bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene screening in Japanese families with complete deficiency of thyroxine‐binding globulin demonstrates that a nucleotide deletion at codon 352 may be a race specific mutation
Authors: Takeda K. , Iyota K. , Mori Y. , Tamura Y. , Suehlro T. , Kubo Y. , Refetoff S. , Hashimoto K.
Published: March 2008

OBJECTIVE Thyroxine‐binding globulin (TBG) is a serum protein that transports 75% of circulating thyroxine. Eleven naturally occurring mutations in the human TBG gene have been identified, ten of which alter the properties of the molecule. Three of these mutations produce complete deficiency of TBG (TBG‐CD) and four are associated with a second mutation in codon 283 (TBG‐poly) which is polymorphic in some ethnic groups but, when present alone, does not alter the properties of the TBG molecule. In this communication we investigate whether two unrelated Japanese families with TBG‐CD harboured the TBG‐CD J mutation in codon 352 associated with TBG‐CD in families residing in more distant locations of the Japanese Islands. In addition we examined the possible association with TBG‐poly and its incidence in the Japanese population.

DESIGN Mutant alleles were identified by amplification of genomic DNAs by the polymerase chain reaction, using altele‐specific oligonucleotide primers.

PATIENTS Eight family members and 25 normal subjects.

MEASUREMENTS Serum free thyroxine and TBG concentration were measured by a conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic DNAs were extracted from white blood cells and specific mutations at codons 352 and 283 were identified by allele‐specific amplification.

RESULTS Three males and three females, whose serum TBG levels were decreased, had mutations at codon 352 as hemizygous and heterozygous, respectively. This mutation was not present in the DNA of any of the related or unrelated subjects with normal TBG concentration. The presence of TBG‐poly was demonstrated in only one heterozygous family member and in six out of 30 alleles (20%) in normal unrelated subjects. The frequency of this TBG polymorphism in the Japanese is similar to that of 16% reported in French Canadians.

CONCLUSIONS We conclude that TBG‐CDJ might be a prevalent cause of complete deficiency of thyroxine‐binding globulin in the Japanese and that TBG‐poly probably appeared before the divergence of human races.
Morbidity and mortality in Cushing's disease: an epidemiological approach
Authors: Etxabe J. , Vazquez J. A.
Published: March 2008

OBJECTIVE Although Cushing's disease is a well documented clinical entity, there is no epidemiological information about it. The present study tries to obtain this information.

DESIGN AND PATIENTS Forty‐nine patients affected by Cushing's disease living in Vizcaya (Spain) between 1975 and 1992 were considered for an epidemiological study.

RESULTS The prevalence of known cases at the end of 1992 was 39.1 per million inhabitants. The average incidence of newly diagnosed cases was 2 4 cases per million people per year. Cushing's disease was more frequent in women (n= 46) than in men (n= 3), with a ratio of 15:1. Diabetes mellitus and hypertension were observed in 38.7 and 55.1% of patients, respectively. Remission of Cushing's disease was achieved in 36 out of 41 patients (87.5%). In general, the mortality was higher than that expected for the control population (standardized mortality ratio, SMR 3.8, 95% confidence interval, CI 2.5–17.9, P<0.03). Concerning the cause of death, the SMR of vascular disease was 5 (95% CI 3.4–48.6, P< 0.05). Higher age, persistence of hypertension and abnormalities of glucose metabolism after treatment, were independent predictors of mortality (multivariate analyses, P<0.01).

CONCLUSIONS Prevalence of Cushing's disease was 39.1 cases/million inhabitants and average incidence was 2.4 cases/million per year. Mortality was elevated, due to vascular disease, associated with higher age, persistence of hypertension and impaired glucose metabolism.
Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin‐releasing hormone agonist pretreated women
Authors: Vollenhoven B. J. , Pearce P. , Herington A. C. , Healy D. L.
Published: March 2008

OBJECTIVE The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin‐releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR.

DESIGN Cytosolic ER and PR binding was assessed by the dextran‐coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA.

PATIENTS Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa.

RESULTS We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and in fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours.

CONCLUSIONS We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding.
Familial dysalbuminaemic hyperthyroxinaemia and inherited partial TBG deficiency: first report
Authors: Langsteger Werner , Stockigt Jan R. , Docter Roel , Költringer Peter , Lorenz Oskar , Eber Otto
Published: March 2008

BACKGROUND Abnormalities of the serum thyroid hormone binding proteins are not uncommon but, when properly asessed, they do not present diagnostic difficulties. In contrast, the presence of two inherited defects of thyroid hormone transport, of the type presented in the family described here, may cause a major problem in diagnosis and has not been described previously.

METHODS All conventional thyroid function tests were carried out. In addition, thyroid hormone binding to serum proteins was assessed by agarose gel electrophoresis, and thyroxine binding globulin by immunoassays and by immunodiffusion. The affinity of TBG for thyroxine and its maximal binding capacity were assessed by Scatchard analysis.

RESULTS Tests carried out on 22 members of the family revealed familial dysalbuminaemic hyperthyroxinaemia in 10 family subjects. All five living siblings of the propositus had familial dysalbuminaemic hyperthyroxinaemia and two tested transmitted this trait to their children and grandchildren. This was not the case with the propositus. Partial thyroxine binding globulin deficiency only, inherited presumably from the propositus' mother, was found in two family members. Both thyroxine binding globulin deficiency and familial dysalbuminaemic hyperthyroxinaemia were detected in the propositus and in his male nephew, masking the typical laboratory abnormalities associated with each of these defects.

CONCLUSIONS Coexistence of two inherited defects of thyroid hormone transport proteins produce atypical thyroid function test abnormalities, which can be misinterpreted as thyroid hormone dysfunction.
Gene deletion causing adrenal hypoplasia congenita and hypogonadotrophic hypogonadism
Authors: Matfin G. , Sheaves R. , Muscatelli F. , Walker A. , Monaco A. , Grant D. , Nwose O. , Wass J. A. H.
Published: March 2008

We report a patient with X‐linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism in whom there were no clinical or biochemical features of either glycerol kinase deficiency or Duchenne muscular dystrophy. (The adrenal hypoplasia congenita and glycerol kinase loci map in Xp21 distal to Duchenne muscular dystrophy, and proximal to DXS727.) DNA isolated from our patient was analysed by PCR amplification with primers for appropriate loci in the Xp21 region. This analysis revealed the absence of DXS319, which lies near the adrenal hypoplasia congenita deletion critical region, and the presence of DXS727, which is distal to the gene. The absence of glycerol kinase deficiency biochemically and clinically was consistent with the presence of one glycerol kinase exon product from PCR primers P17/P18 which lies within the glycerol kinase gene. The hypogonadotrophic hypogonadism is universally found in X‐linked adrenal hypoplasia congenita and is thought to be pituitary in origin. These findings suggest that a gene locus resulting in hypogonadotrophic hypogonadism is present in the Xp21 region and is an integral part of the adrenal hypoplasia congenita gene or in close relationship to it.
Inhibin as a marker for hydatidiform mole: a comparative study with the determinations of intact human chorionic gonadotrophin and its free β‐subunit
Authors: Badonnel Y. , Barbé F. , Legagneur H. , Poncelet E. , Schweitzer M.
Published: March 2008

OBJECTIVE The purpose of the study was to evaluate plasma inhibin as a marker of hydatidiform mole and to compare the results with intact human chorionic gonadotrophin (hCG) and its free β‐subunit.

DESIGN Serial determinations of the plasma concentrations of inhibin, intact human chorionic gonadotrophin and its free β‐subunit in cases of hydatidiform mole over an average period of 140 days.

PATIENTS Five cases of hydatidiform mole, including patients with spontaneous remission after evacuation or persistent trophoblastic disease.

MEASUREMENTS Immunoreactive Inhibin, hCG and free hCG β‐subunit were measured using standard enzyme immunoassays.

RESULTS inhibin and free hCG β‐subunit levels were greater than in normal pregnant women at the same gestational age. Only intact hCG could detect the persistence of trophoblastic tissue.

CONCLUSIONS Our data suggest that inhibin, intact human chorionic gonadotrophin and free β‐subunit might be useful as diagnostic markers of molar pregnancies. However, the original method of intact hCG determination Is still superior for follow‐up.
Comparative effects of GH, IGF‐I and insulin on serum sex hormone binding globulin
Authors: Gafny M. , Silbergeld A. , Kilnger B. , Wasserman M. , Laron Z.
Published: March 2008

OBJECTIVE The serum level of sex hormone binding globulin (SHBG) changes inversely with that of both insulin and Insulin‐like growth factor (IGF‐I), during several nutritional conditions, as well as In response to GH treatment. However, with exogenous IGF‐I administration, endogenous IGF‐I increases, while insulin decreases. In order to study the separate roles of these hormones in controlling SHBG metaboilsm, we compared SHBG levels in patients treated with IGF‐I and GH.

DESIGN AND PATIENTS Serum levels of IGF‐I, Insulin and SHBG were measured before and during the treatment of patients with IGF‐I or GH. Blood samples were drawn in the fasting state, prior to and during therapy, 24 hours after drug administration.

Sixteen children and adults with Laron syndrome (LS) received daily s.c. injections of IGF‐I (120–150μg/kg) for up to 5 months. Three adults with isolated GH deficiency (IGHD) received daily s.c. Injections of GH (0·03–0·06 U/kg) for 16 months. Two groups of nine prepubertal children with constitutional short stature (CSS) received GH (0·1 U/kg/day) for 3 months.

MEASUREMENTS Serum levels of insulin and acid extractable IGF‐I were determined by RIA, and that of SHBG by IRMA.

RESULTS Basal insulin and SHBG levels were within normal range In the LS, IGHD and CSS patients. IGF‐I levels were low in LS and IGHD patients, and normal In the CSS children. The mean peak response to chronic therapy was as follows: In LS patients, IGF‐I administration decreased insulin levels to 62%, and increased SHBG levels by 64% above basal values. Chronic GH therapy in IGHD caused a marked rise in both IGF‐I levels (473%), and insulin levels (96%), and a gradual decline of SHBG to 75% of the basal concentration. In GH treated CSS patients, serum IGF‐I peaked at 80% and insulin levels at 102% above the respective basal levels, while SHBG decreased to 83% after 5 days of treatment.

CONCLUSION The results obtained in Laron syndrome, isolated GH deficiency and constitutional short stature patients treated with IGF‐I or GH, indicate that serum insulin had consistently an inverse relation with the levels of circulating SHBG. No relation was found between IGF‐I and SHBG levels.
Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas
Authors: Hashimoto Kunihiko , Koga Masafumi , Kouhara Haruhiko , Arita Norio , Hayakawa Toru , Kishimoto Tadamitsu , Sato Bunzo
Published: March 2008

OBJECTIVE Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized In human pituitaries. in addition, altered or Insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non‐tumorous and tumorous human pituitaries should be examined.

DESIGN Total RNAs were extracted from non‐tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression.

SAMPLES Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non‐functioning adenomas were obtained at surgery. Two non‐tumorous pituitaries were also included in this study.

MEASUREMENTS The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase‐polymerase chain reaction (RT‐PCR) products.

RESULTS PC2 and PC3 mRNAs in non‐tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT‐PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas.

CONCLUSION The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.
Insulin sensitivity and insulin clearance in cystic fibrosis patients with normal and diabetic glucose tolerance
Authors: Lanng Susanne , Thorsteinsson Birger , Rsder Michael E. , Nerup Jern , Koch Christian
Published: March 2008

OBJECTIVE We studied glucose metabolism and insulin kinetics in cystic fibrosis patients with diabetic and normal glucose tolerance.

DESIGN Measurements of blood glucose and serum free insulin concentrations during hyperinsulinaemic normo‐glycaemic clamp and post‐clamp insulin decay, followed by the calculation of insulin sensitivity (M‐value and M/1 ratio), insulin clearance rate, serum half‐life and apparent distribution space for insulin.

SUBJECTS Cystic fibrosis patients, age range 20–29 years, with diabetes mellitus (n= 10) and normal glucose tolerance (n= 10), and 10 age‐matched control subjects.

RESULTS During the glucose clamp, diabetic cystic fibrosis patients needed less glucose than cystic fibrosis patients with normal glucose tolerance and control subjects (M‐value), and steady‐state serum insulin concentrations were lower in cystic fibrosis patients with diabetic and normal glucose tolerance than in control subjects. The quantity of glucose metabolized per unit of serum insulin concentration (M/l ratio) was similar in the three study groups (median ∼ 145 (μmol/kg/min)/(nmol/l); range 70–252).

insulin clearance rates were higher in cystic fibrosis patients with diabetic (24·4 (19·3–29·9) mi/kg/min) and normal (22·6 (14·9–28·4) mi/kg/min) glucose tolerance than in control subjects (17·5 (15·9–24·2) ml/kg/min). Although Insulin clearance rates were inversely related to body mass index (R(S)=−0·59, P < 0·001), the higher insulin clearance rates in CF patients cannot be accounted for solely by differences in body mass index since the insulin clearance rates were similarly increased in patients with body mass index above and below 20kg/m2(22·7 (14·9–28·4) and 24·4 (19·3–29·9) ml/kg/min, respectively). Serum half‐lives for Insulin were shorter in cystic fibrosis patients (∼4·3 (3·2–7·2) min) than In control subjects (5·9 (3·8–12·5) min), whereas the apparent distribution spaces for Insulin were similar in the three study groups (∼150 (88–391) ml/kg).

CONCLUSIONS Insulin sensitivity, calculated as the quantity of glucose metabolized per kg body weight per unit of serum insulin concentration, is normal in cystic fibrosis patients with normal glucose tolerance and with well controlled diabetes mellitus. The insulin clearance rate is increased in cystic fibrosis patients with diabetic and normal glucose tolerance, owing to a shorter serum half‐life of insulin, whereas the apparent distribution space for insulin is normal.
Insulin‐like growth factor binding protein 1 response to acute insulin induced hypoglycaemia in Type 1 diabetes
Authors: Quin J. D. , Fisher B. M. , MacCulsh A. C. , Beastall G. H. , Small M. , Holly J. M. P. , Cotterill A. M.
Published: March 2008

OBJECTIVES Insulin Is believed to be the prime regulator of Insulin‐like growth factor binding protein 1 (IGFBP‐1) secretion, and In normal subjects acute insulin Induced hypoglycaemla exerts a rapid effect on concentrations of IGFBP‐1, and may also Influence Insulin‐like growth factor I (IGF‐I) concentrations. The rise In IGFBP‐1 concentrations in normal subjects following hypoglycaemia has been suggested to be due to suppression of endogenous insulin secretion. We have examined this further by studying diabetics with no endogenous Insulin secretion.

DESIGN We have compared the IGFBP‐1 response to acute insulin Induced hypoglycaemia in normal subjects and patients with Type 1 (insulin dependent) diabetes mellitus.

METHODS Insulin tolerance test8 were performed using a bolus of Insulin (0·15 U/kg), in six control subjects and six patients with Type 1 diabetes.

MEASUREMENTS Serum levels of IGFBP‐1, insulin, glucose, and IGF‐I were measured at regular Intervals during the insulin tolerance test.

RESULTS Blood glucose fell to a nadir which coincided with the onset of the acute autonomic reaction ‘R’ In both groups. The basal concentration of IGF‐I was significantly lower In the diabetic group at 0·4 ± 0·1 kU/l, compared to 0·9 ± 0·1 kU/l In the control group, but there was no significant change In IGF‐I concentrations In response to hypoglycaemia In either group. Hypoglycaemia provoked a fall In IGFBP‐1 In patients with Type 1 diabetes, from 38 ± 9 μg/l basally to 17 ± 3 μg/l at R + 120 minutes, with a return to basal values of 45 ± 11 μg/l at R + 180 minutes. In the control subjects there was no fall In IGFBP‐1, but a significant Increase to 71 ± 14 μg/l at R + 180 minutes.

CONCLUSION This difference In the IGFBP‐1 response In the presence of a similar glucose response suggests that In Type 1 diabetes there may be different sensitivities to the actions of exogenous Insulin on IGFBP‐1 regulation.
A prospective study of the prevalence of clear‐cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia
Authors: O'Driscoll J. B. , Mamtora H. , Higginson J. , Pollock A. , Kane J. , Anderson D. C.
Published: March 2008

OBJECTIVE To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clear‐cut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women. DESIGN A prospective study of women attending a joint skin/endocrine clinic complaining of these problems. PATIENTS Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed. MEASUREMENTS Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17‐hydroxyprogesterone and PRL. The ovarles were visualized by high‐resolution pelvic ultrasound scanning. RESULTS Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma—In both cases the association may have been fortuitous. Three had clear‐cut 21‐hydroxylase deficiency, one a rare hepatic enzyme deficiency (11‐reductase), one a virilizing adrenal carclnoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone (>5nmol/l). In ail, 13 women had baseline testosterone levels in excess of 5nmol/l. Polycystic ovaries were present in 81 % of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present In two of the women with 21‐hydroxylase deficiency and In the woman with 11‐oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan.

CONCLUSIONS For the exclusion of enzyme deficiencies and virllizing tumours clinical assessment and a single serum testosterone measurement will suffice.
Malignancy‐associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome
Authors: Schweitzer Dave H. , Hamdy Neveen A. T. , Frölich Marijke , Zwinderman Aellko H. , Papapoulos Socrates E.
Published: March 2008

OBJECTIVE Parathyroid hormone‐related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but Its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25‐dihydroxyvitamin D and humoral activity in malignancy‐associated hypercalcaemia.

DESIGN Prospective, cross‐sectional, single‐centre study of patients with documented solid malignancles, hypercalcaemia and suppressed plasma PTH concentrations.

PATIENTS AND METHODS Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N‐CAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid mallgnancles and hypercalcaemia and bone scans were performed.

RESULTS In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25‐(OH)2D concentrations were not appropriately suppressed (>92pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1·6 pmol/l) had lower serum 1,25‐(OH)2,D concentrations than those with elevated levels (>1 6 pmol/l) (47±6 vs 70± 7 pmol/l, respectively; P < 0·04). Serum 1,25‐(OH)2D concentrations were higher in patients with negative bone scans than In those with metastatic bone disease (80 ± 9 vs 50 ± 5 pmol/l; P < 0·01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25(OH)2,D (r= 0·51; P < 0·03) whereas there was no such correlation in those with a positive scan.

CONCLUSION Contrary to current belief, serum 1,25‐(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further Insights into the pathophysiology of malignancy‐associated hypercalcaemia and may help in the clinical management of these patients.
Calcitonin‐producing insulinoma: clinical, immunocytochemical and cytogenetical study
Authors: Bugalho Maria João G. M. , Roque Lúcia , Sobrinho Luís G. , Hoog Anders , Nunes José F. Moura , Aimeida José M. Mendes , Leltão C. Nobre , Santos Jorge R. , Pereira Maria Conceičão , Santos Maria Amparo , Soares Jorge
Published: March 2008

The case of a patient with a large goitre associated with hypercaicitoninaemia and fasting hypoglycaemia is reported. Pentagastrin (PG) test was negative. Repeated measurements of fasting glycaemia, insulin and C peptide established the diagnosis of insulinoma. After localization by endoscopic ultrasonography, a distal pancreatectomy was performed and a small insulinoma was recovered. Glycaemia and calcitonin (cT) became normal. The tumour cells a a strong immunoreactivity for insulin and CT. Cytogenetical evaluation of the tumour revealed a translocation t(1;9) (pl3;p22).
Secondary hypoadrenalism presenting with hypercalcaemia
Authors: Vasikaran S. D. , Tallis G. A. , Braund W. J.
Published: March 2008

We describe a young woman with lymphocytic hypophysitis presenting In the early post‐partum period. She had selective corticotroph failure causing secondary adrenal Insufficiency. At the time of presentation she had transient hyperthyroidism due to thyroiditis, and hypercalcaemia. This is the third case to be described of hypercalcaemia occurring in association with lymphocytic hypophysitis. Hypercalcaemia is not a recognized complication of other forms of pituitary failure. The two previously described cases also had selective corticotroph failure and hyperthyroidism due to thyroiditis. This pattern of presentation supports the concept that thyroid hormone action In the presence of glucocorticoid deficiency is responsible for the increased calcium efflux from bone into the circulation. Reduced renal excretion of calcium due to a reduction in calcium delivery to the glomeruius and increased proximal tubular reabsorption are also implicated in the aetiology of hypercalcaemia associated with adrenal failure.
Is a low skinfold thickness an indicator of osteoporosis?
Authors: Orme S. M. , Belchetz P. E.
Published: March 2008

OBJECTIVE The association between thin skin and osteoporosis has been known for some years. We wished to assess a simple measure of skinfold thickness (SFT) as a screening test for osteoporosis and to study the effect of chronological and menopausal age on SFT in a group of osteoporotic women and normal controls.

DESIGN A case control study of 225 consecutive women who attended an osteoporosis clinic.

PATIENTS We studied 225 women, 141 with osteoporosis (mean age 61·8 ±10·5 years) and 65 normal controls (mean age 59·9 ± 8·8 years), with 19 exclusions.

METHODS Each patient had routine biochemistry, spinal X‐rays and a dual‐energy X‐ray absorptiometry (DEXA) scan of lumbar spine and femoral neck. In addition they had skinfold thickness measured by a single observer using Holtain Tanner Whitehouse callipers over the 4th metacarpal of the right hand.

RESULTS Mean skinfold thickness was lower in the osteoporotic group, 1·6 ± 0·4 mm compared to normals 1·8 ± 0·3 mm (P < 0·0001). SFT did not decline significantly with chronological or menopausal age in the normals (correlation coefficients r=−0·06, r=−0·09) in contrast to the osteoporotic group (correlation coefficients r=−0·52, P < 0·001; r=−0·27, P < 0·0001). Subjects with a SFT of ≤ 1·5 mm had a higher probability of osteoporosis (odds ratio 3·12, 95% confidence Interval 1·58–6·14). Subjects with a SFT of ≥ 2·1 mm had a lower probability of osteoporosis (odds ratio 0·305, 95% confidence interval 0·126–0·740).

CONCLUSION Our results demonstrate a lower mean SFT in osteoporotic compared with normal women, with a negative correlation between SFT and chronological and menopausal age in osteoporotlcs, but not In normal controls. A low skinfold thickness appears to be an indicator of developing osteoporosis and a high SFT may indicate a normal bone mass.
Whole body composition and regional bone mass in women with insulin‐dependent diabetes mellitus
Authors: Compston J. E. , Smith E. M. , Matthews C. , Schofield P.
Published: March 2008

OBJECTIVE Reduced bone mass has been reported In adult patients with insulin‐dependent diabetes mellitus but there are few data on bone density in the axial skeleton or on whole body composition In this group. The aim of this study was to determine whether whole body and regional bone mass are normal in middle‐aged women with insulin‐dependent diabetes mellitus.

DESIGN Total and regional bone mass were measured In 24 post‐menopausal women aged 43–69 years (mean 56·3) with insulin‐dependent diabetes, recruited during routine clinic attendance. Results were compared with those obtained from 24 age and weight‐matched community‐based post‐menopausal women.

MEASUREMENTS Whole body bone mineral Content and bone mass in the lumbar spine and femoral neck were measured by dual energy X‐ray absorptiometry on a Lunar DPX.

RESULTS Whole body bone mineral content was significantly lower in the diabetic women than in community‐based controls (P= 0·02). There was no significant difference between the two groups in whole body bone density or lumbar spine bone density. Mean bone density in the femur was lower in the patient group at all sites assessed (femoral trochanter P= 0·003, femoral neck, P= 0·057). Values for all regional bone density measurements in the diabetic women were within the Lunar reference range (mean ± 2 SD) and at all sites the mean value was close to 100% of the sex and age‐matched reference value. There was no correlation between duration or control of diabetes and bone mass at any site.

CONCLUSIONS Insulin‐dependent diabetes mellitus In middle‐aged women is associated with small reductions in total body bone mineral content and in femoral bone density; the clinical Significance of these findings in terms of subsequent fracture risk remains to be established. No evidence was found In this study for a reduction in whole body or lumbar spine bone density.
High dose topical calcipotriol consistently reduces serum parathyroid hormone levels
Authors: Bourke J. F. , Berth‐Jones J. , Mumford R. , Iqbal S. J. , Hutchinson P. E.
Published: March 2008

OBJECTIVE Calcipotriol is a vitamin D analogue which is an effective topical treatment for chronic plaque psoriasis. It has been reported to have no effect on systemic calcium homeostasis provided the manufacturer's guidelines are adhered to (maximum 100 g of calcipotriol ointment (50 μg/g) per week). However, there have been reports of hypercaicaemla in patients using topical caicipotriol even at recommended doses. The purpose of this study was to investigate the effects of topical calcipotriol in vivo using the recently developed ‘intact’ PTH assay as a more sensitive index of systemic calcium homeostasis.

DESIGN AND PATIENTS Seven patients with extensive psoriasis were recruited for the study. Each patient was admitted to hospital and applied 200 g 01 calcipotrlol (50 μg/g) ointment over the first week followed by 300 g over the second week. in the third week of treatment, patients were treated with 2% crude coal tar which served as a biochemical washout phase.

MEASUREMENTS Serum total adjusted calcium was measured at baseline and three times a week during the study. Twenty‐four‐hour urinary calcium excretion was measured at baseline and twice a week throughout the study. Peak (0400 h) and trough (0900 h) PTH levels were measured at baseline and at the ends of weeks 2 and 3.

RESULTS Serum PTH levels were reduced in every patient after 2 weeks' treatment with caicipotriol and rose after withdrawal. Mean 0400 h PTH fell by 2·58pmolli (95% confidence interval 1·45–3·70) from 5·11 to 2·53 pmol/l (P < 0·01) and mean 0900h PTH fell by 2·08 pmol/l (0·84–3·36) from 4·04 to 1·96 pmol/l (P < 0·01). Mean serum and urine calcium rose during treatment with calcipotriol and fell after withdrawal. Mean adjusted total calcium rose by 0·14mmol/l (95% confidence interval 0·10–0·16) from 2·25 to 2·39 mmol/l (P < 0·01). Mean 24 hour urine calcium excretion rose by 2·09 mmol/24h (0·51–3·26) from 3·40 to 5·49 mmol/24h (P < 0·05). No patient developed hypercalcaemia at any stage of the study although hypercalciuria was recorded transiently in three patients.

CONCLUSION Topical calcipotriol is likely to have a dose dependent effect on systemic calcium homeostasis.
Postural stimulation test in patients with aldosterone producing adenomas
Authors: Feltynowski T. , Ignatowska‐Switaiska H. , Woclal B. , Lewandowski J. , Chodakowska J. , Januszewicz W.
Published: March 2008

OBJECTIVE The purpose of this study was to evaluate the postural stimulation test before and after surgical treatment in patients with aldosterone‐producing adenomas.

DESIGN The retrospective study was made on patients with aldosterone producing adenomas.

PATIENTS The postural stimulation test was analysed in 60 patients with surgically proven aldosterone producing adenoma and In 15 healthy volunteers.

MEASUREMENTS The postural stimulation test was based on measurements of plasma aldosterone, cortisol and renin activity (PRA) at 0800 h and at noon after 4 hours ambulation.

RESULTS The patients were divided into two groups according to the individual pattern of plasma aldosterone concentration following the postural test. Plasma aldosterone concentration decreased or did not change after 4 hours of standing in 42 patients (group 1,70% of total) and increased in 18 patients (group 2, 30% of total). Mean plasma aldosterone was significantly higher in group 1 than in group 2 (1325 ± 164 pmol/l (mean ± SE) and 538 ± 53 pmol/l, respectively). Mean plasma cortisol concentration after 4 hours of upright posture in both groups remained low (242 ± 35 vs 401 ± 63 nmol/l (group 1) and 317 ± 46 vs 367 ± 43 nmol/l (group 2). Mean PRA In both groups was suppressed after 4 hours of upright posture (0·2 ± 0·04 vs 0·2 ± 0·04 pmol/l/s and 0·3 ± 0·06 vs 0·1 ± 0·02 pmol/l/s, respectively).

CONCLUSION Diverse changes In plasma aldosterone and cortisol found in response to the postural test may indicate pathogenetic heterogeneity amongst patients with aldosterone producing adenomas and should be considered during diagnosis of primary aldosteronlsm.
Body composition in active acromegaly during treatment with octreotide: a double‐blind, placebo‐controlled cross‐over study
Authors: Hansen T. B. , Gram J. , Bjerre P. , Hagen C. , Bollerslev J.
Published: March 2008

OBJECTIVE In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin‐like growth factor I (IGF‐I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue.

Treatment with the somatostatin analogue, octreotide, has been shown to reduce GH levels causing reduced hormonal effects on target tissues. We have studied changes in body composition during short‐term reduction in OH level by octreotide in active acromegaly. DESIGN Octreotide was compared to placebo in a double‐blind, cross‐over trial. Dual‐energy X‐ray absorptlometry scanning was employed to calculate body composition. Relations between body composition parameters and clinical signs of acromegaly (finger circumference and foot volume) were studied.

PATIENTS Twelve patients with active acromegaly, confirmed by lack of GH suppression during oral glucose loading, were included. All had pituitary adenomas diagnosed by computed tomography.

MEASUREMENTS Serum GH and IGF‐I. Lean body mass, fat mass and total weight, foot volume and finger circumference.

RESULTS Four weeks of octreotide treatment caused a 75% decrease in GH levels (n= 10), a reduction in IGF‐I from 476 ± 51·9 (mean±SEM) to 233 μg/l ± 46·3 (P < 0·005) and a corresponding decrease In both body weight (2·51 kg ± 0·41) (P <0·005) and lean body mass (2·44 kg ± 0·48) (P < 0·005). No significant changes in fat mass were observed. These findings were paralleled by significant reductions in foot volume (44·50ml ± 17) (P < 0·05) and finger circumference (1·3 mm ± 0·3) (P < 0·05).

CONCLUSIONS Short‐term octreotide therapy reduces growth hormone levels leading to a significant reduction in lean body mass as assessed by dual‐energy X‐ray absorptiometry. Alterations in lean body mass were positively correlated with reductions in foot volume. Thus, simple clinical tests may be valuable in judging the effects of treatment in active acromegaly.
Age as a determinant of the impact of growth hormone therapy on predicted adult height
Authors: Hochberg Zeev , Leiberman Esther , Landau Heddy , Koren Ronit , Zadik Zvl
Published: March 2008

OBJECTIVE Final adult height is determined by both childhood and pubertal growth. The later is a function of growth velocity and bone maturation, and both are regulated by growth hormone. In a study of the safety and efficacy of GH therapy, we analysed the Impact of age on bone maturation and predicted adult height.

PATIENTS AND METHODS The subjects were 65 male patients with GH deficiency, as diagnosed by pharmacological or physiological tests, who participated in a multi‐centre trial and completed 3 years of hGH therapy. The age range at initiation of therapy was 3·1–15·7 years. Subcutaneous injections of hGH were given in a dose of 0·3 mg/kg/week, in thrice‐weekly doses. Calculation of the adult height prediction was performed on annual growth parameters using the Bailey‐Pinneau, TW‐II and Roche methods.

RESULTS The rate of pubertal advancement correlated positively with the child's age at initiation of therapy. The bone age advanced in positive correlation with chronological age, and by the end of 3 years of hGH therapy the δ‐bone age/δchronological age ratio increased to 1·5 for children with an age at start of therapy of 10·7 years. During the adolescent years, the predicted gained height over 3 years of therapy declined, in correlation with age, and became negative at a therapy‐initiation age of 12·9 years.

CONCLUSIONS In a retrospective analysis of a group of children with heterogeneous GH secretory ability, GH induced acceleration of growth, around the age of normal puberty, advanced the age of pubertal onset and accelerated pubertal progression which, in turn, expedited bone maturation and thereby restricted predicted adult height gain from hGH therapy.
Prevalence of thyroid hormone autoantibodies in healthy subjects
Authors: Sakata Shigeki , Matsuda Masafumi , Ogawa Toru , Takuno Hiroshi , Matsul Ikuo , Sarui Hiroshi , Yasuda Keigo
Published: March 2008

OBJECTIVE The prevalence of thyroid hormone autoantibodies in patients with thyroid disorders has been well described, although the results have been variable. However, the prevalence of thyroid hormone autoantibodies in apparently healthy subjects remains unknown and its determination was the main objective of this study. SUBJECTS AND METHODS Sera obtained from 880 healthy subjects (365 men and 515 women) were examined for thyroid hormone autoantibodies by immune precipitation using radiolabelled thyroid hormones or thyroid hormone analogues.

RESULTS Anti‐triiodothyronine (T3) and anti‐thyroxine (T4) antibodies were detected in none (0%) and in 3 (0·34%), respectively, of the 880 individuals studied using radiolabelied thyroid hormones. Similar tests in 385 healthy subjects using radiolabelled thyroid hormone analogues (polyaminocarboxy T3 and T4) showed the presence of anti‐T3 and anti‐T4 antibodies in 3 (0·78%) and in 4 (1·04%), respectively. None of the subjects had both anti‐T3 and anti‐T4 antibodies. Thus, the prevalence of anti‐T3 or anti‐T4 antibodies among healthy population was concluded to be as high as 1·8%. Radiolabelled thyroid hormone analogue binding to purified immuno‐globulin G (IgG), with or without the addition of an excess of uniabelled thyroid hormones, confirmed specific binding of thyroid hormones to the thyroid hormone autoanti‐body‐positive IgGs. The presence and class speciflclty of thyroid hormone autoantibodies was confirmed by the Ouchteriony immunodiffusionlautoradiography method, which showed biphenotypic heavy chain (IgG and IgA) and kappa (κ) light chain specificities. Serum concentrations of free thyroid hormones and TSH in thyroid hormone autoantibody‐positive sera were within the normal range.

CONCLUSIONS These results indicate that the Occurrence of thyroid hormone autoantibodies among the healthy Japanese population is fairly common. However, interference of thyroid hormone autoantibodies in the radio‐Immunnoassay of free thyroid hormones is exceptional.
Thyroid function and thyroid size in normal pregnant women living in an iodine replete area
Authors: Berghout Arie , Endert Erik , Ross Alec , Hogerzeil Hendrlkus V. , Smits Nico J. , Wlerslnga Wilmar M.
Published: March 2008

OBJECTIVE The interpretation of the changes in thyroid hormone concentrations during normal pregnancy is a matter of debate involving, in some geographical regions, enhanced thyrold activity in early pregnancy and a hypothyroid state In the third trimester.

A clinically detectable increase in thyroid size has been found in areas of mild iodine deficiency ('goitre of pregnancy'), but not in iodine replete areas.

DESIGN A prospective study. We have studied thyroid size and function In normal pregnant women living In an iodine replete area.

PATIENTS Healthy women before and during a normal pregnancy resulting from artificial Insemination (n= 10) and other women during the normal menstrual cycle (n= 11), in the iodine replete area of Amsterdam. MEASUREMENTS Thyroid volume was measured by ultrasonography. Plasma T4, free T3, free reverse T3, TSH, thyroxine binding globulln, hCG, progesterone and thyroid autoantibodies were measured.

RESULTS Thyroid volume did not change during prep nancy (data given before pregnancy and during lst, 2nd and 3rd trimesters, respectively: 10·3 ± 5·1, 10·6 ±4·4, 9·6 ± 3·8 and 9·4 ±3·0 ml, NS). Free T4 and free T3 levels declined during pregnancy (13·7±2·0, 13·5 ±4·1, 11·2 ±2·8, 10·2 ±1·6pmol/l, P= 0·005; 4·55 ±0·63, 4·64 ± 0·88, 3·72 ± 0·67 and 4·01 ± 0·75pmol/l, P= 0·003), whereas free reverse T3 levels increased during pregnancy (0·16 ± 0·04, 0·19 ± 0·07, 0·14 ±0·03 and 0·20 ± 0·07pmol/l, P= 0·001). Thyroglobulin levels remained unchanged. Thyroid hormones and thyroid volume did not differ between folllcular and luteal phases of the menstrual cycle.

CONCLUSION Thyrold volume does not increase during pregnancy in iodlne‐replete areas. The decrease in free T4 and free T3 and the Increase in free reverse T3 concentrations during pregnancy resemble the changes in thyroid hormones seen in non‐thyroidal illness. This could be a physiologlcal adaptation enabling energy conservation durlng the high metabolic demands of pregnancy.
Susceptibility to autoimmune thyroiditis in Down's syndrome is associated with the major histocompatibility class II DQA 0301 allele
Authors: Nicholson L. B. , Wong F. S. , Ewins D. L. , Butler J. , Holiand A. , Demaine A. G. , McGregor A. M.
Published: March 2008

OBJECTIVE Abnormalities of immune function, including thyroid autoimmunity, are common features of Down's syndrome, and the genetic associations of autoimmune thyroiditis have been extensively studied In otherwise normal patients with thyroid disease. In this study we have examined the HLA associations of autoimmune thyroid diseases in a cohort of adult subjects with Down's syndrome, to see whether they differed from those found in other populations.

DESIGN AND MEASUREMENTS Restrlction fragment length polymorphism analysis was carried out in 41 subjects whose thyroid status was assessed by measuring thyroid function and autoantibody titres. The genotypes of subjects with and without hypothyroid autoimmune diseases were compared.

SUBJECTS Forty‐one older subjects with Down's syndrome and an average age of 466 years under review by the Maudsley Hospital.

RESULTS Hypothyrold autoimmune disease in thls study group was clearly associated with a 5·5‐kb Taql DQA restriction fragment length polymorphism (Pc= 0·013) corresponding to the major histocompatibility (MHC) class II DQA 0301 allele.

CONCLUSIONS In contrast to Hashlmoto's thyroiditis and atrophic thyroiditis, there is a strong association between class II genotypes and hypothyroid autoimmune disease in Down's syndrome. This implies a role for a gene or genes on chromosome 21 in the development of autoimmune thyroid disease.
Imaging in endocrinology: use of a potential methodology for audit consensus development
Authors: Davies Melanie J. , Howlett Trevor A.
Published: March 2008

OBJECTIVE To explore areas of consensus in the use of imaging techniques in the investigation of endocrine disorders.

DESIGN A postal questionnaire sent to members of the Endocrine Section of the Royal Society of Medicine following a meeting of the Section In January 1993 on Imaging in Endocrinology.

SUBJECTS Fifty‐two specialists completed the questionnaire which was sent in the first mailing after the meeting.

MEASUREMENTS Consensus statements were defined as those In which greater than 75% of respondents either agreed or opposed the statement. Majority support or rejection was defined as greater than 50% In favour with less than 25% opposed or vice versa.

RESULTS Many areas of consensus were defined particularly in the field of the use of Imaging in the investigation of pituitary disease. The questionnaire highlighted difficulties in obtaining a consensus view on the imaging techniques which should be employed in the investigation of thyroid, parathyroid and pancreatic disorders.

CONCLUSION The results are a useful guide to areas in which further discussion and/or research is required. This methodology could, and we believe should, be applied to other areas of endocrine practice. Such results provide an initial data base to develop national audit guide‐lines on the use of imaging techniques in endocrine disorders.
Familial isolated primary hyperparathyroidism
Authors: Kassem M. , Zhang X. , Brask S. , Erlksen E. F. , Mosekilde L. , Kruse T. A.
Published: March 2008

Familial primary hyperparathyroidism (PHPT) Is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long‐term follow‐up data were reported and no genetic linkage studies were performed.

OBJECTIVE We investigated a large family with a familial primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN A family screening study.

PATIENTS Thirty‐seven family members participated in this study including 7 patients who had been previously operated upon for PHPT.

MEASUREMENTS Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24‐hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN‐1) locus.

RESULTS Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS5l(D11S97) was Informative, maximum two‐point lodscore of 2·12 at a recombination fraction of 0·05 confirming linkage to chromosome 11q13.

CONCLUSIONS Familial PHPT can exist as a separate clinical entity. Isolated familial PHPT is caused by mutation in a gene located in the MEN‐1 region on chromosome 11q13, possibly the MEN‐1 locus.