bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudo‐tumours of the thymus after correction of hypercortisolism in patients with ectopic ACTH syndrome: a report of five cases
Authors: Tabarin Antolne , Catargi Bogdan , Chanson Phillppe , Hieronimus Sylvie , Corcuff Jean‐Benoit , Laurent Françols , Harter Michel , Drouillard Jacques , Roger Patrick 
Published: March 2008

SummaryWe report the cases of four patients with occult, and one patient with overt, ectopic ACTH syndrome. Cushing's syndrome was cured by removal of the ACTH secreting tumour, op'DDD, ketoconazole or bilateral adrenalectomy. SIX to 14 months after remission of hypercortisolism, follow‐up computed tomography or magnetic resonance imaging of the thorax revealed in all five patients an anterior mediastinal mass 3‐5 cm in length that suggested a thymic carcinoma. Exploratory thoracotomy was performed in four cases and allowed the removal of an enlarged, but normal, thymus. Histological examination revealed no tumour but showed benign thymic hyperplasia with negative immunostaining for ACTH. Thymic enlargement spontaneously disappeared 11 months after its demonstration in the patient who did not undergo thoracotomy. The mechanism of this abnormality is thought to be thymic depletion resulting from high plasma cortisol concentrations followed by‘rebound’thymic hyperplasia when cortisol levels fall. Physicians involved in the management of patients with Cushing's syndrome must be aware of this entity In order to avert a diagnostic thoracotomy.
Human TRH receptor messenger ribonucleic acid levels in normal and adenomatous pituitary: analysis by the competitive reverse transcription polymerase chain reaction method
Authors: Kaji Hidesuke , Xu Yue , Takahashi Yutaka , Abe Hiromi , Tamaki Norihiko , Chihara Kazuo 
Published: March 2008

SummaryOBJECTIVE Little is known about the mechanism of diversity in in‐vivo hormonal responsiveness to TRH in patients with functional pituitary adenomas. In order to clarify the relation between the responsiveness to TRH and TRH receptor messenger ribonucleic acid (mRNA) expression, we attempted to measure TRH receptor mRNA levels in human pituitary adenoma tissues by competitive reverse transcription polymerase chain reaction (RT‐PCR) method.PATIENTS Pituitary tissue samples were obtained at autopsy from 5 patients without pituitary disease. Pituitary adenoma tissue samples were obtained at surgery from 18 patients with pituitary adenoma (4 non‐functioning, 8 pro‐lactinoma, 4 acromegaly, 1 Cushing's disease and 1 FSH producing adenoma).METHODS Partial TRH receptor cDNA from a human GH producing adenoma cDNA library was ampilfied by PCR under low stringency conditions using primers encoding the transmembrane domains III and VI of pituitary TRH receptor cDNA. The partial sequence of the amplified cDNA determined by a dideoxy‐chain termination method was identical to the corresponding sequence of human TRH receptor cDNA. A competitor was generated by deleting the inner 111 bp from the amplified TRH receptor cDNA and subcloning. RNA extracted from human pituitary was reverse transcribed and co‐amplified with competitor by PCR under higher stringency conditions. The TRH receptor mRNA levels, expressed as the relative intensity against the amplified levels of competitor, were compared among various pituitary tissues.RESULTS The relative TRH receptor mRNA levels of pituitary tissues in patients without pituitary disease were detectable and variable (M±SD) (0·370 ± 0·231, n= 5), and slightly but not significantly lower than those in patients with pituitary tumours (0·598 ± 0·265, n= 18). In patients with prolactinoma, the relative levels of TRH receptor mRNA were quite variable (0·02–1·170, 0·604 ± 0·358, n= 8) and not correlated with PRL responsiveness to TRH (responder 0·457; non‐responder 0·340–0·950). In patients with acromegaly, TRH receptor mRNA was detectable not only in the paradoxical GH responder to TRH (0·718) but also In the non‐responder (0·758 and 0·765). In one patient with Cushing's disease, a relatively low level of TRH receptor mRNA could be detected (0·415). In the patient with a FSH producing tumour whose plasma FSH did not respond to TRH, a small amount of TRH receptor mRNA was detectable (0·447).CONCLUSIONS in patients with functioning pituitary adenomas, hormonal responsiveness to TRH in vivo might not be assessable by TRH receptor mRNA levels in the adenoma cells.
Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature
Authors: Powrie J. K. , Powell Y. , Ayers A. B. , Lowy C. , Sönksen P. H. 
Published: March 2008

SummaryLymphocytic adenohypophysitis can cause pituitary expansion and hypopituitarism closely mimicking the features of a pituitary adenoma. Discrimination between these two conditions is of importance since, despite the similarity of their presentation, there are significant differences in pathophysiology. In contrast to pituitary adenoma, lymphocytic adenohypophysitis occurs almost exclusively in young women in relation to pregnancy, there is a preference for destruction of ACTH and TSH secreting cells and computed tomographic scanning shows uniform contrast enhancement in a proportion of cases. There is, as yet, no proven specific non‐surgical treatment. There are anecdotal reports of a beneficial effect of steroids but there is also evidence that spontaneous resolution may occur. We have reviewed the literature and report two new cases of lymphocytic adenohypophysitis both of whom exhibited early striking diffuse homogeneous contrast enhancement on magnetic resonance imaging scanning which we suggest may be a diagnostic feature of this condition.
Is IGF binding protein‐3 assessment helpful for the diagnosis of GH deficiency?
Authors: Cianfarani S. , Boemi S. , Spagnoli A. , Cappa M. , Argirò G. , Vaccaro F. , Bitti M. L. Manca , Boscherlni B. 
Published: March 2008

SummaryOBJECTIVE The measurement of serum immunoreactive IGFBP‐3 levels has been proposed as a screening test to Identify children with growth hormone deficiency (GHO). We tested the sensitivity and specificity of the IGFBP‐3 assessment In comparison with the measurement of IGF‐I.DESIGN We assessed the IGFBP‐3 and IGF‐I circulating levels in normal subjects and patients with GHD or idiopathic short stature (ISS).PATIENTS Eighty‐two normal subjects, 16 GHD, and 10 children with ISS were studied. Controls were divided into three age groups: group A, 1‐4 years (n= 16); group B, 5‐9 years (n= 35), and group C, 10‐14 years (n= 31)MEASUREMENTS All subjects underwent standard anthropometry. In short patients, GH secretory status was assessed by clonidine and arginine stimulation tests. IGFBP‐3 and IGF‐I circulating levels were measured by radioimmunoassay.RESULTS IGFBP‐3 and IGF‐I levels were closely related (r= 0.51, P < 0.0001) and IGFBP‐3 was less age dependent than IGF‐I (r= 0.57, P < 0.02 vsr= 0.64, P= 0.0001). Sensitivity (true positive ratio) and specificity (true negative ratio) of IGFBP‐3 measurement were 50 and 92% respectively, whereas sensitivity and specificity of IGF‐I assessment were 75 and 90% respectively. Below the age of 5 years, sensitivity was 20% for IGFBP‐3 and 40% for IGF‐I; specificity was 94% for IGFBP‐3 and 88% for IGF‐I.CONCLUSIONS IGFBP‐3 measurement had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF‐I, even in the first years of life, although, due to the high specificity, the finding of subnormal levels of IGFBP‐3 was strongly suggestive of growth hormone deficiency. The presence of low IGFBP‐3 and IGF‐I levels in a short child with normal GH response to provocative tests should prompt further Investigations, such as the determination of spontaneous GH secretion or assessment of the GH binding proteins together with an IGF‐I and/or IGFBP‐3 generation test, In order to Identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definitive test for diagnosing or excluding growth hormone deficiency and detailed analysis of the results of endocrine tests, clinical findings and other laboratory and radiological Information is necessary to maximize diagnostic accuracy
Genetic counselling in complete androgen insensitivity syndrome: trinucleotide repeat polymorphisms, single‐strand conformation polymorphism and direct detection of two novel mutations in the androgen receptor gene
Authors: Davles Helen R. , Hughes Leuan A. , Patterson Mark N. 
Published: March 2008

SummaryOBJECTIVE Androgen Insensitivity syndrome Is a disorder of male sexual development which results In varying degrees of undervlrlllzatlon In 46XY Individuals with functional testes. In the most severe form, complete androgen insensitivity syndrome (CAIS), patients have a normal female appearance. Although CAIS Is not life‐threatening, affected individuals are Infertile and require counselling, gonadectomy, hormone therapy, and sometimes vaginoplasty. Many families therefore request genetic counselling. Defects in the androgen receptor gene account for most if not all cases of CAIS. The purpose of this study was to evaluate the use of the polyglutamlne and polyglycine trinucleotide repeat polymorphisms in the first exon of the androgen receptor gene for carrier status determination In three CAIS families. In two of these families novel mutations In the androgen receptor gene were subsequently identified which allowed confirmation of carrier status and also a prenatal diagnosis to be made in one family.PATIENTS Three CAIS families were studied. The Index cases all presented with a clinical phenotype typical of CAIS.measurements Family members were typed Initially for the polyglutamlne repeat. In one family this was not Informative and the polyglycine repeat was therefore studied. In this and one further family, the androgen receptor gene was sequenced to Identify the mutation causing the CAIS.RESULTS On the basis of Information from trinucleotide repeat analysis carrier status could be assessed In each family. In one family, evidence for somatic instability of the polyglutamlne repeat was found. In the same family, a novel mutation In the androgen receptor gene, which substituted valine for leucine 881, was identified. Other family members were subsequently typed for the mutation and a prenatal diagnosis was performed. A novel mutation was also identified in a second family substituting the glycine codon at position 371 with a stop codon. Other family members were typed for this mutation.CONCLUSIONS Both the polyglutamlne and polyglycine repeat polymorphisms are useful for the genetic counselling of complete androgen Insensitivity syndrome families. In some cases, however, where the family history is limited, more precise information can be provided only once the androgen receptor mutation causing the complete androgen Insensitivity syndrome has been Identified.
DNA synthesis by pituitary tumours, with reference to plasma hormone levels and to effects of bromocriptine
Authors: Lloyd H. M. , Jacobi J. M. , Willgoss D. A. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE In parathyroid adenomas and experimentally in the normal rat pituitary gland, cell replication and secretory activity were previously shown to be correlated. A similar relationship has now been investigated In human pituitary tumours, since this could have relevance to their growth and aetiology. The effect of bromocriptine on the two variables was examined.PATIENTS Data were derived from 50 patients undergoing operation for pituitary tumour, including 15 with acromegaly and 11 with prolactinoma.MEASUREMENTS Preoperative plasma levels of GH, PRL and gonadotrophins were measured by radioimmunoassay. DNA synthesis, an Index of cell replication, was measured in vitro in freshly removed tumour tissue. Nuclear diameter of tumour cells was measured in histological sections and immunostainlng for relevant hormones was carried out on tumour tissue.RESULTS DNA synthesis was correlated (P<005) with plasma hormone levels in cases of prolactinoma, both treated and not treated with bromocriptine, and In a group of putative FSH secreting tumours from male patients. The correlation was not significant in cases of acromegaly. Comparisons of mean values between groups treated and not treated with bromocriptine showed significantly lower DNA synthesis and mean nuclear diameter In prolactinomas under treatment but not In GH secreting tumours.CONCLUSIONS The findings In prolactinomas suggest a close relationship between secretion and tumour cell replication dependent on still undefined agents, but including dopamine, affecting both variables, and isoforms of PRL, which may stimulate or inhibit replication of PRL secreting cells. The basis of the relationship In FSH secreting tumours Is unknown. The relationship was absent In the non‐homogeneous group of GH secreting tumours. When secretion and growth are correlated, the secretory process may be the site of the primary abnormality in the tumour cell. Evidence that bromocriptine inhibits tumour cell replication was obtained for prolactinomas but not for GH secreting tumours.
The evolution of radiation‐induced growth hormone deficiency in adults is determined by the baseline growth hormone status
Authors: Toogood Andrew A. , David W. , Ryder J. , Beardwell Colin G. , Shalet Stephen M. 
Published: March 2008

SummaryOBJECTIVE Recent studies of GH replacement have suggested several beneficial effects for GH deficient adults. It would therefore be helpful to predict the time of onset of GH deficiency after external pituitary irradiation. We have studied the evolution of GH deficiency with time In patients irradiated for pituitary adenomas and other hypothalamic pituitary tumours.DESIGN Analysis of serial peak GH responses to Insulin hypoglycemia following external irradiation to the hypothalamlc‐pitultary axis using statistical models which allowed for age, sex, previous surgery and the pre‐radiotherapy GH peak response.PATIENTS Eighty‐five non‐acromegalic adults (48 male), 75 of whom had either a pituitary adenoma or a craniopharyngioma and 10 who had other tumours in the hypothalamic‐pituitary region. All the patients had received a radiation dose between 37.5 and 45 Gy divided into 15 fractions given over 21 days.MEASUREMENTS The GH responses to an insulin tolerance test (ITT) performed as part of the regular endocrine follow‐up In patients who received Irradiation to the hypothalamic‐pituitary region.RESULTS Three hundred and forty‐five ITTs were performed over a period of 10 years following radiotherapy. There was a decline In the modelled mean peak GH response to an ITT over the first 5 years which then appeared to plateau. Using an extended model, women had higher GH peak responses than men and this difference was maintained throughout the ten‐year period. The magnitude of the post‐radiotherapy peak GH response at any given time was dependent on the baseline peak GH response, but the rate of the decrease was not affected (P= 0.66). To develop severe GH deficiency (peak GH response less than 5mU/l) after radiotherapy it took patients with baseline GH peaks of 30, 20 and 10mU/l approximately 4 years, 3 years and 1 year respectively. Those patients with a baseline GH peak of greater than 50mU/l are unlikely to develop severe GH deficiency within the first 5 years following radiotherapy.CONCLUSION These results provide an insight into the pattern of the decline In GH secretion following radiotherapy in patients with pituitary disease and the factors affecting It. This Information will help the clinician predict the frequency and timing of GH deficiency in patients irradiated for pituitary disease and the potential need for GH replacement therapy.
Bioactive GH‐like immunoglobulins G in active acromegaly: response to long‐term treatment with bromocriptine*
Authors: Campino Carmen , Szecowka Jaroslaw , Lopez Jose M. , Seron‐Ferre Maria 
Published: March 2008

SummaryIn acromegaly, certain forms of circulating immuno reactlve hGH are not true 6H but IgGs which possess G H biological activity (bioactive G H‐like IgGs). In this study, we tested the effect of bromocriptine on circulating bioactive G H‐like IgGs In an acromegalic woman. Increasing doses of oral bromocriptine (2.5, 5.0 and 7.5mg/day) were administered (for 2, 8 and 6 months respectively). TRH tests were performed before treatment and at the end of treatment with each dose. The patient was without detectable pituitary or extra‐pituitary tumour by magnetic resonance imaging. Her serum contained bioactive G H‐like IgGs equivalent to 240mU/l of hGH and elevated insulin‐like growth factor I (IGF‐I; 9500 U/l). Basal hGH was 12.8 μ/l and Increased to 220mU/l 15 min after TRH (200 μg, l.v.). In addition, in the basal samples of each test we measured total IgGs (radial immunodiffusion), bioactive GH‐like IgGs (isolated by Sephadex and protein A affinity chromatography and assayed using the Nb2 cell assay) and IGF‐I(RIA). Bromocriptine treatment gradually reduced serum levels of bioactive GH‐like IgGs and IGF‐I, with significant falls observed first at 10 months of treatment. Bioactive GH‐like IgGs were 240, 240, 36‐0 and <0.124mU/l and IGF‐I levels were 9500,8700,4000 and 3100 U/l at 0,2,10 and 16 months of treatment, respectively. In contrast, IR‐hGH response to TRH decreased after 2 months of treatment to 89 mU/l and to 49.2 mU/l at the end of the study while basal IR‐hGH remained between 13 and 8‐4 mU/l. Basal PRL fell to almost undetectable levels. Bromocriptine treatment decreased the G H response to TRH and the serum concentration of bioactive G H‐like IgGs and IGF‐I. The striking similarity between the pattern of decrease of serum bioactive GH‐like IgGs and IGF‐I supports the presence of an immuno component in our patient's acromegaly
Octreotide exacerbated fasting hypoglycaemia in a patient with a proinsulinoma; the glucostatic importance of pancreatic glucagon
Authors: Gama R. , Marks V. , Wrlght J. , Teale J. D. 
Published: March 2008

SummaryOctreotide, a long‐acting somatostatin analogue, has been used to alleviate hypoglycaemia In patients with Insulinomas. Transient worsening of fasting hypoglycaemia following octreotide has also been described (Stehouwer et al., 1989).We describe a patient with a‘proinsullnoma’in whom octreotide caused rapid and prolonged symptomatic worsening of fasting hypoglycaemia. Catecholamine and Cortisol counterregulatory hormonal responses were normal but those of glucagon and GH were Impaired.Acute neuroglycopaenlc symptoms were present during octreotide induced hypoglycaemia, which was accompanied by and attributed to an acute reduction in pancreatic glucagon secretion in the presence of persistent and unsuppressed hyperproinsullnaemla. This suggests that glucagon may be Important in maintaining glucose homeostasis in chronic hypoglycaemia due to endogenous hyperinsulinlsm even though its concentration in the peripheral blood Is not raised.
Which adults develop side‐effects of growth hormone replacement?
Authors: Holmes Sarah J. , Shalet Stephen M. 
Published: March 2008

SummaryOBJECTIVE Although the nature of the side‐effects of G H replacement In adults are well described, the factors Influencing their development are III understood. The aim of this study was to determine whether there were any characteristics of adults with G H deficiency that predicted whether or not they developed side‐effects of G H replacementDESIGN A 12‐month study (double blind placebo controlled for the first 6 months and open for the second 6 months) of G H replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) In adultsPATIENTS Sixty‐three adults (27 men, 36 women, aged 34.9 ±1.4 (mean ± SE, range 20.1‐59.5 years)) with G H deficiency (peak serum G H response to provocative testing of less than 10mU/l) who took part In a 12‐month study of G H replacement. Twenty‐five patients (40%) did not develop side‐effects, 19 patients (30%) developed side‐effects which did not necessitate a reduction In dose of G H, and 19 patients (30%) required a reduction In dose of G H because of side‐effectsMEASUREMENTS The three groups of patients were compared according to age, height, weight and body mass index (BMI) at entry Into the study and to pretreatment peak serum G H response to provocative testing. They were also compared according to serum concentration of Insulin‐like growth factor (I G F)‐I and IGF binding proteln‐3, and age‐adjusted serum IGF‐I standard deviation score (SDS), at entry Into the study and by change In these measurements after 6 months of GH replacement. The patient's sex, whether GH deficiency was of childhood or adult onset, estimated duration of G H deficiency, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder and previous therapeutic Interventions were also compared In the three groups of patientsRESULTS Those patients who required a reduction In dose of G H because of side‐effects were more likely to have a peak serum G H response of greater than 1 mU/l (P=0.005) and to have adult onset G H deficiency (P = 0‐04) than those who did not develop side‐effects or who did not require a reduction In dose of G H because of side‐effects. In addition, those who needed a reduction In G H dose were older (P = 0‐002), heavier (P = 0‐04) and had a greater BMI (P = 0‐003) than those who did not develop side‐effects. Those who developed side‐effects but did not require a reduction In dose of GH had a greater increment in I G F‐I S D S after 6 months of G H replacement than those who did not develop side‐effects (P‐0‐03). CONCLUSION Side‐effects of G H replacement are more likely to occur In older patients, In those with a peak serum G H response to provocative testing of greater then 1 mU/l, In those with a greater increment In serum I G F‐I S D S whilst receiving G H replacement, In those with greater weight and BMI, and those with adult onset G H deficiency