vs 102+14 mmHg).

Day-time and night-time ambulatory 24-h-systolic and diastolic blood pressures were significantly higher in the true resistant hypertensive patients when compared with white-coat resistant hypertensives (153+15 vs 124+10 mmHg and 97+9 vs 76+6 mmHg all p<0.001). Day-time and night-time ambulatory 24-h-heart rate were significantly higher in the true resistant hypertensive patients when compared with white-coat resistant hypertensives (79+11 vs 71+9 beats/min;p<0.01; 68+9 vs 60+6 beats/min. p<0.001). The ABP readings were analysed by a Fourier series with 4 harmonics. According to the runs test both two groups of patients showed a circadian rhythm for both systolic and diastolic blood pressure. The nocturnal fall in SBP, DBP and HR was not different in both groups of patients.

In conclusion, our findings showed that true resistant hypertensive patients were characterized both by higher heart rate and higher plasma renin activity values as an expression of a possible increased sympathetic activity. Thus, the combination of ABPM with the assessment of the clinical characteristics allow to differentiate better the true drug-resistant hypertension from the white coat resistant hypertension.     

CLINICAL, CYTOGENETICAL, HISTOLOGICAL, IMMUNOLOGICAL AND HORMONAL STUDIES IN A CASE OF TRUE HERMAPHRODITISM

A true hermaphrodite with ambiguous genitalia and 46XX karyotype was studied from 18 months of age to 17 years. At 13 years, he developed an ambiguous puberty, with marked bilateral gynaecomastia and pubic hair score three. A relatively high testosterone level (21 nmol/1), not increased by hCG stimulation, was associated with a high LH level (6IU/1). In the venous blood of the right ovotestis, the steroid concentrations were in the adult male range, especially testosterone (1400 nmol/1). After removal of the right gonad, large fluctuations of oestradiol levels were observed (150–810 pmol/1). The testosterone secretion of the left ovotestis was low, concentrations being 4·2 and 130 nmol/1 in peripheral and gonadal blood respectively at 16 years. A significant LH surge was induced by oral ethinyl-oestradiol before removal of the left gonad. The 5α-reductase activity was normal in pubic skin. In the left gonad the concentrations of cytosol receptors for testosterone and 5α-dihydrotestosterone (DHT) were significant: 14·5 and 65·5 fmol/mg protein respectively. However the plasma DHT level was not increased by hCG. Finally, the presence of H-Y antigen was demonstrated on lymphocytes. This accords with the presence of testicular tissue in an XX subject, and with significant testosterone production. The high testosterone production did not prevent the appearance of a positive oestrogen-LH feedback. The relative peripheral insensitivity to testosterone, is, in some ways, inconsistent with the presence of receptors for androgens.     

SALIVARY CORTISOL LEVELS IN TRUE AND APPARENT HYPERCORTISOLISM

Total plasma cortisol measurements may be misleading when there are variations in the plasma cortisol-binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol-binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic-pituitary-adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary-dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half-life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary-dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

THE LH RESPONSE TO LH-RELEASING HORMONE IN CHILDREN WITH TRUE ISOSEXUAL PRECOCIOUS PUBERTY TREATED WITH CYPROTERONE ACETATE

Fourteen girls and one boy with isosexual precocious puberty were submitted to LHRH stimulation tests, during and without therapy with cyproterone acetate. In addition, fourteen girls with isosexual precocious puberty not receiving any therapy were tested and served as controls. It was found that cyproterone acetate induces suppression of the responsiveness of the pituitary gland to secrete LH on LHRH stimulation. Daily oral therapy was found to be more effective than the regimen of intramuscular depot injections. These findings demonstrate that cyproterone acetate has an antigonadotrophic effect.     

H-Y POSITIVE 46 XX TRUE HERMAPHRODITISM WITH INTRASCROTAL UTERUS

A rare form of true hermaphroditism with hypogonadism, gynaecomastia, presence of an intrascrotal uterus, and 46 XX karyotype, is reported. It is the third published case in the literature since 1965. The presence of H-Y antigen and of testicular tissue in the absence of a Y chromosome is discussed.     

The true value of the TRUE test for allergic contact dermatitis

The development of the thin layer rapid use epicutaneous (TRUE) Test is a history of cooperation between scientists from academia and industry covering several disciplines: medicine, pharmaceutical chemistry, pharmacology, and statistics. The TRUE Test is today a patch test system with documented stability and allergen content. Allergens are incorporated in a dried-in-gel vehicle, which is coated onto a polyester backing to form a patch. Applied to the skin, the allergens are released when the gel becomes moisturized by transepidermal water. This may seem to be a simple technique, but its development required laborious research and solutions to stability and dosage problems. The test has been clinically standardized with serial dilution tests on sensitized patients and validated in comparative multicenter tests. The test is a significant step towards higher reliability of patch testing. Fifteen years of experience and critical investigations are discussed in this article, as are possible improvements such as expansion of the test with new allergens.     

特发性真性性早熟女孩超声显示的子宫和卵巢形态改变与血清LH、FSH和E＿2的关系

对５６例特发性真性性早熟女孩，用Ｂ超检查子宫和卵巢形态，并于同日抽血，用放射免疫法测定ＬＨ、ＦＳＨ和Ｅ＿２。结果显示卵巢容积与三种激素均不相关，但最大卵泡直径与ＬＨ、Ｅ＿２及卵巢总容积显著相关。直径≥４ｍｍ的卵泡呈现率随发育成熟度显著增加，并与子宫腔内膜线可辨率高度相关。Ⅲ期后有＞８ｍｍ的卵泡出现。子宫体容积与ＬＨ和Ｅ＿２均相关。提示卵巢和子宫形态是血ＬＨ和Ｅ＿２水平的组织影像学印迹，其中卵巢有≥４ｍｍ的卵泡（尤其＞８ｍｍ）伴宫腔内膜线可辨，结合垂体－性腺轴激素水平，可对真性性早熟作出诊断