Biomedical subjects

N Thalassinos

Publications and source records attributed to N Thalassinos.

At least 19 recordsLinked to original sources

PubMed2006

Endogenous subclinical hypercortisolism: Diagnostic uncertainties and clinical implications.

Subclinical hypercortisolism (SH) is a newly characterized hormonal disorder that is almost exclusively detected in the context of incidentally discovered adrenal masses. The diagnostic criteria used for the definition of this condition are at present controversial. Amongst the various tests used for the detection of this abnormality (dexamethasone suppression, urinary free cortisol, ACTH levels, midnight serum or salivary cortisol concentrations, ACTH responses to CRH stimulation), the dexamethasone suppression tests (DST) seem to better accomplish the task of unmasking subtle abnormalities of cortisol secretion. Several versions of DST have been used: the 1-mg overnight, the 3-mg overnight and the classical 2-day low-dose DST. This latter test has the theoretical advantage that, by more efficiently suppressing pituitary ACTH secretion, it may provide a measure of the residual (ie non- ACTH-dependent) cortisol secretion from the adrenal mass. In this way, post-dexamethasone cortisol concentrations may quantify the degree of autonomous cortisol hypersecretion. In fact, post-dexamethasone cortisol concentrations have a negative correlation with basal ACTH levels and a positive correlation with midnight cortisol concentrations as well as the size of the incidentally discovered adrenal mass. Most of the existing data indicate that SH detected in the context of adrenal incidentalomas may have some clinically significant implications. In fact, patients with higher post-dexamethasone cortisol concentrations demonstrate higher lipid levels and lower bone mass densities. It has also been suggested that SH may be responsible for biochemical and phenotypic changes reminiscent of the metabolic syndrome. In summary, SH does exist and is associated with a negative impact in patients' health; however, hormonal cut-off criteria for decision-making remain to be defined.

Adrenal Gland Neoplasms↗

PubMed2004

Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome.

OBJECTIVE: Cushing's syndrome (CS) is a well recognized cause of bone loss. Although many previous studies have shown decreased bone mineral density (BMD) in the lumbar spina and proximal femur of patients with endogenous CS, so far, the data estimating BMD in their peripheral skeleton are sparse. The aim of the present study was to evaluate BMD in the forearm and heel of women with newly diagnosed CS and to investigate its possible correlation with serum osteocalcin (BGP) and 24-hour urinary free cortisol levels (UFC). PATIENTS AND METHODS: BMD in the forearm (distal and ultradistal area) of 29 (13 premenopausal and 16 postmenopausal) women with newly diagnosed CS (18 with pituitary adenoma, 10 with adrenal tumor and 1 with ectopic) was measured by dual x-ray absorptiometry (DEXA) and was compared with BMD of 29 age, body mass index (BMI)- and oestrogen status matched healthy controls. Furthermore, in 18 (9 premenopausal and 9 postmenopausal) of the above patients (14 with pituitary adenoma, 5 with adrenal tumor and 1 with ectopic) broadband ultrasound attenuation (BUA) by quantitative ultrasound (QUS) of the heel was estimated and 18 age-, BMI- and oestrogen status matched healthy women served as controls. In all the patients serum BGP and UFC were measured at the time of diagnosis of CS. RESULTS: Compared to their matched controls, BMD in the forearm and BUA values in the heel did not differ in the premenopausal women with CS, while in the postmenopausal group BMD in the forearm was decreased (P < 0.05) but not BUA. Apart from a weak negative correlation between serum BGP and BMD in the ultradistal site of the forearm in premenopausal women (P = 0.05), serum BGP and UFC did not show significant correlation with BMD or BUA. CONCLUSIONS: BMD in the forearm is reduced only in postmenopausal women with newly diagnosed endogenous CS, while BUA in the heel is unaffected in both pre- and postmenopausal patients. Moreover, serum BGP and UFC do not seem to be relevant markers for assessing bone loss in the peripheral skeleton at the time of diagnosis of hypercortisolemia.

Absorptiometry, Photon↗

PubMed2003

Association of vitamin D receptor gene polymorphisms with bone mineral density in postmenopausal women of Hellenic origin.

OBJECTIVES: There are numerous indications that genetic factors play an important role in the pathogenesis of osteoporosis, a common condition characterized by reduced bone mass and increased fracture risk. The vitamin D receptor (VDR) gene has been suggested as a possible candidate gene for the regulation of bone mass but the relationship between VDR polymorphisms and bone mineral density (BMD) is controversial and has not been confirmed by all workers in different ethnic groups studied. METHODS: In order to evaluate the contribution of the VDR alleles in bone mass loss, the BsmI, ApaI and TaqI polymorphisms in the VDR gene were studied in 126 postmenopausal women. RESULTS: It was found that the bb, aa and TT genotypes and the bAT and baT haplotypes were associated with a lower BMD measured at the forearm. CONCLUSIONS: Our analysis reveals a significant association between VDR gene alleles and bone mass in the population studied.

Bone Density↗

PubMed2003

Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas?

OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.

Adrenal Cortex Neoplasms↗

PubMed2003

A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotropin Cushing's syndrome.

Ectopic ACTH hypersecretion is a rare cause of Cushing's syndrome. Bronchial carcinoids are the most common neoplasms causing the occult ectopic ACTH syndrome (EAS). Localization of these tumors is often difficult. The diagnostic utility of somatostatin receptor scintigraphy (SRS) in EAS has been studied in a limited number of patients with conflicting results. Herein we report our experience with 12 consecutive cases. Histological confirmation was obtained in nine patients, the majority being bronchial carcinoids. Among the seven patients with histologically confirmed bronchial carcinoids, SRS was performed in six patients. In three patients SRS correctly localized a bronchial carcinoid tumor at presentation. In the remaining three it became positive after 8, 22, and 27 months during follow-up. In two patients SRS was positive without any finding in the corresponding conventional imaging study. In two patients positive computed tomography/magnetic resonance imaging preceded SRS localization. There was no false positive SRS. Among three patients with highly suspected EAS, SRS was positive in one. Both patients with EAS due to medullary thyroid carcinoma had focal positive uptake. In summary, in this study a substantial number of patients had positive tumor localization by SRS. Therefore, SRS is a useful tool in the evaluation of patients with EAS.

Adrenocorticotropic Hormone↗

PubMed2002

The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing's syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion.

The role of desmopressin, alone or in combination with CRH, in the differential diagnosis between Cushing's disease (CD) and ectopic ACTH secretion (EAS) still remains uncertain. Based on existing data, the desmopressin test is regarded as an alternative to the CRH stimulation test and, when given in combination with CRH, it has been suggested to completely discriminate between patients with CD and EAS. However, assessment of these tests has been limited in only a small number of patients with EAS. Desmopressin is a relatively specific V2 vasopressin receptor (V2R) agonist. Although expression of V3 vasopressin receptor (V3R) is common in tumors with EAS, the expression of V2R has not been extensively investigated. In the present study, we report our findings of the desmopressin and the combined CRH-desmopressin test in a series of patients with CD and EAS; also, the expression of V2R and V3R was investigated in tumors with EAS by a RT-PCR method. We assessed a cohort of 31 patients with ACTH-dependent Cushing's syndrome, including 26 patients with CD and five cases with histologically confirmed EAS. To avoid bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1-specificity at each level of the percent cortisol (F) and ACTH responses to these tests. Following desmopressin administration there was an overlap of the percent F and ACTH responses among patients with CD and EAS, and the area under the ROC curve for both these responses was not significantly different than that occurring by chance. This was also true for the percent F response following the combined CRH-desmopressin test. However, the area under the ROC curve for the percent ACTH rise following the combined test was significantly different; the point of the ROC curve closest to 1 corresponded to a percent ACTH rise of 218% (88% sensitivity and 80% specificity). Expression of V2R and V3R mRNA was investigated in four of the five excised tumors with EAS and revealed the presence of the V2R in all, whereas the V3R mRNA was expressed in three of these cases. In conclusion, in this series the desmopressin test produced a significant overlap of responses between CD and patients with EAS and, therefore, is of limited value in the differential diagnosis of the ACTH-dependent Cushing's syndrome. This is most probably due to the expression of the V2R in tumors with EAS. Moreover, following the combined CRH-desmopressin test only the ACTH but not the F responses were diagnostically useful, but still far from completely discriminating patients with CD and EAS.

ACTH Syndrome, Ectopic↗

PubMed2001

Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) represents an endocrine syndrome characterized by complex pituitary, parathyroid and pancreatic neoplasia. Loss of heterozygosity of the specific region 11q13 has been reported in several tumours from patients with MEN 1 inherited disorder. We present a case of a young patient with familial MEN 1 syndrome with a pituitary adenoma exhibiting monosomy of chromosome 11. The patient presented with a large and rapidly growing pituitary adenoma associated with markedly elevated serum PRL levels, progressive bilateral visual loss and hydrocephalus. The resected adenoma was chromophobic, mainly PRL-producing and to a lesser degree immunoreactive for GH. Fluorescence in situ hybridization (FISH) using an alpha-satellite centromeric probe detected loss of one chromosome 11 copy in almost all pituitary adenoma cells. Clinical and biochemical studies revealed parathyroid hyperplasia and MRI studies detected a pancreatic tumour in addition to the pituitary adenoma. To our knowledge this is the first study reporting monosomy 11 in pituitary adenoma in a patient associated with familial MEN 1 syndrome.

Adenoma↗

PubMed2001

Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies.

Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. So far, only few cases have been described. In all these cases, cortisol was the predominant steroid released in a food-dependent manner, leading to the development of non-ACTH-dependent Cushing's syndrome. In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing's syndrome, on physical examination. Hormonal investigations in morning fasting samples showed slightly elevated androgen levels, low-normal baseline cortisol, normal suppression of cortisol after dexamethasone administration, and ACTH levels that were not suppressed and did stimulate after CRH administration. The elevated urinary free cortisol excretion, in conjunction with an atypical cortisol diurnal rhythm, raised the possibility of an aberrant stimulation of cortisol production by the adrenal tumor. Further studies demonstrated food-dependent secretion of cortisol, which was abolished by prior octreotide administration. Notably, substantial amounts of adrenal androgens were also secreted after food consumption. Removal of the tumor resulted in undetectable cortisol and androgen levels that did not respond to food consumption. Histological examination of the excised tumor revealed an adrenocortical adenomatous nodule originating from the inner zona reticularis, consisting mainly of compact cells. A steroidogenic secretory pattern, indicating the concomitant release of adrenal androgens and cortisol, was also observed in vitro from tumor cells cultured in the presence of GIP. The in vitro secretory response to GIP was higher for the adrenal androgen DHEA, compared with cortisol. The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor. In summary, we describe a patient with a GIP-expressive cortisol and androgen oversecreting adrenocortical nodule with the unusual presentation of hirsutism and not the typical clinical signs of Cushing's syndrome. It is of note that food intake in this patient provoked a substantial increase in both adrenal androgen and cortisol levels that, together with the histological appearance of this nodule, was compatible with a zona reticularis-derived tumor. Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells.

17-alpha-Hydroxyprogesterone↗

PubMed2000

Diurnal changes in glucocorticoid sensitivity in human peripheral blood samples.

The secretion of cortisol, a principle homeostatic regulator in humans, shows a circadian rhythm, with high concentrations in the morning and low levels in the evening and at night. Tissue response to hormones is dependent on hormone concentrations but also on a variety of cellular factors, such as hormone receptors, transcription factors, and activators. In this report, we evaluated whether cell sensitivity to glucocorticoids (GCs) is also subject to diurnal variation using a whole cell system (whole blood samples) stimulated by lipopolysacharide to induce the production of tumor necrosis factor (TNF-alpha); the induction of TNF-alpha is inhibited by dexamethasone. Blood samples obtained in the morning (08.30-09.00 h) and in the evening (22.30-23.00 h) from 37 healthy individuals (18 males, 19 females) aged 29+/-3 years were treated with lipopolysacharide in the presence or absence of 10(-6) M dexamethasone, and the percentage of inhibition of TNF-alpha production was used as an index of sensitivity to GCs. The mean +/- SD in morning samples was 43.5+/-13.8% for the general population, 42.3+/-14.0% for males and 44.6+/-13.8% for females, whereas that in the evening samples was 36.5+/-15.7%, 35.6+/-13.8% and 37.4+/-17.7%, respectively. The results support a significantly increased sensitivity to GCs in the morning hours compared with that in the evening in the general population (P<0.001) as well as in males (P<0.001) and in females (P<0.001). No sex related differences in sensitivity to GCs were observed in the morning or in the evening hours. The sensitive and reproducible assay utilized in this study could also be used to investigate the sensitivity to GCs in various diseases characterized by resistance to GCs and/or alterations in glucocorticoid receptor function.

Adult↗

PubMed2000

The application of a combined stimulation with CRH and desmopressin during bilateral inferior petrosal sinus sampling in patients with Cushing's syndrome.

BACKGROUND: Bilateral inferior petrosal sinus sampling (BIPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). The diagnostic sensitivity of this procedure is improved by the administration of CRH to stimulate ACTH secretion. It has been reported recently that the combined administration of CRH and desmopressin is a more potent stimulus for ACTH release from corticotroph adenomas. We therefore hypothesized that the combined stimulation of ACTH secretion with CRH plus desmopressin may further improve the diagnostic outcome of this procedure. AIMS: To report our experience of the application of combined stimulation with CRH and desmopressin during BIPSS in patients with ACTH-dependent Cushing's syndrome, and to compare these results to those obtained in patients who have undergone BIPSS with CRH stimulation alone. PATIENTS: We studied 34 patients with ACTH-dependent CS: 30 with Cushing's disease (CD) and four with occult ectopic ACTH syndrome (oEAS). A combined stimulation with CRH (100 micrograms i.v.) plus desmopressin (10 micrograms i.v.) during BIPSS was performed in 15 patients with CD, while in a different group of 15 patients with CD, BIPSS was performed with CRH stimulation alone (100 micrograms i.v.). In the patients with oEAS, BIPSS was performed with CRH stimulation in three and CRH plus desmopressin in one patient. RESULTS: In patients with CD the mean peak ACTH levels from the dominant petrosal sinus samples were significantly higher in the group given a combined stimulus than in the group who had only CRH stimulation (mean +/- SD: 1649 +/- 938 vs. 692 +/- 561 ng/l, P < 0. 05). Dominant inferior petrosal sinus/peripheral (IPS/P) ACTH ratios greater than 2 were observed in 15/15 (100%) patients following the combined stimulation with CRH and desmopressin and 13/15 (87%) patients undergoing stimulation with CRH alone. No patient with oEAS had an IPS/P ratio greater than 2. It is of note that the single patient with oEAS studied following a combined stimulation during BIPSS had a IPS/P ratio of less than 2, despite a significant peripheral ACTH and cortisol response. CONCLUSIONS: A combined stimulus using CRH and desmopressin appears to induce a higher ACTH output from pituitary corticotroph adenomas during BIPSS, which may improve the diagnostic sensitivity of this procedure.

Adenoma↗

PubMed1999

Differentiated thyroid cancer: a retrospective analysis of 832 cases from Greece.

OBJECTIVE: To analyse the initial manifestations, pathological findings, therapy, outcome and prognostic factors in patients with papillary and follicular carcinoma. PATIENTS: 832 patients with well differentiated thyroid carcinoma managed in our department during a period of 30 years (1965-1995). Follow-up data were available for 609 patients for a mean of 5.5 years (range 1-38 years), the remainder having been lost to follow-up. RESULTS: The patients were 677 (81%) with papillary and 155 with follicular carcinoma. They were predominantly female (75%), presenting mainly with a single nodule (53%), while at the time of diagnosis 72% had intrathyroidal carcinomas (class I), 17% had nodal metastases (class II), 7% soft tissue invasion (class III) and 4% distant metastases (class IV). Fifty-five percent of the patients had a complete thyroidectomy (36% had a near total or total thyroidectomy and 19% near total or total thyroidectomy plus block dissection), 2.6% received external radiotherapy and 94% had radioactive iodine as part of the treatment of the original disease. Kaplan-Meier survival analysis was used to calculate both cancer related mortality and disease free survival in the patients followed-up. Although mortality (21 cancer-related deaths) was slightly higher for follicular than papillary carcinoma (10% vs. 5% and 16% vs. 10% in 10- and 15-year survival, respectively) the difference was not statistically significant. Extent of disease at diagnosis, male sex, tumour size and age > 60 years affected probability of cancer death. Cox's proportional hazard regression analysis for disease free survival showed that adverse independent prognostic factors were, for papillary carcinoma, male sex, class II or higher, tumour size > 1 cm and age > 60 years, while for follicular, class III or higher, size > 4 cm and age > 40 years. CONCLUSIONS: We conclude that there is a higher prevalence of follicular carcinoma in our country probably due to a moderate degree of iodine deficiency still existing in Greece. Age and extent of disease at diagnosis were important prognostic factors affecting morbidity and mortality, whereas sex, tumour features and histological type were of minor importance. All these prognostic factors and their relative importance should be taken in consideration in the management of this disease.

Adenocarcinoma, Follicular↗

PubMed1999

Assessment of cortisol and ACTH responses to the desmopressin test in patients with Cushing's syndrome and simple obesity.

OBJECTIVE: The desmopressin test has recently been introduced in clinical practice as an adjunctive tool in the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). It has been reported that the majority of patients with pituitary-dependent CS (Cushing's disease, CD) respond to desmopressin, while no such response is usually observed in other forms of this syndrome. In the present study, the responsiveness of the HPA axis to desmopressin was studied in a group of obese subjects. In addition, the ability of desmopressin administration to differentiate between patients with obesity and the various forms of Cushing's syndrome was investigated. DESIGN AND SUBJECTS: Cortisol and ACTH responses to the administration of desmopressin (10 microg bolus i.v.) were examined in 20 consecutive patients with obesity (14 women and six men; BMI range: 34.5-66.7 kg/m2). Obese subjects had no clinical stigmata of CS. In all obese patients, either an overnight (dex 1 mg at 2300 h) (n = 8) or a formal low-dose (dex 0.5 mg 6-hourly for 2 days) (n = 12) dexamethasone suppression test was performed for the exclusion of Cushing's syndrome. Three of eight subjects showed failure of cortisol suppression (i.e. F > 28 nmol/l) to the overnight dexamethasone suppression test, but they had undetectable cortisol levels (< 28 nmol/l) on further testing with the formal 2-day test. All but two of the remaining subjects had undetectable cortisol levels (< 28 nmol/l) following the formal 2-day, low-dose, dexamethasone suppression test. For comparison, desmopressin responses were also tested in 33 patients with CS of varied aetiologies (25 patients with pituitary-dependent CS, three patients with occult ectopic ACTH secretion and five patients with primary adrenal CS). A positive response was considered to be an increment greater than 20% and 50% from baseline levels of cortisol and ACTH, respectively. RESULTS: Mean cortisol (F) and ACTH levels did not differ from the baseline at any time point following desmopressin administration in the obese group (basal F: 417 +/- 41, peak F: 389 +/- 32 nmol/l, P > 0.05; basal ACTH: 33.5 +/- 4.3, peak ACTH: 50.6 +/- 16.6 ng/l, P > 0.05), or in patients with occult ectopic or primary adrenal CS. In contrast, in the group of patients with CD, there was a significant rise in the mean ACTH and F levels from baseline (basal F: 725 +/- 50, peak F: 1010 +/- 64 nmol/l, P < 0.01; basal ACTH: 88.6 +/- 11.8, peak ACTH: 351 +/- 64 ng/l, P < 0.01). Cortisol responses greater than 20% from baseline were observed in 21/25 (84%) patients with CD, but in only 3/20 (15%) of the obese patients. With regard to ACTH, increments greater than 50% over baseline were observed in 23/25 (92%) of patients with CD, and in only 3/20 (15%) of the obese patients. As previously reported, none of the patients with occult ectopic ACTH secretion or primary adrenal CS had a positive response. CONCLUSIONS: The prevalence of subjects who met the criteria adopted to define positive cortisol and ACTH responses to the desmopressin test was significantly higher in the group of patients with Cushing's disease than in the group of patients with obesity. It is therefore suggested that this test may be occasionally useful in the differentiation between simple obesity and the pituitary-dependent form (but not other forms) of Cushing's syndrome.

Adrenocorticotropic Hormone↗

PubMed1998

The low-dose dexamethasone suppression test in patients with adrenal incidentalomas: comparisons with clinically euadrenal subjects and patients with Cushing's syndrome.

OBJECTIVE: Increasing evidence favours subtle glucocorticoid excess in many patients with adrenal incidentalomas. However, existing evidence is based mainly on the overnight dexamethasone suppression test, a test that is commonly abnormal even among clinically euadrenal subjects. The aim of the present study was to evaluate patients with adrenal incidentalomas for subtle glucocorticoid excess by the more specific low-dose dexamethasone test (LDDST). Moreover, since the criteria of what constitutes an abnormal cortisol response following this test have been largely anecdotal, we report our results in comparison with those obtained in clinically euadrenal subjects, and patients with Cushing's syndrome. DESIGN: A prospective study of 57 patients with adrenal incidentalomas with CT characteristics highly suggestive of benign adrenocortical adenomas and 85 clinically euadrenal subjects consisting of 54 obese women with BMI > 30 kg/m2 (range 30-54.7), 13 women with BMI < 30 kg/m2 (range 20.3-29.6) and 18 healthy volunteers (10 women and eight men) over 40 years of age (mean age 51.7 +/- 9.9, range 40-74; mean BMI 30 +/- 6.6, range 20.3-47.5 kg/m2). A retrospective analysis was performed on 60 patients with a confirmed diagnosis of Cushing's syndrome. MEASUREMENTS: All subjects were admitted to the endocrine ward and underwent a standard LDDST, as follows: after a 48-h stabilization period, a 24-h urine collection for basal urinary free cortisol was performed. Basal serum cortisol and plasma ACTH were measured at 0800 h the following day, and subjects were started on dexamethasone 0.5 mg 6-hourly for 2 days. Post-dexamethasone cortisol and ACTH levels were measured at 0800 h, 6 h after the last dose of dexamethasone. RESULTS: Following dexamethasone suppression serum cortisol concentrations became undetectable (< 28 nmol/l) in all clinically euadrenal subjects. In patients with incidentally discovered adrenal masses, post-LDDST cortisol concentrations were undetectable in 12 (21%), between 28-140 nmol/l in 38 (67%), and 140-216 nmol/l in seven (12%) patients; post-LDDST cortisol values correlated positively with the size of the adenoma (r = +0.482, P < 0.001). Post-LDDST cortisol concentrations in patients with Cushing's syndrome ranged from 85 to 1786 nmol/l; in 3/42 (7%) patients with ACTH-dependent Cushing's syndrome cortisol concentrations were < 140 nmol/l. CONCLUSIONS: On the basis of our data in a large group of clinically euadrenal subjects, we suggest that following LDDST cortisol concentrations should become undetectable with the currently used radioimmunoassays. In patients with adrenal incidentalomas, application of the LDDST confirmed the presence of incomplete suppression of cortisol in the majority of patients. We suggest that the LDDST is a sensitive index of autonomous cortisol production in patients with adrenal incidentalomas; following this test a grading of subtle glucocorticoid excess may be obtained but future studies correlating biochemical, clinical and epidemiological data are required, in order to develop widely agreed cut-off levels of clinically significant glucocorticoid excess in these patients.

Adrenal Cortex Function Tests↗

PubMed1998

Elevated post-dexamethasone suppression cortisol concentrations correlate with hormonal alterations of the hypothalamo-pituitary adrenal axis in patients with adrenal incidentalomas.

OBJECTIVE: It has recently been suggested that autonomous cortisol production may lead to subclinical glucocorticoid excess in a substantial number of patients with incidentally discovered adrenocortical adenomas. Following a standard low-dose dexamethasone suppression test (LDDST) cortisol concentrations are frequently incompletely suppressed in patients with adrenal incidentalomas, due to an ACTH-independent secretion of cortisol by the adrenal mass. Thus, post LDDST cortisol concentrations may provide a measure of the degree of autonomous glucocorticoid secretion, but hormonal alterations in relation to post-LDDST cortisol concentrations have not been thoroughly investigated. PATIENTS AND MEASUREMENTS: 61 patients with radiological features highly suggestive of adrenal adenomas were studied. These included 43 women, 18 men; mean age 59 +/- 1.4, range: 25-76 years; BMI 30.9 +/- 0.8 kg/m2 and waist:hip ratio 0.90 +/- 0.016. All subjects underwent a standard LDDST, as follows: after a 48-hr stabilisation period, 24-hr urine collections for basal urinary free cortisol (UFC) were performed. Basal serum cortisol and plasma ACTH were measured at 8 AM and at midnight the following day, and subjects started dexamethasone 0.5 mg 6 hourly for 2 days. Post-dexamethasone cortisol and ACTH levels were measured at 8 AM, 6-hrs after the last dose of dexamethasone. Blood samples for dehydroepiandrosterone sulphate (DHEAS) and serum lipids were obtained on the morning preceding dexamethasone administration. RESULTS: Post-LDDST cortisol concentrations correlated positively with the size of the adenoma (r = +0.527, P < 0.001). There was a negative rank correlation of post-LDDST cortisol concentrations and basal ACTH levels at 0900 h (rs = -0.426, P < 0.001) and DHEAS (rs = -0.380, P = 0.006). Moreover, there was a good rank correlation between DHEAS and basal ACTH levels (rs = +0.456, P < 0.001). A positive rank correlation was observed between post-LDDST cortisol concentrations and midnight cortisol concentrations (rs = +0.317, P = 0.020). As recent studies have suggested that post-LDDST cortisol levels higher than 70 nmol/l may indicate significant hypercortisolism comparisons were also performed between patients divided according to post-LDDST cortisol values into 3 groups: Group A, > 70 nmol/l (19 pts); Group B, 30-70 nmol/l (27 pts); Group C, < 30 nmol/l (15 pts). Although there was no difference in basal cortisol and UFC values between these groups, ACTH and DHEAS levels were significantly lower, and midnight cortisol significantly higher in group A compared to group C patients (P = 0.030, P = 0.017 and P = 0.001 respectively). Cholesterol and triglyceride levels were slightly albeit significantly higher in group A compared to group C patients (P < 0.05). CONCLUSIONS: It is concluded that higher post-low dose dexamethasone cortisol concentrations are associated with lower ACTH and dehydroepiandrosterone sulphate, higher midnight cortisol concentrations and larger adenomas. These findings are consistent with the hypothesis that post-low dose dexamethasone cortisol concentrations represent a useful index in assessing subtle glucocorticoid autonomy in patients with adrenal adenomas.

Adenoma↗

PubMed1997

Regionalization of occult pancreatic insulinomas with the arterial stimulation venous sampling (ASVS) technique.

Non-invasive modalities (ultrasound, computerized tomography, MRI and somatostatin receptor scintigraphy) often fail to localize insulinomas smaller than 1.5 cm in diameter. Recently, regionalization of such occult insulinomas was facilitated by the arterial stimulation and venous sampling (ASVS) technique, using calcium as the insulin secretagogue. However, so far experience with this technique has been limited to a few tertiary referrals centres worldwide. In these case studies we report our experience in three consecutive patients with occult insulinomas. Three consecutive patients (all men 34, 51 and 56 years of age) with insulin-mediated hypoglycaemia were studied. Diagnosis of insulin hypersection was established by the finding of a high amended insulin: blood sugar ratio during fasting. Localization of a pancreatic mass lesion was unsuccessful by ultrasound, CT and/or MRI in all patients. Two patients had negative octreotide scans. In all patients after the infusion of calcium sequentially into the gastroduodenal, splenic and the superior mesenteric arteries, insulin levels rose significantly in right hepatic vein samples giving rise to diagnostic gradients from the splenic artery (in 2 patients) and gastroduodenal artery (in 1 patient), regionalizing insulinomas in the tail and head or neck of the pancreas respectively. The simultaneously obtained angiogram was positive in only 1 patient, in whom it corresponded to the insulin gradient. Regionalization of these occult tumours was subsequently confirmed at laparoscopy in the 2 patients operated. It is concluded, that the arterial stimulation venous sampling technique is an effective method in regionalizing occult insulinomas and should complement invasive angiography whenever the latter procedure is performed.

Adult↗

PubMed1995

Serum soluble interleukin-2 receptors as an index of the biological activity of thyroid hormones in hyperthyroidism.

In order to examine whether serum soluble Interleukin-2 Receptors (sIL-2R) could be used as a marker of the biological effects of the thyroid hormones, we measured the sIL-2R, sex hormone binding globulin and beta-2 microglobulin levels in thirty-three hyperthyroid patients (14 with Graves' disease, 17 with Toxic Nodular Goiter and 2 with toxic adenoma) before and during treatment with antithyroid drugs. We found that serum sIL-2R concentrations of the patients, at diagnosis, were significantly higher compared with normal controls (2424 +/- 1447 vs 459 +/- 184 U/ml). All hyperthyroid patients had sIL-2R levels > mean + 2SD of normal controls, with 28 of the 33 patients having sIL-2R concentrations higher than 1011 U/ml (mean + 3SD of normal controls). Only 15 patients had SHBG levels higher than 3SD above the mean for the normal controls and 28 had SHBG levels 2SD above the mean for the normal controls. Three of the 5 hyperthyroid patients with normal SHBG levels at presentation had abnormally high sIL-2R levels. In all patients sIL-2R levels decreased gradually during therapy down to normal levels when euthyroidism was achieved. A strong positive correlation was found between sIL-2R, SHBG and T3 and T4 concentrations. Serum B2-microglobulin (B2-m) levels were higher than the upper normal limit only in 9 patients, but a significant decrement was observed in all patients when euthyroidism was achieved. The above results indicate that serum sIL-2R levels could be a useful marker of the in vivo biological effects of the thyroid hormones on lymphocytes in hyperthyroid patients.

Adult↗

PubMed1995

Successful localization of an occult ACTH-secreting bronchial carcinoid tumour with 111indium-DTPA labelled octreotide.

Ectopic ACTH secretion due to occult carcinoid tumours is an occasional cause of ACTH dependent Cushing's syndrome. In many cases the ectopic source may be obvious, but sometimes no obvious source is evident, the so-called occult ectopic syndrome. Due to their small size, localization of such occult tumours, particularly bronchial carcinoids, may be extremely difficult. Whole body CT and venous sampling studies have been used but are not always successful in determining the site of such lesions. We report a 40-year-old patient with the ectopic ACTH syndrome due to a 0.6-cm bronchial carcinoid tumour which was successfully localized by 111indium-DTPA labelled octreotide scintigraphy.

ACTH Syndrome, Ectopic↗

PubMed1995

Effectiveness of a long-acting injectable form of bromocriptine in patients with prolactin and growth hormone secreting macroadenomas.

OBJECTIVE: With the development of new long-acting depot preparations of bromocriptine (bromocriptine LAR), we investigated the effectiveness of intramuscular injections of long-acting bromocriptine in patients with prolactin and GH secreting macroadenomas. STUDY DESIGN AND PATIENTS: Fourteen patients with PRL secreting (8 patients) and GH secreting (6 patients) macroadenomas were treated with monthly intramuscular injections of a long-acting and repeatable form of bromocriptine for 3-6 months. A 50-mg monthly dose was administered in the majority of patients with PRL secreting macroadenomas. A 100-mg monthly dose was administered in all patients with GH secreting macroadenomas. MEASUREMENTS: Plasma PRL and/or GH levels were measured 6 and 12 hours after the first injection and then on days 1, 2, 14 and 28 after each injection, up to a maximum period of 6 months. Patients were hospitalized for 48 hours after each injection and were specifically questioned with respect to side-effects. Pituitary imaging with MRI or CT scans was performed in all patients before commencing treatment and was subsequently repeated in 5/8 patients with macroprolactinomas and 5/6 patients with GH secreting macroadenomas after the completion of a 6-month course of treatment. RESULTS: In all patients with macroprolactinomas, serum PRL levels decreased significantly after their first 50-mg injection with nadir levels obtained by 24-48 hours post injection (12815 +/- 8704 vs 1480 +/- 1859 mU/l; mean +/- SD, P < 0.01). At their latest follow-up, on a 50-mg monthly dose, 4 patients developed normoprolactinaemia (PRL levels < 360 mU/l) while two patients demonstrated a significant reduction in serum PRL levels (70 and 87% or pretreatment values). In two patients, although a substantial decrement of serum PRL levels was achieved 12-24 hours post injection, serum PRL levels increased to pretreatment values by day 14 post injection. Both patients received a higher (100 mg) monthly dose which was partially effective in one patient. In two patients with GH secreting macroadenomas, a sustained decrease of elevated GH levels was observed; in two patients, while a substantial reduction of the elevated serum GH levels was achieved 12-24 hours after the first and subsequent injections, serum GH levels increased to pretreatment values by day 14 post injection; in two patients there was no effect on the elevated serum GH levels. Significant tumour shrinkage (24-50%) was observed in 5/5 patients with PRL secreting macroadenomas assessed at completion of a 6-month course of treatment. Significant tumour shrinkage was also documented in 2/5 acromegalics tested (29 and 46% respectively). CONCLUSION: It is concluded that bromocriptine LAR is an effective treatment in the majority of patients with macroprolactinomas; it is also partially effective in some patients with GH secreting macroadenomas.

Adenoma↗