Undetectable urinary free cortisol concentrations in a case of Cushing's disease.
Measurement of the 24-h urinary free cortisol is a valuable screening test of endogenous hypercortisolism and, although false positive results may occur in a few situations, for example endogenous depression, false negative results are unusual. We report a case of a 48-year-old lady with pituitary-dependent Cushing's disease, whose 24-h urinary free cortisol excretion was consistently undetectable in association with increased plasma and salivary cortisol concentrations and reduced dexamethasone suppressibility. The patient had chronic renal impairment (creatinine clearance 21 ml/min) as a consequence of hypertension, despite only modestly increased urea and creatinine concentrations. Urinary free cortisol measurements must be interpreted with caution in patients with renal impairment. (+info)
Primary hepatic carcinoid in a renal transplant patient.
There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases were malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression. (+info)
The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease.
The neuroendocrine protein 7B2 has been implicated in activation of prohormone convertase 2 (PC2), an important neuroendocrine precursor processing endoprotease. To test this hypothesis, we created a null mutation in 7B2 employing a novel transposon-facilitated technique and compared the phenotypes of 7B2 and PC2 nulls. 7B2 null mice have no demonstrable PC2 activity, are deficient in processing islet hormones, and display hypoglycemia, hyperproinsulinemia, and hypoglucagonemia. In contrast to the PC2 null phenotype, these mice show markedly elevated circulating ACTH and corticosterone levels, with adrenocortical expansion. They die before 9 weeks of severe Cushing's syndrome arising from pituitary intermediate lobe ACTH hypersecretion. We conclude that 7B2 is indeed required for activation of PC2 in vivo but has additional important functions in regulating pituitary hormone secretion. (+info)
Venous subarachnoid hemorrhage after inferior petrosal sinus sampling for adrenocorticotropic hormone.
Neurologic complications associated with inferior petrosal sinus sampling for adrenocorticotropic hormone in the diagnosis of Cushing syndrome are rare. Previously reported complications include brain stem infarction and pontine hemorrhage. We report a case of venous subarachnoid hemorrhage with subsequent acute obstructive hydrocephalus occurring during inferior petrosal sinus sampling for Cushing syndrome. (+info)
Natural killer cell activity in the peripheral blood of patients with Cushing's syndrome.
BACKGROUND: Natural killer (NK) cells are CD3(-)CD16(+)CD56(+) bone-marrow-derived lymphocytes mediating first-line defence by direct cytotoxicity against various types of target cells without prior immunization. NK cell activity is positively regulated by immune interferon (IFN-gamma); among hormones, glucocorticoids are potent in vitro and in vivo inhibitors, whereas ACTH and beta-endorphin in many experimental circumstances enhance NK cytotoxicity. DESIGN: We measured NK cytotoxicity of peripheral blood mononuclear cells (PBMC) obtained at 0800h and 2000h from 26 patients with Cushing's syndrome (12 pituitary-dependent, 12 adrenal-dependent and two dependent on ectopic ACTH secretion). In vitro responsiveness to IFN-gamma or cortisol was also tested. METHODS: NK activity was measured in a 4-h direct cytotoxicity assay using K562 cells as targets. Plasma ACTH, serum and urinary free cortisol were concomitantly measured with commercially available kits. RESULTS: Spontaneous activity and responsiveness to IFN-gamma or cortisol were significantly greater in 15 age- and sex-matched controls than in Cushing's patients at 0800h. In pituitary-dependent Cushing's patients, plasma ACTH correlated positively with mean levels of spontaneous NK activity (r=0.64, P<0.05) and negatively with cortisol-dependent percentage inhibition (r=-0.69, P<0.02). In adrenal-dependent Cushing's patients, a negative correlation was observed between levels of spontaneous NK activity and urinary free cortisol (r=-0.67, P<0.02). CONCLUSIONS: Our data indicate that excess endogenous glucocorticoids affect spontaneous NK cell activity and responsiveness to exogenous IFN-gamma or cortisol. The differential patterns observed between pituitary-dependent and adrenal-dependent groups are compatible with a positive immunomodulatory role of pituitary pro-opiomelanocortin-derived peptides that effectively counterbalance, at least partially, glucocorticoid immunosuppression. (+info)
Studies on the "low dose" suppressible Cushing's disease.
Diagnosis of Cushing's disease in most cases can be established by the standard dexamethasone suppression test without difficulty. However, some cases were known to be normally suppressed by the standard low dose of dexamethasone (2 mg daily). The case we encountered recently was also normally suppressed by either the rapid (Nugent) or the standard (Liddle) method. This fact prompted us to study the usefulness of a single dose of 0.5 mg of dexamethasone to suppress the plasma cortisol in the normal. It was concluded that the single oral dose of 0.5 mg of dexamethasone given at 11 p.m. on the previous night suppressed the plasma cortisol efficiently the following morning in the normal, thus making the differentiation of particular cases of Cushing's disease from the normal possible. The disappearance of plasma dexamethasone did not differ significantly between the normal and the Cushing's disease. (+info)
Pituitary tumours in the elderly: a 20 year experience.
The proportion of the elderly in the population is increasing, and the appreciation and management of medical problems in this age group will therefore become more important. We therefore decided to determine the clinical features and types of pituitary tumour presenting in the elderly, and to examine the treatment and outcome in this group. We conducted a retrospective case-note review from a specialist endocrine and neurosurgical unit in a tertiary referral centre. Eighty-four patients aged 65 years and over on diagnosis of a pituitary tumour were referred to the unit between 1975 and 1996. There were 45 males and 39 females, and the mean age was 72.4 years (range 65-86). Over half of the pituitary lesions were non-functioning adenomas (NFAs) (60.7%). GH-secreting tumours were present in 11 (13.1%) and macroprolactinomas in 7 (8.1%). Four patients had microadenomas and 17 had miscellaneous pituitary-related lesions. Visual deterioration was the commonest mode of presentation in 33 (39.3%), but 54 (64.3%) had evidence of visual impairment on detailed examination. Despite the majority of patients (80.8%) having coexisting medical conditions, trans-sphenoidal surgery was performed in 60 (71.4%) and was well tolerated with a zero peri- and post-operative mortality rate, and post-operative complications in 11 (13.1%). Pituitary tumours in the elderly are most frequently NFAs that present with visual deterioration and hypopituitarism. The fact that 46.5% were pan-hypopituitary on diagnosis and that 64.3% of patients had visual impairment suggests a delay in diagnosis in this age group. Despite significant coexisting medical pathology in this large series of patients, surgery was safe and successful in the majority. (+info)
The expression of inhibin/activin subunits in the human adrenal cortex and its tumours.
Inhibins and activins are dimeric proteins of the transforming growth factor-beta superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin alpha, betaA and betaB subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours. In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for beta subunits, suggesting that activins (beta beta dimers) can be expressed in all zones. Inhibin alpha was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins (alpha beta dimers) is restricted. Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both. Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin alpha in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin alpha in tumours associated with Cushing's syndrome again suggests a link with cortisol production. (+info)