bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral catecholamine alterations in adolescents with polycystic ovary syndrome
Authors: Garcia‐Rudaz Cecilia , Armando Ines , Levin Gloria , Escobar María Eugenia , Barontini Marta
Published: March 2003

OBJECTIVE

Polycystic ovary syndrome (PCO) is one of the most common endocrine disorders affecting women. Several lines of evidence have suggested the involvement of the sympathetic nervous system (SNS) in this condition. The present work was designed to assess neurochemically SNS activity in patients during the early stages of PCO.

DESIGN AND PATIENTS

Fourteen patients with PCO (aged 14 to 21 years) were studied on a random day and 9 normal regularly cycling adolescents (aged 14 to 20 years) were studied during the early follicular phase (days 2 to 5).

MEASUREMENTS

Hormonal profile was determined in basal conditions. LH and FSH were also measured after iv administration of 100 μg GnRH. Plasma concentrations of dihydroxyphenylalanine (Dopa), noradrenaline (NA), adrenaline (A), total dopamine (DA) and dihydroxyphenylglycol (DHPG) were determined in basal conditions and in response to GnRH by HPLC with electrochemical detection or a radioenzymatic method. Basal urinary Dopa, catecholamines and catechol metabolites (DHPG, vanillylmandelic acid (VMA), 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), homovanillic acid (HVA), metanephrine (MN) and normetanephrine (NMN)) were determined by HPLC with electrochemical detection.

RESULTS

Basal plasma LH, testosterone, androstenedione, oestrone and LH/FSH ratio were higher (P < 0.01) and serum sex hormone‐binding globulin (SHBG) were lower (P < 0.01) in PCO patients than in control subjects. Basal and GnRH‐stimulated plasma free Dopa, A, NA and total DA were similar in patients and controls. Plasma DHPG was lower (P < 0.01) in PCO patients (4.20 ± 0.30 nmol/l) than in controls (8.0 ± 1.0 nmol/l) throughout the study. Urinary A, NA, DA, Dopa, MN, MHPG, HVA, and VMA were similar in patients and controls. Urinary DHPG was lower (P < 0.01) in PCO patients (0.50 ± 0.02 μmol/d) than in controls (0.73 ±0.09 μmol/d). On the other hand PCO patients had a higher urinary excretion of NMN than controls (PCO: 1.20 ± 0.10; C: 0.78 ± 0.10 μmol/d, P < 0.05).

CONCLUSIONS

Our results show the same endocrinological features in adolescent PCO patients as those reported in adults. The results also demonstrate a peripheral catecholaminergic alteration which suggests an alteration in noradrenaline deamination and/or uptake in adolescent patients. This study however does not permit us to conclude that PCO is primarily caused by this sympathetic alteration.
Decreased regional blood flow in patients with acromegaly
Authors: Chanson Philippe , Megnien Jean‐Louis , Del Pino Murielle , Coirault Catherine , Merli Isabelle , Houdouin Laurence , Harris Alan G. , Levenson Jaime , Lecarpentier Yves , Simon Alain , Chemla Denis
Published: March 2003

BACKGROUND AND AIMS

One‐third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome.

PATIENTS AND CONTROLS

Twelve patients with active acromegaly (five females, seven males; mean (± SD) age, 43 ± 10 years) were studied. Twelve age‐and sex‐matched normal subjects served as controls.

METHODS

Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two‐dimensional pulsed Doppler system (double transducer probe and range‐gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio.

RESUTLS

Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 ± 0.47 (mean ± SD) l/min/m2 body surface area and 116.7 ± 19.4 ml, respectively, while systemic vascular resistance was low (12.5 ± 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 ± 1.26 vs. 5.12 ± 1.74 cm/s, and 16.4 ± 9.4 vs. 25.6 ± 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 ± 61 vs. 83.8 ± 47 mmHg/ml/s/m2, respectively, P < 0.01).

CONCLUSION

While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.
Pituitary apoplexy following metastasis of bronchogenic adenocarcinoma to a prolactinoma
Authors: Hanna  , Williams  , Davies  , Dawson  , Neal  , Scanlon
Published: March 2003

A 42‐year‐old house wife presented with worsening headaches over 6 months in the absence of visual symptoms or symptoms suggestive of focal neurology. She was a life‐long smoker. Systems review was unremarkable apart from secondary amenorrhoea and galactorrhoea of 6 months duration. Her serum prolactin was found to be 620 mU/l (60–400), FT4 12.6 nmol/l (9.8–23.1), TSH 1.38 mU/l (0.35–5.5), oestradiol < 73 pmol/l, LH and FSH of 4.4 and 12.6 mIU/l, respectively. She was on bromocriptine. A presumptive diagnosis of pneumonia, based on pyrexia and CXR findings, was made and she was started on IV antibiotics. Two days later she developed meningism and deterioration of conscious level. (Lumbar puncture results: no organisms, 312 neutrophils and 164 lymphocytes). CT scan revealed a 2.5‐cm pituitary adenoma, with suprasellar extension. A repeat hormonal profile revealed FSH 1.4, LH < 0.3 mU/l, oestradiol < 73 pmol/l, prolactin 488 mU/l (60–400), and low random cortisol at 29 nmol/l. T1‐weighted MRI revealed a large pituitary mass with evidence of haemorrhage. The patient subsequently underwent a transsphenoidal exploration with resection of the pituitary lesion. Whilst awaiting the histopathology results, CT of chest revealed a 1.5‐cm diameter rounded well defined density in the right lower lobe associated with hilar, pre‐ and right para‐tracheal lymphadenopathy. The histopathology of the pituitary lesion, obtained piecemeal, revealed fragments of fibrous tissue infiltrated by sheets of acidophilic prolactin‐positive cells, in keeping with a prolactinoma. In addition, other fragments with blood clot included highly atypical epithelial cells with mitotic figures. These were negative for prolactin but showed HMFG‐and CEA‐positivity, excluding them from a pituitary lineage. Transbronchial biopsy revealed moderately differentiated adenocarcinoma, with evidence of lymphatic spread. The overall conclusion was of bronchogenic adenocarcinoma, metastasizing to a prolactinoma and complicated by apoplexy.
Disturbances of menstruation in hypothyroidism
Authors: Krassas G. E. , Pontikides N. , Kaltsas Th. , Papadopoulou Ph. , Paunkovic J. , Paunkovic N. , H. Duntas L.
Published: March 2003

OBJECTIVES

Most thyroid textbooks describe hypo‐thyroidism resulting in changes in the length of the menstrual cycle and in the amount of bleeding. Our experience at a busy thyroid clinic had given a picture which differs from that presented in the literature. The aim of this study was to determine the frequency and type of menstrual irregularities in premenopausal hypothyroid patients.

DESIGN AND PATIENTS

We investigated the menstrual history, starting 6 months before the discovery of the disease, in 171 female premenopausal hypothy‐roid patients and 214 normal controls, with similar age and body mass index (BMI).

MEASUREMENTS

TSH, TT4, TT3 and thyroid anti‐bodies were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m2.

RESULTS

Of the 171 hypothyroid patients, 131 (76.6%) had regular cycles and 40 (23.4%) irregular periods. Oligomenorrhoea and menorrhagia were the most common features in the latter group. No difference in BMI was found between the patients with or without menstrual abnormalities, or between patients and controls. TSH, TT4 and TT3 levels did not differ between patients with normal and abnormal menstruation. Forty‐six (26.9%) out of 171 patients had subclinical hypothyroidism (group A), 42 (24.6%) mild hypothyroidism (group B) and 83 (48.5%) severe hypothyroidism (group C). Thirty‐seven from group A (80.4%), 32 from group B (76.2%) and 62 from group C (74.7%) had normal periods. These differences were not statistically significant. Eighty‐eight (88.9%) out of 99 patients in whom thyroid antibodies were measured had positive titres. Nineteen (21.6%) of the patients with positive thyroid antibodies had menstrual irregularities. This percentage did not differ from that found in the whole group of patients (23.4%). Out of 214 normal controls, 196 (91.6%) had normal menstruation and 19 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea.

CONCLUSIONS

These data demonstrate that hypo‐thyroidism in women is less frequently associated with menstrual disturbance than was previously described. Also, menstrual irregularities tend to be more frequent in sever hypothyroidism in com‐parison with mild cases, although this finding was not statistically significant. Oligomenorrhoea and menorrhagia are the most common menstrual disturbances.
Incidentally discovered pituitary lesions: high frequency of macroadenomas and hormone‐secreting adenomas — results of a prospective study
Authors: Feldkamp  , Santen  , Harms  , Aulich  , Mödder  , Scherbaum
Published: March 2003

OBJECTIVE

With increasing use of computed tomography and magnetic resonance imaging, pituitary adenomas are being discovered incidentally with increasing frequency. However, limited data are available concerning the clinical importance and natural history of such ‘incicentalomas’. We have undertaken a prospective study to investigate changes in adenoma size and endocrine and visual function in patients with incidentally discovered intrasellar masses.

PATIENTS AND METHODS

Our study included 67 patients with incidentalomas of the pituitary gland during a 5‐year period (1992–96). 50 of these patients were followed up prospectively over a mean period of 2.7 years. Initially, all patients underwent endocrine testing and ophthalmological examinations as well as magnetic resonance imaging or computed tomography scans. These investigations were repeated after 3 months and then annually.

RESULTS

42 (62.7%) out of 67 patients with incidentalomas had microadenomas whereas 37.3% had macroadenomas. Macroadenomas were found more frequently in men (52.2%). Visual field defects could be documented in 4.5% of the patients. Partial deficiency of anterior pituitary function was present in 14.9%. Eight patients (11.9%) had prolactinomas. An increase in adenoma size was detected in 3.2% of the microadenomas and in 26.3% of the macroadenomas within the follow‐up period.

CONCLUSION

Macroadenomas and hormone secreting adenomas are not uncommon in patients with pituitary incidentalomas. Macroadenomas should be closely monitored for tumour enlargement. All patients should undergo biochemical assessment and ophthalmological examination, since endocrine dysfunction or visual field defects may be present at the time a pituitary incidentaloma is detected.
Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience
Authors: Ahmed  , Elsheikh  , Stratton  , Page  , Adams  , Wass
Published: March 2003

BACKGROUND

A number of surgical series have been reported on the treatment of acromegaly and their results vary widely. The acceptable definition of remission has changed in recent years and it is known, though in a small series, that growth hormone levels of > 5 mU/l are still associated with an increased mortality from the condition. We have analysed data at this centre and examined the outcome of transphenoidal surgery for acromegaly, compared our results with recently published series from other centres and also assessed factors which might effect outcome including whether there is any demonstrable effect of the experience of the surgeon on outcome.

PATIENTS AND METHODS

We have analysed data from all of our 139 patients in whom follow up data are available who have undergone initial transphenoidal surgery for acromegaly by one surgeon at this centre, between 1974 and 1995. Follow up was for a median of 5 years (range 1 month to 17 years).

RESULTS

67% of patients achieved the criterion for remission (mean GH < 5 mU/l). Success was related to tumour size and preoperative growth hormone values. Thus 91% of patients with microadenomas were in remission postoperatively compared to 46% of patients with macroadenomas. Analysis of the results according to the year of operation showed an improvement in success rates with time. More than 15 years ago, the success rate according to the growth hormone criteria set was 48% and the failure rate 52%. In contrast in the last 5 years analysed, the overall success rate was 74% with a failure rate of 26% (P < 0.04). The success rate for microadenomas was 50% initially, then remained 100%. The case mix was analysed and no change was found.  We have also demonstrated an improvement in pituitary function (including normalization of preoperative elevated prolactin) with time so that pre 1981 16% of patients' pituitary function improved peri‐operatively but 10 years later this figure had risen to 34% (P < 0.03). There was no change over time in the development of pituitary hypofunction, complication rate or recurrence rate.

CONCLUSION

Surgical treatment is a safe and effective treatment for acromegaly and remains the first choice of treatment for most acromegalic patients. The results of this centre compare favourably with series from other centres. We have demonstrated improved results, both in terms of post operative growth hormone values and pituitary function tests with time and increasing neurosurgical experience. We conclude that outcome for the surgical treatment for acromegaly is best achieved with one surgeon specialising in pituitary surgery. Improved operative outcome thus achieved has major cost implications and avoids the necessity for consideration of postoperative radiotherapy and the use of expensive growth hormone suppressing drugs in the postoperative period.
The effects of age and gender on parathyroid hormone dynamics
Authors: Haden Susan T. , Brown Edward M. , Hurwitz Shelley , Scott Jennifer , Fuleihan Ghada El‐Hajj
Published: March 2003

BACKGROUND AND AIMS

Hyperparathyroidism is a risk factor for bone loss. An age‐related increase in parathyroid hormone (PTH) level has been demonstrated in several studies. It has been suggested that the type II osteoporotic syndrome, a condition of increased prevalence among elderly women, may be at least partially caused by elevations in intact parathyroid hormone (iPTH) levels. To date, however, the effects of age and gender per se on PTH dynamics in healthy subjects independent of other risk factors such as vitamin D deficiency and/or impaired renal function that can impact on parathyroid function, remain unknown. In this study, we used citrate and calcium (Ca) infusions to characterize the impact of age and gender on PTH dynamics in normal subjects.

SUBJECTS AND METHODS

Twelve young women with mean age ± SD of 26.4 ± 1.6 years, 12 young men with mean age of 26.6 ± 1.3 years, 12 older women with mean age of 68.6 ± 1.3 years and 12 older men with mean age of 67.2 ± 1.6 years were studied. The sigmoidal curves relating serum iPTH to serum levels of ionized Ca (Cai) were characterized by maximal and minimal iPTH levels, the set‐points (levels of Cai causing half‐maximal suppression of iPTH), and the slopes of the curves at the set‐points.

RESULTS

Baseline serum Ca, Cai, 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D [1,25(OH)2D3] levels, as well as the set‐points, slopes and minimal values of the sigmoidal curves relating Cai to iPTH, did not differ among the four groups. iPTH levels at baseline were slightly but not significantly higher in the older age groups (P = 0.18). The maximal iPTH level was 25% higher in the older women than in the younger women, although this difference was not significant (P = 0.29). However, the integrated iPTH responses calculated from the areas under the curves (AUC) of iPTH levels vs. time during the calcium and citrate infusions were significantly higher in postmenopausal women than in young women during both infusions and in older men than in young men during the calcium infusion. There was no effect of gender on serum iPTH levels.

CONCLUSIONS

In both women and men, ageing per se, independent of changes in vitamin D economy or renal function, is associated with an increase in integrated PTH secretory response to changes in serum calcium. No alterations in the Cai/iPTH set‐point were present. The biological relevance of these modest increments in integrated iPTH levels during dynamic testing in older healthy men and women remain uncertain.
The innate immune response and type 2 diabetes: evidence that leptin is associated with a stress‐related (acute‐phase) reaction
Authors: Pickup John C. , Chusney Gary D. , Mattock Martin B.
Published: March 2003

OBJECTIVE

Leptin is produced by adipose tissue and controls food intake and body weight. Although blood levels of leptin reflect energy stores, cytokines also stimulate leptin production from fat. Because we have proposed that type 2 diabetes mellitus is associated with a cytokine‐mediated acute‐phase or stress response, part of the innate immune system, we sought evidence that leptin is increased in type 2 diabetes partly as a stress response, independently of obesity and sex.

DESIGN

We selected two groups of type 2 diabetic patients with either a low acute‐phase response (< 2.30 mmol/l serum concentration of the acute‐phase marker sialic acid) or high response (> 2.30 mmol/l sialic acid), but pair‐matched for body mass index (BMI) and sex.

PATIENTS

Twenty type 2 diabetic subjects (11 male, 9 female) in each group, whose body mass index (BMI) and age were comparable (mean ± SD: 28.8 ± 3.8 vs. 28.9 ± 3.8 kg/m2, and 60.7 ± 8.9 vs. 61.9 ± 12.3 years, low vs. high acute‐phase responders, respectively). The glycaemic control was also similar in each group (glycated haemoglobin: 9.1 ± 2.2 vs. 8.9 ± 1.9%).

MEASUREMENTS

Serum concentrations of sialic acid, leptin, interleukin‐6 (IL‐6) (the major cytokine mediator of the acute‐phase response) and cortisol were assayed in fasting venous blood samples from patients and the results compared.

RESULTS

Serum leptin concentration was increased in the high compared to the low acute‐phase group (median 13.2 (range 3.6–55) vs. 8.1 (2.0–22.5) μg/l, P = 0.004). IL‐6 and cortisol concentrations were also higher in the high‐stress group (1.9 (1.0–6.4) vs. 1.4 (0.4–7.5) ng/l, P = 0.02; and 409 (180–875) vs. 290 (157–705) nmol/l, P = 0.02, respectively). Leptin was strongly correlated with BMI (r = 0.61, P < 0.001), but also with sialic acid (r = 0.40, P = 0.01) and IL‐6 (r = 0.38, P = 0.04).

CONCLUSIONS

Serum leptin concentrations in type 2 diabetes are partly related to an acute‐phase or stress response, independent of BMI and sex. The association of hyperleptinaemia with elevated serum cortisol provides a mechanism for leptin resistance in type 2 diabetes (glucocorticoids inhibit the central action of leptin). This study provides further support for the theory that type 2 diabetes is asociated with chronic innate immune activation.
Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort
Authors: Barrère Xavier , Valeix Pierre , Preziosi Paul , Bensimon Michel , Pelletier Bruno , Galan Pilar , Hercberg Serge
Published: March 2003

OBJECTIVE

To study the relative importance of determinants of thyroid volume.

DESIGN

Cross‐sectional study on a sample of subjects issued from the SU.VI.MAX cohort.

SUBJECTS

2987 French subjects (1713 women aged 35–60 years and 1274 men aged 45–60 years). None of them had previous or present thyroid disease.

MEASUREMENTS

Thyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples.

RESULTS

For both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non‐smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non‐smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0.0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35–45 years) had a smaller thyroid volume than non‐users (P = 0.0009).

CONCLUSIONS

The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long‐lasting thyroid enlargement.
The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome
Authors: Nathwani  , Unwin  , Brook  , Hindmarsh
Published: March 2003

INTRODUCTION

Patients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure.

PATIENTS AND METHODS

62 patients with TS, age 5.4–22.4 years, had 24 h‐ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards.

RESULTS

21% of the TS study population had mean systolic and 17% mean diastolic 24 h‐ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night‐time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment.

CONCLUSION

Over 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h‐ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.
Cushing's syndrome associated with a chemodectoma and a carcinoid tumour
Authors: Tremble  , Buxton‐Thomas  , Hopkins  , Kane  , Bailey  , Harris
Published: March 2003

We present a case of Cushing's syndrome where 111In‐octreotide scanning provided evidence for the presence of two neuroendocrine tumours. Uptake in the right neck corresponded to a chemodectoma, but there was no change in the clinical condition or fall in ACTH levels following surgical resection. Uptake in the left chest was assumed to relate to a bronchial carcinoid, but a tumour could not initially be localized on magnetic resonance imaging (MRI), spiral CT scanning or on selective venous sampling.

A 1 cm bronchial carcinoid tumour was identified post‐mortem which immunostained for ACTH. This case demonstrates that 111ln‐octreotide scanning is a useful technique for identifying the source of ectopic ACTH production in difficult cases of Cushing's syndrome. Reliance should not be placed solely on standard imaging techniques to localize the tumour prior to surgery. Although rare, the possibility of a non‐ACTH secreting neuroendocrine tumour should also be considered in patients with ectopic ACTH syndrome, who have positive 111In‐octreotide scans.
Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?
Authors: Koziell A. , Charmandari E. , Hindmarsh P. C. , Rees L. , Scambler P. , Brook C. G. D.
Published: March 2003

Dysfunction of the Wilms’Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumorigenesis and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys‐Drash syndrome is well described. More recently WT1 mutations have also been described In a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3’alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.
Optic chiasmal herniation — an under recognized complication of dopamine agonist therapy for macroprolactinoma
Authors: Jones S. E. , James R. A. , Hall K. , Kendall‐Taylor P.
Published: March 2003

The initial presentation of macroprolactinoma with visual field impairment, especially in males, is well recognized. Successful treatment with dopamine agonist therapy is characterized by a reduction in hyperprolactinaemia and often rapid and progressive resolution of the visual impairment.

A small proportion of patients may subsequently develop a secondary deterioration in both their visual fields and visual acuities despite normalization of prolactin levels and tumour shrinkage. When pituitary apoplexy can be excluded this may result from traction on the optic chiasm which is pulled down into the now partially empty sella.

We report a series of seven patients in whom chiasmal traction is believed to be the cause of their secondary deterioration in visual acuity occurring after dopamine agonist therapy for macroprolactinoma. The clinical history of two patients both of whom had rapid resolution of field defect with bromocriptine therapy but subsequently developed a recurrence of their bitemporal hemianopia is detailed. In both patients MRI scanning showed not only tumour involution but also marked optic chiasm herniation into the pituitary fossa. Surgical treatment was considered too risky; but on reduction of bromocriptine dosage the field defect improved in both cases; there was a modest elevation of prolactin and a degree of tumour re‐expansion. The latter is believed to have released tethering of the optic chiasm and/or its vascular supply and thus obviated the need for surgery.

Regular monitoring of visual fields in patients with macroprolactinoma receiving medical treatment is therefore important. Early recognition of secondary field loss due to chiasmal herniation enables correction of the visual field loss by manipulation of the medical therapy.
Urine calcium and urine sodium concentrations are not related, after adjustment for urine magnesium
Authors: Stein  , Flicker  , Scherer  , Mead  , Walton  , Chick  , Di Carlantonio  , Zajac  , Wark
Published: March 2003

BACKGROUND AND OBJECTIVES

Urine calcium correlates with urine sodium. The aims of this study were to investigate whether the urine sodium–calcium relationship persists into old age and whether it holds after adjustment for urine magnesium.

DESIGN

Cross‐sectional descriptive analysis.

PATIENTS

Residents of two aged care institutions (median age 84 years) who were not taking diuretics, calcium or vitamin D supplements.

MEASUREMENTS

Early morning urine calcium, sodium and magnesium, plasma creatinine and serum 25‐hydroxyvitamin D and parathyroid hormone.

RESULTS

Urine calcium correlated with urine sodium (r = 0.29, P < 0.01) and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine magnesium, the relationship between urine sodium and urine calcium was no longer significant. Forty‐five percent of the interindividual variation in urine calcium was explained by a linear model on the basis of urine magnesium and plasma creatinine.

CONCLUSION

The data indicate that a correlation between urine sodium and calcium persists in very old age. However, this correlation no longer holds after adjustment for urine magnesium. Further studies examining urine calcium excretion should also consider urine magnesium.
Monitoring serum insulin‐like growth factor‐I (IGF‐I), IGF binding protein‐3 (IGFBP‐3), IGF‐I/IGFBP‐3 molar ratio and leptin during growth hormone treatment for disordered growth
Authors: Tillmann  , Patel  , Gill  , Whatmore  , Price  , Kibirige  , Wales  , Clayton
Published: March 2003

OBJECTIVE

Serum IGF‐I levels are monitored during GH replacement treatment in adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GH‐related side‐effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF‐I, IGFBP‐3 and IGF‐I/IGFBP‐3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth.

DESIGN

An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control.

PATIENTS

The study included 31 patients, grouped as (1) GHD (n = 20) and (2) non‐GHD (Turner syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH treatment.

MEASUREMENTS

Serum IGF‐I, IGFBP‐3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non‐GHD groups. IGF‐I, IGFBP‐3 and the calculated IGF‐I/IGFBP‐3 molar ratio were expressed as SD scores using reference values from the local population.

RESULTS

In the GHD group, IGF‐I SDS before treatment was lower compared with the non‐GHD (−5.4 ± 2.5 vs. −1.8 ± 1.0; P < 0.001). IGF‐I (−1.8 SDS ± 2.2) and IGFBP‐3 (−1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non‐GHD group, IGF‐I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP‐3 (1.1 SDS ± 0.9) and IGF‐I/IGFBP‐3 molar ratio peaked at 6 months. In both groups, IGF‐I SDS and IGF‐I/IGFBP‐3 during treatment correlated with the dose of GH expressed as IU/m2/week (r‐values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 μg/l; median after 12 months treatment 2.4 μg/l; P = 0.02) but not the non‐GHD (median before treatment 3.0 μg/l; median after 12 months treatment 2.6 μg/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02).

CONCLUSIONS

The pattern of IGF‐I, IGFBP‐3 and their molar ratio during the first year of GH treatment differed between the GHD and non‐GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose‐dependent increase in serum IGF‐I and IGF‐I/IGFBP‐3 may be associated with adverse effects, serum IGF‐I and IGFBP‐3 should be monitored routinely during long‐term GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD.
Effects of DHEA replacement on bone mineral density and body composition in elderly women and men
Authors: Villareal Dennis T. , Holloszy John O. , Kohrt Wendy M.
Published: March 2003

OBJECTIVE

Dehydroepiandrosterone (DHEA) is a precursor for both oestrogens and androgens. Its marked decline with ageing may influence age‐related changes in tissues influenced by sex hormones. The aim of this study was to determine the effects of DHEA replacement on bone mineral density (BMD) and body composition in elderly women and men with low serum DHEA sulphate (DHEAS) levels.

DESIGN

Prospective 6 month trial of oral DHEA replacement, 50 mg/day.

PATIENTS

Experimental subjects were 10 women and eight men, aged 73 ± 1 years. Control subjects were 10 women and eight men, aged 74 ± 1 years.

MEASUREMENTS

BMD, body composition, serum markers of bone turnover, serum lipids and lipoproteins, oral glucose tolerance, serum IGF‐I, total serum oestrogens and testosterone.

RESULTS

BMD of the total body and lumbar spine increased (mean ± SEM; 1.6 ± 0.6% and 2.5 ± 0.8%, respectively; both P ≤ 0.05), fat mass decreased (− 1.3 ± 0.4 kg; P < 0.01) and fat‐free mass increased (0.9 ± 0.4 kg; P ≤ 0.05) in response to DHEA replacement. DHEA replacement also resulted in increases in serum IGF‐I (from 108 ± 8 to 143 ± 7 μg/l; P < 0.01) and total serum testosterone concentrations (from 10.7 ± 1.2 to 15.6 ± 1.8 nmol/l in the men and from 2.1 ± 0.2 to 4.5 ± 0.4 nmol/l in the women; both P ≤ 0.05).

CONCLUSIONS

The results provide preliminary evidence that DHEA replacement in those elderly women and men who have very low serum DHEAS levels can partially reverse age‐related changes in fat mass, fat‐free mass, and BMD, and raise the possibility that increases in IGF‐I and/or testosterone play a role in mediating these effects of DHEA.
Interleukin‐6 (IL‐6) producing phaeochromocytoma: direct IL‐6 suppression by non‐steroidal anti‐inflammatory drugs
Authors: Shimizu Chikara , Kubo Mitsumasa , Takano Kazuhiko , Takano Akiko , Kijima Hiromichi , Saji Hiroshi , Katsuyama Itaru , Sasano Hironobu , Koike Takao
Published: March 2003

A 35‐year‐old Japanese woman presented with a phaeochromocytoma and demonstrated marked inflammatory reactions and pyrexia as a result of excessive production of interleukin‐6 (IL‐6) by the tumour. Serum IL‐6 level was 262 ng/l (normal; < 4·0 ng/l). Fever and inflammatory markers were largely overcome by the administration of the nonsteroidal anti‐inflammatory drug, naproxen, and all symptoms disappeared soon after the tumour was excised. Immunohistochemical study revealed positive staining using an antihuman IL‐6 antibody and Northern analysis showed increased IL‐6 mRNA levels in the tumour. Cultured tumour cells showed IL‐6 protein synthesis, and nonsteroidal anti‐inflammatory drugs such as naproxen and indomethacin directly inhibited IL‐6 release. These results indicate that the effects of naproxen in vivo were due, at least in part, to direct suppression of IL‐6 secretion from the tumour.
Cardiac phaeochromocytoma presenting with severe hypertension and chest pain
Authors: Sawka A. M. , Young W. F. , Schaff H. V.
Published: March 2003

Cardiac phaeochromocytoma is a rare cause of endocrine hypertension. We report a case of a 25‐year‐old woman, who presented with severe hypertension and intermittent chest pain. The patient denied typical phaeochromocytoma spells of palpitation, headache, and diaphoresis. The 24‐hr urinary excretion of norepinephrine was increased sevenfold above the upper limit of normal; however, the excretion of total metanephrines, epinephrine, and dopamine were normal. Computed tomography (CT) scan of the abdomen was normal. An 131I‐labelled metaiodobenzylguanidine (MIBG) scan was falsely negative while the patient was taking labetalol. The cardiac phaeochromocytoma was localized with indium‐111‐pentetreotide scintigraphy and chest magnetic resonance imaging scan. Repeat 123I‐MIBG scintigraphy was positive after discontinuing labetalol. The cardiac phaeochromocytoma was located in the right atrial groove, adjacent to the tricuspid valve, and contained multiple feeder arteries from the right coronary artery. After treatment with volume expansion, α‐methyl‐p‐tyrosine, and α‐ and β‐adrenergic blockade, surgical resection was performed. While under cardiopulmonary bypass, coronary bypass grafting and tricuspid annuloplasty were performed to facilitate the complete surgical resection of the 4·5‐cm tumour. The surgical course was uncomplicated, with complete cure of hypertension and normalization of catecholamine excretion. Post‐operative cardiac function, as measured by echocardiogram, was normal. Although cardiac phaeochromocytoma may be highly vascular, invasive and difficult to resect, it can be cured.
Management of a pregnant patient with Graves' disease complicated by thionamide‐induced neutropenia in the first trimester
Authors: Davison S. , Lennard T. W. J. , Davison J. , Kendall‐Taylor P. , Perros P.
Published: March 2003

A 31‐year‐old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times.

Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.
An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic–pituitary disease
Authors: Leong K. S. , Walker A. B. , Martin I. , Wile D. , Wilding J. , MacFarlane I. A.
Published: March 2003

OBJECTIVE The insulin tolerance test (ITT) is usually regarded as the ‘gold standard’ for the assessment of the hypothalamic–pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra‐indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra‐indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic–pituitary disease.

DESIGN AND PATIENTS An audit of 500 GST was performed in 374 patients with hypothalamic–pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes.

RESULTS In the vast majority peak GH (84·4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side‐effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly.

CONCLUSIONS This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out‐patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.
Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection
Authors: Parra Adalberto , Ramírez‐Peredo Jorge , Larrea Fernando , Cabrera Víctor , Coutiño Blanca , Torres Indiana , Angeles Angélica , Pérez‐Romano Beatriz , Ruiz‐Argüelles Guillermo , Ruiz‐Argüelles Alejandro
Published: March 2003

OBJECTIVE The aims of the study were: (1) to assess dopaminergic tone in a group of HIV infected men and the bioactivity and the molecular species of their circulating PRL in comparison with healthy men and (2) to search for a correlation between serum PRL and CD4+ T lymphocytes and viral load.

DESIGN In a cross‐sectional study the effect of acute dopaminergic blockade with intravenous metoclopramide on serum PRL (both immunoreactive and biologically active), TSH and PRL circulating molecular isoforms was evaluated.

PATIENTS Twenty untreated HIV infected men category C2 or C3, mean (SD) age 26·9 (6·3) years, were compared to 14 clinically healthy HIV‐negative men, age 25·4 (2·3) years.

MEASUREMENTS Under fasting conditions and following metoclopramide administration duplicate measurements of serum immunoreactive PRL, bioactive PRL (PRL dependent Nb2 lymphoma cell assay) and immunoreactive TSH were performed. The molecular species of circulating PRL were determined by immunoblot analysis, CD4+ T lymphocytes by flow cytometry and the viral load using a nucleic acid sequence‐based amplification assay.

RESULTS In HIV infected men fasting bioactive (but not immunoreactive) PRL was higher (P = 0·03), but the stimulated PRL (both immunoreactive and bioactive) was lower than in healthy men throughout the test (P ≤ 0·01). Fasting serum TSH was similar in HIV‐infected and healthy men while its response to metoclopramide was absent in the former but not in the latter (P = 0·049). A 23·5‐kD PRL was the predominant circulating isoform both in patients and healthy men. Considering HIV‐infected and healthy men, CD4+ T lymphocytes correlated negatively with fasting bioactive PRL (P = 0·008) and positively with the area under the PRL (both immunoreactive and bioactive) curves (P < 0·001). The viral load was negatively correlated with the area under the curve of the bioactive/immunoreactive ratio (P = 0·008).

CONCLUSIONS The raised fasting bioactive PRL, the diminished response of both immunoreactive and bioactive PRL and the absent TSH response to metoclopramide in HIV infected men, suggest the existence of a decreased, but not absent dopaminergic tone. A monomeric form of PRL was the predominant circulating species, as in healthy men, and this hormone seems to be associated both with CD4+ T lymphocytes and the viral load.
Desmopressin stimulation test before and after pituitary surgery in patients with Cushing's disease
Authors: Losa Marco , Mortini Pietro , Dylgjeri Suela , Barzaghi Raffaella , Franzin Alberto , Mandelli Carlo , Giovanelli Massimo
Published: March 2003

OBJECTIVE The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results.

PATIENTS AND METHODS One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37·2 ± 1·3 years, were studied. All patients, except three, repeated the test 5–6 days after surgery. Desmopressin (10 µg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively.

RESULTS Mean basal plasma ACTH level was 17·3 ± 1·7 pmol/l and rose to a peak level of 42·7 ± 4·9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 ± 19 nmol/l and rose to a peak level of 814 ± 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84·1%) had an ACTH and 84 patients (78·5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27·2 ± 8·3 pmol/l, 781 ± 86 nmol/l) than in desmopressin responders (15·4 ± 1·2 pmol/l, 535 ± 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70·4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow‐up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery.

CONCLUSIONS Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.