bluuebunny/crossref_metadata_2025 huggingface dataset:
PERIPHERAL K CELLS IN GRAVES’DISEASE AND HASHIMOTO'S THYROIDITIS IN RELATION TO CIRCULATING IMMUNE COMPLEXES
Authors: ENDO Y. , ARATAKE Y. , YAMAMOTO I. , NAKAGAWA H. , KURIBAYASHI T. , OHTAKI S.
Published: March 2008

A plaque assay was employed to quantify the number of peripheral K cells in autoimmune thyroid diseases. The percentages of peripheral K cells determined were 3·1 ± 2·2% and 3·3 ± 1·3% (mean ± SD) in forty‐one patients with Graves’disease and twenty‐two patients with Hashimoto's thyroiditis, respectively, which were significantly lower than 5·3 ± 2·5% in 22 normal subjects. Circulating immune complexes (ICs) were measured by three different methods. The positivity of these ICs was investigated in relation to the level of peripheral K cells. The percentage of peripheral K cells in the patients positive for ICs was found to be lower than that in the patients negative for any ICs. Moreover, it was observed that the number of detectable K cells from a normal subject was significantly decreased by incubating the K cells with sera of patients positive for ICs. These results suggest that the decrease of peripheral K cells in the patients with autoimmune thyroid diseases may be due to saturation of K cell Fc receptors by binding ICs.
INCREASED SERUM CONCENTRATION OF T4‐BINDING GLOBULIN IN PATIENTS WITH HYPOGAMMAGLOBULINAEMIA
Authors: LEVER A. , BIRD DAPHNE , BYFIELD P. G. H. , LALLOZ M. R. A. , WEBSTER A. D. B. , HIMSWORTH R. L.
Published: March 2008

Patients with hypogammaglobulinaemia have been regularly found to have abnormal conventional thyroid function test results. The abnormality is due to an increased plasma concentration of T4‐binding globulin (TBG). As the prevalence of autoimmune thyroid disease is probably increased in hypogammaglobulinaemia this further abnormality in the plasma proteins may lead to diagnostic confusion. Administration of gammaglobulin by infusion causes a rapid but transient fall in plasma concentrations of TBG and T4 which is probably due to a temporary redistribution of the plasma proteins.
EXTERNAL PITUITARY IRRADIATION AS A CAUSE OF TRH DEFICIENCY IN PATIENTS WITH PITUITARY ADENOMAS*
Authors: MACFARLANE I. A. , SHALET S. M. , BEARDWELL C. G. , APPLEGATE G. , ROBINSON E. L. , SUTTON M. L.
Published: March 2008

The influence of external pituitary irradiation (XRT) on thyrotroph function and PRL secretion was studied in twenty‐five patients with pituitary adenomas, of whom eight had acromegaly. Twenty‐one patients had undergone subtotal operative removal of their adenomas 8–190 weeks (median 12 weeks) before XRT. Following irradiaton there was a significant reduction in peak serum TSH levels in response to i.v. TRH (P < 0·05, compared with before XRT). Peak TSH levels returned to normal at 3 months. Similarly a transient reduction in TRH‐stimulated β‐TSH release was observed. Serum T3 and T4 concentrations also fell after XRT, the levels at 3 months being significantly lower than control values (P<0·02), though no difference was seen at 6 and 12 months. A delayed (hypothalamic) serum TSH response to TRH (60 > 20‐min level) developed at 6 months. In contrast, PRL concentrations (basal and TRH stimulated) were not altered during the 12 months following XRT. These findings demonstrate that thyrotroph function can be transiently impaired following external pituitary irradiation. None of the patients studied required T4 replacement therapy. The development of a delayed TSH response to i.v. TRH may indicate endogenous TRH deficiency. It was not associated with supra‐sellar tumour enlargement in our patients and may be due to hypothalamic damage by irradiation.
PRO‐OPIOCORTIN RELATED PEPTIDES IN HUMAN PITUITARY AND ECTOPIC ACTH SECRETING TUMOURS
Authors: RATTER SALLY J. , GILLIES GLENDA , HOPE J. , HALE ANN C. , GROSSMAN A. , GAILLARD R. , COOK D. , EDWARDS C.R.W. , REES LESLEY H.
Published: March 2008

Basal and stimulated secretion of N‐terminal pro‐opiocortin (Pro‐γ‐MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel‐chro‐matographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1–39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.
FAILURE OF INHIBITION BY TRH OF L‐DOPA STIMULATED GH SECRETION IN PATIENTS WITH ALCOHOLIC CIRRHOSIS OF THE LIVER
Authors: ZANOBONI ALBERTO , ZECCA LUCIANO , ZANOBONI‐MUCIACCIA WANDA
Published: March 2008

We have investigated the effects of a single oral dose of L‐Dopa (500 mg) or of an i.v. infusion of TRH (1 mg dissolved in 400 ml of saline solution) or both administered together, on GH release in men with alcoholic cirrhosis of the liver, and compared them with responses in normal subjects. The results obtained in normal subjects confirm that TRH does not modify plasma GH levels, L‐Dopa elevates GH concentrations, while the administration of these two drugs together significantly inhibits GH release induced by oral L‐Dopa. In contrast, in patients with alcoholic cirrhosis of the liver, the following results were obtained:

TRH infusion significantly increased plasma GH levels which were steadily elevated throughout the experiment;

oral administration of L‐Dopa provoked a significant rise in blood GH over the basal values similar to that observed in normal subjects;

when TRH and L‐Dopa are administered at the same time a GH increase like that observed after L‐Dopa alone was obtained.

These results clearly demonstrate that in patients with alcoholic cirrhosis of the liver the normal inhibitory effect of TRH on L‐Dopa induced GH release is completely lost.
SOMATOSTATIN‐28 AND SOMATOSTATIN‐14 SUPPRESSION OF ARGININE‐, INSULIN‐, AND TRH‐STIMULATED GH AND PRL SECRETION IN MAN
Authors: MILLAR R. P. , KLAFF L. J. , BARRON J. L. , LEVITT N. S. , LING N.
Published: March 2008

GH and PRL responses to arginine infusion and to the combined pituitary stimulation test (0·1 u/kg of insulin, 200 μg of TRH, 100 μg of LHRH) were compared in five normal men during infusions of somatostatin‐14 (SS‐14) and somatostatin‐28 (SS‐28), and during control infusions of vehicle alone. SS‐14 and SS‐28 were infused at a rate of 1·8 nmol/kg over 210 min. Arginine (0·5 g/kg) was infused from 30 to 60 min and the combined pituitary stimulation test commenced at 120 min. Arginine (0·5 g/kg) infused from 30 to 60 min induced an increase in GH secretion in all subjects and this increase was completely abolished in these same subjects when infused with SS‐14 and SS‐28. Arginine‐induced hyperglycaemia was significantly greater during infusion of SS‐14 and further enhanced by infusion of SS‐28. A small increase in PRL secretion occurred after arginine infusion and this was not inhibited by SS‐14 or SS‐28. Insulin and TRH administration induced marked increases in both GH and PRL secretion. The mean GH increase was significantly inhibited by SS‐14 and SS‐28 up to 165 min but not thereafter. The PRL increase was significantly inhibited by SS‐28 but not by SS‐14 and this greater efficacy was also indicated by administering different doses of SS‐28 to one subject. Taken together with the demonstration that SS‐28 is released from the median eminence, these findings indicate that SS‐28 has a hormonal role in the regulation of GH and PRL secretion.
HUMAN ERYTHROCYTE INSULIN RECEPTORS IN NORMAL MALE AND FEMALE SUBJECTS
Authors: WAJCHENBERG B. L. , LERARIO A. C. , EL‐ANDERE W. , OHNUMA L. Y. , SOUZA I. T. TOLEDO E
Published: March 2008

Human red blood cells (RBC) have been shown to have highly specific insulin receptors. We have studied the binding characteristics of insulin to these receptors in erythrocytes from normal male and female subjects on their usual diet and physical activity. There were no significant differences in insulin binding in erythrocytes from females between the two phases of the menstrual cycle. However, the receptor concentration was higher in the 2nd half of the cycle accompanied by a reduction in affinity.

Binding curves of 125‐I‐insulin to RBC from males were higher than females in either phases of the menstrual cycle, primarily due to an increase in receptor concentration when compared to females in the follicular phase and mediated by an increased affinity at low receptor occupancy when compared to females in the luteal phase.

We speculated that the differences in the binding characteristics of 125I‐insulin to RBC insulin receptors are mediated by differences in the levels of sex hormones.
SERUM TRIIODOTHYRONINE AND HYPERTHYROIDISM IN A POPULATION SAMPLE OF WOMEN
Authors: NYSTRÖM E. , BENGTSSON C. , LINDQUIST O. , LINDBERG S. , LINDSTEDT G. , LUNDBERG P.‐A.
Published: March 2008

The serum T3 assay has been regarded as the most sensitive single test for hyperthyroidism although impaired conversion of T4 to T3 in non‐thyroidal illness (NTI) might decrease its diagnostic sensitivity. The present report gives experience from the T3 assay in middle‐aged females under conditions similar to those in a general health survey. The assays were performed during two periods with an interval of six years.

In 1974–75 we studied a representative sample (n= 1283) of women of ages 44, 52, 56, 60 and 66 years in Göteborg, Sweden. Individuals with serum T3 concentration > mean + 2·5 SD were selected for a follow‐up study (n= 21). Of 16 individuals with no previous thyroid disease and no present treatment with thyroid hormones or oestrogens, 14 were subjected to a TRH‐stimulation test giving a normal TSH response in 10 cases having T3 concentrations up to mean + 3·5 SD. Four women with serum T3 concentration ≥ mean + 3·5 SD had previously unrecognized autonomous function thyroid function, of whom two developed hyperthyroidism after two years.

The original population sample was reinvestigated after six years in 1980‐81 (n= 1138) together with an additional sample of women giving a total sample of 1422 women of ages 26, 38, 50, 58, 62, 66 and 72 years. Of the females studied in 1974–75 eight had developed hyperthyroidism between the two studies; three of these had raised serum T3 at the investigation in 1974–75. No case of hyperthyroidism had been missed by the T3 assay in the 1974–75 study. Of individuals with serum T3≥mean + 2·5 SD selected for a follow‐up (n= 29) at least five were found to have previously unrecognized thyroid autonomy.

We found a raised serum T3 to be associated with hyperthyroid (n= 2) and euthyroid GRAVES' disease, autonomously functioning thyroid adenoma(s), possible painless subacute thyroiditis, possible thyrotoxicosis factitia, diminished thyroid reserve and thyroid substitution therapy.

Since we did not correct for variations in protein binders a number of individuals with oestrogen‐associated rise of total T3 were identified, but the rises were usually modest. The incidence of hyperthyroidism for the original sample as calculated for the six‐year period was 1.3 cases/1000 women/year whereas the prevalence by 1980‐81 was 13 cases/1000 women.

We conclude that a single T3 determination will in most cases be sufficient for the diagnosis of clinical hyperthyroidism in a non‐hospitalized population. Our study indicates some of the problems associated with the follow‐up of a general screening for hyperthyroidism, the possible benefit of which remains to be studied.
RELATIONS BETWEEN IMMUNOREACTIVE SOMATOMEDIN C, INSULIN AND T3 PATTERNS DURING FASTING IN OBESE SUBJECTS
Authors: CAUFRIEZ A. , GOLSTEIN J. , LEBRUN P. , HERCHUELZ A. , FURLANETTO R. , COPINSCHI G.
Published: March 2008

Plasma glucose, immunoreactive somatomedin‐C (Sm‐C), GH, insulin (IRI) and T3 were measured daily in 20 obese subjects before and during a 9‐day fast. Control levels of Sm‐C were normal and exhibited no significant correlation with any of the other parameters investigated. During fasting there were no consistent variations in GH, but significant decreases occurred in blood glucose, IRI, T3 and Sm‐C levels. While individual Sm‐C patterns varied widely, as a group the fasting Sm‐C values showed a positive correlation with the fasting IRI and T3 levels, and with control body weight. These findings suggest that the decrease in Sm‐C which occurs during caloric deprivation may be the result of concomitant decreases occurring in T3 and IRI levels.
PLASMA DISAPPEARANCE OF OVINE CORTICOTROPHIN‐RELEASING FACTOR IN MAN
Authors: TSUKADA T. , NAKAI Y. , KOH T. , TSUJII S. , IMURA H.
Published: March 2008

Disappearance of immunoreactive ovine corticotrophin‐releasing factor (IR‐oCRF) from plasma after a single intravenous injection of ovine corticotrophinreleasing factor (oCRF) was studied in man in the morning and evening. Synthetic oCRF (80 μg) was injected intravenously to four normal male volunteers at 0900 h or at 2200 h. Blood samples were drawn before and 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after the oCRF injection. Plasma IR‐oCRF was measured by a specific radioimmunoassay for OCRF. Plasma concentrations of IR‐oCRF after oCRF injections in the morning and in the evening did not differ significantly (P>0·05). Disappearance of IR‐oCRF was modelled with a two‐exponent function by using a non‐linear least squares computer program. The metabolic clearance rate, the apparent initial volume of distribution, the plasma half‐life for the fast component and that for the slow component calculated from all eight tests in the morning and evening were 1·49·0±05 ml/min·kg, 44·4±1·7 ml/kg, 6·8±0·7 min and 46·2±2·3 min (mean ± SEM), respectively. This relatively long half‐life may be responsible for the prolonged biological effect of oCRF administered intravenously. There were no significant differences between parameters of IR‐oCRF disappearance curves in the morning and those in the evening (P>0·05).
HORMONAL EFFECTS OF GnRH AGONIST IN THE HUMAN MALE: II. TESTOSTERONE ENHANCES GONADOTROPHIN SUPPRESSION INDUCED BY GnRH AGONIST
Authors: BHASIN S. , HEBER D. , STEINER B. , PETERSON M. , BLAISCH B. , CAMPFIELD L. A. , SWERDLOFF R. S.
Published: March 2008

Superactive analogues of gonadotrophin releasing hormone and testosterone, when administered together, synergistically inhibit gonadotrophin secretion and spermatogenesis in the rat. In order to determine whether testosterone also enhanced gonadotrophin suppression by GnRH agonist in the human male, two groups of four normal male volunteers first received either 10 or 100 μg of a GnRH agonist D(Nal2)6GnRH (GnRH‐A) daily for 10 d. After at least a 50 d recovery period, the same subjects received a single injection of 200 mg of testosterone oenanthate (TE) on day 1 in addition to the same dose of GnRH‐A daily for 10 d. Serum LH, FSH and testosterone (TS) concentrations were measured dailyjust prior to the next analogue dose, and on days 1 and 10 at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h after the analogue injection.

Daily administration of both 10 and 100 μg of GnRH‐A alone resulted in an early phase of stimulation followed by progressive decline in LH, FSH and testosterone to levels below baseline by day 10 despite continued administration of GnRH‐A. Addition of testosterone to 10 μg of GnRH‐A resulted in hormonal responses identical to those seen with GnRH‐A alone. Combined treatment of testosterone with 100 μg of GnRH‐A did not blunt the peak LH and FSH responses on day 2, but resulted in significantly lower LH (mean integrated responses: 187 ± 30 vs. 234 ± 42 mIU‐d/ml) and FSH (mean integrated responses: 20·6 ± 3·3 vs. 32·8 ± 4·2 mIU‐d/ml) responses from days 3 to 11. By day 11, all subjects receiving combined treatment (GnRH‐A 100 μg+testosterone oenanthate) had undetectable serum FSH levels. In contrast, serum FSH concentrations on day 11 after treatment with GnRH‐A alone were 43·6 ± 8·9% of control and none of the subjects had values below the limit of detection. Serum testosterone levels in the combined treatment group did not fall below baseline by day 10 in either the 10 (161·4 ± 48%) or the 100 μg GnRH‐A groups (104·6 ± 11·2%), while in the group receiving GnRH‐A alone, testosterone levels declined to 45·6 ± 8·3% and 80±18·8% with the 10 and 100 μg dose respectively.

We conclude that addition of a suppressive dose of testosterone to an appropriate dose of GnRN‐A significantly enhances gonadotrophin suppression by GnRH‐A in the human male. Combined use of testosterone and GnRH‐A might be of importance in the development of a male contraceptive to achieve the desired suppression of spermatogenesis while avoiding androgen deficiency.
DIRECT AND QUANTITATIVE MEASUREMENT BY IMMUNOPRECIPITATION ASSAY OF ANTI‐THYROTROPHIN RECEPTOR ANTIBODIES IN SERA OF PATIENTS WITH GRAVES' DISEASE
Authors: de BRUIN T. W. A. , van der HEIDE D. , QUERIDO A. , KROL MARIA C.
Published: March 2008

The presence of anti‐TSH receptor antibodies in the sera of 32 patients with untreated GRAVES' disease, 21 patients with euthyroid autonomous multinodular goitre, nine patients with Hashimoto's disease and 22 normal controls, was investigated by means of a direct and quantitative immunoprecipitation assay (IPA). A comparison was made between the IPA anti‐TSH receptor antibody titres, the thyrotrophin‐binding inhibitor immunoglobulins (TBII) index determined by radio‐receptor assay and the presence of circulating immune complexes (CIC); no correlation was found. Twenty‐six (81%) of the 32 untreated patients with GRAVES' disease were IPA‐positive; 16 (50%) had a positive TBII index. None of the patients with euthyroid autonomous multinodular goitre and none of the normal controls were IPA‐positive and their TBII index was normal in all cases. Of the nine patients with Hashimoto's disease seven were IPA‐positive and three had a positive TBII index. Of ten patients with GRAVES' disease still in remission none was IPA‐positive and their TBII index was normal. Of 18 patients who relapsed after treatment, 13 were IPA‐positive and only five had a positive TBII index. In seven patients with GRAVES' disease studied serially, anti‐TSH receptor antibodies remained present in the sera of four, although the TBII indices normalized. For the five patients who relapsed, a rise in the anti‐TSH receptor antibody titre at the time of the relapse was observed. It is concluded that not all anti‐TSH receptor antibodies cause TSH‐binding inhibition in the radio‐receptor assay, and further evidence has been obtained that anti‐TSH receptor antibodies are the cause of the hyperfunctioning of the thyroid gland in GRAVES' disease.
MALIGNANT PHAEOCHROMOCYTOMA: CLINICAL, BIOCHEMICAL AND SCINTIGRAPHIC CHARACTERIZATION
Authors: SHAPIRO B. , SISSON J. C. , LLOYD R. , NAKAJO M. , SATTERLEE W. , BEIERWALTES W. H.
Published: March 2008

We have evaluated thirty patients with malignant metastatic phaeochromocytoma with regard to clinical features, indices of catecholamine secretion, histology of lesions and a number of imaging procedures including scintigraphy with the recently developed sympathetic tissue‐seeking radiopharmaceutical 131I‐metaiodobenzylguanidine (131I‐MIBG). The primary tumour was extraadrenal in 13 cases. The commonest site of metastases was the axial skeleton (20 cases), followed by liver (four cases), lymph nodes (four cases), peritoneum (two cases) and lung (three cases). The malignancies were indolent, the mean time following the initial diagnosis was 9·18 years (range 0 to 33 years) and the mean duration of known metastases 3·71 years (range 0 to 18 years). There was a wide range of abnormalities in plasma and urinary catecholamines which did not correlate with the extent of tumour spread, histological pattern (mitotic index, Zellballen pattern, capsular or vascular invasion pleomorphism or necrosis) or 131I‐MIBG uptake by tumour deposits. 131I‐MIBG scintigraphy was found to be a useful technique for determining the extent of metastatic disease in most cases (26 of 30) and in some patients (16 of 30) was more sensitive than other radiological procedures. No false positive scans were encountered.
LONG‐TERM RESULTS OF ADRENAL SURGERY IN PATIENTS WITH CUSHING'S SYNDROME DUE TO ADRENOCORTICAL ADENOMA
Authors: VÄLIMÄKI M. , PELKONEN R. , PORKKA LEENA , SIVULA A. , KAHRI A.
Published: March 2008

Fourteen of 16 patients with Cushing's syndrome due to adrenal adenoma who had undergone adrenal surgery in the period 1967‐1981 participated in a follow‐up study 1 to 15 (mean 4·5) years after the operation. There were 14 unilateral and two bilateral adenomas. Two patients have died: one from postoperative complications, the other by suicide 10 years after surgery. None of the patients relapsed and none showed clinical features of Cushing's syndrome. However, five patients remained obese and four hypertensive. Furthermore, in the female patients the bone mineral density was lower than in age‐matched controls. The function of the pituitary‐adrenal axis recovered slowly. Postoperative replacement therapy was withdrawn 3 to 28 (mean 11·8) months after surgery in all but one patient. The function of the remaining adrenal gland was completely normal in 10 patients. In two patients the plasma cortisol response to ACTH‐stimulation was still blunted and associated with elevated plasma ACTH‐levels. The plasma ACTH‐level was low in the only patient having persistent hypocortisolism. In conclusion, the results show that most patients with Cushing's syndrome due to adrenal adenoma recover fully after surgery. In some patients, however, the suppressed pituitary and/or adrenal fail to resume normal function.
THE DIFFERENTIAL DIAGNOSIS OF CYSTIC NECK MASSES BY THE DETERMINATION OF THYROGLOBULIN CONCENTRATIONS IN THE ASPIRATES
Authors: KAWAMURA S. , KISHINO B. , MIYAUCHI A. , TAKAI S. , TAJIMA K. , MASHITA K. , TARUI S.
Published: March 2008

Thyroglobulin (Tg) concentrations in the aspirates of various types of cystic neck masses were measured by RIA to assess the usefulness of this determination in differential diagnosis. The subjects consisted of 16 patients, whose final diagnoses were all established on the basis of operative results; three patients had follicular thyroid adenomas (F‐Ad), 11 had papillary thyroid carcinomas (P‐Ca), one had a thyroglossal duct cyst (TDC) and one had a lateral cervical cyst (LCC). Tg concentrations in the cyst fluids of F‐Ad and P‐Ca were very high (0·042–2·83 mg/ml) compared with serum Tg concentrations. There was no difference in Tg concentrations in the fluids of P‐Ca between primary lesions (n= 5) and metastatic lesions (n= 6). On the other hand, Tg concentrations of TDC and LCC were very low (< 100 ng/ml). Difficulty was experienced in diagnosing three patients, even though they had been examined by all nonsurgical diagnostic techniques. However, an occult thyroid carcinoma with lymph node metastasis was diagnosed by demonstrating a high Tg concentration in the aspirate of the cystic lymph node. T3 concentrations in cyst fluids of F‐Ad were higher than those of P‐Ca. T3 concentrations in the fluids of P‐Ca, TDC and LCC did not differ, and were similar to serum T3 levels. Cytology of cyst fluids was positive in four of 10 patients examined with P‐Ca. In conclusion, we can clearly confirm the thyroid origin of a cystic neck mass by demonstrating a high Tg concentration in the aspirate. This is especially useful for diagnosis in patients with thyroid carcinoma, including occult thyroid carcinomas with cystic lymph node metastasis.
THE EFFECT OF ENDOGENOUS AND EXOGENOUS GONADOTROPHIN‐RELEASING HORMONE ON THE PROLACTIN RESPONSE TO TRH
Authors: GOOREN L. J. G. , VAN DER VEEN E. A. , VAN KESSEL H. , HARMSEN‐LOUMAN W.
Published: March 2008

The prolactin response to TRH in a group of patients with Kallmann's syndrome was found to be significantly lower compared to a group of hypergonadotrophic hypogonadal patients. Since levels of testicular products are comparably low in both groups, we hypothesize that high endogenous LHRH production might be associated with an increased prolactin response to TRH. In support of this, we were, indeed, able to establish a positive correlation between the magnitude of the prolactin response to TRH and basal and LHRH‐stimulated LH/FSH levels (the latter serving as an index of endogenous LHRH production) in: (1) eugonadal men, (2) men with Kallmann's syndrome, (3) oestrogen‐treated agonadal men, (4) men with severely impaired spermatogenesis and, (5) agonadal men. A direct relation between LHRH and the prolactin response to TRH was demonstrated in a group of eugonadal men, the prolactin response to TRH being greater after prolonged LHRH pretreatment. We speculate that an increase of endogenous or exogenous LHRH might be associated with decreased hypothalamic dopamine secretion which could directly increase prolactin synthesis. Indirectly, decreased dopamine secretion could augment the potency of TRH in releasing prolactin.
LACK OF ENDOGENOUS OPIOID INHIBITORY TONE ON LH SECRETION IN EARLY PUBERTY
Authors: FRAIOLI F. , CAPPA* M. , FABBRI A. , GNESSI L. , MORETTI C. , BORRELLI PATRIZIA , ISIDORI A.
Published: March 2008

Thirteen normal children, seven males and six females, during early puberty (I‐II according to Tanner), have been studied. Each subject was injected at weekly intervals and in random order with 100 μg of LHRH, 0·2 mg/kg of naloxone and 0·9% saline in single bolus. The gonadotrophin response was evaluated. The administration of naloxone failed to elevate LH levels in any of the subjects studied, even in those who showed a clear gonadotrophin response to LHRH. Unlike the response noted in adults, endogenous opiates do not appear to exert a tonic inhibitory influence on LH secretion during early pubery.
PITUITARY CELLULAR HYPERSENSITIVITY IN IDIOPATHIC HYPOPITUITARISM
Authors: SOBEL D. O. , GUTAI J. P. , RABIN B. S. , MONDINO B. J. , FIREMAN P.
Published: March 2008

Lymphocyte transformation in response to a saline extract of human pituitary was used to evaluate anti‐pituitary immunity in patients with idiopathic hypopituitarism. Nine normal subjects and three children with idiopathic hypopituitarism were studied. Lymphocytes of one patient were significantly reactive to pituitary extract (beyond the 95% tolerance limits of the normal subjects) at five and eleven months after the diagnosis of hypopituitarism. The anti‐pituitary hypersensitivity appeared organ specific since there was no lymphocyte reactivity to human thyroid extract in this patient. The presence of alopecia universalis, dystrophic nails and a primary immunodeficiency state suggests an autoimmune basis of his hypopituitary state. Due to hypogammag‐lobulinaemia and the lack of pituitary cell antibodies in this child, a humoral role in the development of his hypopituitarism is not supported.
VALUE OF THE 30 MIN ACTH‐TEST IN ASSESSING HYPOTHALAMIC‐PITUITARY‐ADRENOCORTICAL FUNCTION AFTER PITUITARY SURGERY IN CUSHING'S DISEASE
Authors: KEHLET H. , LINDHOLM J. , BJERRE P.
Published: March 2008

Adrenocortical responses to a 30 min ACTH‐test were measured before pituitary surgery and 8‐12 d, 2‐3 months and 6 months after, in 13 patients with Cushing's disease. The decrease in adrenocortical response to the short ACTH‐test performed 8‐12 d postoperatively correlated with the outcome as assessed 6 months after surgery. Adrenocortical response to ACTH became subnormal or borderline 8‐12 d after surgery in patients demonstrating postoperative HPA insufficiency. These results add further support to the value of the short ACTH‐test in assessing integrated HPA function in various clinical situations.
AN INVESTIGATION OF THE BIOLOGICAL ACTIVITY OF PARATHYROID HORMONE IN PSEUDOHYPOPARATHYROIDISM: COMPARISON WITH VITAMIN D DEFICIENCY
Authors: ALLGROVE J. , CHAYEN J. , JAYAWEERA P. , O'RIORDAN J. L. H.
Published: March 2008

Circulating parathyroid hormone was studied in patients with pseudohypoparathyroidism and compared with that in normal subjects and patients with hypocalcaemia due to postsurgical or idiopathic hypoparathyroidism or vitamin D deficiency. The cytochemical bioassay was used to measure bioactivity and an amino‐terminal specific immunoradiometric assay was used to measure immunoreactivity. In normal subjects (n= 12) the concentration of bioactive parathyroid hormone was 1.1–5.9 pg/ml. It was higher in patients with newly diagnosed, untreated pseudohypoparathyroidism (n= 4, range 20–53 pg/ml) and similarly raised in patients with untreated vitamin D deficiency (n= 9, range 23–74 pg/ml). The degree of hypocalcaemia was similar in these two groups of patients. By contrast, the concentration of bioactive parathyroid hormone was low (less than 0.6 pg/ml) in four patients with untreated postsurgical or idiopathic hypoparathyroidism. Restoration of normocalcaemia reduced the concentrations of bioactive PTH in both pseudohypoparathyroidism and vitamin D deficiency. Thus, in this respect the parathyroid glands in both conditions appeared to respond to the circulating calcium concentration. Immunoreactive PTH was also raised in patients with untreated pseudo‐hypoparathyroidism and vitamin D deficiency, but restoration of normocalcaemia did not always reduce immunoreactive PTH to normal in these patients. Thus, there can be dissociation between bioactivity and immunoreactivity even when the PTH is measured in an amino‐terminal specific assay.
GLOMERULOSA FAILURE IN CONGENITAL ADRENOCORTICAL UNRESPONSIVENESS TO ACTH
Authors: DAVIDAI GIORA , KAHANA LUNA , HOCHBERG ZEEV
Published: March 2008

We report two children of a family with congenital adrenocortical unresponsiveness to ACTH. Repeated stimulation of the adrenal by Synthetic 1–24 ACTH (Synacthen) failed to increase cortisol secretion, but produced significant rises of serum aldosterone. This was, however, associated with increased plasma renin activity. Only when the renin‐angiotensin effect was eliminated, by a converting enzyme blocker, did Synacthen fail to affect serum aldosterone. These data support the view that glucocorticoid deficiency in this disorder results from unresponsiveness to ACTH and that development of the zona glomerulosa and normal aldosterone secretion is achieved by action of the renin‐angiotensin system.
CORRELATION BETWEEN SKIN GLYCOSYLATION AND GLYCAEMIC CONTROL IN HUMAN DIABETES
Authors: PAISEY R. , HOPTON M. , HARTOG M.
Published: March 2008

Glycosylation of human skin has been measured by an adaptation of the thiobarbituric acid reaction on samples obtained mainly at autopsy from normal and diabetic subjects. The mean (± 1 SD) glycosylation of skin from 33 normal subjects was 0.072 ± 0.012 μmol fructosamine/100 mg wet weight tissue compared with 0.127 ± 0.034 μmol (P < 0.01) in the 10 diabetic subjects. There was a correlation between mean blood glucose levels in the 6 months before death and skin glycosylation in the diabetics, (r= 0.71, P= 0.025), but no correlation between age, sex, or the presence or absence of diabetic complications and skin glycosylation. Skin glycosylation in samples from four non diabetics was increased from 0.075 ± 0.015 to 0.126 ± 0.01 μmol fructosamine/100 mg wet weight tissue (P < 0.01) after incubation with 50 mmol/1 glucose solution for 7 d at 37°C.
PLASMA GROWTH HORMONE SUPPRESSIVE EFFECT OF BROMOCRIPTINE IN ACROMEGALY. EVALUATION BY PLASMA GH DAY PROFILES AND PLASMA GH CONCENTRATIONS DURING ORAL GLUCOSE TOLERANCE TESTS
Authors: NORTIER J. W. R. , CROUGHS R. J. M. , THIJSSEN J. H. H. , SCHWARZ F.
Published: March 2008

In most studies reporting favourable results of chronic bromocriptine treatment in acromegaly, plasma GH levels are measured at fixed intervals during the day. Negative results are reported in one major study measuring plasma GH levels during oral glucose tolerance tests (Lindholm et al., 1981). This study does not mention the time interval between the last dose of bromocriptine and the performance of an OGTT, but due to the short duration of action of bromocriptine this may be critical. Therefore, in the present report the plasma GH suppressive effect of bromocriptine in acromegaly is studied using plasma GH day‐profiles as well as OGTT's during continued bromocriptine administration and OGTT's at two different time intervals after the last dose of bromocriptine. Twelve patients with clinically active acromegaly were treated with 10–20 mg bromocriptine for 6–9 months. After 6–9 months during continued bromocriptine administration the plasma GH suppressive effect of bromocriptine was evaluated by the mean of four plasma GH determinations during the day and by the mean of seven plasma determinations during oral glucose tolerance tests (OGTT's) performed 1 h, 10 h and 34 h after the last dose. The percentage decrease of the mean plasma GH level during the day induced by chronic bromocriptine treatment showed a good correlation (r= 0·86, P< 0·001) with the percentage decrease of the mean plasma GH level during OGTT, if the post‐treatment test was carried out one hour after the last dose of bromocriptine. When OGTT was performed 10 h after the last dose no significant correlation (r= 0·17) was found and after 34 h a rebound of the mean plasma GH level occurred in eight patients. It is concluded that measurement of the mean plasma GH level during the day or during OGTT are equally effective indicators of the suppressive effect of bromocriptine treatment on GH secretion in acromegaly if the OGTT is performed 1 h after the last dose of bromocriptine.
THE EFFECT OF RADIOIODINE AND ANTITHYROID DRUGS ON SERUM LONG ACTING THYROID STIMULATOR PROTECTOR (LATS‐P). A THREE YEAR PROSPECTIVE STUDY
Authors: HARDISTY C. A. , FOWLES A. , MUNRO D. S.
Published: March 2008

Over a three year period we have studied the effect of either a one year course of Carbimazole or a single dose of radioiodine in a group of 46 patients with GRAVES' disease. Initially, in untreated patients LATS‐P was present in 39 (85%) but at the end of the study was only detectable in 19 (41%), The clinical outcome in 29 patients initially treated with carbimazole correlated well with changes in serum LATS‐P which persisted in 18. Thirteen of these ultimately required radioiodine or sub‐total thyroidectomy. With radioiodine two patterns of response were seen, in some LATS‐P levels declined, whereas in others transient increases were seen usually during the first year but subsequently fell. There was no difference in clinical response between the two groups. Overall, the study indicates that serum LATS‐P is related to the clinical course of GRAVES' disease but there remains a minority of patients in whom the activity cannot be detected.
HEREDITARY CONGENITAL GOITRE WITH THYROGLOBULIN DEFICIENCY CAUSING HYPOTHYROIDISM
Authors: MEDEIROS‐NETO G. A. , KNOBEL M. , CAVALIERE H. , SIMONETTI J. , MATTAR E.
Published: March 2008

The thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21‐year‐old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12·9–20·0 μg/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80–220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3+T4 and MIT+DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg‐like proteins (RIA) in the thyroid soluble protein extract was only 16–122 μg/g (normal: 50–70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18–20S) thyroglobulin. Only one peak (3·6–4·1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.
PLASMA NORADRENALINE AND BLOOD PRESSURE IN HYPOTHYROID PATIENTS: EFFECT OF GRADUAL THYROXINE TREATMENT
Authors: MANHEM P. , HALLENGREN B. , HANSSON B.‐G.
Published: March 2008

High plasma noradrenaline (PNA) levels have been reported in hypothyroid patients and hypothyroidism has been associated with hypertension. To explore the relationship between PNA and blood pressure (BP) in hypothyroid patients, and the effects of gradual thyroxine replacement, a prospective study was performed comparing BP, heart rate (HR) and PNA in a normotensive and a hypertensive group of hypothyroid patients before and during gradual thyroxine substitution. Thyroxine treatment reduced the BP; the reduction in supine BP was greater in the hypertensive than in the normotensive group. HR increased similarly in both groups during treatment. PNA was elevated in the normotensive group before treatment and decreased gradually during thyroxine treatment. The hypertensive group had normal PNA levels. The present study indicates that normotensive, in contrast to hypertensive, hypothyroid patients have increased sympathetic nervous activity. Although the mechanism is unclear, thyroid replacement therapy can reverse hypertension in hypothyroid patients.
CORTICOTROPHIN RELEASING FACTOR: EFFECTS ON CIRCULATING GUT AND PANCREATIC PEPTIDES IN MAN
Authors: LYTRAS N. , GROSSMAN A. , REES LESLEY H. , SCHALLY A. V. , BLOOM S. R. , BESSER G. M.
Published: March 2008

As a CRF‐like peptide has been isolated from human gut, we investigated the effect of synthetic CRF‐41 100 μg on gut and pancreatic peptides in six normal subjects. There was a significant rise in pancreatic polypeptide compared to a control infusion, but no change in plasma insulin, pancreatic glucagon, gastrin, somatostatin, motilin, neurotensin, gastric inhibitory peptide, or cholecystokinin was seen. In addition, there was no change in circulating met‐enkephalin. We conclude that the rise in pancreatic polypeptide seen after CRF administration may suggest a role for a CRF‐like peptide in the control of pancreatic function.
A SENSITIVE AND SELECTIVE RADIOIMMUNOASSAY FOR SERUM 24, 25‐DIHYDROXYCHOLECALCIFEROL IN MAN
Authors: HUMMER L. , CHRISTIANSEN C.
Published: March 2008

We have developed a sensitive and selective radioimmunoassay for 24, 25‐dihydroxycholecalciferol (24,25(OH)2D3). Antisera with a high titre and affinity to 24, 25(OH)2D3 were raised in rabbits immunized with a protein conjugate of the 3‐hemisuccinate derivative of 24, 25(OH)2D3. Serum samples were extracted by methanol/dichloromethane and the lipid extracts purified on Sephadex LH 20 and chromatographed by single step HPLC on a straight phase silica column. The radioimmunoassay is capable of measuring 24, 25(OH)2D3 in the ‘24, 25(OH)2D complex’ isolated by HPLC and containing the comigrating metabolites: 24, 25(OH)2D3, 24, 25(OH)2D2, 25(OH)D3‐26, 23 lactone and 25, 26(OH)2D2. The detection limit of 2 pg/assay tube is a marked improvement, compared to the competitive protein binding assay using rachitic rat serum. Measured by the radioimmunoassay 24, 25(OH)2D3 ranged from 0·05 to 1·96 ng/ml with a mean of 0·85 ng/ml in 34 healthy adults. For comparison 24, 25(OH)2D, measured simultaneously by competitive protein binding with rachitic rat serum, ranged from 0·1 to 4·0 ng/ml with a mean of 1·76 ng/ml.
HYPOTHALAMIC GROWTH HORMONE RELEASING FACTOR DEFICIENCY FOLLOWING CRANIAL IRRADIATION
Authors: AHMED S. R. , SHALET S. M.
Published: March 2008

The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1–44) on GH release has been studied in 10 patients with radiation‐induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/l) and to arginine stimulation (median peak GH 2.9 mU/l), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 /μg) of hp GRF1‐44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/l; range 22–57 mU/l) to hp GRF1‐44, similar in magnitude and timing to that seen in the four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1‐44, ITT and to arginine was a result of radiation‐induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future.
THE LEVELS AND SUBCELLULAR DISTRIBUTION OF HORMONES AND MARKER ENZYMES IN PITUITARIES FROM CONTROL SUBJECTS AND PATIENTS WITH PROLACTINOMAS, ACROMEGALY OR FUNCTIONLESS PITUITARY TUMOURS
Authors: DE MARCO L. , MASHITER K. , PETERS T. J.
Published: March 2008

Pituitary homogenates were prepared from patients undergoing pituitary ablation for breast or prostatic carcinoma (controls) and from patients with either PRL‐ and GH‐secreting pituitary adenomas or from patients with ‘functionless’ pituitary tumours. The principal subcellular organelles, plasma membrane, lysosomes, mitochondria, endoplasmic reticulum, cytosol and hormone‐containing granules were characterized by sucrose density gradient centrifugation. Tissue from patients with prolactinomas showed hormone granules, lysosomes and endoplasmic reticulum of lighter density than controls; cytosol, mitochondria and plasma membrane were similar. PRL‐secreting tumours showed a 2‐fold increase in PRL content with significant reduction of LH, FSH and GH. Activities of various lysosomal enzymes, except for PRL proteolytic activity, were significantly reduced. Similar conclusions were found for GH‐secreting pituitary adenomas with a striking reduction in PRL proteolytic activity. Functionless tumours showed significant amounts, though reduced compared to control tissue, of all hormones. In contrast to the hormone‐secreting adenomas, the activity of the lysosomal enzyme N‐acetyl‐β‐glucosaminidase was significantly increased compared to control tissue.
META‐IODOBENZYLGUANIDINE IN METASTATIC PHAEOCHROMOCYTOMA
Authors: STEWART R. J. , ANDERSON J. R. , LAIRD J. D. , ATKINSON A. B. , KENNEDY T. L
Published: March 2008

A case of metastatic phaeochromocytoma is presented. Meta‐iodobenzylguanidine was used to locate the tumour but failed to show two functioning abdominal metastatic deposits. Although meta‐iodobenzylguanidine appears to be highly specific for phaeochromocytoma, a negative scan does not exclude a functioning tumour with confidence.
RECURRENCE OF NONTOXIC GOITRE WITH AND WITHOUT POSTOPERATIVE THYROXINE MEDICATION
Authors: GEERDSEN J. P. , FRØLUND L.
Published: March 2008

The incidence of postoperative recurrence of nontoxic goitre was evaluated in 175 patients. The average observation period was 8.8 years. Levothyroxine (Eltroxin) had been taken by 104 of these patients as long‐term prophylaxis against goitre recurrence. Ten (9.5%) of the 104 had recurrence. The other 71 patients received no or only brief thyroxine medication postoperatively. In this group there were eight recurrences (11.3%). The difference was not significant, nor did the two groups differ significantly in regard to sex and age distribution, pathologic anatomy and observation time. Routine long‐term administration of thyroxine after thyroid resection is not justified from the results of this study.
THE ACUTE EFFECTS OF A DOPAMINE ANTAGONIST (DOMPERIDONE) ON LUTEINISING HORMONE, FOLLICULE STIMULATING HORMONE, PROLACTIN AND THYROTROPHIN SECRETION IN POLYCYSTIC OVARIAN SYNDROME: DIFFERENTIAL EFFECT OF OVULATION
Authors: MURDOCH A. P. , DUNLOP W. , KENDALL‐TAYLOR P. , WATSON M. J.
Published: March 2008

An alteration of the hypothalamic dopaminergic regulation of LH secretion has been implicated in the abnormal LH secretion of polycystic ovarian syndrome (PCOS). To investigate this, the acute effect of dopamine (DA) receptor blockade on LH, FSH, PRL and TSH secretion was determined. No effect was observed on either LH or FSH secretion in the PCOS patients or in normal women and LH pulsatility appeared to be maintained. When the PCOS patients were divided into those who ovulated in the preceding cycle and those who were anovulatory, it was observed that the ovulatory patients had a normal PRL and TSH response; whereas in the anovulatory patients, the PRL rise was blunted and the TSH response was absent. We conclude that this study gives no evidence to support the hypothesis of altered hypothalamic DA regulation of LH secretion in PCOS. The lack of LH response to DA blockade suggests that a physiological role of DA in the control of LH secretion seems unlikely as determined under these experimental conditions. The differences in PRL and TRH response may reflect anovulation rather than a fundamental abnormality in PCOS.
TRANSSPHENOIDAL MICROSURGERY FOR CUSHING'S DISEASE
Authors: SEMPLE C. G. , THOMSON J. A. , TEASDALE G. M.
Published: March 2008

Nineteen patients thought to have Cushing's disease were treated by trans‐sphenoidal microsurgery; the type of operation performed depended upon the findings in the individual patient. Seventeen patients remitted. Failures occurred in a patient with an invasive macroadenoma and in a patient who was subsequently found to have a thymic carcinoid tumour secreting ACTH. One patient who remitted suffered a recurrence during pregnancy, 30 months after operation. The ten patients (Group I) who had a selective removal of a microadenoma or a limited resection of the gland were often GH deficient, but seven regained cortisol reserve and all ten regained normal pituitary‐thyroid and pituitary‐gonadal responses. By contrast abnormalities of pituitary function were common in nine patients who had a radical or total hypophysectomy. We conclude that transsphenoidal microsurgery is the best treatment for Cushing's disease and that, when feasible, a selective microadenomectomy is the most appropriate operation.