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Biomedical subjects

B Ambrosi

Publications and source records attributed to B Ambrosi.

At least 19 recordsLinked to original sources
PubMed2001

Assessment of cure and recurrence after pituitary surgery for Cushing's disease.

BACKGROUND: The treatment of choice in Cushing's disease is transsphenoidal adenomectomy with a recurrence rate ranging 9-23%. We investigated whether abnormal hormonal responses may predict the relapse in "operated" patients followed-up for a long period. METHOD: Sixty-eight surgically treated patients with Cushing's disease were followed-up for 12-252 months. Forty-eight patients underwent selective adenomectomy, 17 enlarged adenomectomy and 3 underwent total hypophysectomy. After surgery ACTH and cortisol levels were measured after stimulatory (desmopressin and CRH) and inhibitory tests (dexamethasone and loperamide). FINDINGS: After operation 46 patients were cured (group A), 15 patients only normalized cortisol levels (group B), 7 patients were surgical failures. During the follow-up, a disease-free condition was maintained in 48 of 61 cases (79%), while a recurrence occurred in 13 patients (21%, 5 of group A and 8 of group B). In 5/13 patients who relapsed an absent inhibition after dexamethasone and an exaggerated response to CRH test preceded the recurrence. In 5 other patients the relapse was suspected by loperamide test. In the 3 remaining cases, positive responses to desmopressin preceded the recurrence. In 7/13 patients who relapsed the pituitary tumour was visualized by MRI/CT imaging. INTERPRETATION: During the follow-up a careful assessment of ACTH dynamics is needed. Although no single test can reliably predict the late outcome, individual patients at risk for relapse may be identified by abnormal responses to desmopressin, CRH and loperamide tests; particularly, the persistent responsiveness to desmopressin may be a criterion of risk for recurrence in patients who only normalized cortisol levels after surgery.

Adenoma↗
PubMed2001

Androgen secretion in ectopic ACTH syndrome and in Cushing's disease: modifications before and after surgery.

The role of ACTH in the control of adrenal androgen secretion is known, although the possible existence of other regulatory factors has been also suggested. While some data concerning Cushing's disease have been reported, only few studies concerned androgen levels in ectopic ACTH secretion. The aim of this study was to evaluate serum DHEA-S, androstenedione (A) and testosterone (T) levels in 36 women with ACTH-dependent Cushing's syndrome (30 with Cushing's disease and 6 with ectopic ACTH secretion) before and after surgery. Two men with ectopic ACTH production were also studied. In 30 women with Cushing's disease serum DHEA-S (9.6 +/- 0.9 micromol/l), A (15.2 +/- 1.2 nmol/l) and T (4.1 +/- 0.5 nmol/l) were higher than in controls (p < 0.01): elevated DHEA-S, A and T values were found in 8, 18 and 17 cases, respectively. After adenomectomy in 15 apparently cured patients DHEA-S, A and T levels were low at 1 - 3 months and at 6 - 12 months after surgery. At 18 - 24 months, DHEA-S remained low in spite of cortisol normalisation. In ectopic Cushing's syndrome, A levels were significantly higher (23.1 +/- 4.9 nmol/l) than in Cushing's disease (p < 0.05), while no differences were found in DHEA-S and T levels. Two patients had elevated DHEA-S values, 3 women had high T levels and 7 of the 8 patients had very high A concentration that was lowered in 3 operated cases. In conclusion, the pattern of adrenal androgen secretion is rather different in patients with pituitary or with ectopic Cushing's syndrome. While the frequency of DHEA-S and T alterations is similar, androstenedione secretion is greatly increased in the latter condition. It is suggested that in ACTH-secreting non-pituitary tumours, the production of a POMC-derived peptide, although unidentified, may lead to preferentially stimulated androstenedione secretion, without affecting other enzymatic pathways.

ACTH Syndrome, Ectopic↗
PubMed2001

Blunted vascular and renal effects of exogenous atrial natriuretic peptide in patients with cushing's disease.

The role of atrial natriuretic peptide (ANP) in glucocorticoid hypertension is still controversial, as glucocorticoids enhance the secretion of ANP in vivo, but reduce its biological activity in vitro. In isolated cells, for example, the cGMP response to ANP is suppressed by dexamethasone. We tested the in vivo relevance of this observation by comparing the cGMP, endocrine, and renal responses to exogenous ANP in patients with Cushing's disease (CD; n = 10) and in a matched group of essential hypertensives (EH; n = 8) and normotensive controls (N; n = 4). alpha-human-ANP was infused at 0.01 microg/kg/min for 120 min with a 30-min recovery period; hormonal and arterial pressure measurements were performed at 30-min intervals, and renal parameters were measured at baseline and after infusion. There was a 4-fold increase in plasma ANP in all groups, but the increments in plasma cGMP were about 50% lower in CD than in N and EH; urinary cGMP was similarly lower in CD (247 +/- 61 vs. 529 +/- 146 and 384 +/- 54 nmol/150 min, respectively). This was associated with a reduced peak increase in hematocrit in CD (+2.6 +/- 0.9%) compared with N (+6.6 +/- 0.9%) and EH (+7.1 +/- 0.7%; P < 0.05 CD vs. both); the diuretic and natriuretic effects of ANP were also lower in CD than in EH with very similar systemic pressure levels (382 +/- 63 vs. 848 +/- 130 mL/150 min, and 61 +/- 14 vs. 113 +/- 14 mmol/150 min, respectively; P < 0.05 for both). The increments in plasma and urinary cGMP in response to physiological doses of ANP are thus blunted in CD patients compared with those in N and EH. This biochemical defect is associated with reduced capillary permeability and a lesser diuretic and natriuretic effect. These data are compatible with an impairment of the biological activity of ANP in glucocorticoid hypertension in humans.

Adult↗
PubMed2001

A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma.

BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while medical treatment is more effective in reducing PRL levels and tumour mass. In this study the effectiveness of surgical, medical and radiant approaches on clinical symptoms, PRL levels and tumour size were compared in a large series of patients with macroprolactinomas. METHODS: One hundred and thirty-two patients (63 males and 69 females) were followed-up. Eighty-three patients were operated by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated by TSS, radiotherapy and dopamine agonists. One hundred and four patients were treated by medical therapy: 49 patients were only administered dopamine agonists and 55 were given dopamine agonists after unsuccessful surgery and/or radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/-319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was found in 15 patients (18%). The pituitary adenoma was completely removed in the 15 cases, in whom serum PRL normalized. Sexual function was restored in 57 percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104 patients (89 percent;). Sexual function was restored in 74 percent; of women and in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be considered the first choice treatment in macroprolactinomas, while the surgical approach is recommended when neurological compressive symptoms are present and in patients resistant or intolerant to dopamine agonists. Radiotherapy may be indicated only in the patients in whom medical and surgical therapy have not been successful.

Adult↗
PubMed2000

Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome and in patients with adrenal incidentaloma.

It is known that either chronic glucocorticoid administration or endogenous hypercortisolism frequently induce an hypercoagulable condition. Since little is known about the evaluation of markers of haemostatic and fibrinolytic systems in other adrenal disorders, we studied plasminogen activator inhibitor (PAI-1), tissue-plasminogen activator (t-PA), fibrinogen and von Willebrand factor antigen (vWF-Ag) levels in 11 patients with Cushing's syndrome and in 12 patients with adrenal incidentaloma. In patients with Cushing's syndrome mean PAI-1, t-PA and vWF-Ag levels did not significantly differ from those found in 50 age- and sex-matched controls, while mean fibrinogen levels were significantly higher in patients (337.0+/-39.1 mg/dl) than in normal subjects (278.9+/-8.4 mg/dl). Patients with adrenal incidentaloma showed PAI-1, t-PA and vWF-Ag mean levels superimposable to those in controls, while fibrinogen (319.7+/-27.9 mg/dl) was slightly, although not significantly, higher than in normals. Considering the limits of normal values (as mean+/-2 SD) obtained in the control group, high PAI-1 levels were found in 2 patients with Cushing's syndrome and in 3 patients with incidentaloma. An elevation of fibrinogen levels was found in 3 patients with Cushing's syndrome and in 3 with incidentaloma. Increased vWF-Ag levels were found only in 1 patient with Cushing's syndrome. An increased t-PA level was occasionally observed only in the patient with adrenal carcinoma. On the whole, an alteration of at least one of haemostatic and fibrinolytic parameters was detected in 55% of the patients with Cushing's syndrome and in 42% of those with adrenal incidentaloma. In conclusion, early alterations of coagulation and fibrinolytic systems may be found in some patients with adrenal disorders, thus suggesting the opportunity of an accurate follow-up in order to identify possible risk factors for cardiovascular disease and thromboembolism.

Adrenal Gland Neoplasms↗
PubMed2000

Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease.

OBJECTIVE: To evaluate the plasma ACTH and serum cortisol responses to desmopressin in patients with Cushing's disease either before or after pituitary adenomectomy during long-term follow-up, and to compare the results with those obtained after corticotrophin-releasing hormone (CRH) testing. DESIGN: Plasma ACTH and serum cortisol concentrations were evaluated after the administration of desmopressin (10 microg i.v.) or CRH (1 microg/kg i. v.) in 34 patients with Cushing's disease. Twenty-four patients with active Cushing's disease were evaluated both before and after transsphenoidal pituitary surgery (TSS); these patients were followed up for 1-36 months. Ten patients were studied only after a long-term period (1-19 years, median 4 years) after TSS (six patients), TSS plus external pituitary irradiation (three patients) and TSS plus radiosurgery (one patient). RESULTS: In 24 patients with active Cushing's disease a significant ACTH/cortisol response (P<0.001) was induced by either desmopressin (ACTH from a baseline of 15.3+/-2.7 pmol/l to a peak of 40.9+/-7.3 pmol/l; cortisol from 673+/-59 nmol/l to 1171+/-90 nmol/l) or CRH (ACTH from a basal of 14. 2+/-2.5 pmol/l to a peak of 47.2+/-7.7 pmol/l; cortisol from 672+/-50 nmol/l to 1192+/- 80 nmol/l). In all patients a positive cortisol response to desmopressin was found. After pituitary adenomectomy the 14 'cured' patients were followed up for 1-36 months; desmopressin administration never induced ACTH or cortisol responsiveness in any patient. In contrast, a progressive recovery of ACTH and cortisol responses after CRH was observed at different intervals of time in all patients but one. Five patients, in whom the cortisol concentration only normalized after surgery, showed a persistent responsiveness to desmopressin, and two of them relapsed 12 and 24 months later. In five patients who were not cured, the hormonal responsiveness to either CRH or desmopressin was similar before and after operation. Of 10 patients studied only after long-term follow-up, six were cured and a normal response to CRH was present, whereas no changes in ACTH/cortisol concentrations were induced by desmopressin. The other four unsuccessfully operated patients underwent pituitary irradiation and showed different and equivocal hormonal responses to desmopressin and to CRH. CONCLUSIONS: During the postoperative follow-up of patients with Cushing's disease, the maintenance or the disappearance of the hormonal response may be related to the persistence or the complete removal of adenomatous corticotrophs, respectively. It is suggested that desmopressin test should be performed in the preoperative evaluation and follow-up of patients with ACTH-dependent Cushing's syndrome.

Adolescent↗
PubMed1998

Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing's syndrome and in patients with adrenal incidentaloma.

Although steroid-induced negative effects on bone and collagen have been well described in corticosteroid-treated patients, few studies have extensively evaluated bone and collagen turnover in patients with endogenous Cushing's syndrome. In this work serum bone-Gla protein (BGP), C-terminal cross-linked telopeptide of type I collagen (ICTP) and N-terminal propeptide of type III procollagen (PIIINP) levels were determined in patients with active (n = 12) and preclinical (n = 6) Cushing's syndrome, adrenal incidentalomas (n = 35) and in healthy controls (n = 28). In patients with overt Cushing's syndrome, serum BGP (0.9+/-0.2 ng/ml), ICTP (2.7+/-0.2 ng/ml) and PIIINP (1.9+/-0.2 ng/ml) levels were significantly lower (P < 0.0001) than in controls (5.5+/-0.2, 3.9+/-0.2 and 3.2+/-0.2 ng/ml respectively). In preclinical Cushing's syndrome, serum BGP (2.5+/-0.8 ng/ml), ICTP (2.2+/-0.1 ng/ml) and PIIINP (2.2+/-0.2 ng/ml) levels were significantly lower than in normal subjects (P < 0.0001, P < 0.0001 and P < 0.02 respectively), being similar to those recorded in overt Cushing's syndrome. In patients with adrenal incidentaloma, serum BGP (4.2+/-0.5 ng/ml) and ICTP (2.9+/-0.2 ng/ml) levels were significantly lower than those found in controls (P < 0.05 and P < 0.001 respectively), while serum PIIINP levels (3.6+/-0.2 ng/ml) did not differ from those of normals. In particular, 9/35 patients with adrenal incidentaloma had markedly depressed BGP levels (<2.0 ng/ml; mean 0.8+/-0.1 ng/ml): all patients of this subgroup showed an exaggerated 17-hydroxyprogesterone increase after ACTH administration. In the same patients, serum ICTP (3.0+/-0.4 ng/ml) and PIIINP (3.6+/-0.2 ng/ml) levels did not differ from those found in the incidentaloma group. In conclusion, our study indicates that bone and collagen turnover are markedly affected in patients with overt and preclinical Cushing's syndrome. Although patients with adrenal incidentaloma do not show any signs or symptoms of overt hypercortisolism, the presence of reduced BGP and ICTP levels might be considered a further index of an 'abnormal' pattern of steroid secretion in some of them. As a consequence, the presence of early alterations in markers of bone turnover might be useful for selecting those patients who need more accurate follow-up of the adrenal mass.

Adrenal Gland Neoplasms↗
PubMed1998

The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function.

The possibility of assessing hypothalamic-pituitary-adrenal (HPA) function by the standard ACTH test (250 microg) has been widely discussed in the past years and compared with the role of the insulin tolerance test (ITT). Recently, it was shown that low doses of ACTH, such as 1 microg i.v., induce a maximal adrenal response and, by reducing the discrepancies compared with the ITT also allow one to detect mild forms of secondary hypoadrenalism. In the present study the 1 microg ACTH test was performed in patients with hypothalamic-pituitary disease in order to assess adrenal function, and the results have been compared with those obtained after the insulin test. Fifty-seven patients (31 men and 26 women, aged 19-73 years) with hypothalamic-pituitary diseases were studied: 51 patients were affected with pituitary tumor and 6 patients had hypothalamic disorders. All these patients and 18 healthy volunteers (7 men and 11 women, aged 19-46 years) received 1 microg i.v. ACTH injection. In addition, the ITT (0.1-0.15 U/kg body weight) was performed in all patients. In normal subjects mean cortisol levels significantly (P<0.001) increased from a baseline of 393+/-43 nmol/l to a peak of 770+/-41 nmol/l after 1 microg ACTH. In 44 patients with hypothalamic-pituitary disease 1 microg ACTH caused a cortisol rise similar to that of normal subjects (from 332+/-17 to 769+/-24 nmol/l; P<0.001), while an impaired response (from 124+/-23 to 312+/-46 nmol/l) was observed in 13 cases (23%), 7 of them with low morning cortisol levels (10-127 nmol/l) and 6 with basal values at the lower limit of normality. The cortisol response to ITT was compared with that obtained after the 1 microg ACTH test: 10 patients failed both challenges, 4 patients who passed the ACTH test failed the ITT, while 3 patients who failed the ACTH test passed the ITT. The 23 out of 57 patients (40%) who showed a cortisol peak greater than 750 nmol/l after 1 microg ACTH had a normal response to ITT. A positive correlation between cortisol peaks after ACTH and after insulin was also found (r = 0.68, P<0.001). Assuming a 100% accuracy of ITT, the low dose ACTH test yielded a 71% sensitivity and a 93% specificity. In conclusion, the low-dose ACTH test is a useful, safe and inexpensive tool for the initial assessment of HPA function in patients with hypothalamic-pituitary disease. In fact, the ITT is unnecessary when cortisol peaks are greater than 750 nmol/l after 1 microg ACTH and also when very low cortisol basal levels indicate an overt hypoadrenalism. Within these limits the ITT is mandatory and its important role in the recognition of secondary adrenal failure is further confirmed.

Adrenocorticotropic Hormone↗
PubMed1997

Long-term results of treatment for craniopharyngioma in children.

Results of the treatment of 27 children with craniopharyngioma are reported. A subfrontal pterional approach was used in 55.6% of cases, a transsphenoidal and a transcallosal or transcortical approach in 25.9% and 18.5% of cases, respectively. Radical removal was the goal of surgery and was achieved in 70.8% of cases treated as primary surgery. The operative mortality was 3.7% and was due to hypothalamic failure. Most (81.4%) patients were followed up, for a mean of 7 years. Patients were evaluated according to a functional evaluation scale and outcome categories proposed by us. The scale takes account of tumor (recurrences and their eventual evolution); visual functions; endocrine functions (mainly hypothalamic), attainment of endocrine balance and drug regimen; headache; and psychosocial function. Recurrences were observed in 17.6% of patients treated with radical surgery and in 42.8% of those treated with limited surgery plus radiotherapy. A progressive amelioration of visual, endocrine and neuropsychosocial functions from the intervention to follow-up was observed in the majority of patients. Complete tumor excision was associated in 85% of cases with a low score on the functional scale, reflecting a high functional performance. Adequate substitution therapy maintained endocrine balance in 81% of patients. Since the intervention a progressive decrease in the number and dosages of medications has been observed. The majority of patients were again able to lead a normal social life. Small stature, obesity, headache, and emotional and sexual disturbances were frequent cause of long-term disability even despite adequate drug regimens. The functional evaluation scale we propose is a simple and effective tool that can be easily used during routine evaluation of patients with craniopharyngioma.

Adolescent↗
PubMed1997

Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess.

OBJECTIVE: To assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushing's disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing. DESIGN AND SUBJECTS: Plasma ACTH and serum cortisol levels were evaluated after the administration of desmopressin (10 micrograms i.v.), CRH (1 microgram/kg i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After pituitary adenomectomy desmopressin and CRH were administered again to 13 of the patients who had undergone pituitary surgery for their Cushing's disease. RESULTS: In 16 patients with Cushing's disease with microadenoma a positive ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2 other patients were responsive only to desmopressin and 2 only to CRH, while in 1 patient equivocal responses to both tests were found. The persistence of a hormonal response to desmopressin after pituitary adenomectomy for Cushing's disease correlated with unsuccessful surgery, while, contrary to CRH, absent ACTH/cortisol rises were found in cured patients 1 and 12 months after operation. In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH administration did not cause any ACTH/cortisol rise. Significant ACTH rises occurred after both desmopressin and CRH testing in patients with Addison's disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise of ACTH levels after CRH, while a similar response after desmopressin occurred in only one of them. CONCLUSIONS: Desmopressin is able to stimulate ACTH and hence cortisol release in Cushing's disease. It may be a useful test in patients with doubtful responses to CRH test, in those exhibiting responses to CRH indistinguishable from those of normal subjects and in the postoperative follow-up of Cushing's disease. In some patients with abolished or reduced cortisol feed-back at hypothalamic-pituitary level the sensitivity of normal corticotrophs to desmopressin is enhanced.

ACTH Syndrome, Ectopic↗
PubMed1997

Loperamide test: a simple and highly specific screening test for hypercortisolism in children and adolescents.

The overnight dexamethasone (DXM) test can give false-positive results in a few conditions (e.g. stress, strenuous exercise, depression, anorexia, anxiety, anticonvulsive therapy) in diagnosing simple obesity and hypercortisolism (HC). The loperamide (LP; a peripheral opioid agonist) test has proven useful in such conditions in adults. Thirty-one obese subjects (age 10.0-19.7 y) were studied by both overnight DXM test and LP test (8 mg orally, samples for cortisol at 0, 90, 150, 180 and 210 min) on 2 separate days. LP suppressed cortisol (< or = 138 nmol l-1) at a dose of 0.1 mg kg-1 bw (half the minimum recommended dose for the drug's antidiarrhoea effect) in 14 subjects who had normal urinary (< 4970 nmol l-1) and serum (< 552 nmol l-1) cortisol, in the absence of signs and symptoms of HC (group A). The DXM test failed to suppress cortisol in three subjects in group A, two of whom were on anticonvulsive treatment. The LP test suppressed cortisol in all of 13 subjects with elevated urinary and/or serum cortisol and/or with signs or symptoms of HC (but in whom HC was subsequently excluded on clinical grounds) (group B), while the DXM test failed to suppress cortisol in three subjects of this group. One of these was under anticonvulsive treatment and one suffered from anxiety and depression. In four patients with Cushing's syndrome (group C) neither DXM nor LP could suppress cortisol levels. Therefore, the sensitivity was 100% for both DXM and LP, while the specificity was 84% for DXM and 100% for LP. No side-effects were observed with either drug. In conclusion, LP is a useful alternative to DXM in those particular conditions that can affect its specificity in children.

Adolescent↗
PubMed1996

Modifications of biochemical markers of bone and collagen turnover during corticosteroid therapy.

Serum bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and aminoterminal propeptide of type III procollagen (PIIINP) levels were determined in 8 patients with autoimmune disorders (2 with systemic lupus erythematosus, 3 with rheumatoid arthritis, 2 with Sjögren's syndrome and 1 with mixed connective tissue disease) before and after 1, 2 and 4 months of treatment with oral prednisone (at a dosage of 1 mg/kg bw/day, p.o. during the first month, then reduced to 0.1-0.2 mg/kg bw/day). Before treatment mean serum BGP (mean +/- SE: 5.3 +/- 0.4 ng/ml) and ICTP (2.8 +/- 0.2 ng/ml) levels were similar to those recorded in an age and sex matched control group (n = 40: 5.4 +/- 0.1 ng/ml and 4.1 +/- 0.3 ng/ml, respectively). On the other hand, serum PIIINP levels (2.2 +/- 0.3 ng/ml) were significantly (p < 0.008) lower than those found in controls (3.3 +/- 0.2 ng/ml). During glucocorticoid therapy, serum BGP levels significantly decreased after 1 month (2.9 +/- 0.4 ng/ml; P < 0.001), but returned to baseline values after 2 and 4 months of treatment (4.7 +/- 0.4 ng/ml and 5.3 +/- 0.3 ng/ml, respectively). On the contrary, no significant changes were observed in serum ICTP levels during treatment (1st month: 2.7 +/- 0.4 ng/ml; 2nd month: 3.0 +/- 0.4 ng/ml; 4th month: 2.4 +/- 0.3 ng/ml). Serum PIIINP mean concentration significantly decreased after 1 (1.6 +/- 0.3 ng/ml; P < 0.004) and 2 months of glucocorticoid administration (1.5 +/- 0.2 ng/ml; P < 0.01); after 4 months, serum PIIINP levels were again reduced as before therapy (1.8 +/- 0.2 ng/ml). In conclusion, our study shows the presence of normal bone turnover indexes and of altered collagen synthesis in patients with autoimmune disorders. The use of high doses of oral steroids is associated with a prompt decrease of bone formation and collagen synthesis, without any significant changes in bone resorption; however, the negative effects on bone formation and collagen synthesis seem to revert after lowering corticosteroid dosage. Serial determinations of the markers of bone and collagen turnover are able to give useful and reliable information on the peripheral effects of steroids excess.

Adult↗
PubMed1996

Value of buserelin testing in the evaluation of hirsute women.

It has been recently reported that many hirsute women are affected with functional ovarian hyperandrogenism (FOH)-a term that encompasses the heterogeneous polycystic ovary syndrome- and show an abnormal ovarian steroidogenic response to gonadotropin-releasing hormone (Gn-RH) agonists. The aims of the present study were to determine the prevalence of FOH by the assessment of 17-hydroxyprogesterone (17-OHP) response to the Gn-RH agonist buserelin, to correlate these abnormal responses to other parameters suggestive of PCOS, and to assess the possible adrenal origin of hyperandrogenism. Therefore, in 33 consecutive women with hirsutism serum LH, FSH, 17-OHP, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), cortisol levels were evaluated in basal conditions and after the administration of buserelin (0.5 mg sc) and ACTH (tetracosactide 0.25 mg iv). Two patients were affected with a non classic congenital adrenal hyperplasia (CAH)-21OH deficiency. In 5 other women ACTH test caused a rate increase 17-OHP (30-0)/30 min > 19 nmol/L/min (0.25 +/- 0.03; mean +/- SE), suggesting the possible existence of heterozygote non classic CAH-21OH. One patient showed a DHEA-S response to ACTH (from 10.3 to 17.2 mumol/L), which was compatible with late-onset 3 beta-Hydroxy-delta 5 steroid dehydrogenase deficiency. Out of the 25 patients with normal responsiveness to ACTH, 11 women (group A) showed higher 17-OHP and A levels, in comparison to normal women, both in basal conditions (17-OHP = 4.18 +/- 0.72 vs 1.74 +/- 0.34 nmol/L, p < 0.005; A = 11.8 +/- 1.2 vs 6.0 +/- 0.7 nmol/L, p < 0.05) and after buserelin (17-OHP = 15.61 +/- 1.31 vs 6.96 +/- 0.9 nmol/L; A = 19.0 +/- 1.9 vs 7.5 +/- 0.8 nmol/L; p < 0.001). In 6 of these 11 patients basal and buserelin-stimulated LH levels were higher than in normals. The remaining 14 patients (group B) showed normal baseline and buserelin-stimulated 17-OHP and A concentrations. In this group only 2 patients had high basal and stimulated LH levels. An augmented LH/FSH ratio was present in 5 and 1 cases of groups A and B, and polycystic ovaries at ultrasonography were observed in 7 and 8 cases of groups A and B, respectively. It is to note that an abnormal 17-OHP response to buserelin was present also in 3 of the 5 patients with abnormal 17-OHP rise after ACTH test, suggesting an adrenal and ovarian cause of hyperandrogenism. In conclusion, an abnormal response to one or both stimulation test was present in 57% of cases: an adrenal origin of hirsutism was detected in 15%, a combined adrenal and ovarian origin was found in 9% and an ovarian cause was present in 33%. Buserelin testing is an useful means to reveal the presence of FOH.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Serum bone Gla protein and carboxyterminal cross-linked telopeptide of type I collagen in patients with Cushing's syndrome.

Serum bone Gla protein, a marker of bone formation, and carboxyterminal cross-linked telopeptide of type I collagen levels, an index of bone resorption, were evaluated in eight patients with active Cushing's syndrome and in four with 'preclinical' Cushing's syndrome, before and after surgery. In basal conditions, serum bone Gla protein levels were significantly lower (p < 0.0001) in patients with active Cushing's syndrome (1.0 +/- 0.35 ng/ml) than in controls (5.4 +/- 0.15 ng/ml); two out of four patients with the 'preclinical' form had reduced bone Gla protein levels, while in the other two cases levels were in the normal range. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (3.0 +/- 0.4 ng/ml), although slightly reduced, were similar to those recorded in controls (4.1 +/- 0.3 ng ml), both in patients with active and with preclinical Cushing's syndrome. After surgery serum levels of both marker proteins significantly increased in seven out of eight patients with active Cushing's syndrome; in one patient, who was not cured after surgery, bone Gla proteins levels remained lower than in normals, while levels of carboxyterminal cross-linked telopeptide of type I collagen had a transient increase after six months. In the two patients with a 'preclinical' Cushing's syndrome who underwent surgery, a significant rise of the levels of both marker proteins was observed, similar to that observed in patients with active Cushing's syndrome. It was concluded that serial determinations of these new markers of bone formation and resorption may be usefully employed to follow-up the clinical course of Cushing's syndrome and provide information on the rate of bone turnover in response to medical and/or surgical therapies. Moreover, the evaluation of these markers in preclinical states of Cushing's syndrome might suggest the need for surgery.

Adult↗