bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐LIPOTROPHIN AND β‐ENDORPHIN PLASMA LEVELS DURING PREGNANCY
Authors: GENAZZANI A. R. , FACCHINETTI F. , PARRINI D.
Published: March 2008

β‐lipotrophin (β‐LPH) and β‐endorphin (β‐EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G‐75 column chromatography in plasma samples from controls (ten healthy males and twenty‐six young women in early follicular phase), from eighty‐two pregnant women in weeks 9–40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in β‐LPH (120·6 ± 8·5 pg/ml) or β‐EP (31·1 ± 2·4 pg/ml) plasma levels or in their molar ratio (1·34 ± 0·09) (MR). β‐LPH plasma levels increased in early pregnancy (13–16 weeks) (185·0 ± 27·1 pg/ml) and remained high until weeks 21–24, then declining to levels similar to those of controls. β‐EP plasma levels were significantly depressed in weeks 9–12 (20·7 ± 5·3 pg/ml), subsequently increasing to a maximum at weeks 36–37 (42·7 ± 6·8 pg/ml). β‐LPH/β‐EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that β‐LPH and β‐EP present different patterns throughout pregnancy and that β‐EP levels increase progressively, reaching the highest concentrations at term. At delivery, both β‐LPH and β‐EP showed maximum values (β‐LPH: 230·2 ± 20·4 pg/ml; β‐EP: 78·0 ± 7·4 pg/ml) and a MR of 1·02 ± 0·10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in β‐LPH and β‐EP plasma levels. Cord blood specimens showed a wide range of values (β‐LPH:75–347 pg/ml; β‐EP: 16–287 pg/ml) with a MR of 1·21 ± 0·14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by β‐LPH levels of 119·4 ± 26·4 pg/ml and β‐EP levels of 29·6 ± 7·5 pg/ml.
THE DYNAMICS OF PROLACTIN SECRETION DURING THE PUERPERIUM IN WOMEN
Authors: VEMER H. M. , ROLLAND R.
Published: March 2008

This study deals with serum prolactin concentrations during various conditions in the early puerperium in an attempt to investigate some characteristics of the mechanisms responsible for the regulation of the lactotrophes. In nursing, in non‐nursing, non‐medicated and in non‐nursing, bromocriptine‐treated women prolactin and 17β‐oestradiol were measured during the early puerperium. In the first and the third group this was repeated during and after challenge with oestradiol‐benzoate. The pituitary responsiveness to TRH was also determined in these two groups, challenged and unchallenged with oestradiol‐benzoate. Nursing women had higher prolactin levels than the non‐nursing groups, while bromocriptine decreased prolactin to very low levels. Non‐nursing non‐medicated women had prolactin values between those of nursing and those of bromocriptine‐treated mothers. The already elevated prolactin levels in nursing women were not influenced by chronic oestradiol administration. In non‐nursing puerperal women treated with bromocriptine, exogenous oestradiol caused a significant rise in plasma prolactin. The prolactin response to TRH in nursing women was clearly reduced in comparison with the normal menstrual cycle. In the bromocriptine‐treated group the basal concentration of prolactin and its response to TRH stimulation was similar to normal non‐pregnant women. In nursing and in non‐nursing women treated with bromocriptine prolactin responses to TRH were increased after oestradiol challenge.
WITHDRAWAL OF ENDOGENOUS SYMPATHETIC DRIVE LOWERS BLOOD PRESSURE IN PRIMARY ALDOSTERONISM
Authors: NICHOLLS M. G. , JULIUS S. , ZWEIFLER A. J.
Published: March 2008

We were able to observe the effect of withdrawal of endogenous sympathetic drive in a hypertensive patient with an aldosterone‐secreting adrenal adenoma. Acute stimulation of both carotid sinus nerves lowered blood pressure to normotensive or hypotensive levels by reducing peripheral resistance. When chronic carotid sinus nerve stimulation was discontinued, peripheral resistance and blood pressure increased. These data suggest that the sympathetic nervous system is important in the maintenance of hypertension in established primary aldosteronism.
CONTROL OF GONADOTROPHIN SECRETION BY STEROID HORMONES IN CASTRATED MALE TRANSSEXUALS. II. EFFECTS OF ANDROGENS ALONE AND IN COMBINATION WITH OESTRADIOL ON THE SECRETIONS OF FSH AND LH
Authors: GOH H. H. , KARIM S. M. M. , RATNAM S. S.
Published: March 2008

Twenty‐nine infusions in twenty castrated male transsexual volunteers were carried out over a period of 7 h with subjects lying in the supine position. The effects of different doses of testosterone and its Sα‐reduced metabolites as well as the effect of testosterone in combination with oestradiol on gonadotrophin secretion were evaluated. Different and varying degrees of suppression of plasma levels of FSH and LH were observed. The infusions of 2·4 mg testosterone, 5α‐androstan‐3α‐17β‐diol (3α‐diol), 5α‐androstan‐3β17β‐diol (3β‐diol) but not dihydrotestosterone (DHT) caused significant suppression of LH. FSH, on the the other hand was not significantly inhibited by the androgens at this rate. At higher doses all four androgens suppressed LH secretion significantly. FSH was similarly suppressed by the androgens except by DHT. A differential effect on FSH and LH secretions was noted with the combined regime of testosterone and oestradiol. The combined regime did not cause a significantly higher degree of FSH suppression compared with either 200 μg of oestradiol or 12 mg of testosterone infused alone. The level of LH, however, was suppressed to a greater extent than either of the hormones when given alone. The inhibitory effect of testosterone demonstrated in this study could be due to the parent hormone or its 5α‐reduced metabolites. Pharmacological doses of testosterone could exert a greater degree of LH suppression through its conversion to oestradiol. It is likely that oestradiol and testosterone act on gonadotrophin secretion through different mechanisms and that they have an additive suppressive effect on the secretion of LH but not FSH. The potencies for the androgens to suppress gonadotrophin secretion can be ranked as: 3α‐diol = 3β‐diol > testosterone > dihydrotestosterone.
IMPAIRED DOPAMINERGIC CONTROL OF THYROID STIMULATING HORMONE SECRETION IN CHRONIC RENAL FAILURE
Authors: WEETMAN A. P. , WEIGHTMAN D. R. , SCANLON M. F.
Published: March 2008

After administration of intravenous metoclopramide, a dopaminergic receptor blocking agent, no rise in thyroid stimulating hormone (TSH) could be found in patients with chronic renal failure, in contrast to non‐uraemic controls. Basal TSH values were normal in the uraemic patients but the TSH response to thyrotrophin‐releasing hormone (TRH) was significantly reduced. These results suggest that a discrete abnormality in the hypothalamo—pituitary axis exists in uraemia which may in part be due to interference with central dopaminergic control by a uraemic toxin.
THE EFFECT OF GROWTH HORMONE ON THE LEYDIG CELL RESPONSE TO CHORIONIC GONADOTROPHIN IN BOYS WITH HYPOPITUITARISM
Authors: KULIN H. E. , SAMOJLIK EUGENIUSZ , SANTEN R. , SANTNER S.
Published: March 2008

Eleven boys with growth hormone (hGH) deficiency received human chorionic gonadotrophin (hCG) stimulation tests for the assessment of Leydig cell function before, during, and after 1 year of treatment with somatotrophin. Two patients entered puberty during the course of the study protocol. Analysis of the data in nine prepubertal boys revealed an augmentation of testosterone (T) responses to hCG in the presence of hGH. In six of these individuals in whom dihydrotestosterone (DHT) was determined, a similar augmentation in responsiveness of this steroid was found in the presence of hGH. Three prepubertal boys exhibited poor T responses to the basal hCG test with only partial improvement following hGH. In man growth hormone may be an important permissive factor in Leydig cell activity during periods of changing testicular function such as occur in utero or during puberty.
H‐Y POSITIVE 46 XX TRUE HERMAPHRODITISM WITH INTRASCROTAL UTERUS
Authors: BOUCEKKINE C. , MENASRIA A. , CHOUITER A. , BENELKADI N. , BENMILOUD M.
Published: March 2008

A rare form of true hermaphroditism with hypogonadism, gynaecomastia, presence of an intrascrotal uterus, and 46 XX karyotype, is reported. It is the third published case in the literature since 1965. The presence of H‐Y antigen and of testicular tissue in the absence of a Y chromosome is discussed.
PITUITARY—ADRENOCORTICAL FUNCTION IN PATIENTS DURING TREATMENT WITH THE ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR CAPTOPRIL
Authors: ANGELI A. , BISBOCCI D. , ORLANDI F. , PACCOTTI P. , TABASSO R. , TAMAGNONE C. , LAVEZZARO G. C.
Published: March 2008

To study effects on pituitary‐adrenocortical activity of a sustained block of angiotensin II formation, six ‘drug‐resistant’ patients with essential hypertension were studied before and during treatment with an inhibitor of the angiotensin‐converting enzyme (Captopril, SQ 14,225). The drug was given in increasing doses (100–400 mg/day) for 2 weeks whilst patients received a moderately restricted sodium intake (60–80 mmol/day). Immunoreactive ACTH, cortisol, aldosterone, plasma renin activity (PRA) and the activity of the angiotensin‐converting enzyme (ACE) were measured in blood samples drawn at 0800–0900 h. Urinary excretion of cortisol and aldosterone were measured in 24‐h urine collections. Further information on pituitary‐adrenocortical function was obtained by measuring serial plasma corticosteroid levels after submaximal stimulation with a synthetic ACTH preparation. ACTH and cortisol did not change an observation which does not support the hypothesis that glucocorticoid activity is influenced by a decrease in plasma angiotensin II concentrations.
CUSHING'S DISEASE PRESENTING AS AMENORRHOEA WITH HYPERPROLACTINAEMIA: REPORT OF TWO CASES
Authors: JURNEY T. H. , DE RUYTER H. , VIGERSKY R. A.
Published: March 2008

Two patients with Cushing's disease first presented with amenorrhoea, hyperprolactinaemia, and normal tomograms of the sella turcica. Both women underwent trans‐sphenoidal removal of a pituitary microadenoma resulting in a decreased serum prolactin concentration in both, and cessation of galactorr‐hoea and return of menses in one of them. One woman became ACTH deficient while the other has persistent Cushing's disease. A survey of the literature on Cushing's disease and prolactinomas shows the association to be uncommon. A likely mechanism is secretion of both hormones by the microadenomas. These two patients illustrate the need for screening other pituitary hormone function in patients with hyperprolactinaemia.
ABNORMAL PANCREATIC POLYPEPTIDE RESPONSE TO INTRAVENOUS GLUCOSE IN URAEMICS. A POSSIBLE MECHANISM BEHIND IMPAIRED GLUCOSE TOLERANCE IN URAEMIA
Authors: HALLGREN R. , FJELLSTROM K. ‐E. , LUNDQUIST G.
Published: March 2008

Glucose handling and insulin secretion were studied in chronic haemodialysis patients and correlated with circulating levels of immunoreactive pancreatic polypeptide (PP). No correlation was found between the elevated basal levels of PP and the K‐rate or the maximum insulin response after a single intravenous injection of glucose. Fifty‐three per cent of the patients had a normal glucose tolerance defined as a K‐rate more than 1. This group of uraemics had a tendency to an exaggerated insulin response compared with the controls but no significant changes of serum‐PP levels after a glucose stimulus were observed. In contrast, uraemic patients with a K‐rate less than 1 and normal insulin response, showed significant increases of serum‐PP at 4 and 6 min after glucose administration. Among all uraemic patients we found a significant inverse correlation between the K‐rate and the early PP response (Pc0.05) and a significant positive correlation between the K‐rate and the early insulin response (P<O.O5). PP release in response to acute hyperglycaemia may be one mechanism behind impaired glucose handling in uraemics, either by reducing peripheral insulin activity or by preventing insulin secretion sufficient to overcome the decreased tissue sensitivity to insulin.
OPIATES CONTROL ACTH THROUGH A NORADRENERGIC MECHANISM
Authors: GROSSMAN A. , BESSER G. M.
Published: March 2008

The administration of 16 mg of naloxone to six normal male subjects produced a significant rise in plasma cortisol. Pre‐treatment with the noradrenergic α1‐antagonist, thymoxamine 0.2 mg/kg, blocked this rise. It is suggested that opiate inhibition of the pituitary—adrenal axis is mediated via a noradrenergic pathway.
DETERIORATION OF RENAL BONE DISEASE IN PATIENTS TREATED WITH SALMON CALCITONIN
Authors: CUNDY T. , KANIS J. A. , HEYNEN G. , PATON S. , EARNSHAW M. , WOODS C. G.
Published: March 2008

Twelve patients with chronic renal failure and osteitis fibrosa were treated for periods of 1–9 months with thrice‐weekly injections of 10–200 iu salmon calcitonin. Treatment had no significant effects on symptoms of bone disease and side effects were common. A transient fall in plasma alkaline phosphatase levels occurred in only three patients, and both plasma alkaline phosphatase and hydroxyproline levels rose in the majority of patients. Radiographic signs of hyperparathyroidism increased in seven of the nine patients treated for longer than 3 months. Paired bone biopsy specimens in nine patients showed significant increases in osteoblast counts, but no changes in the indices of resorption. These treatment‐induced changes were reversed when treatment with 1,25‐dihydroxyvitamin D3 was substituted for calcitonin. The use of this regimen of salmon calcitonin is not recommended in the long‐term management of hyperparathyroid bone disease in chronic renal failure.
THE INVOLVEMENT OF THE PENTOSE SHUNT IN THYROID METABOLISM AFTER STIMULATION WITH TSH OR WITH IMMUNOGLOBULINS FROM PATIENTS WITH THYROID DISEASE. 1. THE GENERATION OF NADPH IN RELATION TO STIMULATION OF THYROID GROWTH
Authors: DREXHAGE H. A. , HAMMOND LINDA J. , BITENSKY LUCILLE , CHAYEN J. , BOTTAZZO G. F. , DONIACH DEBORAH
Published: March 2008

It has been shown previously that both thyrotrophin (TSH), and also immunoglobulins (Ig) derived from patients with goitrous Graves’disease, stimulate DNA‐synthesis in guinea‐pig thyroid tissue maintained in vitro. Here we describe the use of the same in vitro system and methods of quantitative cytochemistry to test the effect of these substances on the generation of NADPH, which is another indicator of the potential for growth. As could be predicted by its trophic action, TSH stimulated the generation of NADPH by glucose 6‐phosphate dehydrogenase. The Ig‐fraction from normal subjects depressed this activity. The Ig‐fraction from Graves’disease patients with goitres stimulated the generation of NADPH, whereas the Ig from patients with Graves’disease but with minimal enlargement of the thyroid gland behaved like normal Ig. A similar lack of stimulation was found with Ig from patients with Pendred's syndrome, other dyshormonogenetic goitres, and autonomous single adenomas. In all specimens tested, there was good correlation between the amount of DNA‐synthesis, measured by Feulgen cytophotometry, and the activity of glucose 6‐phosphate dehydrogenase activity that generated NADPH. These results support the concept that there is a distinct type of autoantibody that influences thyroid growth.
TREATMENT OF ACROMEGALY BY TRANS‐SPHENOIDAL OPERATION, 90‐YTTRIUM IMPLANTATION AND BROMOCRIPTINE: RESULTS IN 230 PATIENTS
Authors: QUABBE H‐J.
Published: March 2008

Two hundred and thirty patients with acromegaly were diagnosed and treated in a prospective cooperative study in twelve university clinics. Primary treatment was: trans‐sphenoidal surgery (152 patients), trans‐sphenoidal surgery with additional cryotherapy (eighteen patients), Yttrium‐90‐implantation (thirty patients), bromocriptine (thirty patients). The results of endocrine assessment before treatment and 6 months after operation, 90‐Y implantation or commencement of bromocriptine therapy are reported.

The best results (low GH, no or little deterioration of pituitary function, low complication rate) were achieved by trans‐sphenoidal surgery, especially in patients with intrasellar tumours (basal GH < 5 ng/ml in 59·7%). Results were less good with increasing tumour size. Additional cryosurgery was accompanied by a high rate of anterior pituitary insufficiency and is no longer employed. Yttrium‐90‐implantation resulted in less improvement in GH levels (basal GH < 5 ng/ml in 51·7. of patients with intrasellar tumours), a high rate of pituitary insufficiency and more complications. Bromocriptine treatment was least effective in lowering GH concentrations (basal GH < 5 ng/ml in 33% of patients with intrasellar tumours).

Different criteria for treatment success were compared. In the entire group, basal GH concentrations below 5 ng/ml were attained in 51·7. of all patients whose values were higher than this prior to treatment. Suppressibility of GH below 2 ng/ml during glucose loading occurred in only 34·9%. An abnormal GH response to TRH/LHRH was present in 47·2. before and in 43·4% after/during treatment. The prognostic significance of this latter finding must be evaluated by further study.
ADRENOCORTICAL FUNCTION IN CHILDREN WITH PRECOCIOUS SEXUAL DEVELOPMENT DURING TREATMENT WITH CYPROTERONE ACETATE
Authors: STIVEL M. S. , KAULI R. , KAUFMAN H. , LARON Z.
Published: March 2008

Adrenal function was studied in thirty‐two children with precocious sexual development who were being treated with cyproterone acetate (CPA) at doses ranging from 68 to 175 mg.m2. day for periods lasting from 2 to 79 months. In eighteen children the adrenocortical function evaluation was made before and during CPA treatment. In these eighteen patients, the mean basal plasma cortisol level during the morning hours was 11·2±4·6 μg/dl (m±SD) before treatment and fell significantly to 7·2±4·1 μg/dl (P < 0·02) during therapy. In fifteen patients tested during insulin hypoglycaemia the cortisol peak fell from 21·6±5·5 μg/dl before treatment to 16·7±6·8 μg/dl (P < 0·05) during CPA therapy. There was a significant inverse correlation between this peak and the dose of CPA but no correlation was found between the cortisol response and duration of treatment. In eight of twenty patients tested, urinary free cortisol levels were undetectable during treatment. No change in basal plasma ACTH levels was demonstrated using standard radioimmunoassay techniques. In the patient receiving the highest dose of CPA and showing complete suppression of the adrenal axis, prolonged stimulation with ACTH‐Depot demonstrated a responsive adrenal gland. Addition of a replacement dose of cortisol to the CPA treatment led to the rapid development of the typical signs of Cushing's syndrome. It was concluded that despite the evidence of adrenal suppression by CPA, cortisol supplementation is not necessary and may even be contra‐indicated.
THE PARTICIPATION OF HYPOTHALAMIC DOPAMINE IN MORPHINE‐INDUCED PROLACTIN RELEASE IN MAN
Authors: DELITALA G. , GROSSMAN A. , BESSER G. M.
Published: March 2008

In order to assess the role of dopamine in opiate‐induced prolactin secretion, morphine alone or in combination with the dopamine blocker metoclopramide, or the L‐aromatic aminoacid decarboxylase inhibitor benserazide, was administered to a group of normal adult men. Morphine (10 mg) stimulated prolactin release in all subjects; however, the effect was totally abolished when 10 mg metoclopramide or 200 mg benserazide were given before the opiate agonist. The prolactin releasing effect of a sub‐maximal metoclopramide dose (1 mg) was potentiated by morphine. In vitro, benserazide was totally inactive in stimulating prolactin release by isolated anterior pituitary cells. Moreover, benserazide failed to alter the inhibiting action of dopamine on prolactin release.

The data suggest that opiates stimulate prolactin release in man by acting through dopaminergic mechanisms.
MALE GONADAL FUNCTION IN COELIAC DISEASE: III. PITUITARY REGULATION
Authors: FARTHING M. J. G. , REES LESLEY H. , DAWSON A. M.
Published: March 2008

Pituitary regulation of gonadal function was investigated in 39 consecutive men with treated and untreated coeliac disease and in an intestinal disease control group of 19 men with Crohn's disease of similar age and general nutritional status. Basal serum FSH concentration was increased in 10 of the coeliacs (26%) compared to only two of 19 men with Crohn's disease (11%). This abnormality was observed with equal frequency in both treated and untreated coeliacs, and was not associated with oligospermia. Serum LH concentration was increased in eight of 15 untreated coeliacs (53%) with sub‐total villous atrophy, an abnormality which unlike the elevation of serum FSH, appears to return towards normal after gluten withdrawal. Serum LH was high in coeliacs despite marked elevation of the free testosterone index. Exaggerated responses of FSH and LH to LHRH were found in 89% and 45% respectively, of coeliacs with sub‐total villous atrophy. However, exaggerated responses of LH alone were found more frequently in coeliacs than in men with Crohn's disease (P <0.02) and unlike the exaggerated FSH responses, LH responses were closely related to jejunal morphology. Exaggerated responses of FSH and LH in coeliacs were commonly found when basal gonadotrophin concentrations were normal. The occurence of exaggerated gonadotrophin responses could not be related to plasma concentration of testosterone, dihydrotestosterone, oestradiol or the free testosterone index. Serum prolactin was modestly raised in 25% of untreated and partially treated coeliacs and in the same proportion of men with Crohn's disease. Elevated serum prolactin concentrations never exceeded 809 mU/1 and were not associated with impotence or infertility. This study provides further evidence that in men with coeliac disease there is a derangement of pituitary regulation of gonadal function. This would seem to be part of a wider disturbance of central regulatory mechanisms of endocrine function in coeliac disease.
INCREASED FREQUENCY OF HLA‐DR3 AND 5 IN THE SYNDROMES OF PAINLESS THYROIDITIS WITH TRANSIENT THYROTOXICOSIS: EVIDENCE FOR AN AUTOIMMUNE AETIOLOGY
Authors: FARID N. R. , HAWE B. S. , WALFISH P. G.
Published: March 2008

We studied fifty patients with painless thyroiditis with transient thyrotoxicosis (PTTT) and a low radioiodine thyroidal uptake. In 25 PTTT occurred post‐partum (P) and in the remainder was unrelated to pregnancy (U). Seventeen patients with classical subacute thyroiditis were studied for comparison. All patients were typed for HLA‐A, B, C, DR antigens. Four of the P patients had recurrences with each pregnancy; two had one previous attack of U; three had a maternal history of GRAVES' disease; 76% of the P patients had small to moderate goitres and 76% antimicrosomal antibody titres at > 1:400. HLA‐B35 was found in 24% of P patients compared to 17% of controls; 71% of patients with subacute thyroiditis were, by contrast, B35. Two of P were HLA‐B8 positive (versus 25% of controls); 11 patients were HLA‐DR3 positive and 15 (60%) HLA‐DR5 positive compared to 23% and 27% of controls yielding a relative risk (RR) = 2·50 (P < 0·05) and 3·83 (P < 0·005), respectively. All four P patients with recurrences carried HLA‐DR5. Thirteen of 25 patients in the U subgroup were HLA‐DR3, yielding a RR = 3·38 (P < 0·01); seven were HLA‐DR5, with a non‐significant RR = 1·12; four of U had first degree relatives with either autoimmune thyroid disorders or Type 1 diabetes mellitus. Thus, both P and U are associated with HLA‐DR3, the P subgroup had in addition an increased frequency of DR5. The observed HLA associations for the PTTT syndromes favours an autoimmune rather than viral aetiology.
CHANGING PATTERNS OF SEX DISTRIBUTION IN FAMILIAL MEDULLARY CARCINOMA OF THE THYROID AND ASSOCIATED PHAEOCHROMOCYTOMA
Authors: MINOPOLI MARIAROSARIA , BORDI C.
Published: March 2008

Analysis of 49 kindreds with the familial form of medullary thyroid carcinoma (MTC) reported up to 1973 revealed a non‐random sex distribution of 220 affected members, with a predominance of females among patients presenting with MTC and of males among patients presenting only with phaeochromocytoma. This pattern of sex distribution has completely disappeared among 201 patients from 47 kindreds reported in more recent years, MTC now being equally distributed between the two sexes. It is suggested that this change is related to the different diagnostic approach predominant in each period of time and that MTCs discovered at a preclinical stage by calcitonin screening are equally distributed between the sexes, while females predominate when tumours have progressed until they are clinically evident.
SPINAL BONE MINERAL CONTENT IN MYXOEDEMA AND THYROTOXICOSIS. EFFECTS OF THYROID HORMONE(S) AND ANTITHYROID TREATMENT
Authors: KRØLNER B. , JØRGENSEN J. VESTERDAL , NIELSEN S. PORS
Published: March 2008

The effects of thyroid hormones and antithyroid treatment upon lumbar spine bone mineral content (lumbar BMC) were studied in a consecutive series of patients with myxoedema and thyrotoxicosis, respectively. All patients were investigated in the untreated state and 3‐monthly during appropriate treatment for 1 year by using dual‐photon [153Gd] absorptiometry. Patients with myxoedema (n= 8) did not differ from normal individuals as regards initial lumbar BMC, but levothyroxine‐treatment caused significant reduction in this variable. The median decrease in lumbar BMC after 1 year was 8·9% (95% confidence limits 1·5–15·4%,P< 0·05). This loss of bone might be attributed to an inappropriate increase in bone turnover in the euthyroid state. It is as yet uncertain whether it predisposes to spinal osteopenia. Median lumbar BMC in patients with thyrotoxicosis (n= 25) was 12·6% (2·0–16·6%,P< 0·05) lower than that of normal individuals before the beginning of treatment. Lumbar BMC increased during antithyroid therapy. The median gain in bone mineral after 1 year was 3·7% (1·6–9·6%,P< 0·01). These findings suggest that excess of thyroid hormones leads to negative spinal bone mineral balance. The revealed bone loss was clinically insignificant, however, and it appeared to be at least partially reversible after antithyroid treatment.
PLASMA AND SALIVARY ANDROSTENEDIONE AND DIHYDROTESTOSTERONE IN WOMEN WITH HYPERANDROGENISM
Authors: BAXENDALE P. M. , JACOBS H. S. , JAMES V. H. T.
Published: March 2008

Sensitive radioimmunoassays (RIA) have been developed to measure salivary and plasma androstenedione and dihydrotestosterone levels in normal women, women with polycystic ovaries (PCO) and idiopathic hirsutism, and patients on antiandrogen therapy. There was a highly significant correlation (r= 0·92, P < 0·001) between the concentration of androstenedione in saliva and the unbound concentration in plasma. The unbound plasma androstenedione was measured in the dialysate by RIA and ranged from 6·0–10·4% of the total concentration. Salivary and plasma androstenedione levels in patients with PCO (185 ± 72 pg/ml (n= 11) and 3262 ± 814 pg/ml (n= 12) respectively) and in those with hirsutism (151 ± 110 pg/ml (n= 25) and 2177 ± 1096 pg/ml (n= 25)) were significantly higher than levels in normal women (78 ± 30 pg/ml (n= 18) and 787 ± 355 pg/ml (n= 18)). A good correlation (r= 0·82, P < 0·001) was also found between salivary and unbound plasma dihydrotestosterone concentrations. Salivary and plasma dihydrotestosterone levels in patients with PCO (8·2 ± 3·3 pg/ml (n= 9) and 167 ± 45 pg/ml (n= 11) respectively and hirsutism (6·0 ± 2·1 pg/ml (n= 14) and 176 ± 69 pg/ml (n= 17)) were significantly higher than levels in normal women (4·5 ± 1·3 pg/ml (n= 17) and 90 ± 44 pg/ml (n= 16)), although there was a large overlap between groups. A similar decrease was observed in salivary and plasma androstenedione levels after treatment with cyproterone acetate (CA) and ethinyl oestradiol (EE) for 3 months. Plasma dihydrotestosterone levels remained elevated in 47% of treated women whereas only 21% of cases had raised salivary dihydrotestosterone levels. It is concluded that, as with testosterone salivary androstenedione and dihydrotestosterone measurements give a good reflection of their biologically active levels in normal, hyperandrogenic and CA + EE treated women.
RADIOIMMUNOASSAY OF 1,25‐DIHYDROXY VITAMIN D2: STUDIES ON THE METABOLISM OF VITAMIN D2 IN MAN
Authors: FRAHER L. J. , ADAMI S. , CLEMENS T. L. , JONES G. , O'RIORDAN J. L. H.
Published: March 2008

A sensitive radioimmunoassay for 1,25‐dihydroxy vitamin D2 was developed using a sheep antiserum which preferentially reacts with 1‐hydroxylated forms of vitamin D. An improved isolation procedure was also developed using acetonitrile for the initial extraction of serum followed by chromatography on cartridges of C18 silica and high pressure liquid chromatography eluted with a ternary solvent system to separate 1,25‐dihydroxy vitamin D2 and 1,25‐dihydroxy vitamin D3. 25‐hydroxy vitamin D2 and 25‐hydroxy vitamin D3 were separated by further reverse phase high pressure liquid chromatography prior to competitive protein binding assay. The limits of detection were 4.3 pmol/l (2.0 pg/ml) for the 1,25‐dihydroxy metabolites and 1.25 nmol/l (0.5 ng/ml) for both 25‐hydroxy vitamin D2 and 25‐hydroxy vitamin D3. 25‐hydroxy vitamin D2 ranged from 2.0 to 11.3 nmol/l (0.8–4.5 ng/ml) with a mean of 4.75 nmol/l (1.9 ng/ml) in thirteen healthy British adults and this accounted for 9.0% of the mean total 25‐hydroxy vitamin D. 1,25‐dihydroxy vitamin D2 was detected in the sera of only one of these subjects whereas 1,25‐dihydroxy vitamin D3 was present in all ranging from 48 to 163 pmol/l (20–65 pg/ml) with a mean of 100 pmol/l (42 pg/ml).

Both 1,25‐dihydroxy vitamin D2 and 1,25‐dihydroxy vitamin D3 were detected in the sera of hypoparathyroid patients treated with vitamin D2 but the relationship between 25‐hydroxy vitamin D and 1,25‐dihydroxy vitamin D was complex. For example, when an excess of 25‐hydroxy vitamin D2 was present the serum concentration of 1,25‐dihydroxy vitamin D3 was disproportionately high. Conversely, in patients who had previously been treated with vitamin D2 but were receiving only vitamin D3 at the time of study, the major 25‐hydroxy metabolite was in the vitamin D3 form and there was a disproportionately high amount of 1,25‐dihydroxy vitamin D2. Total 1,25‐dihydroxy vitamin D ranged from 110 to 400 pmol/l (45–165 pg/ml) and was above the upper limit of normal for 1,25‐dihydroxy vitamin D3 in half of these hypoparathyroid patients treated with pharmacological doses of vitamin D.
SERUM THYROGLOBULIN IN ACUTE AND CHRONIC LIVER DISEASE
Authors: HEGEDÜS L. , KASTRUP J. , FELDT‐RASMUSSEN ULLA , PETERSEN P. HYLTOFT
Published: March 2008

In view of the widespread use of serum thyroglobulin determination in the follow‐up of patients with differentiated thyroid carcinoma, the influence of acute and chronic liver disease on serum thyroglobulin concentration was investigated in thirty‐seven consecutive patients with histologically proven alcoholic liver cirrhosis and twenty‐three patients with acute non‐alcoholic hepatitis. Seventy‐four healthy volunteers served as controls.

Serum thyroglobulin concentration was significantly elevated in cirrhosis: median 29·5 μg/l, (range 4·3‐94·0 μg/l) compared to controls: median 16·0 μg/l, (range 4·8‐89·6 μg/l), (P< 0·001). Serum thyroglobulin concentration in patients with acute hepatitis: median 16·2 μg/l, (range 7·9‐70·0 μg/l) was not significantly different from controls. The level of free‐T3‐index was significantly reduced and the level of free‐T4‐index was significantly elevated in both cirrhosis and hepatitis compared to controls. Serum TSH concentration was significantly elevated in cirrhosis compared to hepatitis and controls. Serum thyroglobulin levels were positively correlated to levels of free‐T3‐index (r= 0·35,P< 0·05) and T3/T4‐ratio (r= 0·40,P< 0·05) but not to levels of serum TSH or free‐T4‐index or any of the liver function tests in any of the groups.

In conclusion, our results do not clearly indicate whether the elevated serum thyroglobulin level in cirrhosis was caused by an impaired elimination and/or an increased secretion from the thyroid gland. The increase in serum thyroglobulin concentration in chronic alcoholic liver disease was not of a magnitude likely to cause misinterpretation of results obtained during the follow‐up of patients with differentiated thyroid carcinoma.
INFLUENCE OF 1α‐(OH)D3 ADMINISTRATION ON BONE AND BONE MINERAL METABOLISM IN PATIENTS ON CHRONIC GLUCOCORTICOID TREATMENT; A DOUBLE BLIND CONTROLLED STUDY
Authors: BRAUN J. J. , BIRKENHÄGER‐FRENKEL D. H. , RIETVELD A. H. , JUTTMANN J. R. , VISSER T. J. , BIRKENHÄGER J. C.
Published: March 2008

We have performed a double‐blind placebo controlled study of 1α‐hydroxyvita‐min D3 (1α‐(OH)D3) 2 μg daily for 6 months, in 14 patients receiving long‐term glucocorticoid treatment. Patients were matched for age, sex, underlying disease and dose of glucocorticoid.

Initial values for serum calcium, phosphorus and alkaline phosphatase were in the normal range. Two of the 14 patients showed an increased serum immunoreactive parathyroid hormone (iPTH) concentration. Serum 25‐hyd‐roxyvitamin D and 1,25‐dihydroxyvitamin D (l,25‐(OH)2D) were normal but the average 24,25‐dihydroxyvitamin D (24,25‐(OH)2D) was low.

The histomorphometrically determined trabecular bone volume of an iliac crest biopsy appeared to be low in 6 patients. The average active bone resorption and osteoid seams were increased, while the average osteoblast seams were within the normal range. Treatment with 1α‐(OH)D3 raised 47Ca2+ intestinal absorption and 24 h urinary Ca2+ excretion significantly at 3 and 6 months and at 6 months serum iPTH concentration and 24 h urinary hydroxyproline excretion had fallen significantly in the treated group. During treatment with 1α‐(OH)D3 the serum 1,25‐(OH)2D and 24,25‐(OH)2D levels increased significantly.

In all cases of the 1α‐(OH)D3‐group, the second bone biopsy, taken at the end of the treatment period, showed a decrease of active resorption and a more positive course of trabecular bone volume than the biopsy of the placebo‐treated counterpart: trabecular bone volume remained constant or even increased in the 1α‐(OH)D3‐group. In both groups osteoid seams and osteoblast seams did not change significantly. We conclude that treatment with 1α‐(OH)D3 during 6 months inhibits the increased bone resorption seen in glucocorticoid‐induced bone disease, while bone formation is not suppressed by this therapy.
PHAEOCHROMOCYTOMA AND DIABETES MELLITUS: FURTHER EVIDENCE THAT α2 RECEPTORS INHIBIT INSULIN RELEASE IN MAN
Authors: ISLES C. G. , JOHNSON J. K.
Published: March 2008

An insulin‐dependent diabetic presenting with thirst, polyuria and weight loss was noted to be hypertensive and shown subsequently to have a right adrenal phaeochromocytoma. Pre‐operative control of both diabetes and hypertension was achieved with propranolol and phenoxybenzamine, but not with propranolol alone. Full recovery with restoration of normal glucose tolerance and blood pressure followed successful surgery. Analysis of this patient's response to medical therapy provides further evidence that α2 receptors inhibit insulin release in man. Since as many as one‐third of phaeochromocytomas are not detected during life, this diagnosis should be considered as an uncommon cause of carbohydrate intolerance in patients with diabetes mellitus, especially if accompanied by continuous or paroxysmal hypertension.
NEGATIVE FEEDBACK EFFECTS ON ACTH SECRETION BY CORTISOL IN CUSHING'S DISEASE
Authors: READER S. C. J. , DALY J. R. , ALAGHBAND‐ZADEH J. , ROBERTSON W. R.
Published: March 2008

Bioassayable plasma ACTH and corticosteroid levels were measured during constant infusions of low doses of cortisol (3–15 mg/h) into normal subjects and into two patients with Cushing's disease. Plasma ACTH levels decreased significantly in all subjects within 60 min from the start of the infusion. The rate of rise of plasma corticosteroid levels concomitant with this feedback suppression were considerably higher in the patients with Cushing's disease (> 13 nmol/l/min) than in normal subjects (3–6 nmol/l/min). In one of the Cushing's patients, ACTH secretion resumed in spite of the corticosteroid levels rising at a rate of > 20 nmol/l/min. It is concluded that cortisol‐induced suppression of ACTH secretion may be operational in Cushing's disease but that the mechanism is less sensitive than in normal subjects.
TESTOSTERONE AND Δ4‐ANDROSTENEDIONE IN THE SALIVA OF PATIENTS WITH KLINEFELTER'S SYNDROME
Authors: WELLEN J. J. , SMALS A. G. H. , RIJKEN J. C. W. , KLOPPENBORG P. W. C. , BENRAAD Th. J.
Published: March 2008

This study compares salivary and total plasma levels of testosterone and androstenedione in healthy controls and chromatin positive patients with Klinefelter's syndrome. The mean plasma testosterone level in fifteen Klinefelter patients was significantly lower than in ten control subjects, but the mean androstenedione levels were similar. Saliva of the normal men and patients with Klinefelter's syndrome did not differ significantly in binding potency for testosterone or androstenedione. The mean salivary testosterone level in the Klinefelter patients was significantly lower than in the controls but again salivary androstenedione levels were similar. Although testosterone as well as androstenedione showed a fair correlation between the salivary and plasma concentrations, preliminary data suggested that salivary testosterone levels better characterize the clinical state of androgenicity than do plasma levels. When salivary testosterone and androstenedione were expressed as a percentage of total steroid levels in plasma, the ratios for both steroids were similar in Klinefelter patients and healthy controls and closely approximated to the reported percentages of free steroid levels in plasma. The absolute salivary testosterone concentrations also were almost identical to the reported free plasma hormone levels.

Together the data provide indirect evidence that in Klinefelter patients testosterone and androstenedione binding in plasma and saliva does not differ from that in normal men, and measurement of salivary steroids, by reflecting their free hormone concentration in plasma, may be useful in evaluating endocrine function in both health and disease.
T LYMPHOCYTE SENSITIZATION AND SUPPRESSOR T LYMPHOCYTE DEFECT IN PATIENTS LONG AFTER TREATMENT FOR GRAVES’DISEASE
Authors: HOW JACQUES , TOPLISS DUNCAN J. , STRAKOSCH CHRISTOPHER , LEWIS MARK , ROW VAS V. , VOLPÉ ROBERT
Published: March 2008

Circulating thyroid autoantibodies, T lymphocyte sensitization and suppressor T lymphocyte function were examined in thirty‐nine patients who had been treated for a mean of 10±2 years previously for hyperthyroid Graves’disease. Nineteen had been treated with radioactive iodine (131I), two with subtotal thyroidectomy, and eighteen were in long‐term remission after previous propylthiouracil (PTU) therapy. Sensitization of T lymphocytes to human thyroid antigen was studied by means of a modified migration inhibition factor test, using T lymphocyte enriched preparations, and antigen‐specific suppressor T lymphocyte function was assessed by the ability of T lymphocytes to suppress the production of migration inhibition factor by sensitized T lymphocytes of patients with active Graves’disease in response to human thyroid antigen. Despite effective correction of the hyperthyroid state in all patients, T lymphocyte sensitization to human thyroid antigen was still demonstrable in twelve of nineteen patients treated with 131I (63%), in nine of eighteen patients in remission after PTU treatment (50%) and in one of two patients after thyroidectomy. All those showing such sensitization also manifested a suppressor T lymphocyte defect. In three of the patients (all after 131I therapy) showing no such sensitization, there was nevertheless evidence of a suppressor T lymphocyte defect. On the other hand, thirteen patients (nine in the post‐PTU group, four in the post‐131I group) showed evidence of complete immunological remission. There was no correlation between the abnormal immunological findings and the number of years after treatment of the hyperthyroidism.

The present study indicates that T lymphocyte sensitization and the underlying defect in suppressor T lymphocyte function are persistent in the majority of patients with Graves’disease years after 131I destructive therapy, and occur independently of the hyperthyroid state. These findings are consistent with the concept that an inherited defect in suppressor T lymphocyte function plays a primary role in the pathogenesis of Graves’disease. In addition, long‐term remissions following non‐ablative antithyroid drug therapy appear to be of two types, namely, those in which immunoregulation has been restored, and those with remission in spite of a continuingly active immunological process.
THYROID STATUS IN VARIOUS DEGREES OF PROTEIN–CALORIE MALNUTRITION IN CHILDREN
Authors: ONUORA C. , MAHARAJAN G. , SINGH AJIT , ETTA K. M.
Published: March 2008

The thyroid functional parameters of 102 children with protein–calorie malnutrition (PCM) classified as undernourished, marasmic, kwashiorkor and marasmic–kwashiorkor were studied by measuring the serum T4, T3, T3 percentage uptake (T3%UT), free thyroxine index (FTI), and (in a few subjects) TSH. Total plasma proteins, albumin and globulin were also estimated. T4 was increased markedly in the undernourished children and significantly decreased in kwashiorkor and marasmic–kwashiorkor groups. There was a consistent and significant fall in T3 levels of all PCM children. From normal values, the fall in T3 levels was progressive in the order of undernourished, marasmic, kwashiorkor and the marasmic–kwashiorkor states. The T3%UT was increased above normal in the marasmic, kwashiorkor and marasmic–kwashiorkor conditions. The FTI decreased somewhat in marasmus and kwashiorkor groups and was very low in marasmic–kwashiorkor. Total protein and albumin levels were above normal in the undernourished but became markedly depressed in the marasmic–kwashiorkor children. The changes in the levels of both T4 and T3 in our observations are well correlated with the levels of plasma proteins in the undernourished, marasmic and kwashiorkor states but not in the marasmic–kwashiorkor group.
EFFECT OF METOCLOPRAMIDE ON THE SECRETION OF ALDOSTERONE AND OTHER ADRENOCORTICAL STEROIDS
Authors: NAGAHAMA S. , FUJIMAKI M. , KAWABE H. , NAKAMURA R. , SAITO I. , SARUTA T.
Published: March 2008

The aim of this study was to determine the effect of metoclopramide, a dopamine antagonist, on the secretion of aldosterone and other adrenocortical steroids in normal subjects. An i.v. bolus injection of 10 mg of metoclopramide significantly increased the plasma PRL, plasma aldosterone and 18‐hydroxy‐corticosterone, but the plasma renin activity, plasma deoxycorticosterone, corticosterone and cortisol remained unchanged. The changes in plasma aldosterone induced by metoclopramide were significantly correlated with the basal levels of plasma aldosterone and renin activity. These results suggest that the response of plasma aldosterone to metoclopramide in normal subjects is influenced by the basal activity of renin–angiotensin–aldosterone system and the late step of aldosterone synthesis is stimulated by metoclopramide.
CALCITONIN AND POSTMENOPAUSAL OSTEOPOROSIS
Authors: LEGGATE J. , FARISH ELIZABETH , FLETCHER C. D. , McINTOSH W. , HART D. M. , SOMMERVILLE J. M.
Published: March 2008

Fasting serum calcitonin levels were measured in 54 postmenopausal women who had for 10 years been taking part in a double blind trial to assess the effect of the synthetic oestrogen, mestranol, on postmenopausal bone loss. There were no differences in calcitonin levels between mestranol treated and placebo groups, Fifteen of the women were challenged with a calcium infusion to measure the secretory reserve of calcitonin. Oestrogen treatment did not increase the calcitonin response to calcium infusion. The three patients who exhibited the greatest responses were placebo treated. Bone density was measured by γ‐ray absorptiometry over the ten year period and the annual rate of change of bone density calculated. No correlation could be found between basal calcitonin level or calcitonin reserve and change in bone density. Our results indicate that postmenopausal osteoporosis is not caused by a deficiency of calcitonin and that the action of oestrogen therapy to prevent bone loss does not involve calcitonin.
THE EFFECT OF KETANSERIN, A SPECIFIC SEROTONIN ANTAGONIST ON THE PRL, GH, ACTH AND CORTISOL RESPONSES TO HYPOGLYCAEMIA IN NORMAL SUBJECTS
Authors: PRESCOTT R. W. G. , KENDALL‐TAYLOR P. , WEIGHTMAN D. R. , WATSON M. J. , RATCLIFFE W. A.
Published: March 2008

The role of serotonin in the prolactin, growth hormone, ACTH and cortisol responses to hypoglycaemia has been investigated in normal subjects using a selective serotonin (5HT2) receptor antagonist, ketanserin. Circulating concentrations of these hormones were measured after administration of insulin (0·1 units/kg body weight iv) to eight normal male subjects with and without simultaneous iv ketanserin (10 mg). Plasma glucose fell to less than 2·0 mmol/l in all subjects and was unaffected by ketanserin. Ketanserin induced a 50% decrease in the serum prolactin response to hypoglycaemia, 45 and 60 min after administration of insulin (increase in serum prolactin at 60 min: 1145 ± 295 mU/l without ketanserin; 558 ± 176 mU/l with ketanserin, P < 0·05). The peak ACTH response was reduced by 30% (95·3 ± 33·6 ng/l without ketanserin; 60·0 ± 22·9 ng/l with ketanserin, P < 0‐05) but the plasma cortisol response was not significantly altered. The serum growth hormone response was unaffected by serotonin blockade. These findings suggest that serotonin, probably acting through 5HT2 receptors, is involved in the stimulation of prolactin and ACTH release but not in the release of growth hormone, during insulin induced hypoglycaemia.
CIRCANNUAL RHYTHMS OF PLASMA GROWTH HORMONE, THYROTROPIN AND THYROID HORMONES IN PREPUBERTY
Authors: BELLASTELLA A. , CRISCUOLO T. , PERRONE A. MANGO L. , SINISI A. A. , FAGGIANO M.
Published: March 2008

To clarify the occurrence of circannual GH, TSH, T4 and T3 rhythms in prepuberty we have been studying, for a four year period, 150 healthy subjects, aged 6–10, by cross‐sectional design. Plasma samples were taken at 0800 h and all hormones were measured by RIA. The occurrence of any circannual rhythm was statistically investigated by the cosinor method. A significant rhythm was validated (P= 0.02) only in TSH secretion, with annual crest time in December; GH, T4, T3 did not show a circannual rhythm. Our results seem to strengthen the hypothesis that the thyroid hormones, at least before puberty, do not play an important role in the regulation of circannual TSH periodicity.
MALIGNANT FOLLICLES OF A DIFFERENTIATED THYROID CARCINOMA RELEASING IODINATED THYROGLOBULIN INTO THE LYMPHATIC VESSELS
Authors: And F. GEBEL , STUDER H.
Published: March 2008

Serial sections across a follicular thyroid carcinoma taken from a 71‐year‐old woman with hyperthyroidism and grossly elevated serum thyroglobulin were examined by PAS staining and autoradiographic techniques. PAS positive material, presumably thyroglobulin, was found in the interstitial network between follicles. Some of this material was autoradiographically positive for 125I within 17 h after tracer application. Direct connections between the lumina of tumour follicles and the lymphatic vessels surrounding them were identified. These channels can explain the release of iodinated thyroglobulin by some differentiated carcinomas.