Effect of ketoconazole on CRH-induced ACTH and cortisol release in patients with Cushing's disease.
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Adolescent↗
Biomedical subjects
P Loli
Publications and source records attributed to P Loli.
Use of ketoconazole in the treatment of Cushing's syndrome.
The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period. Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another. The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.
17-Hydroxycorticosteroids↗
Transsphenoidal microsurgery for Cushing's disease.
The study shows the results of transsphenoidal microsurgery in 23 patients with Cushing's disease (CD). Out of the 21 patients with tumour confined to the sella, 18 who had selective adenomectomy, and 1 who underwent total hypophysectomy had correction of hypercortisolism. None of the patients with extrasellar extension of the tumour was cured. In 2 cases no adenoma was found intra-operatively. Post-operative hypoadrenalism was documented in all the patients who remitted clinically. By 3-26 months after surgery, adequate cortisol secretion was found in 12 patients, nine of whom regained diurnal variation of cortisol secretion and ten cortisol responsiveness to hypoglycaemia; a normal or near normal response of cortisol to CRF was documented in 11 out of 17 patients tested. Thyroid and gonadal function was restored in all but two patients in clinical remission, whereas GH responsiveness to hypoglycaemia appeared impaired in 11. Two patients had recurrence of the disease 2 and 3 years, respectively, after successful adenomectomy. In our experience transsphenoidal selective adenomectomy is an effective treatment for most patients with CD; additional therapeutic approaches should be considered for patients bearing pituitary tumours with extrasellar extension, whose surgical outcome is often disappointing.
Adenoma↗
Cushing's disease and marked hyperprolactinemia in a patient with a pituitary macroadenoma: effectiveness of bromocriptine treatment.
The case of a young boy bearing a pituitary PRL secreting adenoma (20-30,000 ng/ml) with the unusual association of clinical and endocrinological features of Cushing's disease successfully treated with bromocriptine is described. Brain computed tomography evidenced a huge pituitary adenoma leading to visual field defects and raised intracranial pressure. Due to the very large size of the tumor, which rendered the complete neurosurgical removal unlikely, medical treatment with bromocriptine (10 mg/day) was started. Follow-up for more than six months demonstrated an impressive reduction of tumor size, the lowering of prolactin levels into the normal range, the normalization of visual field, and the regression of both clinical and biochemical signs of hypercortisolism.
Adenoma↗
Lack of ACTH lowering effect of sodium valproate in patients with ACTH hypersecretion.
The effect of an oral dose of 200 or 400 mg sodium valproate (DPA) on ACTH and cortisol secretion was assessed in 11 patients with Cushing's disease (3 bilaterally adrenalectomized), 3 patients with Nelson's syndrome and 6 patients with Addison's disease. In none of the patients examined DPA induced changes in ACTH (and cortisol) levels appreciably different from the fluctuations recorded after placebo administration. The effect of a long term administration of sodium valproate (600-1000 mg/day) was evaluated in 2 patients with active Cushing's disease and in 1 patient with Nelson's syndrome (3 weeks, 3, 9 months respectively); in the 2 patients with Cushing's disease ACTH and cortisol secretion, 17-hydroxy-corticosteroids (17-OHCS) urinary excretion did not change during DPA treatment. Similarly the cortisol response to hypoglycemia and the 17-OHCS urinary excretion after dexamethasone were not normalized. Long term DPA administration did not induce either clinical or hormonal modifications in the patient with Nelson's syndrome. These findings do not support the possibility that a deficiency of a GABAergic system plays a role in the pathogenesis of ACTH hypersecretion. DPA does not seem to be of therapeutical value in the medical management of Cushing's disease and Nelson's syndrome.
Addison Disease↗
Inhibitory effect of cyproheptadine on ACTH secretion in patients with Addison's disease.
In 14 patients with Addison's disease plasma levels of ACTH were studied after administration of a single oral dose (16 mg) of cyproheptadine. The drug administration was followed by an inhibition of ACTH release. These results support the view that cyproheptadine may exert an inhibitory effect on ACTH secretion in subjects whose corticosteroid feedback mechanism is normal. We hypothesize that the effect of cyproheptadine might be related to its anti-serotonin or anti-histaminergic action.
Addison Disease↗
Effects of sulpiride induced hyperprolactinaemia in patients with Turner's syndrome.
In order to evaluate the interference of prolactin (PRL) on some aspects of pituitary-gonadal derangement observed in patients with hyperprolactinaemic amenorrhoea (HA), a GnRH stimulation test (100 micrograms i.v.) was performed on twenty-one patients with hyperprolactinaemia without evidence of pituitary tumour and in nine subjects with Turner's syndrome (TS) before and after sulpiride administration (200 mg/day orally, for 3 months). In patients with HA an enhanced response of gonadotrophins to GnRH was observed. In patients with TS a further increase of the gonadotrophin hyper-responsiveness to the releasing hormone occurred when hyperprolactinaemia was induced by chronic sulpiride administration. Since, in these patients, appreciable ovarian steroidogenesis is lacking, a direct effect of the increased plasma PRL at the hypothalamo-pituitary level is likely. In hyperprolactinaemic amenorrhoea pituitary hyper-responsiveness may not be due to PRL effects on ovarian steroidogenesis.
Adolescent↗