bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF CHRONIC ANOVULATION IN THE POLYCYSTIC OVARY SYNDROME: NORMALIZATION OF SEX‐HORMONE‐BINDING GLOBULIN LEVELS AFTER CLOMIPHENE‐INDUCED OVULATION
Authors: EDEN J. A. , PLACE J. , CARTER G. D. , ALAGHBAND‐ZADEH J. , PAWSON M. E.
Published: March 2008

A group of anovulatory patients with polycystic ovaries (PCO) was given clomiphene citrate and compared with three control groups: normal women having spontaneous, ovulatory cycles, patients with PCO having spontaneous, regular, ovulatory cycles, and anovulatory patients without PCO. Comparisons were made at precise points of the menstrual cycle (taking the day of ovulation as day 0), using ultrasound estimates of mean follicular diameter, uterine volume, and endometrial thickness, and biochemical measurements of LH, FSH, oestradiol (E2), testosterone (T), progesterone (P) and sex‐hormone‐binding globulin (SHBG). Before clomiphene treatment, the anovulatory patients with PCO had significantly lower levels of SHBG and higher follicular phase concentrations of LH than all three control groups. After two cycles of clomiphene‐induced ovulation, the serum LH concentration fell significantly and levels of SHBG increased significantly to levels similar to those found in spontaneously ovulating women with normal ovaries. It is likely that the loss of the usual considerable rise in E2 in both the follicular and luteal phases of ovulatory cycles is the main reason for the low SHBG found in the PCO syndrome. The loss of the normal P‐induced gonadotrophin suppression may be a factor in allowing LH levels to rise.
EFFECTS OF PROTRACTED HYPOTHYROIDISM ON PITUITARY FUNCTION AND STRUCTURE IN ENDEMIC CRETINISM
Authors: BOYAGES STEVEN , HALPERN JEAN‐PIERRE , MABERLY GLEN F. , EASTMAN CRESWELL J. , CARR PETER , DEZHONG YU , CHUAN‐YI YOU , CHENEN JIN
Published: March 2008

Pituitary function and structure were assessed in 69 endemic cretins from western China. In hypothyroid cretins (TSH > 10 mIU/1), CT imaging of the pituitary revealed adenoma in five of 20 (25%) and partially empty sella (PES) in a further eight of 20 (40%). The majority of tumours were microadenomas and showed a relation with higher levels of serum TSH but not with duration of hypothyroidism. Dynamic pituitary testing with TRH and GnRH in four patients with adenoma on CT gave a flat TSH response but significant rises in serum PRL, GH, LH and FSH concentrations. Hyperprolactinaemia (> 350 mIU/1) was present in hypothyroid cretins only (13 of 26; 50%) and serum PRL showed a curvilinear relation with serum TSH levels (r = 0.7, P< 0.0001). Hypogonadism was seen in approximately half the cretins with high PRL levels. Our data suggest that severe protracted thyroid hormone deficiency may result in thyrotrophin adenomas of the pituitary gland. Disturbances of growth, puberty, and sexual function in endemic cretins are explained by the secondary effects of thyroid hormone deficiency on pituitary function.
HEREDITARY LOCALIZED PRURITUS IN AFFECTED MEMBERS OF A KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A (SIPPLE'S SYNDROME)
Authors: NUNZIATA V. , GIANNATTASIO R. , DI GIOVANNI G. , D'ARMIENTO M. R. , MANCINI M.
Published: March 2008

We describe a kindred with medullary thyroid carcinoma and phaeochromocy‐toma (MEN 2A or Sipple's syndrome) in which a cutaneous manifestation is only present in affected members. These members felt an intense itching in an area 5–10 cm in length and passing through the scapular region where, after long‐term scratching, the skin appears hyperkeratotic and pigmented. Cutaneous biopsies proved negative for dermis nerve abnormality. This restricted itching strongly suggests dominant transmitted hereditary localized pruritus which was described many years ago in a family which was apparently free from inherited diseases. In the examined kindred this skin peculiarity was said to have appeared before the patients reached 10 years of age and, therefore, prior to the biochemical manifestation of the thyroid tumour. Three children of the last generation, aged 4 to 11 years, all of whom presented this cutaneous manifestation, were considered unaffected because of normal basal and stimulated calcitonin, but thyroid C‐cell hyperplasia was recently proved in the eldest. In this MEN 2A kindred the presence of such a characteristic hereditary itch in affected members may be considered as a phenotypic marker giving advance warning of medullary thyroid carcinoma.
GROWTH HORMONE‐RELEASING FACTOR INCREASES SERUM PROLACTIN CONCENTRATIONS IN NORMAL SUBJECTS AND IN PATIENTS WITH PITUITARY ADENOMAS
Authors: SERRI O. , SOMMA M. , RASIO E. , BRAZEAU P.
Published: March 2008

We have examined the serum growth hormone (GH) and prolactin (PRL) response to growth hormone releasing factor (hGRF‐(l‐44)NH2: (GRF) I μg/ kg i.v. bolus) in 16 acromegalic patients (eight of whom were hyperprolactinae‐mic), 13 patients with microprolactinoma, and 14 healthy subjects. The GH responses to‐TRH and to the somatostatin analogue SMS 201–995 were also studied in acromegalic patients. In these, and in patients with microprolactinoma, GH responses after GRF (P<0.001 vs saline) were variable. The absolute GH increase (calculated as area under the curve) in acromegalic patients (2489 ± 920 μg/l min), or in patients with microprolactinoma (1322 ± 279 μg/l min) was not different from that in controls (2238 ± 633 μg/l min). In addition, a significant increase in PRL release was observed after GRF in comparison to saline in acromegalic patients (P<0.01), in patients with microprolactinoma and in normal subjects (P<0001). The PRL increase was significantly correlated with basal PRL levels in acromegalic patients (r= 0.99, P <0.001) and in patients with microprolactinomas (r = 0.61, P<0.05). Furthermore, a significant correlation was found between GH rise after GRF and basal GH, and between GH rise after GRF and GH decrement after SMS in patients with acromegaly. These results suggest that GRF can stimulate PRL release by actions on the normal pituitary and on pituitary adenomas, including microprolactinomas. Moreover, the data suggest that in acromegaly there is a relative functional deficiency of hypothalamic somatostatin.
IS THE POLYCYSTIC OVARY A CAUSE OF INFERTILITY IN THE OVULATORY WOMAN?
Authors: EDEN J. A. , PLACE J. , CARTER G. D. , ALAGHBAND‐ZADEH J. , PAWSON M.
Published: March 2008

Ovulatory women with polycystic ovaries (PCO) were compared with ovulatory women with normal ovaries, using high‐resolution ultrasound and biochemical parameters to compare precise points in the menstrual cycle taking the day of ovulation as day 0. The PCO group had higher median follicular phase LH (days ‘menses’, −5, −3), FSH (days −5, −3) testosterone (days −3, −2) and free androgen index (days −5, −3, −1) than the controls. Women with PCO had a longer follicular phase and larger follicles. These results suggest that abnormal secretion of LH and free testosterone may contribute to the subfertility of women with PCO, possibly by premature activation of the oocyte or by interfering with folliculogenesis.
BODY COMPOSITION IN ACROMEGALY
Authors: BENGTSSON BENGT‐ÅKE , BRUMMER ROBERT‐JAN M. , EDEN STAFFAN , BOSAEUS INGVAR
Published: March 2008

Total body water (TBW) and potassium (TBK) were measured in untreated acromegalic patients seen between 1956 and 1984 and the results were compared to values predicted from height (BH), weight (BW), age and sex, using data from a large number of healthy subjects (n= 476). Normal body weight for each patient (BWnorm) was predicted from BH and sex, the regression equations being derived from a representative population sample (n= 4017). The BH for each patient was compared with data on BH in 15 000 Swedes. The patients were significantly taller than the control population (P<0.001). In 107 (70%) of the 156 patients BH was above the median. Patients with an early onset of the disease were taller than those with a later onset. TBK and TBW were significantly higher than predicted from observed BW (P< 0.001) and so was the quotient extracellular water (ECW)/intracellular water (ICW). Body fat (BF), on the other hand, was lower than predicted (P< 0.001).

Observed BW in male acromegalics was 8–1 kg higher than predicted from healthy subjects of the same BH (BWnorm), a difference explained by an average increase of 4.7 kg in body cell mass (BCM) (P<0.001) and 7.1 kg in extracellular water (P<0.001) simultaneously with a mean decrease of 3.7 kg in BF (P<0.01). Female acromegalics weighed on average 6.4 kg more than healthy women, a difference explained by an increase in BCM of 3.3 kg (P<0.001) and in ECW of 4.6 kg (P<0.001) concomitantly with a decrease in BF of 1.5 kg.

Mean hGH concentration at diagnosis correlated inversely with the quotients observed/predicted BF (P< 0.01) and B W/BWnorm (P<0.05) but not with the quotients observed/predicted TBK, TBW or ECW/ICW.
PROLACTIN‐INHIBITING ACTIVITY OF GnRH ASSOCIATED PEPTIDE IN CULTURED HUMAN PITUITARY CELLS
Authors: WORMALD PATRICIA J. , ABRAHAMSON MARTIN J. , SEEBURG PETER H. , NIKOLICS KAROLY , MILLAR ROBERT P.
Published: March 2008

The 56‐amino‐acid extension of GnRH in the human GnRH precursor (pHGnRH 14–69 or GAP) has previously been shown to inhibit PRL secretion from cultured rat pituitary cells. We have studied the effect of GAP and shorter sequences on prolactin secretion from human and rat pituitary cells. Bacterially synthesized GAP inhibited PRL secretion from human pituitary cells. At 10−6 M GAP inhibition of prolactin release was 67.7% which was similar to that observed in rat pituitary cells (65.5%). A series of shorter peptide sequences (pHGnRH 14–26, pHGnRH 14–36, pHGnRH 14–37·NH2, pHGnRH 28–36, pHGnRH 38–49 and pHGnRH 51–66) which are potentially processed from GAP at basic amino acid residues had no effect on prolactin secretion from human or rat pituitary cells at doses up to 10−5 M.
RETURN OF OVARIAN FUNCTION FOLLOWING SPONTANEOUS ABORTION
Authors: DONNET M. L. , HOWIE P. W. , MARNIE M. , COOPER W. , LEWIS M.
Published: March 2008

Assays of first morning urine samples for oestrone‐3‐glucuronide, LH and pregnanediol‐3‐glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post‐partum (range 13–103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P < 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68–8 IU/g C; P <0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P < 0.02). The mean luteal phase length of 12–9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P < 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.
HLA ANTIGENS IN ASIAN INDIAN PATIENTS WITH Graves'DISEASE
Authors: TANDON N. , MEHRA N. K. , TANEJA V. , VAIDYA M. C. , KOCHUPILLAI N.
Published: March 2008

A study of 57 Asian Indian patients with Graves'disease revealed a significant increase in the frequency of HLA‐DQW2 (61.4%) as compared to the control population (22.6%) giving a relative risk of 5.4. Less prominent but statistically significant increase in the frequency of HLA‐A10 (29.8% patients as opposed to 10.5% controls) and HLA‐B8 (28.1% patients as opposed to 8.7% controls) was also observed. Further, patients carrying the phenotypes HLA‐A10 and HLA‐B8 were more prone to develop the disease at a younger age. Two HLA haplotypes, namely A10‐B8 and B8‐DR3, were found in significant linkage disequilibrium in our patients with Graves'disease. Patients carrying these haplotypes also had a tendency to develop the disease at an earlier age.
RAPID ESCAPE OF CORTISOL FROM SUPPRESSION IN RESPONSE TO I. V. DEXAMETHASONE IN ANOREXIA NERVOSA*
Authors: ESTOUR B. , PUGEAT M. , LANG F. , LEJEUNE H. , BROUTIN F. , PELLET J. , ROUSSET H. , TOURNIAIRE J.
Published: March 2008

The suppressive effect of dexamethasone (Dex) on plasma cortisol and β‐ lipotrophin (βLPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and βLPH levels during oral or i. v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P < 0.0001) during oral or i. v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i. v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (< 50 nmol/1) by 0800 h on the day following infusion. In the patients who were reinvestigated after re‐feeding and weight gain (n = 9), a normal suppression of cortisol in response to i. v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.
ANALYSIS OF HLA‐DQB AND HLA‐DPB ALLELES IN Graves'DISEASE BY OLIGONUCLEOTIDE PROBING OF ENZYMATICALLY AMPLIFIED DNA
Authors: WEETMAN A. P. , ZHANG LI , WEBB SANDRA , SHINE B.
Published: March 2008

We have tested the possible association of HLA‐DQB and HLA‐DPB alleles with Graves'thyrotoxicosis, with or without severe ophthalmopathy, by polymerase chain amplification of genomic DNA and allele‐specific oligonucleotide probing. There was no significantly abnormal distribution of DQB alleles compared to 50 control subjects except for a reduced prevalence of DQw 3.1 in the Graves'patients with severe ophthalmopathy (x2= 6.23, P < 0.02). HLA‐DPB 2.1/8 was found in only 1 of 40 of these patients compared with 15 of the controls (x2= 11.49, P <0‐001). Ten of 48 patients with Graves'disease but without clinically significant eye involvement were HLA‐DPB 2.1/8 positive, not significantly different from controls, but significantly different from the ophthalmopathy group (x2= 6.70, P < 0.01). The other DPB alleles in both groups of Graves'disease patients were the same as controls. These results suggest that HLA‐DPB 2.1/8 may confer a protective effect in Graves'disease with respect to ophthalmopathy.
EFFECT OF NALOXONE ON NEUROHYPOPHYSEAL PEPTIDE RESPONSES TO BREAST FEEDING AND BREAST STIMULATION IN MAN
Authors: JOHNSON M. R. , ANDREWS M. A. , SECKL J. R. , LIGHTMAN S. L.
Published: March 2008

We have investigated the role of endogenous opioid peptides in the release of oxytocin (OT) in response to breast feeding and breast stimulation in humans. Five breast feeding women were studied on two separate occasions within 4 weeks of delivery. Saline or naloxone, 4 mg bolus and 6 mg/h, was administered intravenously, in random order. Blood samples were taken at regular intervals. In the saline‐infused group OT rose from a baseline of 1.1 |Mp 0.1 pmol/l (mean |Mp SEM) to a peak of 7.0 |Mp 0.9 after 6 min, and in the naloxone‐infused group from 1.0 |Mp 0.1 pmo1/1 to 5.8 |Mp 1–3 (P < 0.05). There were no significant differences between the two groups at any time point. Plasma vasopressin (AVP) did not change. In the second study six women in the luteal phase of the menstrual cycle were investigated on two occasions at least 48 h apart. They were similarly infused with either naloxone or saline in random sequence. A mechanical breast pump provided breast stimulation. In saline‐infused women OT levels rose from a baseline of 1.0 |Mp 0.1 pmol/1 (mean |Mp SEM) to a peak of 10 |Mp 1.1 (P < 0.05) after 6 min, and in naloxone infused women from 1.1 |Mp 0.1 pmol/l to 3.0 |Mp 1.4 (NS). There were no differences in OT between the groups. AVP did not change. We conclude that endogenous opioid peptides do not modulate OT release during breast feeding or breast stimulation in women.
INAPPROPRIATELY ELEVATED PLASMA INSULIN‐LIKE GROWTH FACTOR II IN RELATION TO SUPPRESSED INSULIN‐LIKE GROWTH FACTOR I IN THE DIAGNOSIS OF NON‐ISLET CELL TUMOUR HYPOGLYCAEMIA
Authors: TEALE J. D. , MARKS V.
Published: March 2008

The diagnosis of non‐islet cell tumour (hypoinsulinaemic) hypoglycaemia has been complicated by contradictory biochemical evidence. Although insulin‐like growth factor II (IGF‐II) has been identified as the hypoglycaemic agent, plasma levels are often not elevated. In this study specific radioimmunoassay procedures for the measurement of IGF‐I and IGF‐II are described. Reference data on plasma IGF‐II concentrations in relation to a wide range of IGF‐I levels have been accumulated using plasma samples from acromegalic, hypopituitary and insulinoma (i.e. hyperinsulinaemic hypoglycaemia) patients as well as normal subjects from all age groups. The reference data indicate that a low plasma IGF‐I value is normally associated with a relatively low plasma IGF‐II level. Within a group of hypoinsulinaemic hypoglycaemia patients, a small number, invariably with evidence of a neoplasm, had low plasma IGF‐I concentrations but apparently normal IGF‐II levels. We propose that, in such cases, an apparently normal plasma IGF‐II value is inappropriately high for the low plasma IGF‐I level and, in association with non‐ketotic hypoinsulinaemia and suppressed plasma growth hormone (GH), is diagnostic of a non‐islet cell tumour as the cause of hypoglycaemia.
ROLE OF CHOLINERGIC MUSCARINIC PATHWAYS ON THE FREE FATTY ACID INHIBITION OF GH RESPONSES TO GHRH IN NORMAL MEN
Authors: PEÑALVA ANGELA , GAZTAMBIDE SONIA , VAZQUEZ JOSE ANTONIO , DIEGUEZ CARLOS , CASANUEVA FELIPE F.
Published: March 2008

In order to explore the mechanisms by which free fatty acids (FFA) inhibit GH secretion, we studied the effect of the acetylcholinesterase inhibitor pyridostigmine (120 mg p. o.) on the FFA blockade of GH responses to the administration of GHRH (100 μg i. v.) in seven normal subjects. GHRH‐induced GH secretion was significantly reduced following elevation of circulating FFA levels by lipid‐heparin infusion and significantly potentiated by previous pyridostigmine treatment. Peak GH levels following combined administration of pyridostigmine plus lipid—heparin plus GHRH were significantly higher (P < 0.01) than after GHRH alone and significantly lower than after pyridostigmine plus GHRH (P < 0.01). In conclusion, central cholinergic activation by pyridostigmine, with the presumed reduction in somatostatin discharge, reversed the blocking effect of FFA on GHRH‐stimulated GH release. Conversely, FFA were able to reduce even a maximal GH stimulation by pyridostigmine plus GHRH.
BAROREFLEX‐GOVERNED SYMPATHETIC OUTFLOW TO MUSCLE VASCULATURE IS INCREASED IN HYPOTHYROIDISM
Authors: FAGIUS JAN , WESTERMARK KERSTIN , KARLSSON ANDERS
Published: March 2008

Microelectrode recording of muscle nerve sympathetic activity (MSA), which is baroreflex‐governed and involved in cardiovascular homeostasis, was made in five patients with hypothyroidism and in seven patients with hyperthyroidism prior to treatment and after recovery to euthyroidism. Patients with hypothyroidism had a higher level of MSA when hypothyroid than after recovery (mean |Mp SEM 39.3 |Mp 7.1 and 26.8 |Mp 7.9 bursts/min, respectively, P < 0.05), whereas hyperthyroidism was not accompanied by a change in the number of sympathetic bursts/min. The response of MSA to manouvres known to influence the neural outflow via baroreceptors and other receptor inputs was not changed with altered thyroid function. The findings provide direct evidence of an increased sympathetic activity in hypothyroidism, but suggest that other physiological properties of MSA are intact in thyroid disease.
THE EFFECT OF GALANIN ON BASELINE AND GHRH‐INDUCED GROWTH HORMONE SECRETION IN OBESE CHILDREN
Authors: LOCHE S. , PINTUS S. , CELLA S. G. , BOGHEN M. , VANNELLI S. , BENSO L. , MÜLLER E. E. , CORDA R. , PINTOR C.
Published: March 2008

We have evaluated the effect of the administration of galanin (Gal), a newly identified hypothalamic peptide, on baseline and GHRH‐induced GH rise in five obese children and in seven controls. The GH response to GHRH (hpGRF(1–29), 1 μg/kg i. v.), and to Gal (15 μg/kg/h for 1 h), evaluated both as the maximum GH peak and as integrated area under the curve (AUC), was significantly lower in the obese children than in the controls. Simultaneous administration of Gal plus GHRH significantly increased the GH response to GHRH in all the obese subjects, so that their mean peak GH levels and AUC after Gal plus GHRH were similar to those of the control children after GHRH. Also, in control children Gal caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean AUC after Gal plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Our data indicate that obese children have a blunted GH response to Gal, which, however, is able to enhance the GH response to GHRH. This observation strengthens the view that the mechanism of action of Gal involves modulation of endogenous somatostatin (SRIH) release. In addition, similarity between the effects of Gal and pyridostigmine on baseline and GHRH‐stimulated GH release in obese children may indicate the existence of a cholinergic link in the action of Gal.
THYROID FUNCTION IN CHORIOCARCINOMA: DEMONSTRATION OF A THYROID STIMULATING ACTIVITY IN SERUM USING FRTL‐5 and HUMAN THYROID CELLS
Authors: KENNEDY R. L. , SHERIDAN E. , DARNE J. , GRIFFITHS H. , DAVIES R. , PRICE A. , COHN M.
Published: March 2008

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 3612 |MX 103 IU/1 compared to 76.2 |MX 103 IU/1 in the other patients (P < 0.01). Purified hCG stimulated iodide uptake into FRTL‐5 cells with 25 |MX 103 IU/1 being equivalent in potency to 1 mU/1 of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 |MX 103 IU/1 compared to 37.1 |MX 103 IU/1 in the other eight sera (P < 0.01). Six men with hCG‐secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL‐5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 |Mp 1.81 pmol/mg cell protein compared to 67.0 |Mp 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P < 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.
THE EPIDEMIOLOGY OF THYROTOXICOSIS IN NEW ZEALAND: INCIDENCE AND GEOGRAPHICAL DISTRIBUTION IN NORTH CANTERBURY, 1983–1985
Authors: BROWNLIE B. E. W. , WELLS J. E.
Published: March 2008

In a 3‐year (1983‐1985) epidemiological study of thyrotoxicosis in North Canterbury, New Zealand, the annual incidence was 25.8 per 100 000 (female 40.7, male 10.5). Thyroid scintiscanning showed that 64% had diffuse hyperplasia (DH), 27% toxic multinodular goitre (TMG), 7% toxic uninodular goitre (TUG), and 2% zero uptake. The calculated annual incidence of toxic diffuse goitre (DH) was 15 per 100 000, and for toxic nodular goitre (TMG and TUG combined) was 8 per 100 000. The age‐related incidence for toxic diffuse goitre peaked in middle life whereas toxic nodular goitre showed an increasing incidence with age. There was no significant seasonal variation or rural/urban difference in incidence. Analysis of geocoded addresses did not identify areas of high incidence. The variable duration of symptoms prior to diagnosis limits the search for possible environmental trigger factors. North Canterbury was an endemic goitre area prior to the introduction of iodized salt 50 years ago, and the incidence of toxic nodular goitre is likely to fall in future.
LONG‐TERM TREATMENT OF METASTATIC MEDULLARY THYROID CARCINOMA WITH THE SOMATOSTATIN ANALOGUE OCTREOTIDE
Authors: MAHLER C. , VERHELST J. , DE LONGUEVILLE M. , HARRIS A.
Published: March 2008

Three patients with symptomatic metastatic medullary thyroid carcinoma (MTC), one with sporadic form and two with MEN IIa, were treated with the long‐acting somatostatin analogue octreotide (SMS 201–995, Sandoz) for 3 to 17 months. Octreotide was administered subcutaneously in a starting dose of 0.6 to 1.0 mg/day by automatic pump (Travax ASH6, Travenol). Symptoms of diarrhoea, weight loss and malaise improved in all patients. Maximal percentage decrease in mean serum calcitonin was 47, 52 and 81% of the basal values, and was observed 1–3 months from the beginning of treatment. Likewise, carcinoembryonic antigen (CEA) levels initially dropped to 45, 60 and 63% of the levels before therapy. A continuing effect was seen in the two patients with MEN Ha after 15 and 17 months of treatment. However, after the initial decrease, calcitonin (CT) levels went up again to 67 and 68% of the basal values and the dose of octreotide had to be increased to 1.5 mg and 2.0 mg/day. CEA also returned to 84 and 105% of the pretreatment titres. Response to 1.5 mg/day octreotide was lost in the patient with the sporadic form of disease after 3 months. Side‐effects were minimal. Effects on tumour size could not be evaluated. These suggest that octreotide might be a valuable adjuvant in the long‐term management of metastatic MTC. Tachyphylaxis may occur.
HORMONAL PROFILES FOLLOWING CLOMIPHENE CITRATE THERAPY IN CONCEPTION AND NONCONCEPTION CYCLES
Authors: (SCHWARTZ) ZEEV SHOHAM , BORENSTEIN RICHARD , LUNENFELD BRUNO , PARIENTE CLARA
Published: March 2008

The hormonal profiles following clomiphene citrate (CC) administration during a single cycle were compared in infertile women who conceived and in those who did not. Of 41 treated patients, ovulation was assumed to have occurred in 28 and was confirmed by clinical pregnancy in five. In the 28 women who presumably ovulated, two distinct patterns of hormonal secretion were observed. A normal response was exhibited by 17 patients (including the five who became pregnant). The other 11 patients exhibited an abnormal response, characterized by significantly higher luteinizing hormone (LH)/follicle‐stimulating hormone (FSH) ratios than in the normal response group from day 9 until the occurrence of the LH peak (days 9 and 10, P > 0.05; days 11 and 12, P > 0.001), and significantly higher oestradiol (E2) levels throughout the cycle (P > 0.01). In addition, in comparison with the normal response group their LH levels during the follicular phase were significantly higher (P > 0‐05) but their LH peaks at ovulation were significantly lower (P > 0.02). Moreover, their progesterone levels, in contrast to those in the normal response group, began to increase prior to the LH peak and remained high during the early and mid‐luteal phases. None of the women who exhibited this abnormal gonadotrophin response to CC therapy achieved a clinical pregnancy. Exposure to high LH levels in the follicular phase following CC therapy seems to reduce the rate of fertilization and/or to contribute to early embryonic loss.
CV205–502, A NEW NON‐ERGOT DOPAMINE AGONIST, REDUCES PROLACTINOMA SIZE IN MAN
Authors: BARNETT P. S. , DAWSON J. M. , BUTLER J. , COSKERAN P. B. , MACCABE J. J. , McGREGOR A. M.
Published: March 2008

Seven patients with large prolactin‐secreting pituitary adenomas were treated for 8 weeks with once‐daily doses of the new, potent, non‐ergot, long‐acting dopamine agonist CV205–502. In five patients previous treatment with bromocriptine had failed to control their disease or been poorly tolerated and had therefore ceased. In all seven patients serum prolactin levels fell over the 8‐week period of CV205–502 treatment with the decrease ranging from 33 to 99%. Associated with this decline in prolactin all patients showed symptomatic improvement with two of the five women beginning to menstruate and the two patients with visual field impairment showing marked improvement. Tolerance of the drug, with doses at 8 weeks ranging from 0.075 to 0.3 mg, was excellent with only minimal and transient side‐effects being noted in three patients in none of whom was discontinuation of therapy necessary. In one patient non‐compliance after 6 weeks of therapy was associated with a rapid return of her serum prolactin towards pretreatment levels. In all seven patients the clinical and biochemical improvement was accompanied by a marked reduction in tumour size. Since the introduction of bromocriptine, an ergot alkaloid‐derived dopamine agonist (Thorner et al., 1980), into clinical practice in the early 1970s its role in the treatment of hyperprolactinaemic states has become well established (Besser et al., 1972). In patients with proved prolactin‐secreting pituitary adenomas (prolactinomas) the use of bromo‐criptine has been shown to be associated not only with suppression of prolactin secretion and restoration of gonadal function but also with reduction in adenoma size (McGregor et al., 1979). Bromocriptine is currently the treatment of choice for large prolactinomas (macroadenomas) (Vance and Thorner, 1987). Whilst the majority of patients with macroadenomas treated with bromocriptine show a decline in prolactin levels, in the
LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE SECRETION PATTERNS IN FEMALE ATHLETES WITH AND WITHOUT MENSTRUAL DISTURBANCES
Authors: PIRKE K. M. , SCHWEIGER U. , BROOCKS A. , TUSCHL R. J. , LAESSLE R. G.
Published: March 2008

Thirty‐one young female athletes and 13 age‐matched sedentary controls were studied throughout one menstrual cycle or over a 6 week period. Blood was sampled on 5 days per week. Episodic gonadotrophin secretion was measured in the early follicular phase and in the late luteal phase by blood sampling over a 12‐h period at 15‐min intervals. Eight athletes had anovulatory cycles, nine had impaired progesterone (P4) secretion during the luteal phase and 14 had normal cycles as judged from oestradiol (E2) and P4 plasma levels. Athletes with normal cycles had shorter cycles, lower E2 maxima at midcycle, and lower E2 and P4 concentrations during the luteal phase than had sedentary controls. Episodic luteinizing hormone (LH) secretion in the early follicular phase was significantly impaired in the anovulatory athletes: the average LH values over 12 h and the number of secretion episodes were significantly reduced. No significant changes were seen in follicle stimulating hormone secretion.
EFFECTS OF CALCITONIN ON GH RESPONSE TO PYRIDOSTIGMINE IN COMBINATION WITH hGHRH (1–29) NH2 IN NORMAL ADULT SUBJECTS
Authors: GIUSTINA ANDREA , BODINI CORRADO , BOSSONI SIMONETTA , DOGA MAURO , GIRELLI ANGELA , PIZZOCOLO GIUSEPPE , WEHRENBERG WILLIAM B.
Published: March 2008

Studies in man demonstrated that salmon calcitonin (sCT) administration blunts the pituitary GH response to GH‐releasing hormone (GHRH). However, the mechanisms underlying this inhibitory action of CT in man are unclear. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is hypothesized to enhance the GH response to GHRH in normal subjects probably via a decrease in the somatostatinergic tone. The aim of the present study was to investigate the mechanism of the inhibitory action of sCT on the GH response to human GHRH (1–29) NH2 by concomitant PD administration in normal humans. The GH response to GHRH was significantly suppressed by prior administration of sCT. Pretreatment of subjects with PD significantly enhanced the GH response to GHRH but did not alter the inhibitory actions of sCT. We conclude that sCT is able to inhibit GHRH‐stimulated GH secretion in man without influencing the hypothalamic somatostatinergic tone.
SERUM FORMS OF TESTOSTERONE IN MEN AFTER AN hCG STIMULATION: RELATIVE INCREASE IN NON‐PROTEIN BOUND FORMS
Authors: COOKE R. R. , MCINTOSH R. P. , MCINTOSH J. G. A. , DELAHUNT J. W.
Published: March 2008

A postulated function of steroid binding proteins in serum is to smooth changes in steroid levels. To test this, testosterone levels in six normal men were increased by injecting 6000 IU hCG i.m., and changes in serum forms of testosterone were measured. Blood was collected every 10 min for 2.5 h and then once a day for 4 days. By day 4 the mean serum testosterone level had risen to 178%±13% (SEM) of a mean basal level (first five samples). This rise was less than that in free testosterone (221%±18%), which was in turn less than the rise in the non‐SHBG‐bound fraction (255%±19%). The concentrations of SHBG and albumin were constant. Thus, two putative bioactive fractions of testosterone, the free and non‐SHBG‐bound, increased to a greater extent than did total testosterone. Because the binding protein concentrations were constant, this implies they may act not as a buffer, but as an enhancer of active testosterone over this time interval.
THYROTOXICOSIS DUE TO PITUITARY RESISTANCE TO THYROID HORMONES. SUCCESSFUL CONTROL WITH D THYROXINE: A STUDY IN THREE PATIENTS
Authors: DOREY F. , STRAUCH G. , GAYNO J. P.
Published: March 2008

Selective pituitary resistance to thyroid hormone (PRTH) is responsible for thyrotoxicosis due to inappropriate secretion of TSH. The TSH suppressive action of D‐thyroxine (DT4) has been previously documented in euthyroid and hypothyroid subjects. This prompted us to treat with DT4 three patients with PRTH uncontrolled by anti‐thyroid drugs (ATD) alone or supplemented with bromocriptine, and whose follow‐up had been complicated by atrial fibrillation in two patients. Because of 100% cross‐reactivity between the D and L isomers of T4 and T3 in our RIAs, thyroglobulin (Tg) was used as an index of thyroid secretion. Under ATD, TSH and Tg levels were respectively: 35 mIU/l and 670.5 pmol/1 (patient 1), 87 mIU/1 and 453 pmol/1 (patient 2) and 110 mIU/1 and 906 pmol/1 (patient 3). When DT4 was added (patient 1, 3 mg daily; patients 2 and 3, 2 mg daily) to the same dose of ATD, plasma TSH and Tg levels fell but were still over the upper limit of normal and thyrotoxicosis persisted as illustrated by a recurrence of atrial fibrillation in one patient. When ATD were withdrawn and DT4 given alone (2 mg daily) all symptoms subsided within 1 month while TSH and Tg levels fell within the normal range. TSH normalization was documented within 1 week in one patient. After 16‐27 months of follow‐up the patients remained clinically euthyroid and plasma TSH and Tg levels were normal (patient 1, 0.65 mIU/1 and 5.6 pmol/l; patient 2, 1.4 mIU/1 and 49.8 pmol/l; patient 3, 0.83 mIU/1 and 104.2 pmol/l, respectively) as were the peripheral indexes of thyroid hormones actions serum enzymes, SHBG, ferritin and echocardiographic parameters. We conclude that DT4 at a daily dose of 2 mg is able to control safely thyrotoxicosis due to PRTH. DT4 could be tried as the first treatment of PRTH.
THE GROWTH HORMONE INDEPENDENT INSULIN‐LIKE GROWTH FACTOR‐I BINDING PROTEIN BP‐28 IS ASSOCIATED WITH SERUM INSULIN‐LIKE GROWTH FACTOR‐I INHIBITORY BIOACTIVITY IN ADOLESCENT INSULIN‐DEPENDENT DIABETICS
Authors: TAYLOR A. M. , DUNGER D. B. , PREECE M. A. , HOLLY J. M. P , SMITH C. P. , WASS J. A. H. , PATEL S. , TATE V. E.
Published: March 2008

The relationship between the growth hormone independent insulin‐like growth factor binding protein (BP‐28) and serum insulin‐like growth factor‐I (IGF‐I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in‐vitro effects of purified BP‐28 from amniotic fluid on serum IGF‐I stimulated and basal cartilage sulphation and compared serum IGF‐I bioactivity obtained from 24‐h serum profiles from each diabetic subject with serum concentrations of BP‐28 and IGF‐I measured by specific radioimmunoassays. Purified BP‐28 inhibited serum IGF‐I stimulated and basal cartilage sulphation in vitro, in a dose‐dependent manner. Serum IGF‐I bioactivity of diabetic sera showed a change in activity over the 24‐h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP‐28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long‐acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long‐acting insulin administered in the morning. IGF‐I concentrations did not change over the 24‐h period in each individual. The data shows that BP‐28 inhibits serum IGF‐bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP‐28. We propose that BP‐28 is one of the IGF‐I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic.
PRESENCE OF BOTH STIMULATING AND BLOCKING TYPES OF TSH‐RECEPTOR ANTIBODIES IN SERA FROM THREE PATIENTS WITH PRIMARY HYPOTHYROIDISM
Authors: KASAGI K. , TAKEDA K. , GOSHI K. , TAKAMATSU J. , HIDAKA A. , HATABU H. , MISAKI T. , IIDA Y. , KUMA K. , KONISHI J.
Published: March 2008

A case report of three patients with primary hypothyroidism who had potent TSH‐binding inhibitor immunoglobulins (TBII) and both thyroid stimulating (TSAb) and thyroid stimulation‐blocking antibodies (TSBAb) has been described. Two patients displayed symptoms and signs indistinguishable from those in primary myxoedema (cases 1 and 2), and another patient had a history of Graves'disease (case 3). TBII, TSAb and TSBAb activities were 90.0, 1084.2 and 94.5% in case 1, 91.5, 826.6 and 95.8% in case 2, 76.0, 230.0 and 95.0% in case 3, respectively (normal range, < 11.0%, < 145.0 and < 22.0%, respectively. The results indicate that both stimulating and blocking types of TSH‐receptor antibodies exist in these patients. The possible mechanism whereby hypothyroidism developed has been discussed.
LOW‐DOSE PITUITARY IRRADIATION FOR ACROMEGALY
Authors: LITTLEY M. D. , SHALET S. M. , SWINDELL R. , BEARDWELL C. G. , SUTTON M. L.
Published: March 2008

External radiotherapy has been used as primary treatment for acromegaly in 29 patients and in combination with surgery in 41 patients in whom growth hormone levels remained elevated postoperatively. Fourteen further patients who did not receive radiotherapy have also been studied, four of whom had undergone surgical treatment. Radiotherapy schedules consisted of 20 Gy in eight fractions over 11 days (n=23) or 35‐40 Gy in 15 fractions over 21 days (n=47). Growth hormone hypersecretion was either unchanged or increased with time in non‐irradiated patients. In those patients who underwent radiotherapy, the likelihood of the mean GH level during GTT falling to < 5 mU/l was unaffected by the total dose of radiation administered. However, patients with a pre‐radiotherapy GH level of < 30 mU/1 showed a significantly increased probability of achieving a post‐ radiotherapy GH level < 5 mU/1 (P=0.002). Previous surgery, initial serum prolactin and the age or sex of the patient did not predict the successful outcome of radiotherapy. In view of the known dose dependency of radiation‐induced hypopituitarism, lower radiation dose schedules (20 Gy; eight fractions in 11 days) can be used in acromegaly with some benefit, especially in younger patients. However, all patients should undergo operative removal of as much GH‐secreting tissue as possible, in order to lower GH levels and increase the probability of achieving a cure following radiotherapy.
AMINOPROPYLIDINE DIPHOSPHONATE (APD) IN MILD PRIMARY HYPERPARATHYROIDISM: EFFECT ON CLINICAL STATUS
Authors: SCHMIDLI R. S. , WILSON I. , ESPINER E. A. , RICHARDS A. M. , DONALD R. A.
Published: March 2008

Mild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non‐specific. Accordingly, we employed the hypocalcaemia effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo‐controlled cross‐over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49±0.04 SEM mmol/l) after APD when compared to control values (2.70±0.06 mmol/l, P< 0.001). Twenty‐four‐hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P <0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side‐effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients.
THE EFFECT OF OXYTOCIN INFUSION ON ADENOHYPOPHYSEAL FUNCTION IN MAN
Authors: PAGE S. R. , ANG V. T. Y. , JACKSON R. , WHITE A. , NUSSEY S. S. , JENKINS J. S.
Published: March 2008

The responses of the adenohypophyseal hormones adrenocorticotrophin (ACTH), growth hormone (GH), thyroid stimulating hormone (TSH), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) to sub‐maximal doses of hypothalamic releasing factors were studied in six lean male volunteers (age 23‐35 years) with and without infusions of oxytocin (OXT). OXT infusion (mean plasma concentration 133.6±2.6 pmol/1) completely inhibited the plasma ACTH responses to corticotrophin releasing hormone (CRH) (saline, peak increment ACTH 1.61±0.75 pmol/l; OXT, peak increment ACTH — 0.04±0.28 pmol/l; P < 0.05). OXT infusion had no significant effect on the GH response to growth hormone releasing hormone (GHRH), the TSH and prolactin responses to thyrotrophin releasing hormone (thyroliberin, TRH) or the LH and FSH responses to gonadotrophin releasing hormone (luteoliberin, GnRH). The data support a role for OXT in the modulation of ACTH secretion in man.
IMPAIRED SECRETION OF PARATHYROID HORMONE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RELATIONSHIP TO INFLAMMATORY ACTIVITY
Authors: EKENSTAM EVA AF , BENSON LARS , HÄLLGREN ROGER , WIDE LEIF , LJUNGHALL SVERKER
Published: March 2008

Hypocalcaemic tests, employing infusion of EDTA over 1 h, were performed in 22 patients with rheumatoid arthritis (RA) and 14 healthy controls. The basal levels of calcium and parathyroid hormone (PTH) were not significantly different in the two groups. The RA patients displayed a markedly impaired PTH response during infusion of EDTA compared with the controls although the reduction of plasma ionized calcium was similar. The PTH response was furthermore significantly, inversely, related to the inflammatory activity measured as sedimentation rate (r= 0.65; P < 0.01), i.e. the more pronounced the inflammation, the less the capacity to secrete PTH. Since secretion of PTH is related to the intracellular calcium concentration of the parathyroid cells, these findings are in line with previous observations of a higher intracellular calcium content in inflammatory disease. They also support the earlier indications of reduced bone turnover in inflammatory arthritides. An insufficient parathyroid function could be one factor contributing to bone disease in these conditions.
PROLONGED TREATMENT WITH THE GnRH ANALOGUE BUSERELIN DOES NOT AFFECT α‐SUBUNIT PRODUCTION BY THE PITUITARY GONADOTROPH
Authors: KWEKKEBOOM D. J. , LAMBERTS S. W. J. , BLOM J. H. M. , SCHROEDER F. H. , DE JONG F. H.
Published: March 2008

Seven patients with metastatic prostatic cancer were treated with biodegradable implants of the GnRH analogue buserelin and six were treated with buserelin intranasally. After 4‐24 weeks of treatment mean serum testosterone concentrations were significantly lower in the patients treated with implants than in those treated intranasally (0.7 vs 1.7nmol/1 respectively; P < 0.01). Also, serum LH concentrations were significantly lower in the group treated with implants. Serum α‐subunit concentrations were significantly higher than pretreatment values during buserelin treatment. However, the sum of the concentrations of α‐subunit present either as free α‐subunit or as a part of LH did not differ significantly from pre‐treatment values after 8 weeks or more of buserelin treatment. During buserelin treatment serum LH concentrations measured by radioimmunoassay (RIA) were higher than those measured by immunoradiometric assay (IRMA). Cross‐reactivity of α‐subunit in the LH RIA accounted for many, but not all, of the observed discrepancies. We conclude that: (1) the principal long‐term effect of prolonged buserelin administration on the pituitary gonadotroph is the suppression of LHβ production, while α‐subunit production is not affected; (2) the serum concentrations of bioactive LH are better reflected by LH concentrations measured by IRMA than by those measured by RIA. (3) Subcutaneous application of biodegradable buserelin implants is more effective in suppressing serum LH and testosterone concentrations than intranasal buserelin application.
THE LOSS OF CIRCADIAN RHYTHM FOR INTACT PARATHYROID HORMONE AND NEPHROGENOUS CYCLIC AMP IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM
Authors: LOGUE F. C. , FRASER W. D. , GALLACHER S. J. , CAMERON D. A. , O'REILLY D. St J. , BEASTALL G. H. , PATEL U. , BOYLE I. T.
Published: March 2008

The measurement of serum intact parathyroid hormone (PTH) (1‐84) over a 24‐h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N‐cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1‐84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1‐84) secretion.