bluuebunny/crossref_metadata_2025 huggingface dataset:
RESPONSE TO NEUROTRANSMITTER MODULATING DRUGS IN PATIENTS WITH CUSHING'S DISEASE
Authors: KOPPESCHAAR H. P. F. , CROUGHS R. J. M. , THIJSSEN J. H. H. , SCHWARZ F.
Published: March 2008

We designed a systematic study of patients with Cushing's disease to compare the results of acute experiments with cyproheptadine, sodium valproate and bromocriptine with the results of chronic treatment with sodium valproate. In 13 patients the plasma Cortisol response to single doses of 2.5 mg bromocriptine, 6 mg cyproheptadine and 300 mg sodium valproate was assessed over 4.8 h. All patients were then treated with sodium valproate 200 mg three times a day for a period of 3 months. Subjects were classified as responders when there was a reduction in plasma Cortisol by at least 50% below the basal level in two consecutive plasma samples during one of these tests, and/or clinical remission and normalization of Cortisol production rate during sodium valproate treatment. Four patients responded significantly to at least one of the agents (group I) and 9 did not (group II). In group I three patients were bromocriptine responsive and one of these responded also to cyproheptadine; in this patient both sodium valproate and cyproheptadine were able to induce a remission during chronic treatment. In the one patient of the responder group who was bromocriptine insensitive, sodium valproate treatment also induced a remission. In two patients of the responder group sodium valproate treatment was ineffective. However, in both patients chronic treatment with bromocriptine induced a marked clinical improvement associated with a decrease of Cortisol production rate. There was no difference between the groups in sex, age, clinical presentation, duration or severity of hypercortisolism. In one patient in group I a macroadenoma with suprasellar extension was present, while a microadenoma was detected in four patients in group II. There was no difference in the sensitivity of Cortisol secretion to the suppressive effect of overnight or 5 h infusion of dexamethasone between the two groups, and PRL levels were normal in all. These data show that responsiveness of patients with Cushing's disease to neurotransmitter modulating drugs is not associated by specific clinical or biochemical characteristics. Bromocriptine tests most reliably predict the chances for successful medical treatment. However, non‐responsiveness to acute administration of neurotransmitter modulating drugs does not exclude with certainty their usefulness during chronic treatment.
RAPID IMPROVEMENT IN VISUAL FIELD DEFECTS FOLLOWING BROMOCRIPTINE TREATMENT OF PATIENTS WITH NON‐FUNCTIONING PITUITARY ADENOMAS
Authors: D'EMDEN M. C. , HARRISON L. C.
Published: March 2008

The role of bromocriptine in the treatment of non‐functioning pituitary tumours is not yet defined. Patients with these tumours who present with visual field defects usually undergo immediate surgery. Three consecutive patients are reported: each had rapid improvement in their visual field defects following bromocriptine 7.5 mg/d before surgery. Histological and immunohistochemical examination confirmed that their tumours were non‐functioning chromophobe adenomas. Their responses indicate that bromocriptine may have a role in the management of some patients with non‐functioning pituitary tumours.
EFFECTS OF SOMATOSTATIN ANALOGUE SMS 201–995 IN NON‐INSULIN‐DEPENDENT DIABETES
Authors: DAVIES R. R. , MILLER MARGARET , TURNER S. J. , WATSON M. , McGILL A. , ØRSKOV H. , ALBERTI K. G. M. M. , JOHNSTON D. G.
Published: March 2008

The 24‐h hormonal and metabolic profiles obtained in five non‐insulin‐dependent diabetics receiving twice daily s.c. injections of the long‐acting somatostatin analogue SMS 201–995 (50 μg) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201–995 but changes in lactate, pyruvate, glycerol and 3‐hydroxybutyrate were minor. All five subjects suffered gastrointestinal side‐effects. SMS 201–995 (50 μg) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24‐h GH secretion and causes significant side‐effects in patients with non‐insulin‐dependent diabetes mellitus.
OVULATORY DISTURBANCES IN PATIENTS WITH LUTEAL INSUFFICIENCY
Authors: HAMILTON C. J. C. M. , EVERS J. L. H. , DE HAAN J.
Published: March 2008

In order to study ovulatory disturbances in patients with luteal insufficiency we evaluated 210 cycles of 170 women from infertile couples by ultrasonographic follicle measurements and hormonal determinations. Only cycles with evidence of luteinization were included into the study. Mid‐luteal progesterone (P) levels were determined in relation to the ultrasonographic ovulation time or, where the follicle failed to rupture, in relation to the LH peak. In spontaneous cycles with a mid‐luteal P level below 32 nmol/l (10 ng/ml) a luteinized unruptured follicle (LUF) was found in 71.1 % of cycles, whereas in spontaneous cycles with a mid‐luteal P level above 32 nmol/l only 7.9% cycles exhibited a failure of the follicle to rupture. The same phenomenon was encountered in cycles in which agents had been given to induce ovulation. The incidence of LUF cycles in an average infertility population could be calculated to be as high as 50% if the mid‐luteal P level is below 32 nmol/l and as low as 4% if the mid‐luteal P level is above 32 nmol/l. The geometric mean mid‐luteal P level in spontaneous LUF cycles was 32.5 nmol/l, compared to 55.2 nmol/l in spontaneous ovulatory cycles (P < 0001). We conclude that in patients with luteal insufficiency a high incidence is found of a failure of the follicle to rupture. The entrapment of the oocyte in the unruptured follicle constitutes an important cause of infertility in these patients.
SOMATOMEDIN‐C LEVELS IN TREATED AND UNTREATED PATIENTS WITH ACROMEGALY
Authors: ROELFSEMA F. , FRÖLICH M. , VAN DULKEN H.
Published: March 2008

With the aid of a recently developed commercially available radioimmunoassay for Somatomedin‐C (Sm‐C) we measured the Sm‐C levels in 38 controls, 24 untreated acromegalics, 45 inactive acromegalics and five pituitary dwarfs. With the exception of the dwarfs, the age and sex distributions for the various groups were similar. In inactive acromegalics the basal GH level (calculated as the mean of four blood samples taken during the day) was < 5 mU/1; it was depressed to, or less than, 2‐5 mU/1 during the 100 g oral glucose tolerance test. The mean Sm‐C level found for control subjects was 20‐4 ± 5.1 nmol/1 and for untreated patients 85‐6 ± 25‐7 nmol/1 (mean ± SD, P<0.001). The mean Sm‐C level for inactive patients who had undergone surgery and invariably showed a normalized paradoxical reaction to TRH was 18‐2 ± 7‐1 nmol/1 (NS) vs 16.1+8.2 nmol/1 (NS) for those who underwent surgery plus postoperative pituitary radiation therapy. Only one out of 45 inactive acromegalics exhibited an increased Sm‐C level. The Sm‐C levels correlated significantly not only with the log GH levels (r= 0–82) but also with the fasting insulin/glucose ratio the integrated incremental insulin levels, the maximal insulin increase and the integrated glucose levels during the oral glucose tolerance test as well as the 24‐h urinary excretion of calcium and hydroxyproline. The prolactin level did not influence the Sm‐C level; however the Sm‐C levels were lower in inactive patients with an impaired GH release during insulin‐induced hypoglycaemia than in patients with an adequate release (i.e. > 12 mU/1). These results demonstrate that the Sm‐C levels are increased without exception in active acromegaly and normal in inactive patients, so that this measurement can be used for assessment of the activity of the disease.
AMENORRHOEA IN CYSTIC FIBROSIS
Authors: STEAD R. J. , HODSON M. E. , BATTEN J. C. , ADAMS J. , JACOBS H. S.
Published: March 2008

Menstrual history in relation to nutritional status and lung function was assessed in 45 adolescent and adult patients with cystic fibrosis (CF). Twenty patients had regular menstrual cycles (of whom six had been pregnant), 12 had primary or secondary amenorrhoea, 11 had irregular cycles and two were pre‐menarcheal. Patients with regular menstruation had a significantly higher body mass index and percentage body fat (estimated from skinfold thickness measurements) than those with amenorrhoea (P<lt;0.001), and also better lung function (P<lt;0.01). A linear discriminant analysis indicated that of the four indices studied percentage body fat was the most important predictor of menstrual function. Ovarian and uterine morphology were studied by ultrasonography in 28 patients and 17 healthy controls. In 10 patients multicystic ovaries were noted. Even in patients with regular cycles uterine size was reduced (P<lt;0.01) and in those with amenorrhoea appeared to be related to thinness. Amenorrhoea in CF is an appropriate adaptive response in preventing pregnancy, but the resultant oestrogen deficiency and psychological effects must be considered.
BROMOCRIPTINE TREATMENT OF WOMEN WITH CLOMIPHENE‐RESISTANT POLYCYSTIC OVARY SYNDROME
Authors: POLSON D. W. , MASON H. D. , FRANKS S.
Published: March 2008

Twenty‐three patients with polycystic ovary syndrome and anovulatory infertility have been treated with bromocriptine. All had previously failed to respond to clomiphene. Twenty had normal serum prolactin concentrations and, of these, four (20%) developed regular ovulatory cycles. All three women with moderate hyperprolactinaemia ovulated regularly on bromocriptine so that, overall, seven of 23(30%) responded, which was a significantly higher proportion than that observed during a control period of no treatment. A further eight women ovulated at least once during the study period but these occasional ovulations were no more common during bromocriptine than with either clomiphene or no treatment. No suppression of LH was noted except during the luteal phase of ovulatory cycles and there was no change in the pattern of pulsatile release of LH. Testosterone and androstenedione concentrations remained elevated and unchanged. We conclude that bromocriptine may be expected to induce ovulation in hyperprolactinaemic women with polycystic ovary syndrome but that there is no clear indication for its use in clomiphene‐resistant patients with normal serum prolactin concentrations.
AMIODARONE IODINE‐INDUCED HYPOTHYROIDISM: RISK FACTORS AND FOLLOW‐UP IN 28 CASES
Authors: MARTINO E. , AGHINI‐LOMBARDI F. , MARIOTTI S. , BARTALENA L. , LENZIARDI M. , CECCARELLI C. , BAMBINI G. , SAFRAN M. , BRAVERMAN L. E. , PINCHERA A.
Published: March 2008

Amiodarone, an iodine‐rich drug widely used for the treatment of cardiac tachyarrhythmias, may induce either hyperthyroidism or hypothyroidism. Of 467 patients chronically treated with this drug referred to our institution, amiodarone iodine‐induced hypothyroidism (AIIH) developed in 28 patients (6%). AIIH patients were subdivided into two groups according to the presence (group A) or absence (group B) of underlying thyroid abnormalities. Thyroid autoantibodies were present in 10 of 19 patients from group A and 0 of 9 patients from group B. The thyroid 24‐h radioiodine uptake (RAIU) was evaluated in 15 patients: low values (<4%) were found in three patients and detectable values (7–50%) were observed in 12. Perchlorate discharge tests were positive in all four patients tested. Follow‐up data were available in 20 patients (16 in group A and four in group B). Hypothyroidism was transient in 12 (60%) and persistent for several months after amiodarone withdrawal in eight (40%). While all patients in group B had transient hypothyroidism, 50% of patients with underlying thyroid abnormalities (group A) had persistent hypothyroidism. Thyroid autoantibodies were found in seven of eight patients with persistent hypothyroidism and in only three of 12 patients with transient hypothyroidism. Conversely, seven of 10 patients with positive thyroid autoantibodies had persistent hypothyroidism and 9 of 10 patients with undetectable thyroid autoantibodies had transient hypothyroidism. These data indicate that: (i) AIIH may develop in patients with or without underlying thyroid abnormalities; (ii) RAIU is inappropriately elevated in many patients with AIIH; (iii) intrathyroidal iodine is not organified; (iv) serum thyroid autoantibodies represent a risk factor for the development of AIIH; (v) AIIH spontaneously remits after amiodarone withdrawal in patients without thyroid abnormalities, but may persist in patients with concomitant thyroid disorders, especially those with circulating thyroid autoantibodies.
ANTI‐TSH ANTIBODY WITH HIGH SPECIFICITY TO HUMAN TSH IN SERA FROM A PATIENT WITH GRAVES' DISEASE: ITS ISOLATION FROM, AND INTERACTION WITH, TSH RECEPTOR ANTIBODIES
Authors: AKAMIZU T. , MORI T. , KASAGI K. , KOSUGI S , MIYAMOTO M. , NISHINO K. , SUGAWA H. , YOKOTA T. , NAKAMURA H. , KONISHI J. , IMURA H.
Published: March 2008

A patient with thyrotoxic Graves' disease had an apparent measurable level of serum TSH (2–5 μU/ml) by double‐antibody radioimmunoassay (RIA). The serum IgG bound with both [125I]human(h)TSH and [125I]bovine(b)TSH. The [125I]hTSH binding was more effectively displaced by human than bovine TSH, whereas [125I]bTSH binding was displaced exclusively by bTSH. Scatchard analyses revealed that [125I]hTSH binding showed two components, whereas [125I]bTSH binding had only one component. Serum TSH determined by RIA became undetectable 21 months after antithyroid drug treatment with a parallel decrease of [125I]hTSH binding IgG activity. Four thyrotrophin binding inhibitory immunoglobulins (TBII) from other patients did not interfere with the binding of the patient's serum to [125I]h‐ or bTSH. Furthermore, the in‐vitro thyroid stimulating activities of three thyroid stimulating antibodies (TSAb) were not affected by the addition of this patient's IgG. On the other hand, this patient's Ig (3 mg/ml) abolished the in‐vitro thyroid stimulation by bTSH (100 /μU/ml), but did not affect that by hTSH (100 /μU/ml). The anti‐hTSH antibody, TSH receptor antibody and anti‐bTSH antibody in the serum, which contains TSAb as well as anti‐TSH antibodies, could be partially purified by hTSH‐agarose and subsequently by guinea pig fat cell membrane affinity absorptions. However, the anti‐hTSH antibody fraction obtained had both hTSH binding activity and thyroid stimulating activity, and this fraction did not show any inhibitory effect on the in‐vitro thyroid stimulation of autologous TSH receptor antibody or hTSH. The possible significance of anti‐TSH antibodies is discussed.
CV 205‐502: A NEW LONG‐ACTING DRUG FOR INHIBITION OF PROLACTIN HYPERSECRETION
Authors: RASMUSSEN C. , BERGH T. , WIDE L. , BROWNELL J.
Published: March 2008

CV 205–502, an octahydrobenzo(g)quinoline, is a new non‐ergot long‐acting prolactin inhibitor. The substance was given to 24 hyperprolactinaemic women for 7 d. The women were randomized to one of three dose regimens, 0.01 mg, 0.03 mg or 0.06 mg daily. Two patients in each group were given placebo. Frequent blood samples were obtained during days 1, 7 and 8. The prolactin levels in serum were depressed dose‐dependently in all patients given active substance. In group 1 (0.01 mg) the dose was insufficient to induce normal serum prolactin levels except in one woman, while two women in group 2 (0.03 mg) and four in group 3 (0.06 mg) became normoprolactinaemic. The depressant effect on prolactin secretion lasted for 24 h in group 2 and 3. Side‐effects were mild and transient. No change in blood pressure was observed. CV 205–502 was an effective and long‐acting drug for treatment of patients with hyperprolactinaemia in this short‐term study and this new drug deserves investigation of its usefulness in long‐term treatment.
CELLULAR AND HUMORAL IMMUNITY IN PATIENTS WITH HYPERTHYROID GRAVES' DISEASE BEFORE, DURING AND AFTER ANTITHYROID DRUG TREATMENT
Authors: van OUWERKERK B. M. , KRENNING E. P. , DOCTER R. , BOS G. , van OUDENAREN A. , BENNER R. , HENNEMANN G.
Published: March 2008

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal. If changes in T cell subpopulations are present in Graves' disease, they are at least not measurable in peripheral blood.
EVALUATION OF DIAGNOSTIC CRITERIA FOR LEYDIG CELL TUMOURS IN ADULT MEN REVEALED BY GYNAECOMASTIA
Authors: KUHN J. M. , MAHOUDEAU J. A. , BILLAUD L. , JOLY J. , RIEU M. , GANCEL A. , ARCHAMBEAUD‐MOUVEROUX F. , STEG A. , LUTON J. P.
Published: March 2008

Gynaecomastia caused by Leydig cell tumours (LCT) in adult men may appear a long time before clinical evidence of testicular swelling. To evaluate the diagnostic criteria for LCT, hormonal status was studied in 14 cases and compared with results of a control group (CG) and 10 men with idiopathic gynaecomastia (IG). The mean plasma T level was significantly (P< 0.005) lower in LCT (16.7 ± 1.7 SEM nmol/l) than in CG (23.0 ± 1.3 nmol/l). However, individual plasma T levels were in the normal range in 9/14 LCT. The mean plasma E2 level was significantly (P < 0.001) higher in LCT (204.9 ± 27‐6 pmol/1) than in CG (87.9 ± 7.7 pmol/l). However, individual plasma E2 levels were in the normal range in 5/14 LCT. In LCT, neither means of basal gonadotrophin levels nor the gonadotrophin responses to LHRH were different from CG. The mean of the plasma T responses to hCG did not differ between LTC, CG and IG. However the mean of E2 peak responses appeared significantly (P< 0.005) higher in LCT (735.3 ± 103.4 pmol/l) than in CG (420.5 ± 40.4 pmol/l). The mean of the E2 peak responses was significantly (P< 0.001) lower in IG (196.5 ± 33.4 pmol/l) than in CG. Likewise the mean of plasma E2 levels, measured on day three following hCG administration, remained significantly (P < 0.001) higher in LCT (662 ± 94 pmol/l) than either in CG (228 ± 14 pmol/l) or in IG (158 ± 25 pmol/l). On day 3 following hCG administration, there was no overlap in individual plasma E2 levels between either LCT and CG or LCT and IG. In all LCT, plasma β‐hCG levels were in the normal range. A testicular echogram, performed in 12 LCT, confirmed the presence of a palpable tumour in 10 and revealed an occult tumour in two cases. We conclude that normal plasma β‐hCG levels, a prolonged plasma E2 response to hCG and testicular echogram appear to be the best criteria for early diagnosis of LCT responsible for gynaecomastia in adult men.
EFFECT OF ORAL ADMINISTRATION OF MELATONIN ON GH RESPONSES TO GRF 1–44 IN NORMAL SUBJECTS
Authors: VALCAVI R. , DIEGUEZ C. , AZZARITO C. , EDWARDS C. A. , DOTTI C. , PAGE M. D. , PORTIOLI I. , SCANLON M. F.
Published: March 2008

In order to investigate the role of melatonin on the neuroregulation of GH secretion, eight healthy male volunteers each underwent four separate tests in random order separated by at least 1 week. Following oral administration of melatonin (500 mg at – 60 min and at – 30 min) plasma GH levels were higher than after placebo at 45 min (mean + SEM 2.9 ± 0.8 vs 0.9 ± 0.4 ng/ml, P<0‐01) and 60 min (mean ± SEM 2.9 ± 0.4 vs 0.8 ± 0.1 ng/ml, P<005). Likewise, after prior administration of melatonin, GH responses to GRF 1‐44 (1 μg/kg i.v. at 0 min) were greater than placebo plus GRF at 15 min (mean ± SEM 22‐4 ± 6‐1 ng/ml vs 11.3 ± 2.3 ng/ml, P <005), 45 min (mean ± SEM 26.2 ± 5.3 ng/ml vs 13.3 ± 2.5 ng/ml, P < 0.01) and 60 min (mean ± SEM, 24.7 ± 7.4 ng/ml vs 11.1 ± 2.5 ng/ml, P <0.05). In contrast we did not observe any effect of either 10−9M, 10−7M or 10−5M melatonin on in‐vitro basal GH release and GH responses to 10−8M GRF by rat anterior pituitary cells in monolayer culture. These data suggest that melatonin plays a facilitatory role in the neuroregulation of GH secretion, probably by acting at the hypothalamic level.
LEUCOCYTE SODIUM TRANSPORT IN ACROMEGALY
Authors: NG L. L. , EVANS D. J.
Published: March 2008

The leucocyte sodium pump was studied in patients with active and treated acromegaly. The ouabain‐sensitive 22Na+ efflux rate constant was significantly raised in active acromegaly (median 2.71 [range 2.33‐3.20] vs 2.32 [1.55‐3.67] h−1, P< 0.008) and was lowered into the normal range with successful treatment. Plasma GH and insulin levels and skin fold thickness on the dorsum of the hand were positively correlated with this efflux rate constant (rs= 0.56, P<0.02; rs= 0.57, P<0.02; rs= 0.57 P<0.04, respectively). GH, in vitro, stimulated ouabain‐sensitive efflux in leucocytes at a concentration of 25 mU/1. We propose that this action of GH may explain the sodium retaining and calorigenic effects and possibly the stimulation of amino acid uptake by the hormone. The activity of the leucocyte sodium pump in acromegaly may be associated with other indices of disease activity.
CARDIOVASCULAR AND HORMONAL RESPONSES TO THYROTROPHIN RELEASING HORMONE IN ACROMEGALICS
Authors: LEVER E. G. , TROSSER A. , SMITH C.
Published: March 2008

The effect of TRH (200 μg) on blood pressure, pulse rate, TSH and GH release was investigated in 10 acromegalics, four patients with non‐GH secreting pituitary tumours, and seven normal controls. TRH produced a rapid‐onset, short‐lived pressor response in the acromegalic group (A mean blood pressure 33 mmHg) compared to the two control groups (P < 0.001). There was no response to the same volume of saline. The pressor response in the acromegalic group was not different in those who did or did not release GH. The pressor response to TRH was linearly related over the range 50–200 μg. Measurement of plasma noradrenaline and plasma renin activity during TRH testing in six acromegalics indicated that the pressor effect was neither mediated by adrenergic mechanisms, nor the renin‐angiotensin system. Echocardiographic monitoring in five of these six patients showed that there was a significant increase in directly measured end systolic, end diastolic dimensions and heart rate (all P < 002), and calculated stroke volume (P < 0001) and cardiac output (P<0.01) without changes in systemic vascular resistance. These data suggest that increase in preload, probably via venoconstriction, is the most likely factor producing the pressor response to TRH in acromegalics.
EVALUATION OF T4 AND T3 BINDING KINETICS IN THE THYROXINE BINDING GLOBULIN ABNORMALITY OF AUSTRALIAN ABORIGINES
Authors: MOHR V. S. , BARLOW J. W. , TOPLISS D. J. , O'DEA K. , STOCKIGT J. R.
Published: March 2008

Low serum total T4 associated with subnormal concentrations of thyroxine binding globulin (TBG) has been reported in up to 40% of euthyroid Australian aborigines. It has been suggested that these subjects show both diminished concentration of TBG and reduced TBG affinity for T4 (Same et al., 1985). We have compared 12 euthyroid aborigines with low T4 (total T4 44±5 nmol/1) and aborigines with normal T4 (T4 99±9 nmol/1, n= 12) using measurements of free T4 and T3 by equilibrium dialysis. TBG was measured both by RIA (Henning, Berlin, FRG) and a method dependent on T4 binding (Corning Immophase). Aborigines with low T4 showed lower levels of free T4 (12.6±0.6 cf. 18.7±1.0 pM), free T4 index (66±8 cf. 98±13), total T3 (1.1±0.2 cf. 1.6±0.3 nmol/1), TBG RIA (140±0.6 cf. 25.0±1.2 ng/1), and TBG Immophase (9.0±0.5 cf. 22.0±1.2 mg/1) (P±0.01), but free T3 (5.3±0.4 cf. 4.7±0.4 pM) and TSH (1.9±0.2 cf. 1.8±0.2 mU/1) were not significantly different from the values found in aborigines with normal T4. Scatchard analysis of T4 and T3 binding was performed using serum diluted 1:20 000 for T4 and 1:500 for T3 (barbitone buffer pH 8.6, 4°C, dextran‐coated charcoal separation). In euthyroid low T4 aborigines compared to those with normal T4, both T4 capacity (106±14 cf. 238±13 nM, P±0.01) and affinity (5–05±1010 cf. 8.47±1010 M−1, P±0.05) were significantly reduced. Similarly, both T3 capacity (62±10 cf. 154±16 nM, P±0.01) and affinity (1.67×109 cf. 2.28×109 M−1, p <0.02) were reduced. A substantial minority of euthyroid Australian aborigines have a TBG variant characterized by both reduced capacity and affinity of T4 and T3. These findings suggest that TBG may be both qualitatively and quantitatively abnormal in these subjects.
ANOMALOUS BINDING CHARACTERISTICS OF HUMAN THYROXINE BINDING GLOBULIN DUE TO A DILUTION‐DEPENDENT SEPARATION ARTEFACT
Authors: STOCKIGT J. R. , LIM C‐F. , TOPLISS D. J. , ARNOTT R. D. , MOHR V. S. , BARLOW J. W.
Published: March 2008

Contrary to the accepted view, a recent study using Sephadex column separation suggested that thyroxine binding globulin (TBG) binds T4 and T3 with similar affinity, but with a much larger capacity for T4 than T3. We have evaluated this finding by comparing this separation method with equilibrium dialysis, taking account of the effect of serum dilution with each method. Estimates of free T4 fraction by equilibrium dialysis (with magnesium chloride precipitation) were valid over a wide range of serum dilutions. In contrast, Sephadex column separation gave a major overestimate of free hormone (underestimate of binding) in less diluted serum, indicating that this method cannot be used to establish a value for T4 affinity independent of serum dilution. Such a systematic error will result in a greater underestimate of affinity for the ligand with higher affinity when two ligands are compared at a single serum dilution. By equilibrium dialysis at 37°C, the affinity of T4 for TBG was ∼13‐fold higher than that of T3, while the capacity of TBG for both T4 and T3 was close to the concentration of immunoreactive TBG. The previous report of similar T4 and T3 affinities appears to be due to a dilution‐dependent underestimate of T4 affinity inherent in Sephadex column separation. Direct comparison of binding kinetics of various ligands requires a separation method that is valid over a wide range of binding protein concentrations.
THE DISTRIBUTION OF OESTRADIOL IN PLASMA IN RELATION TO UTERINE CROSS‐SECTIONAL AREA IN WOMEN WITH POLYCYSTIC OR MULTIFOLLICULAR OVARIES
Authors: POLSON D. W. , FRANKS S. , REED M. J. , CHENG R. W. , ADAMS J. , JAMES V. H. T.
Published: March 2008

The uterine cross‐sectional area (UXA) of women with polycystic (PCO) or multifollicular ovaries (MFO) is significantly larger and smaller, respectively, than those of normal women during the early‐mid‐follicular phase of the menstrual cycle. In the present study the distribution of oestradiol in plasma from normal women and women with PCO or MFO was measured to determine if differences in the available fractions of oestradiol could account for the differences in UXA of women with PCO or MFO. No differences in plasma levels of oestradiol were detected and the concentrations of oestradiol present in a free state or bound to albumin were similar in normal women and women with PCO or MFO. The concentration of oestrone was significantly higher in plasma from women with PCO (516 ± 120 pmo1/1, mean ± SD) than in plasma from women with MFO (389 ± 91 pmo1/1) or normal women (376 ± 89 pmo1/1). Differences in UXA for women with PCO or MFO as compared with normal women cannot therefore be attributed to differences in available oestradiol concentrations. It is possible that abnormalities in oestrogen metabolism within uterine or other tissues may account for the UXA of women with PCO or MFO. Increased plasma oestrone levels in women with PCO may provide more substrate for conversion to oestradiol within the uterus whilst the smaller UXA of women with MFO may reflect both lack of normal cyclical increases of oestradiol and formation of biologically inactive oestradiol metabolites.
RECOVERY OF LUTEAL FUNCTION AFTER INTERRUPTION OF GONADOTROPHIN SECRETION IN THE MID‐LUTEAL PHASE OF THE MENSTRUAL CYCLE
Authors: POLSON D. W. , SAGLE M. , MASON H. D. , KIDDY D. , FRANKS S.
Published: March 2008

Ovulation was induced by a pulsatile infusion of GnRH in a patient with hypogonadotrophic amenorrhoea. In order to investigate the effect of short‐term withdrawal of gonadotrophin support in the luteal phase, the pulsatile infusion was stopped 3 d after ovulation and restarted 48 h later. After stopping the pump gonadotrophin and progesterone concentrations fell rapidly to very low levels, but when the infusion was restarted progesterone concentrations returned to normal mid‐luteal values. Menstruation occurred 14 d after the LH surge. We conclude that normal progesterone secretion by the corpus luteum can be restored after temporary withdrawal of gonadotrophin support.
BETA‐ENDORPHIN INFUSION FAILS TO MODULATE THE HORMONAL AND METABOLIC RESPONSE TO SURGERY
Authors: LACOUMENTA S. , YEO T. H. , BURRIN J. M. , HALL G. M.
Published: March 2008

The effects of an i.v. infusion of synthetic human β‐endorphin on the hormonal, metabolic and cardiovascular responses to surgery were investigated in female patients undergoing pelvic surgery. A β‐endorphin infusion (2 μg/kg as a bolus at induction of anaesthesia + 10 μg/kg/h for the first hour of surgery) increased plasma β‐endorphin immunoreactivity to values at least 100‐fold greater than those seen during surgery in a control group of patients. In spite of this massive increase the only significant findings were a transient augmentation of the expected hyperglycaemic response and increased plasma glucagon values. There were no significant changes in ACTH, GH, insulin and Cortisol secretion, in blood concentrations of lactate or glycerol, or in cardiovascular variables. Complete dissociation between plasma and cerebrospinal fluid concentrations of β‐endorphin was found even when plasma values exceeded 10000 pmol/1 in the presence of anaesthesia and surgery. These results show that the increases in circulating β‐endorphin immunoreactivity associated with clinical stress states are unlikely to modulate the associated hormonal, metabolic and cardiovascular changes.
RESOLUTION OF HYPERGASTRINAEMIA AFTER PARATHYROIDECTOMY IN MULTIPLE ENDOCRINE NEOPLASIA SYNDROME TYPE I (MEN TYPE I)
Authors: MACLEOD A. F. , AYERS B. , YOUNG A. E. , MEDD W. E. , SÖNKSEN P. H.
Published: March 2008

The treatment of choice for gastric acid hypersecretion in MEN type I has now changed from total gastrectomy to the long‐term administration of H2 receptor blockers or similar agents. However, the importance of parathyroidectomy for the concomitant hypercalcaemia is not fully realized. A case is reported of a subject with MEN type I, who was initially treated with parathyroidectomy and H2 receptor blockade. Following parathyroidectomy, there was a rapid fall of the markedly elevated gastrin levels to the upper limit of the normal range. During follow‐up of 2–5 years, there has been no increase in serum gastrin, and the subject's gastric symptoms have resolved, despite the cessation of H2 blockade. Infusion of calcium to pre‐operative levels and superimposed secretin stimulation after this period of time closely reproduced the pre‐operative hypergastrinaemia. On screening, the subject's only child was found to have hypercalcaemia but normal serum gastrin levels and pituitary function; parathyroidectomy has been carried out. No abnormality of gastrin secretion has been found during follow‐up. This case highlights the importance of early parathyroidectomy in this syndrome.
FALSE LOCALIZATION OF AN ALDOSTERONOMA BY DEXAMETHASONE‐SUPPRESSED ADRENAL SCINTIGRAPHY
Authors: HERD G. W. , SEMPLE P. F. , PARKER D. , DAVIDSON J. K. , HILDITCH T. E. , FRASER R.
Published: March 2008

A patient with primary aldosteronism had bilateral adrenal tumours on computed tomography. Selenocholesterol scintigraphy showed uptake by the larger right adrenal gland and a tumour in the gland was also visualized by venography. In contrast, measurements of aldosterone concentrations in adrenal venous blood lateralized to the left side. At surgery the left adrenal gland contained an aldosteronoma and the right adrenal gland a large nonfunctioning adenoma. Thus, selenocholesterol scintigraphy incorrectly localized the functioning adrenal tumour.
CIRCULATING TSH LEVELS MEASURED WITH AN IMMUNOCHEMILUMINOMETRIC ASSAY IN PATIENTS TAKING DRUGS INTERFERING WITH BIOCHEMICAL THYROID STATUS
Authors: EVANS P. J. , WOODHEAD J. S. , WEEKS I. , SCANLON M. F.
Published: March 2008

Serum TSH was measured using a high sensitivity immunochemiluminometric assay (ICMA) in patients receiving anticonvulsant drugs, heparin or nonsteroidal anti‐inflammatory agents (NSAIs) and the results compared with those from groups of age‐ and sex‐matched controls. The TSH results have also been compared with those of estimates of free thyroid hormone levels using Amerlex analogue method reagents. All patients were clinically euthyroid and TSH concentrations were in the normal, euthyroid range and did not differ significantly in any group studied. In contrast, Amerlex free T4 levels were significantly reduced in the patients treated with phenytoin (P < 0001), carbamazepine (P < 001), sodium valproate (P < 001) and heparin (P < 0001). Patients treated with NSAI agents showed no significant change in free T4 levels. Amerlex free T3 levels were also significantly reduced in the patients treated with phenytoin (P < 0–005), carbamazepine (P < 0–005) and heparin (P < 0–001) but not in those treated with sodium valproate or NSAIs. These data support the view that measurement of circulating TSH with an assay of sufficient precision in the relevant range provides a reliable way of assessing thyroid status and could be used to exclude hyperthyroidism in patients taking the medications investigated in this study.
ENDOCRINE ASPECTS OF PITUITARY STALK ENLARGMENT
Authors: PUIG M. L. , WEBB S. M. , DEL POZO C. , de JUAN M. , SERRANO S. , VILARDELL E.
Published: March 2008

Four patients with various endocrine deficiences of a predominantly hypothalamic nature are described, in whom computed topographic scans demonstrated pituitary stalk enlargement. In one, a disseminated papular skin eruption with regional pleomorphism and spontaneous regression appeared 4 years after the development of the initial symptoms of diabetes insipidus, and led to a diagnosis of xanthoma disseminatum, a rare type of histiocytosis. It is suggested that this patient's endocrine dysfunction is also due to histiocytic involvement of the hypothalamus and/or pituitary stalk. In view of the prolonged lapse of time between the initial endocrine manifestations and the eventual diagnosis, even though no cause is apparent in the other three patients, it is suggested that close follow‐up be carried out to rule out such a possibility in patients with this endocrine‐radiological entity.
LITHIUM INHIBITS THE ACTION OF FLUDROCORTISONE ON THE KIDNEY
Authors: STEWART P. M. , GRIEVE J. , NAIRN I. M. , PADFIELD P. L. , EDWARDS C. R. W.
Published: March 2008

A patient with autoimmune Addison's disease treated with hydrocortisone and fludrocortisone became mineralocorticoid‐deficient whilst taking lithium carbonate for a bipolar illness. During an in‐patient metabolic balance study she required 1.0 mg fludrocortisone daily and dietary sodium supplementation to make plasma renin activity and serum potassium normal, and to abolish postural hypotension. We present data to suggest that lithium carbonate inhibits the action of fludrocortisone on the distal renal tubule.
IMMUNOHISTOCHEMICAL STUDY OF CALCITONIN GENE‐RELATED PEPTIDE IN HUMAN MEDULLARY CARCINOMA AND C CELL HYPERPLASIA
Authors: WILLIAMS E. D. , PONDER B. J. , CRAIG R. K.
Published: March 2008

The distribution of calcitonin and calcitonin gene‐related peptide (CGRP) has been studied by immunohistochemistry in normal, hyperplastic and neoplastic C cells. Fewer normal C cells contained immunoreactive CGRP than calcitonin, though both peptides can be co‐expressed by a single cell. In the hyperplastic C cells that accompany familial medullary carcinoma immunohistochemistry was strongly and diffusely positive for both CGRP and calcitonin. In contrast, in medullary carcinoma, whether sporadic or familial, little CGRP was identified; often only a few strongly positive cells were found in a negative background, while immunoreactive calcitonin was commonly present in large amounts. The findings suggest that CGRP immunohistochemistry may be of value in identifying hyperplastic C cells, and that CGRP levels should be studied in medullary carcinoma families.
LONG‐TERM SUPPRESSION OF A TESTOSTERONE‐PRODUCING OVARIAN TUMOUR BY OESTROGEN/PROGESTOGEN THERAPY
Authors: DRIFE J. O. , O'MALLEY B. P. , ROSENTHAL F. D.
Published: March 2008

A 44‐year‐old lady presenting with hirsutism was found to have a testosterone‐secreting Leydig cell tumour of the right ovary. Serum testosterone levels were adequately suppressed for 8 years by combined oestrogen/progestogen preparation (Microgynon 30, Schering, West Sussex). The fall in gonadotrophin and testosterone levels during therapy and their rise after stopping therapy suggests that the tumour was gonadotrophin dependent.
THE IMPACT OF LONG‐TERM THERAPY BY A MULTIDISCIPLINARY TEAM ON THE EDUCATION, OCCUPATION AND MARITAL STATUS OF GROWTH HORMONE DEFICIENT PATIENTS AFTER TERMINATION OF THERAPY
Authors: GALATZER A. , ARAN O. , BEIT‐HALACHMI N. , NOFAR E. , RUBITCHEK J. , PERTZELAN A. , LARON Z.
Published: March 2008

Forty‐two GH deficient patients (14 isolated GH deficiency (IGHD), 28 multiple pituitary hormone deficiencies (MPHD), 23 males and 19 females) were evaluated after termination of hGH therapy and achievement of final height. IGHD patients were found to score higher in intelligence quotients (IQ) than the MPHD patients. The educational and occupational achievements of all patients positively correlated with their IQ level. Three patients achieved only elementary education, 26 completed high school and 13 had higher education. Thirty patients who had completed their education were employed, whereas 12 continued to study. Seventeen of the male patients and five females served in the Army. Eight patients were married and half of the single patients reported having a stable relationship with the opposite sex. The hypopituitary patients did not differ in five out of seven subscales of the human services rehabilitation scale when compared to a normal control group. These results which vary from those previously reported demonstrate the importance of long‐term psychosocial counselling initiated at the time of diagnosis as part of the therapeutic approach in hypopituitary patients.
HYPERPROLACTINAEMIA AND MICROADENOMAS IN PRIMARY HYPOTHYROIDISM
Authors: THOMAS D. J. B. , TOUZEL R. , CHARLESWORTH M. , WASS J. A. H. , BESSER G. M.
Published: March 2008

The presence at presentation of hyperprolactinaemia and abnormalities on high resolution computed tomographic (CT) scanning of the pituitary gland have been documented in 19 patients with primary hypothyroidism. The changes on thyroid hormone replacement were followed for up to 28 months after presentation. At presentation serum PRL was elevated in 12 subjects (454 to 2612 mU/1); after stabilization of thyroid replacement PRL remained raised in 9 patients (525 to 1888 mU/1) despite 10‐18 months of treatment. Pretreatment CT scans showed enlarged pituitaries in 11 patients with suprasellar extension in five. In 11 patients there was initially an area of low attenuation suggesting a microadenoma and on rescanning this appearance remained in five patients. Hyperprolactinaemia in hypothyroid patients does not always return to normal with thyroid hormone replacement.
CONTINUOUS SUBCUTANEOUS PUMP INFUSION OF SOMATOSTATIN ANALOGUE SMS 201‐995 VERSUS SUBCUTANEOUS INJECTION SCHEDULE IN ACROMEGALIC PATIENTS
Authors: CHRISTENSEN S. E. , WEEKE J. , ØRSKOV H. , MØLLER N. , FLYVBJERG A. , HARRIS A. G. , LUND E. , JØRGENSEN J.
Published: March 2008

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 μg/24 h. Subcutaneous injections (33 μg) induced impressive suppression of serum GH lasting 3‐6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 rig/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4‐102 ng/ml) implying either that adequate suppression by the SMS 201‐995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201‐995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201‐995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin‐C immunoreactivity (all patients) decreased from 496 ± 129 (mean ± SD) to 385 ± 100 ng/ml (P < 0 003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 ± 76 ng/ml).
CORRELATION BETWEEN FUNCTION OF THE PITUITARY‐THYROID AXIS AND METABOLISM OF CATECHOLAMINES BY THE FETUS AT DELIVERY
Authors: FUKUDA S.
Published: March 2008

The relationship between the pituitary‐thyroid axis and the metabolism of catecholamines has been studied in 33 maternal, arterial and venous cord blood specimens obtained at the time of normal vaginal delivery, following uncomplicated pregnancies. Ten fetal cord blood samples were collected at the time of elective caesarean section. Levels of noradrenaline and 3,4‐dihydroxyphenyl‐acetic acid (DOPAC) were measured in all these samples, using the high performance liquid chromatography (HPLC)‐electrochemical detection method, and TSH was measured by radioimmunoassay. In cord arterial blood samples at vaginal delivery the levels of plasma noradrenaline and serum TSH were significantly increased, but those of DOPAC, which reflects central dopaminergic activity, were unchanged when compared to samples obtained at elective caesarean section. Within the same samples there was a significant correlation between the levels of plasma noradrenaline and those of serum TSH. Noradrenaline is believed to have a stimulatory and dopamine an inhibitory influence on TSH secretion. The fetal thyroid gland seems to respond adequately to the stimulus of TSH at term. The present study suggests that catecholamines, especially noradrenaline, may regulate secretion of TSH from the pituitary gland in the fetus at delivery and that elevation of TSH probably induces a subsequent rapid increase in thyroid hormones in the neonate.
SUCCESSFUL MANAGEMENT OF CUSHING'S DISEASE DURING PREGNANCY BY TRANSSPHENOIDAL ADENECTOMY
Authors: CASSON I. F. , DAVIS J. C. , JEFFREYS R. V. , SILAS J. H. , WILLIAMS J. , BELCHETZ P. E.
Published: March 2008

Pregnancy in patients with Cushing's syndrome is rare. It is associated with a high fetal loss, increased frequency of preterm labour and excessive maternal morbidity. We describe a patient who became pregnant while investigations for hypertension were being done. Cushing's disease was diagnosed and the patient had transsphenoidal pituitary surgery at 22 weeks gestation. To our knowledge this is the first time this operation has been done during pregnancy for this condition. Cushing's disease was controlled, but because of worsening hypertension, she had a caesarean section at 30 weeks gestation. Subsequently her blood pressure fell and her hydrocortisone replacement therapy is being withdrawn. Her daughter is now thriving after initial problems with pneumothoraces.
DISTINCTIVE FEATURES OF PROLACTIN SECRETION IN ACROMEGALIC PATIENTS WITH HYPERPROLACTINAEMIA
Authors: SERRI O. , ROBERT F. , COMTOIS R. , JILWAN N. , BEAUREGARD H. , HARDY J. , SOMMA M.
Published: March 2008

We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL > 80 ng/ml or > 1600 mU/l), basal plasma PRL and the TRH‐induced response correlated with basal plasma GH (correlation coefficients of 0‐9, P < 0 001 and 0‐74, P <0 02, respectively). The PRL response to TRH also correlated with GH response to TRH (r= 0 38, P <0 01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ ml), and in those with normal plasma PRL (< 20 ng/ml or < 400 mU/1), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.