bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perinatal consequences of maternal hypothyroidism in early pregnancy and inadequate replacement
Authors: Wasserstrum Nathan , Ananla Carol A. 
Published: March 2008

SummaryMaternal hypothyroidism may be associated with a variety of pregnancy complications.OBJECTIVE We have evaluated the perinatal consequences of maternal hypothyroidism in early and late gestation.DESIGN Retrospective study of pregnant women, with quasi‐experimental design comparing different subjects.SUBJECTS Forty‐three pregnancies In 42 women with hypothyroidism ‐ either biochemically hypothyroid or with a history of hypothyroidism on adequate replacement ‐ and no other preexisting medical conditions.MEASUREMENT Free thyroxine index (FTI), TSH, and haematocrit at Initial antepartum presentation and near term gestation. Pregnancy outcome variables Including: rate of Caesarean section performed for fetal distress in labour, neonatal weight percentile, and gestational age at birth.RESULTS Of 42 hypothyroid pregnancies, six were complicated by fetal distress In labour leading to Caesarean section. Five of these six were severely hypothyroid (defined as FTI ≤ 0.6 (normal range 1.1–4.4)) on initial antepartum presentation. In contrast, of the 36 pregnancies without fetal distress, only four initially presented severely hypothyroid (P<0.001). Conversely, 56% (5/9) of pregnancies which Initially presented severely hypothyroid were subsequently complicated by Caesarean section for fetal distress in labour. This compared to 3% (1/33) among those who presented either mildly hypothyroid or euthyroid on replacement (P<0.0001). Fetal distress correlated with low FTI (P<0.001) and high TSH at Initial presentation. However, It was independent of FTI near term. A relation between fetal distress and TSH near term did not reach statistical significance. Fetal distress also correlated with low maternal haematocrit on admission to labour and delivery (P<0.05), but was Independent of haematocrit and gestational age at Initial presentation, neonatal weight percentile, and gestational age at birth.CONCLUSIONS Severe maternal hypothyroidism early in gestation Is strongly associated with fetal distress in labour. This suggests that (1) Inadequate maternal replacement leads to fetal distress and (2) maternal thyroid status in early gestation may exert Irreversible effects on the fetus, the placenta, and/or on subsequent maternal adaptations to pregnancy. Early adequate replacement therapy Is especially prudent in pregnant women presenting with severe hypothyroidism.
Assessment of GH status in acromegaly using serum growth hormone, serum insulin‐like growth factor‐I and urinary growth hormone excretion
Authors: Bates A. S. , Evans A. J. , Jones P. , Clayton R. N. 
Published: March 2008

SummaryOBJECTIVE It Is still not clear what Is the most suitable method for monitoring progress of acromegaly. The aim of this study was to assess the relative merits of serum GH, serum IGF‐I and urinary GH (uGH) excretion in the follow‐up of acromegalic subjects.SUBJECTS AND METHODS Thirty‐six acromegalic patients each had a GH day series performed consisting of five serum GH measurements, together with an estimate of serum IGF‐I and uGH. The first sample taken for serum GH was fasting (basal) whilst the third (1430 h) was arbitrarily chosen as a random value. uGH was measured from two overnight collections and the mean value used for subsequent data analysis.MEASUREMENTS Serum GH and IGF‐I were measured by radioimmunoassay whilst uGH was estimated by an Immunoradlometric assay using commercially available reagents.RESULTS There is a highly significant linear correlation between serum GH and IGF‐I following log transformation of these two variables (r=0.85; P<0.0001). Analysis of the raw data shows that the relation is in fact curvilinear rendering IGF‐I less useful as a surrogate for Integrated GH secretion at high levels of serum GH. There is a strong linear correlation between both a singleton basal serum GH and uGH (r=0.78; P<0001) and the mean of five measurements (day series) and uGH (r=0.81; P<0.0001). Both uGH and IGF‐I are excellent predictors of those patients with persistent elevation of serum GH, identifying 95 and 96% respectively with serum GH>5mU/l. We have identified a number of patients, however, with persistent elevation of IGF‐I in the presence of serum GH<5mU/l and normal uGH. Until the significance of these findings with respect to long‐term outcome is known, serum GH should continue to be used In the follow‐up of these patients. An alternative, which reflects integrated overnight GH secretion, Is uGH which is convenient and easy to collect as an outpatient and correlates strongly with serum GH.CONCLUSION Acromegalic patients can be conveniently followed on an outpatient basis using a combination of uGH and serum IGF‐I. Measurements of serum GH can be reserved for those with discrepant results.
Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin‐like growth factor‐l and urinary growth hormone excretion
Authors: Bates A. S. , Evans A. J. , Jones P. , Clayton R. N. 
Published: March 2008

SummaryOBJECTIVES The benefits of treating adults with G H deficiency are now well recognized although the criteria for deciding which patients to treat are still not clear. At present the ‘gold standard’ Is the Insulin stress test (IST) which Is unpleasant and potentially dangerous, particularly in patients with hypopituitarism. The aim of this study was to determine whether alternative methods of assessing GH status are reliable in predicting GH deficiency.SUBJECTS AND METHODS Forty‐four patients with unequivocal G H deficiency (peak 1ST <2mU/l) and 17 with partial deficiency (peak 1ST 2‐10 mU/I) were studied. Each patient was assessed clinically with respect to the number of other pituitary axes affected and biochemically with an estimate of urinary G H excretion (uGH) and serum IGF‐I. These markers were then related to GH status as defined by Insulin stress testing.MEASUREMENTS Insulin stress tests were performed using 0.1 units/kg I.v. and accepted with a blood glucose <2mmol/l. Serum GH and IGF‐I were measured by radioimmunoassay whilst uGH was estimated by an Immunoradlometric assay using commercially available reagents. uGH was estimated from the mean of two overnight urine collections which consisted of all urine passed from last voiding through to the first morning sample.RESULTS The presence of unequivocal G H deficiency (peak 1ST <2mu/l) was predictable if 2 or more other pituitary axes were affected (90%). U G H declined significantly with the level of peak 1ST response (P < 0‐001) and almost so with the number of other deficient hypothalamic‐pituitary axes affected (P= 0‐057). Thus, u G H accurately reflected G H status and showed good separation from normal controls In patients less than 40 years (specificity 79%) and between 40 and 60 years (specificity 67%). Above this age the method is less specific (36%). Patients excreted significantly less G H than controls in all three age groups (P < 0.01). Subnormal levels of IGF‐I were strongly predictive of unequivocal G H deficiency (91 % with subnormal IGF‐I have a peak 1ST G H lt; 2 mU/l) although a normal value does not reliably exclude the diagnosis.CONCLUSIONS A diagnosis of adult G H deficiency can be reliably made without the need for an insulin stress test by using a combination of low urinary G H excretion, subnormal I G F‐I levels and clinical assessment with regard to the number of other pituitary axes affected.
Complex glycerol kinase deficiency: an unusual cause of salt‐wasting in males
Authors: Balducci R. , Municchi G. , Toscano V. , Mangiantini A. , Sabatinl R. , Calola S. , Tedeschl B. , Orlandl L. , Boscherlni B. 
Published: March 2008

SummaryWe report the case of a male Infant who at 10 days of life presented with salt‐wasting. Congenital adrenal hyperplasia was excluded on the basis of normal 17α‐hydroxy‐progesterone plasma levels evaluated before the onset of steroid replacement therapy. The Incidental finding of hypertriglyceridaemia led us to suspect the condition of complex glycerol kinase deficiency which was confirmed by the direct measurement of serum glycerol (7.16 mmol/l, normal range 0.02–0.21). Serum creatine kinase was markedly elevated (5963 U/l, normal range 37–290). High resolution cytogenetic Investigation of peripheral blood showed a small Interstitial deletion within Xp21. The same deletion was found In the patient's mother although not In his maternal grandmother. We present this case in order to emphasize the necessity of evaluating plasma triglycerides in all neonatal males with salt‐wasting which can not be explained by congenital adrenal hyperplasia. Plasma triglycerides measurement carried out using a routine clinical method which measures glycerol released after llpolysis facilitates early recognition of this syndrome, and enables appropriate therapy and subsequent genetic counselling.
An audit of oestradiol levels and implant frequency in women undergoing subcutaneous implant therapy
Authors: Buckler H. M. , Kalsl P. K. , Cantrill J. A. , Anderson D. C. 
Published: March 2008

SummaryOBJECTIVES The aim of the study was to review our long‐term use of subcutaneous oestradiol (E2) Implant therapy for the treatment of climacteric symptoms In post‐menopausal women. On the grounds that the aim Is to restore premenopausal serum E2 levels, our declared clinical policy Is not to repeat Implants even in the presence of symptoms If serum E2 levels are >400pmol/l. Therapy was with 50 mg E2 implants inserted subcutaneously In the lower abdominal wall.DESIGN All women who had attended the gynaecological/endocrinological clinic who had received subcutaneous E2 implants for the relief of climacteric symptoms between December 1981 and 1992 were Included.RESULTS Between December 1981 and December 1992, 275 women received a total of 759.50 mg E2 Implants. The median length of Implant therapy was 34.2 months (range 3.7–109.5 months), and the median number of implants per patient was 4 and ranged from 1 to 13. One hundred and twenty‐nine women had more than four implants and their mean recorded serum E2 level was 425±187 (mean ±SD) pmol/l; the mean level over the first 24 months of therapy was 408±157pmol/l. This was not different from the mean value of the remaining period of therapy (439±168pmol/l). Following the second Implant there was no significant progressive rise in serum E2 with time and implant number and the mean E2 level per patient was no higher in those patients who received implants more frequently. The mean time between the first two implants was 9.7±0.4 months and between subsequent ones was 11.7±0.5 months. After the first two Implants there was no progressive change in this interval with time.CONCLUSION This study shows that effective, safe and sympathetic management of women with oestrogen deficient symptoms may be achieved by use of two criteria to determine re‐treatment; the return of symptoms, and a serum E2 level no higher than 400pmol/l. Once therapy is established, E2 Implants may need to be prescribed only on an annual basis. There appears to be no justification for giving E2 Implants more frequently as this policy achieves satisfactory (physiological) premenopausal E2 levels and good symptomatic relief without any evidence for accumulation of E2 or ‘tachyphylaxis’.
Changes in bone mass and metabolism after surgery for primary hyperparathyroidism
Authors: Garton Mark , Martin James , Stewart Alison , Krukowskl Zygmunt , Matheson Norman , Roblns Simon , Loverldge Nigel , Reld David 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Bone mass Is often reduced In patients with primary hyperparathyroidism (pHPT) and Is usually partially reversible after parathyroidectomy. However, site specific and overall skeletal benefits of surgery in mild asymptomatic pHPT remain uncertain.DESIGN Cross‐sectional and longitudinal studies.PATIENTS Fourteen patients (12 women and 2 men) with pHPT.MEASUREMENTS Baseline bone mass was assessed at the lumbar spine, left hip and whole body using dual‐energy X‐ray absorptiometry, and at the left os calcls using broad‐band ultrasound attenuation. Changes in bone mass, serum Intact PTH and osteocalcin, and urinary pyrldlnium cross‐link excretion were recorded In 10 patients followed for 6 months after surgery.RESULTS (1) Cross‐sectional study: Baseline measurements at the lumbar spine and hip were Inversely related to both the serum PTH concentration and the weight of the parathyroid gland removed at surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had Increased significantly at the femoral neck, greater trochanter, whole body and os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and pyrldlnium cross‐link excretion all fell significantly after surgery. The percentage Increment In whole body bone mineral content at 6 months was proportional to the baseline PTH.CONCLUSION In primary hyperparathyroidism, preoperative reductions and post‐operative gains in bone mass are proportional to the Initial serum PTH concentration. Mild primary hyperparathyroidism probably does not cause appreciable bone loss at clinically relevant fracture sites such as the spine and hip, and In such cases the overall skeletal benefits of surgery are likely to be negligible.
Mammosomatotroph adenoma causing gigantism in an 8‐year old boy: a possible pathogenetic mechanism
Authors: Dubuis J‐M. , Deal C. L. , Drews R. T. , Goodyer C. G. , Lagacé G. , Asa S. L. , Van Vliet G. , Collu R. 
Published: March 2008

SummaryThe pathophysiology of mammosomatotroph adenomas remains unclear. We studied a mammosomatotroph adenoma removed from an 8‐year old boy with a 5‐year history of growth acceleration and acromegalic gigantism at presentation. Elevated basal GH (mean 28 μg/I) and PRL (mean 120 μg/I) plasma levels were observed, as well as paradoxical responses of GH to l‐dopa, TRH and oral glucose administration; PRL was reduced by l‐dopa and slightly Increased by TRH; GHRH stimulated release of both GH and PRL. Two operations were required to remove the very large tumour and the patient was treated with bromocriptine before the second. Hormonal secretion by tumour explants in culture was evaluated under basal conditions and after stimulation or inhibition. High levels of GH and PRL were secreted for up to 24 days. Furthermore, GHRH and TRH caused a dose‐related stimulation of both hormones, while somatostatin and dopamine were effective in suppressing either basal or stimulated hormone release only at very high (μm) concentrations. Intracellular events were studied by determination of the guanosine triphosphate binding (G) protein levels and adenylate cyclase (AC) activity in the tumour tissue. Before bromocriptine treatment, AC activity was very high in the tumour and could be further stimulated by various agents; very high levels of the AC‐stimulatory G protein α subunit Gsα and very low amounts of the AC‐Inhlbiting G protein α subunit G13α and of the phosphollpase C‐stlmulatlng G protein α subunit Gqα were found In the tumour. After bromocriptine, baseline AC activity was normalized and could no longer be stimulated; Gs.α and G13α levels were unchanged while those of Gqa were normalized. Screening of tumour DNA after amplification by polymerase chain reaction followed by single‐strand conformational polymorphism analysis did not reveal any mutations In the hot spots of G protein a subunits (αsα12, αo2 and α11) genes or In the H‐ras and p53 genes. Gs,α and GH transcription factor‐1 (pit‐1) expression were evaluated by amplification of cDNA. While the mRNA expression of pit‐1 decreased after bromocriptine treatment, that of Gs,α increased. These data suggest the possibility of an oncogenic process involving overexpresslon of Gs,α, resulting In chronic activation of adenylate cyclase. Furthermore, our results suggest that the antisecretory and antiprollferatlve effects of bromocriptine may be mediated through a decrease In Pit‐1 secondary to the inhibition of adenylate cyclase activity.
Effectiveness of a long‐acting injectable form of bromocriptine in patients with prolactin and growth hormone secreting macroadenomas
Authors: Tsagarakis S. , Tsiganou E. , Tzavara I. , Nikolou H. , Thalassinos N. 
Published: March 2008

SummaryOBJECTIVE 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 ail 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 <360mU/l) while two patients demonstrated a significant reduction In serum PRL levels (70 and 87% of 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 (100mg) 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.
A simplified gonadotrophin‐releasing hormone test for precocious puberty
Authors: Cavallo A. , Richards G. E. , Busey S. , Michaels S. E. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE The gonadotrophin‐releasing hormone (GnRH) test is Important for the evaluation of children with disorders of puberty. Traditionally, the test determines the peak LH and the peak FSH responses from 5 to 8 blood samples, which makes It cumbersome and costly. We suspected that the test could be simplified to require fewer hormonal measurements.DESIGN A retrospective clinical study.PATIENTS Subjects were 44 girls and 7 boys with signs of precocious puberty, of whom 39 were diagnosed as definite central precocious puberty. Fifty‐five diagnostic tests and 39 tests for suppression during GnRH‐analogue treatment were reviewed.MEASUREMENTS LH and FSH were measured In serum samples obtained during a standard GnRH test. Parameters: LH and FSH responses and the LH: FSH ratio at 30, 45 and 60 minutes, and the respective peak levels. For each parameter, the sensitivities and specificities were estimated and the receiver operating characteristic curve was constructed.RESULTS The receiver operating characteristic curves for the LH responses at 30,45 and 60 minutes and at peak were similar and showed high specificities and sensitivities for the diagnosis of central precocious puberty. A single LH cut‐off (15IU/I) had diagnostic sensitivity >90% and specificity >80% for LH concentrations at 30,45 or 60 minutes and peak, and sensitivity >90% to detect suppression. Calculations of the LH: FSH ratio did not Improve the diagnostic accuracy of the GnRH test achieved by LH alone.CONCLUSIONS A single LH determination 30 minutes after GnRH administration is as useful as the peak LH; FSH measurements are unnecessary for the differential diagnosis of central precocious puberty. We propose that for the diagnosis of central precocious puberty and for treatment monitoring, the GnRH test to be simplified to LH measurement in a single blood sample at 30 minutes.
Thyroid cancer management
Authors: Hardy Kevin J. , Walker Brian R. , Lindsay Robert S. , Kennedy R. Lee , Seckl Jonathan R. , Padfield Paul L. 
Published: March 2008

SummaryOBJECTIVE Thyroid cancer is the commonest endocrine malignancy, yet management remains controversial. Many endocrinologists advocate diagnosis by fine needle aspiration (FNA), treatment by thyroidectomy, ablative radioiodine (131I) and TSH suppression, together with follow‐up with 131I scans or thyroglobulin (Tg) measurements. 131I (therapy or diagnosis) Is given only when TSH Is >30 mIU/I. With this strategy in mind, the aim of the present study was to audit existing clinical practice In a large Edinburgh teaching hospital to establish whether a need existed for local guidelines for the management of thyroid cancer.DESIGN AND PATIENTS Retrospective case‐note audit of 46 patients, aged 55 (range 26–86) years, admitted between 1988 and 1993 with a diagnosis of thyroid cancer.RESULTS Diagnosis: Our FNA false negative rate was high (13%), aspiration technique varied considerably, and cytological reporting was not standardized. Treatment: Three (11%) patients received 131I despite suboptimal TSH levels because of poorly developed mechanisms to prevent this, and 7 (25%) patients had Inadequate suppression of TSH as a result of poor interspecialty communication. Follow‐up: Three (11%) patients were scanned despite TSH levels <30mIU/I, and In 5 (18%) Tg checks were incomplete.CONCLUSIONS This audit Identifies several shortcomings from what might be considered optimum management of thyroid cancer; practice was far from uniform even among the endocrinologists within a single hospital and Interdisciplinary communication was poor. A locally agreed and Implemented protocol should address most of these problems and Improve the care of thyroid cancer patients.
Clinical and genetic changes in a case of a Cushing's carcinoma
Authors: Bates A. S. , Buckley N. , Boggild M. D. , Bicknell E. J. , Perrett C. W. , Broome J. C. , Clayton R. N. 
Published: March 2008

SummaryA 30‐year‐old presented In 1984 with a clinically nonfunctional tumour which subsequently developed Into a metastatic corticotrophlnoma from which he died despite surgery In 1984,1986 and 1991 and external radiotherapy In 1986. Molecular genetic analysis of tumour and metastatic tissue revealed loss of heterozygosity at loci on the autosomes 1p, 3p, 10q26,11q13 and 22q12. Tissue taken at surgery In 1986 also revealed positive cytoplasmic Immunostalning for p53 protein. No such staining was evident in tissue taken at first surgery in 1984. Further analysis of Invasive pituitary adenomas may reveal loci associated with such behaviour, enabling better prediction of subsequent clinical outcome than is possible using standard histological techniques, and delivery of early, aggressive treatment to those tumours which show molecular markers associated with a poor prognosis.