bluuebunny/crossref_metadata_2025 huggingface dataset:
Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient with multiple endocrine neoplasia type I
Authors: Daniels M. , Newland P. , Dewar J. H. , White M. C. , Kendall‐Taylor P.
Published: March 2008

OBJECTIVE The aim was to Investigate the hormone secretory products of a pituitary tumour from a patient with multiple endocrine neoplasia type I (MEN I) utilizing cell culture and Immunoassay techniques.

DESIGN Adenoma tissue was enzymically dispersed and established In cell culture. Medium was collected for hormone measurement after 2 days, and also after 24‐hour periods during long‐term culture. In addition, tissue fixed at surgery was analysed by Immunocytochemistry and electron microscopy.

PATIENT The subject was a 59‐year‐old male with a clinical history characteristic of familial MEN I syndrome. MEASUREMENTS Pituitary hormones in serum and culture medium were measured by fully characterized radiolmmunoassays.

RESULTS Preoperative serum LH and FSH levels were normal, or slightly elevated, and there was a progressively blunted gonadotrophin response to GnRH throughout the 8 years prior to adenomectomy. TRH Induced a small, paradoxical Increase In serum gonadotrophin levels 2 weeks preoperatively. Post‐operative pituitary hormone responses to standard stimulation tests showed an active normal pituitary. In vitro, the pituitary tumour cells secreted only gonadotrophins and glycoprotein hormone α‐subunit. The fixed tumour tissue immunostained for α‐subunit alone, and electron microscopy confirmed the presence of secretory granules with diameters of 100–280 nm. Gonadotrophin secretion continued throughout 77 days in long‐term culture, but whilst LH was released at a steady rate, that of FSH transiently increased between days 29 and 48 in vitro.

CONCLUSIONS These data demonstrate that a pitultary tumour associated with the MEN I syndrome secreted gonadotrophins in vitro.
Re‐evaluation of the captopril test for the diagnosis of primary hyperaldosteronism
Authors: Hambling C. , Jung R. T. , Gunn A. , Browning M. C. K. , Bartlett W. A.
Published: March 2008

OBJECTIVE We aimed to re‐evaluate the captopril test in the diagnosis of primary hyperaldosteronism.

DESIGN Serum aldosterone and plasma renin activity were measured supine prior to and 60, 90, 120 minutes after oral captopril, 25 mg.

PATIENTS We have performed this test in ten patients with primary hyperaldosteronism, two with hypertension and secondary hyperaldosteronism and in ten normokalaemic patients with essential hypertension.

MEASUREMENTS Validity was assessed by mathematical prediction methods.

RESULTS Using a ratio of aldosterone to plasma renin activity >1400 pmol/l per μg/ml/h as a predictor of primary hyperaldosteronism, the captopril test had a sensitivity of 100%, a specificity of 83% and a predictive value of 82% with a 60‐minute post captopril evaluation being sufficient. Nevertheless, this test was only marginally superior to a careful analysis of the supine values where a similar ratio In the presence of a normal or suppressed plasma renin activity predicted primary hyperaldosteronism with a sensitivity also of 100% but a slightly lower specificity of 75% and predictive value of 77%.

CONCLUSION Application of the captopril test to patients identified as abnormal by screening confirms all cases of primary hyperaldosteronism but false positive or equivocal results, necessitating further Investigation, may occur In some patients with esssential hypertension.
Determination of bone mineral density by quantitative computed tomography and single photon absorptiometry in subclinical hyperthyroidism: a risk of early osteopaenia in post‐menopausal women
Authors: Lehmke J. , Bogner U. , Felsenberg D. , Peters H. , Schleusener H.
Published: March 2008

OBJECTIVE There is evidence that treatment with L‐thyroxine Increases the risk of early osteopaenia. The aim of our study was to Investigate the effect of subclinical hyperthyroidism in patients on TSH‐suppressive L‐thyroxine in view of the increased risk of decalcification.

DESIGN Measurements of bone mineral density were performed in patients with subclinical hyperthyroidism at different scanning sites of varying trabecular portion. Bone mineral values as well as biochemical data were compared to those of normal controls.

PATIENTS Fifty patients (nine men, 25 premenopausal and 16 post‐menopausal women) on TSH‐suppressive doses of L‐thyroxine were investigated after removal of thyroid cancer.

MEASUREMENTS Dual energy quantitative computed tomography was used for osteodensitometry in the lumbar spine. Single photon absorptiometry from a 126I source was applied to the calcaneus, midshaft radius and distal as well as proximal scanning sites of the distal radius. Normal bone mineral values for each measurement site were taken from healthy reference populations.

RESULTS A significant decrease of bone mineral density in the calcaneus was found in 26 of 50 patients. Bone mass assessment yielded a 9.1% decrease of mean bone mineral content in all patients compared to controls (P < 0.01). The decrease in post‐menopausal women was 22% (P < 0.001). In premenopausal women bone mineral density changes in the calcaneus were not statistically significant. Cortical measurement sites like the midshaft radlus and the proximal scanning site of the distal forearm showed a 14.8% (P < 0.05) and 10.8% (P= NS) decalcification in post‐menopausal women but normal values at the distal scanning site. The lumbar spine was not affected by subclinical hyperthyroidism in either pre or post‐menopausal women. In hypoparathyroid patients, bone density did not essentially differ from normals. There was no significant correlation between bone mineral values and duration of treatment or osteocalcin values.

CONCLUSIONS Our data suggest that TSH suppressive L‐thyroxine treatment has a detrimental effect on the appendicular skeleton in post‐menopausal women. Additional effects of oestrogen deficiency and subclinical hyperthyroidism might lead to accelerated bone loss requiring close supervision to determine the smallest dose needed for suppression of the pituitary‐thyroid axis.
Adrenocortical dysfunction in paracoccidioidomycosis: comparison between plasma β‐lipotrophin/adrenocorticotrophin levels and adrenocortical tests
Authors: Moreira Ayrton C. , Martinez Roberto , Castro Margaret , Ellas Luclla L. K.
Published: March 2008

OBJECTIVE Paracoccidioidomycosis is an important cause of Addlson's disease in South America. We have carried out an extensive and prospective study on paracoccidioidomycosis comparing glucocorticoid, mineralo‐corticoid and androgen function with adrenal regulators, ACTH/β‐LPH and plasma renin activity (PRA).

PATIENTS AND METHODS Forty‐seven male patients with active paracoccidioidomycosis were studied consecutively together with 20 healthy controls. On day 1, plasma aldosterone and PRA levels were measured in blood samples obtained from patients in the supine and erect position. On day 2 at 0900 h, baseline plasma samples were taken for ACTH, β‐lipotrophin (β‐LPH), cortisol, corticosterone, aldosterone, androstenedlone (Δ4‐A) and dehydroeplandrosterone sulphate (DHEA‐S). ACTH 1–24 (250 μg) was given i. v. and blood samples for these steroid assays were taken at 1 and 2 hours.

RESULTS Five patients (10%) had Addison's disease with high basal plasma ACTH and β‐LPH, and low cortisol levels after the ACTH test. In the remaining 42 patients, baseline ACTH and β‐LPH levels and plasma cortisol after ACTH were within the normal range. A high percentage of patients presented with reduced corticosterone (21% of patients) and aldosterone (23%) secretion and increased PRA (31%). Plasma Δ4‐A (19%) and DHEA‐S (50%) levels were also reduced.

CONCLUSIONS The frequency of Addison's disease among our patients with paracoccidioidomycosis was 10%. In addition, a subset of patients presented with adrenal dysfunction detected by mineralocorticoid or androgen tests. In parallel to pathological lesions a functional adaptation may occur during adrenal involvement in paracoccidioidomycosis.
Increased free testosterone but normal 5α‐reduced testosterone metabolites in obese premenopausal women
Authors: Glagulll V. A. , Pergola G. De , Glorgino F. , Clgnarelll M. , Abbaticchlo G. , Vermeulen A. , Glorgino R.
Published: March 2008

OBJECTIVE The aim of the study was to investigate whether the absence of increased 5α‐reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels.

DESIGN As in hyperandrogenicity there generally exists evidence for increased 5α‐reductase activity, we measured, as parameters of 5α‐reductase activity, plasma levels of 5α‐androstane‐3α,17β‐diol glucuronlde (ADG) and androsterone glucuronlde (ADTG) as well as their precursor levels in obese women without hirsutlsm, obese hirsute women, non‐obese hirsute women, and non‐obese, non‐hirsute women.

PATIENTS Eighty‐two premenopausal women (20–45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non‐obese hirsute and 14 obese hirsute women.

MEASUREMENTS Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis.

RESULTS Compared to controls, mean free testosterone levels were increased (P <0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P <0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P <0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P <0.01), in the normal range in obese hirsute, and decreased in obese women (P <0.01).

CONCLUSIONS These results show that, despite the presence of higher free testosterone levels, neither 5 α‐reductase activity (as suggested by normal androstanediol glucuronlde levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism.
Effects of chronic GnRH analogue administration on gonadotrophin and α‐subunit secretion in post‐menopausal women
Authors: Oppenheim Daniel S. , Bikkal Helen , Crowley William F. , Klibanskl Anne
Published: March 2008

OBJECTIVE To investigate in detail the regulation of LH, FSH, and α‐subunit secretion by a GnRH agonist analogue under physiological conditions of gonadotrophin elevation.

SUBJECTS Six normal healthy post‐menopausal women.

DESIGN Subjects were given D‐Trp6‐Pro9‐Net‐GnRH (GnRHa), 32 μg/kg, subcutaneously, dally for 24 days. On days 1, 2, 3, 4, 7, 11, 14, 17, 21, and 24, blood samples before and after GnRHa injection were taken. Sampling was continued off GnRHa twice a week for 4 weeks and then on days 66, 76, and 98. GnRH tests (100 μg l. v.) were performed on days 0, 24, and 98.

MEASUREMENTS All serum samples were analysed for LH, FSH, and α‐subunit levels.

RESULTS LH and FSH levels reached a maximum on day 2 after which there was a steady decline to day 24. LH did not begin to rise again until day 44 (20 days off GnRHa), then rose steadily. FSH began to rise earlier, on day 34 (10 days off GnRHa). α‐Subunit levels also showed maximum elevation on day 2 but remained equally elevated throughout the period of GnRHa administration and then fell rapidly to baseline by day 34. LH, FSH, and α‐subunit responses to i. v. GnRH were absent on day 24 and were equivalent to baseline on day 98.

CONCLUSIONS We conclude that there is a striking dissociation in the regulation of gonadotrophin and α‐subunit secretion in response to GnRHa in normal post‐menopausal women. Gonadotrophin secretion is profoundly suppressed during GnRHa administration and recovers only after a long delay post‐treatment, while α‐subunit is markedly stimulated and recovers rapidly. The difference between this pattern and that seen in patients with pituitary tumours could be useful for diagnosis.
The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement*
Authors: Phillppou George , Koutras Demetrios A. , Plperlngos Gregory , Souvatzoglou Athanasslos , Moulopoulos Spyrldon D.
Published: March 2008

OBJECTIVE To clarify the duration and the extent of the antithyroid effect of lodides In hyperthyroldlsm, and to Investigate whether Iodides have an additional perlpheral effect on the metabollsm of thyrold hormones, as has been reported for some organic IodIne compounds.

DESIGN The effect on the perIpheral thyroId hormone levels of 150 mg of potassIum Iodide dally (equIvalent to 114 mg of IodIde) foro 3–7 weeks was compared In 21 hyperthyroId patients and 12 healthy controls. A possible effect of IodIde on the perIpheral metabollsm of thyroId hormones was Investigated by assessing the serum levels of thyroid hormone In 12 hypothyroid patients on thyroxine replacement for 2 weeks.

PATIENTS There were 21 thyrotoxic patients, 12 healthy hospital controls, and 12 patients with complete or near‐complete hypothyroldlsm, on thyroxine replacement.

MEASUREMENTS The following were measured before and at weekly intervals after Iodide administration: (1) pulse rate, (2) serum T4, (3) serum T3, (4) serum TSH, (5) serum thyroxlne‐binding capacity (TBC), (6) serum rT3, (7) serum thyroxine‐binding globulln (TBG), (8) the free‐T4 Index, calculated as T4/TBC.

RESULTS In the hyperthyroid patients serum T4, T3 and rT3 decreased, whereas serum thyroxlne‐binding globulin and thyroxine binding capacity Increased. Serum T3, however, did not become completely normal In all cases. After 21 days, serum T4 and T3 started Increasing again in some cases, but other patients remained outhyrold even after 6 weeks. In the normal controls there was a small but significant and consistent decrease In serum T4, T3 and rT3 and an Increase In serum TSH. Finally, In the T4‐treated hypothyroid patients there was no consistent change, except for an Increase of serum T4 at 1 and 14 days and a decrease of serum TSH the first day.

CONCLUSION Iodides in hyperthyroldlsm have a variable and unpredictable Intensity and duration of antlthyrold effect. Their antithyroid effect Is smaller In normal controls. They have no Important effect on the peripheral metabolism of thyroid hormones.
Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours
Authors: Vieau D. , Linard C. G. , Mbikay M. , Lenne F. , Chretien M. , Luton J. P. , Bertagna X.
Published: March 2008

OBJECTIVE AND DESIGN Pro‐opiomelanocortin gene expression is a ubiquitous phenomenon which takes place not only in the pituitary but also in many normal and tumoral non‐pituitary tissues. However, the clinical features of the ectopic ACTH syndrome are rarely encountered. To further investigate this problem we examined series of normal human pltuitaries and endocrine tumours evaluating the tissue content of pro‐oplomelanocortin peptides, and the state of neuroendocrine differentiation as Indicated by the biochemical marker 7B2.

PATIENTS AND MEASUREMENTS Tissue concentration of 7B2, pro‐opiomelanocortin products (joining peptide and β‐endorphin) were measured in 13 pituitary corticotrophic adenomas and 13 non‐pituitary tumours associated with the ectopic ACTH syndrome (five out of 20 bronchial carcinold tumours, two out of 19 phaeochromocytomas, one out of 11 medullary thyroid carcinomas, three pancreatic and two thymic carcinold tumours). Molecular weight forms of immunoreactive 7B2 and 7B2 RNA messenger were determined using Western and Northern biot analysis respectively.

RESULTS In all tissues examined, concentrations of Immunoreactive β‐endorphin (fmol/mg tissue wet weight) showed widely distributed values from <0.7 to 1340000, which were correlated (r= 0.975, P <0.01) with that of immunoreactive joining peptide, another pro‐oplomelanocortin fragment. In the 13 non‐pituitary tumours associated with the ectopic ACTH syndrome, immunoreactive β‐endorphin concentrations ranged from 8.6 to 548000, whereas in normal and tumoral pituitaries they varied from 16600 to 364800, and 5000 to 1340000, respectively.

Immunoreactive 7B2 was detected In 67 of 68 neuroendocrine tumours. Tissue concentrations (fmol/mg tissue wet weight) of immunoreactive 7B2 varied from 135 to 1787 in pituitary tumours; from <0.5 to 555 In bronchial carclnolds; from 21.7 to 793 In phaeochromocytomas; from < 1.6 to 948 In medullary thyroid carcinomas. Western blot analysis showed a predominant molecular weight form of immunoreactive 7B2 at 22 kDa. Northern blot analysis of RNA extracted from ACTH secreting pituitary and non‐pituitary tumours showed a predominant signal hybridizing at 1.5 kb with a 7B2 probe.

CONCLUSION These results show that all ACTH secreting tumours have biochemical markers for neuroendocrine differentiation. Tissue concentrations of pro‐opiomelanocortin peptides are variable, being extremely high in the most benign tumours and low in those with an aggressive growing pattern, and are not correlated with the biochemical neuroendocrine markers.
Acromegaly and its treatment in the McCune‐Albright syndrome
Authors: Premawardhana L. D. K. E. , Vora J. P. , Mills R. , Scanion M. F.
Published: March 2008

The McCune‐Albright syndrome, comprising polyostotic fibrous dysplasia, cutaneous plgmentation and endocrine hyperfunction, is occasionally complicated by acromegaly due to a pituitary adenoma. We report a patient with the McCune‐Albright syndrome and acromegaly, who developed secondary hypothyroldism and hypoadrenalism, In whom surgical removal of the pituitary tumour was technically difficult. A combination of a long‐acting somatostatin analogue (‘Sandostatin’) and external Irradiation were therefore used as treatment.
Regulation by glucocorticoids of interferon gamma‐induced HLA‐DR antigen expression in cultured human orbital fibroblasts
Authors: Heufelder Armin E. , Bahn Rebecca S. , Smith Terry J.
Published: March 2008

OBJECTIVE The purpose of this study was to determine whether glucocorticoids can block the induction of HLA‐DR antigen expression by interferon gamma in human fibroblasts in culture.

DESIGN AND PATIENTS Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids.

MEASUREMENTS Cultures were analysed for HLA‐DR expression using quantitative immunoblotting and indirect immunofluorescence.

RESULTS Glucocorticoids could block HLA‐DR induction in a dose‐dependent manner. At 10‐8 mol/1, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P <0.004) and 56% (P <0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10‐5 mol/1, RU 38486 blocked virtually the entire glucocorticoid effect.

CONCLUSIONS These results suggest that glucocorticoids can regulate HLA‐DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor.
Luteinizing hormone response to clomiphene citrate in central precocious puberty
Authors: Morelra Ayrton C. , Castro Margaret , Maclel Lea M. Z. , Hiltner Angela N.
Published: March 2008

OBJECTIVE The aim of the present study was to determine the LH response to clomiphene citrate administration in children with central precocious puberty and different bone ages to gain insight into the hypothalamic maturation mechanism.

PATIENTS AND METHODS Twelve children with untreated central precocious puberty were studied. Five had central nervous system lesions and seven had idiopathic central precocious puberty. Their chronological and bone ages ranged from 1·7 to 8·8 years and 3·5 to 13·5 years, respectively. Clomiphene citrate (3 mg/kg/day) was administered orally for 7 days. Blood samples were collected on days 0, 6 and 8. LH and FSH were determined by RIA. The results were compared with GnRH responses or with bone age.

RESULTS No Increase over basal LH levels was detected in four patients, but increased LH levels were detected in the remaining eight during clomiphene administration. The shift from negative to positive responses was around 8–9 years bone age. The sum of LH responses (days 6 and 8) to clomiphene citrate, and particularly the 8th‐day LH levels, were significantly correlated with their respective bone age (r= 0·83). However, the LH responses to GnRH were not significantly correlated with bone age or with LH responses to clomiphene.

CONCLUSIONS This study shows that the LH responsiveness to clomiphene citrate In central precocious puberty increases with skeletal maturation, indicating that the activation of the hypothalamic pubertal mechanism in central precocious puberty may progress in a gradual sequence. These changes in LH response to clomiphene in central precocious puberty mimic those observed with the development of normal puberty, but occur at a much earlier age.
The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions
Authors: Mullis P. E. , Brickell P. M.
Published: March 2008

OBJECTIVE Familial isolated growth hormone deficiency (IGHD) type IA is characterized by a complete absence of human growth hormone (hGH) resulting in most cases from either a 6·7 or 7·7 kb deletion of DNA containing the hGH‐1 gene. These patients have a strong initial anabolic response to exogenous recombinant hGH (r‐hGH) therapy, frequently associated with the development of immune intolerance to r‐hGH which causes an arrest of response to r‐hGH replacement. This disorder is inherited as an autosomal recessive trait.

PATIENTS AND DESIGN In two pregnancies at risk, the polymerase chain reaction (PCR) was applied as a method for identifying hGH‐1 gene deletions in DNA obtained by chorionic villus sampling (CVS) in the first trimester.

RESULTS Homozygotes for the 6·7kb deletion of DNA containing the hGH‐1 gene were easily and conclusively detected by the absence of 1900, 761 and 712bp fragments after Smal digestion of the polymerase chain reaction products. In contrast, the pattern found in heterozygotes for the hGH‐1 gene deletion was difficult to distinguish from the pattern found in normal homozygotes.

CONCLUSIONS We conclude that the polymerase chain reaction method is valuable for diagnosing individuals who are homozygous for hGH‐1 gene deletions, while heterozygotes and normal individuals may be difficult to distinguish from each other. We suggest that, in these cases, Southern blotting remains the analysis to perform.
Endocrine dysfunction in Kearns‐Sayre syndrome
Authors: Harvey J. N. , Barnett D.
Published: March 2008

Kearns‐Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction.

Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperal‐dosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroldism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroldism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroldism was found.
Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery
Authors: Kautzky‐Willer A. , Pacinl G. , Niederle B. , Schernthaner G. , Prager R.
Published: March 2008

OBJECTIVE Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of β‐cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure.

SUBJECTS We studied 16 patients with pHPT, before and 12 weeks after parathyroldectomy; eight of these patients were re‐evaluated one year after surgery. The control group consisted of 18 healthy volunteers.

DESIGN AND MEASUREMENTS All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual.

RESULTS The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 ± 0.5 vs 9.5 ± 1.5 x 104/min/(μU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 ± 0.002 vs 0.03 ± 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 ± 4769 vs 16864 ± 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85.2 vs 76.2%,
P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6.1 x 104/min/(μU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either.

CONCLUSIONS Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially amellorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.
The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex
Authors: van der Lely A. J. , Harrls A. G. , Lamberts S. W. J.
Published: March 2008

OBJECTIVE We investigated the relationship between age, sex, pituitary tumour volume, serum GH, PRL and IGF‐I levels with the responsiveness of GH to TRH, bromocriptine and octreotide in patients with acromegaly.

DESIGN We performed a retrospective study. Correlations were determined between all variables using univariate regression analysis.

PATIENTS One hundred previously untreated acromegalic patients were studied (60 males (age 23–76; mean 49 years) and 40 females (age 25–83; mean 51 years)).

MEASUREMENTS We studied tumour volume, fasting morning circulating levels of GH, PRL and IGF‐I, mean 24‐hour circulating GH levels and the acute GH responses to TRH, bromocriptine and octreotide.

RESULTS Tumour size was related to serum and mean 24‐hour GH levels, but not to IGF‐I. Circulating IGF‐I and GH levels were related only for the group of patients whose fasting and unsuppressed GH level was 80 mU/l (40 μg/l) or less. Older patients tended to have lower circulating GH and IGF‐I levels. There was a close similarity in the responsiveness of tumorous GH secretion to TRH, bromocriptine and octreotide. An elevated serum PRL level predicted a stronger inhibitory response of bromocriptine on GH. The sensitivity of GH release to octreotide was highest in elderly (especially male) acromegalics, as well as in patients with lower IGF‐I levels.

CONCLUSIONS Hormone secretion by GH secreting pituitary tumours, as well as circulating IGF‐I levels, tend to be lower in elderly patients. These tumours are more sensitive to octreotide, especially in elderly male patients. This suggests that octreotide might be used especially successfully as a primary medical therapy in elderly, male acromegalics.
High serum sex hormone‐binding globulin (SHBG) in premature thelarche
Authors: Belgorosky A. , Chaler E. , Rivarola M. A.
Published: March 2008

OBJECTIVE We determined serum sex hormone‐binding globulin (SHBG), serum dehydroepiandrosterone sulphate, serum oestradiol and serum testosterone and its fractions in girls with premature thelarche.

DESIGN Blood was drawn from girls with recently diagnosed (3–12 weeks) premature thelarche. Serum was kept frozen for at least one year before hormonal determination to exclude precocious puberty by clinical evaluation. PATIENTS Seventeen girls with premature thelarche aged 0.83–7.16 years were studied, and compared with a group of 22 normal prepubertal girls.

MEASUREMENTS SHBG was measured by saturation analysis and serum dehydroepiandrosterone sulphate, serum total oestradiol and serum total testosterone were determined by radioimmunoassay. Non‐SHBG‐bound testosterone and free testosterone were calculated from an equation derived from the law of mass action.

RESULTS Median serum SHBG in premature thelarche was 137 nmol/l (range 64–221), significantly higher than in normal controls, 93.7 (32–172) (P < 0.05) non‐parametric test of medians. Serum SHBG decreased significantly with age in controls but not in premature thelarche. No difference was found in serum dehydroepiandrosterone sulphate. Median serum total testosterone (0.34 nmol/l, 0.17–0.97), median serum non‐SHBG‐bound testosterone (0.04 nmol/l, 0.02–0.10) and median free testosterone (2.2 pmol/l, 1.0–4.5) were significantly lower in premature thelarche than in control (P < 0.001).

CONCLUSIONS Serum SHBG is high and bioavailable T is low in girls with premature thelarche. This might alter the oestrogen/androgen ratio in the breast.
Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome
Authors: Saunders P. T. K. , Padayachi T. , Tincello D. G. , Shalet S. M. , Wu F. C. W.
Published: March 2008

OBJECTIVE Determine the sequence of the androgen receptor gene in men with impaired responsiveness to androgens in order to identify the molecular basis of their under‐virilization.

DESIGN Blood samples were used as the source of genomic DNA. Portions of the androgen receptor gene were amplified by polymerase chain reaction and sequenced.

PATIENTS Samples were obtained from three patients and five normal fertile controls. Patients were all 46 XY and were undervirilized with ambiguous external genitalia, gynaecomastla and infertility.

MEASUREMENTS Total cellular DNA was purified from peripheral blood leucocytes. Pairs of ollgonucleotide primers designed to flank the individual exons of the androgen receptor gene were synthesized. The specific regions of the androgen receptor were amplified from the samples of cellular DNA by polymerase chain reaction. Amplified DNA was purified, sequenced and compared to the published sequence.

RESULTS In all three patients point mutations in the androgen receptor gene were detected but no defects were detected in samples from normal controls. In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the DNA binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect.

CONCLUSION Patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methlonine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein.
Oestrogen secreting Leydig cell tumour and GnRH agonist in‐vivo and in‐vitro studies
Authors: Kerlan Véronique , Nahoul Khalil , Abalaln Jean‐Hervé , Mangln Philippe , Bercovici Jean‐Pierre
Published: March 2008

OBJECTIVE The purposes of our study concerning two patients with oestrogen secreting Leydig cell tumour were to determine whether endogenous LH levels are involved in testicular tumour steroidogenesis and whether aromatase activity of oestrogen secreting Leydig cell tumours is directly or indirectly dependent on LH levels.

MEASUREMENTS E2 and T were evaluated after hCG Injection (5000IU) during 96 hours. Bio and Immuno LH, T, E2, were determined at the basal state and after administration of D‐Trp‐6‐GnRH agonist (3.75 mg) every 3 weeks. The abnormal testis was removed after the third injection and testicular venous blood was collected during the operation. Testicular tumour was incubated with 4‐14C‐T. RESULTS Oestradiol (E2) response to hCG injection (5000 IU) was prolonged and exaggerated while that of testosterone (T) was similar to that of the controls. The aromatase index (E2/T) remained elevated even 96 hours after hCG. Intramuscular injection of the GnRH agonist, D‐Trp‐6‐GnRH (3.75 mg) resulted in a reduction of immunoreactive and bloactive LH. T was decreased to about 10% of baseline levels and E2 fell from 240 to 36 pmol/l. In the blood of the spermatic veins collected in the course of surgery, E2 levels were found to be lower in comparison with the controls. E2 was found to be twofold higher in the spermatic vein draining the tumoral side than in that of the contralateral testis. Incubation of the testicular tumours with 4‐14C‐T, displayed a reduced aromatase activity (conversion of T to E2:0.3 and 0.1% in patients 1 and 2 respectively).

CONCLUSIONS The kinetics of E2 response to hCG administration would suggest a modification of the regulation of the aromatase activity in this type of oestrogen secreting tumour. A certain endogenous LH level may be necessary to supply a sufficient quantity of T substrate, and to maintain aromatase activity of such Leydig cell tumours secreting oestrogens. These tumours seem to be responsive to endogenous LH levels.
Pituitary histology in Cushing's disease
Authors: Kruse Anders , Klinken Lelf , Holck Susanna , Lindholm Jörgen
Published: March 2008

OBJECTIVE We assessed pituitary histology in patients with Cushing's disease.

DESIGN Systematic histological assessment of pituitary tissue removed at surgery.

PATIENTS Thirty‐six consecutive patients cured from Cushing's disease by transsphenoidal neurosurgery.

MEASUREMENTS Microscopical examination of all available tissue removed at operation.

RESULTS After selective removal of tissue supposed to represent an adenoma in 25 patients this could be histologically verified in 18. In the 11 patients who had undergone a total hypophysectomy an adenoma could be demonstrated in three patients only, despite a systematic search of the entire pituitary gland. Only in 21 of the 36 cured patients (58%) could an adenoma be verified.

CONCLUSIONS Combining the present results with previous reports there is strong reason to believe that in some patients with Cushing's disease no histological lesion in the pituitary is verifiable.
Treatment of osteoporosis with parathyroid peptide (hPTH 1–34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone
Authors: Bradbeer Jeremy N. , Arlot Monique E. , Meunler Pierre J. , Reeve Jonathan
Published: March 2008

OBJECTIVE We wished to determine whether treatment of vertebral osteoporosis with human parathyroid peptide 1–34 (hPTH 1–34), given as a daily injection with supplementary treatment with hormone replacement therapy (HRT), increases cancellous bone area in the ilium by increasing the size of packets of new bone.

DESIGN AND MEASUREMENTS The width of packets of cancellous bone (wall width) was measured at random intercepts and mean values calculated. Cancellous bone area and perimeter were also measured. Indices of trabecular separation and the complementary quantity trabecular number were derived according to Parfitt's method, as well as trabecular width. Patients were used as their own controls and changes in these indices calculated. Correlations were calculated for data obtained from independent measurements.

PATIENTS We studied eleven women with post‐menopausal osteoporosls, diagnosed by fractures after exclusion of causes of secondary osteoporosis.

RESULTS One woman did not comply with her HRT therapy. In the others, treatment with hPTH 1–34 + HRT restored the characteristically depressed pre‐treatment values of wall width to normal. Trabecular width increased approximately four times more than wall width. Changes in wall width correlated with changes in cancellous bone area; however, bone area increased considerably more than could be accounted for statistically by changes in wall width. A decrease in trabecular separation was found to account for the additional increase in bone area (P=0.056).

CONCLUSION hPTH 1–34 + oestrogen and progestagen therapy increases the width of packets of new cancellous bone with consequent increases in the width of trabecular plates.
Post‐pregnancy osteoporosis associated with hypercalcaemia
Authors: Reid I. R. , Wattie D. J. , Evans M. C. , Budayr A. A.
Published: March 2008

A lactating 31‐year‐old woman who developed four vertebral fractures 1–2 months after the delivery of her first child is described. She was hypercalcaemic (serum calcium up to 2.99 mmol/l), and urinary excretion of both calcium and hydroxyproline (an index of bone resorption) were markedly elevated. Serum levels of parathyroid hormone and 1,25‐dlhydroxyvltamin D were suppressed, but parathyroid hormone‐related peptide was above normal. There was severe axial osteopenia, as assessed by dual‐energy X‐ray absorptiometry. The biochemical abnormalities were reversed within 2 weeks of weaning, with the exception of the parathyroid hormone‐related peptide concentration, which declined more gradually. This appears to be the first description of the abnormalities in calcium metabolism and bone density from early in the course of post‐pregnancy osteoporosis and it Indicates that this condition is associated with high levels of osteolysis which return to normal after weaning. This rapid reversal of the metabolic abnormalities accounts for the inconclusive nature of previous descriptions of postpregnancy osteoporosis, in which investigations were more delayed. It also emphasizes the importance of weaning in the management of women presenting with this condition. A possible aetiological role for parathyroid hormone‐related peptide is discussed.
Spin echo nuclear magnetic resonance studies on intact erythrocytes: changes in cellular metabolism as a consequence of carbimazole therapy
Authors: Reglinski J. , Smith W. E. , Wilson R. , Buchanan L. M. , McKillop J. H. , Thomson J. A.
Published: March 2008

OBJECTIVE Because the exact mechanism of action of carbimazole is uncertain, nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular changes in erythrocytes from Graves' patients following a course of carbimazole therapy.

DESIGN NMR spectroscopy was carried out using intact erythrocytes obtained from Graves' patients prior to and at 2 and 12 months after carbimazole treatment. The data were correlated with thyroid hormone and antibody levels. PATIENTS Twenty patients (four males; 16 females) with newly diagnosed and previously untreated Graves' disease were enrolled into the study. Assessments were made prior to the commencement of therapy and after 2 and 12 months on treatment. Of the 20 patients assessed at 0 and 2 months only 12 completed the study.

MEASUREMENTS The oxidation‐reduction balance of erythrocyte glutathione was measured directly using 1H spin echo NMR spectroscopy of intact cells. Thyroid hormone and antibody levels were measured using reported methods.

RESULTS At 2 and 12 months a significant (P <0.01) oxidation of the erythrocyte glutathione was observed. Of the four thyroid related markers (T3, T4, TRAb and TSH) assessed in this study both T3 (P <0.001) and TRAb (P <0.001) were observed to correlate with the NMR observed changes in glutathione. However, in‐vitro experiments indicated that carbimazole does not affect red cell glutathione directly.

CONCLUSIONS A model is presented which uses the hydrated iodium cation (I+), the natural product of T4 conversion to T3, as a chemical oxidant which can produce the observed clinical alteration in intracellular glutathione in ex‐vivo erythrocytes. It is suggested that a major factor in the action of carbimazole in Graves' disease may be to stimulate the function of the deiodinase enzymes.
Thyroid function tests are rarely abnormal in patients with severe hyperemesis gravidarum
Authors: Wilson R. , McKillop J. H. , MacLean M. , Walker J. J. , Fraser W. D. , Gray C. , Dryburgh F. , Thomson J. A.
Published: March 2008

OBJECTIVES There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women.

PATIENTS The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls.

MEASUREMENTS Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured.

RESULTS While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients.

DISCUSSION None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.
The effect of morphine and naloxone administration on plasma oxytocin concentrations in the first stage of labour
Authors: Lindow Stephen W. , Spuy Zephne M. , Hendricks M. Salle , Rosselli Andrew P. , Lombard Carl , Leng Gareth
Published: March 2008

OBJECTIVE We Investigated the effect of an oplate (morphine) and an opiate antagonist (naloxone) on the maternal secretion of oxytocin in the first stage of labour.

DESIGN Patients were randomized to receive either morphine 5 mg (n= 9), naloxone 1.2 mg (n= 10) or sterile water (n= 9) which was injected intravenously.

PATIENTS Healthy women in the first stage of labour between 3 and 6 cm dilated with no prior analgesia or oxytocin administration were recruited for the study.

MEASUREMENTS Peripheral maternal oxytocin levels were measured by radloimmunoassay for 15 minutes before and 15 minutes after administration of the assigned substance. Sampling was at 2.5 minute intervals.

RESULTS Significant reduction in the mean oxytocin concentration was found in the patients who received morphine (— 2.62 pmol/l/sample) but no change was found in the naloxone group (+ 0.57 pmol/l/sample) when compared with controls (+ 0.64 pmol/l/sample).

CONCLUSION Maternal oxytocin secretion is inhibited by exogenous opiates in the first stage of labour while an effect of opiate antagonism was not demonstrated.
The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects
Authors: Valcavi Roberto , Zini Michele , Davoli Simona , Portionli Italo
Published: March 2008

OBJECTIVE We have investigated the late GH rise occurring 3–5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects.

DESIGN Placebo or 75 g oral glucose was given to the normal subjects 3 hours before 120 mg oral pyridostigmine or placebo. Four tests were carried out at random. Test 1: placebo (0 min) + placebo (180 min); test 2: glucose (0 min) + placebo (180 min); test 3: placebo (0 min) + pyridostigmine (180 min); test 4: glucose (0 min) + pyridostigmine (180 min).

SUBJECTS We studied eight normal subjects (four male and four female), ages 19–29 years, body mass indices 18–22 kg/m2.

MEASUREMENTS Plasma glucose and serum GH concentrations were measured for 6 hours after oral glucose or placebo administration.

RESULTS Pyridostigmine treatment significantly enhanced the GH releasing effect of prior (3 h) oral glucose. Late GH peak obtained by oral glucose loading rose from (mean±SEM) 17.4±4.6 to 37.2±9.0 mU/l (P < 0.05) after pyridostigmine, while GH peak following placebo plus pyridostigmine was 12.4 ± 2.0 mU/l (P < 0.05 vs glucose plus pyridostigmine). The analysis of GH area under curves (AUCs) in the second phase of the tests (180–360 min) confirmed that glucose plus pyridostigmine released a greater amount of GH (4128±764 mU/l/3h) than glucose (1694±494 mU/l/3h, P < 0.001) or pyridostigmine alone (1292±150 mU/l/3h, P < 0.001).

CONCLUSIONS Pyridostigmine, an indirect cholinergic drug likely to inhibit somatostatin secretion from the hypothalamus, enhanced the late GH releasing activity of oral glucose. There is evidence that glucose suppresses plasma GH initially by increasing hypothalamic somatostatin release. This would result in an increase in the pituitary stores of GH.