bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON THE TREATMENT OF IDIOPATHIC GYNAECOMASTIA WITH PERCUTANEOUS DIHYDROTESTOSTERONE
Authors: KUHN J‐M. , ROCA R. , LAUDAT MARIE‐HÉLÈNE , RIEU M. , LUTON J‐P. , BRICAIRE H.
Published: March 2008

We have studied clinical and endocrine parameters in a group (group A) of forty men referred to us because of persistent idiopathic gynaecomastia (of more than 18 months duration), before and during the administration of percutaneous dihydrotestosterone (DHT). The endocrine parameters (testosterone (T), 17 β‐oestradiol (E2), DHT, gonadotrophins (FSH and LH) and prolactin (PRL)), were compared to those of control groups of 12 healthy men on DHT therapy (group B) and 10 on placebo (group C).

Local administration of DHT was followed by the complete disappearance of gynaecomastia in 10 patients, partial regression in 19 and no change in 11 patients after 4 to 20 weeks of percutaneous DHT (125 mg twice daily). Before treatment the T + DHT/E2 ratio was significantly (P < 0.001) lower in group A 244·21 (SEM) than in groups B and C (361·21) while T, DHT and E2 concentrations were all within the normal range. During DHT treatment plasma hormone levels were measured in 26 patients from group A: DHT levels increased significantly (day 0: 1.63 ± 0.14 nmol/1; day 15: 12.8 ± 1.6 nmol/1, P < 0.001) while T and E2 levels fell significantly (T: day 0:22.6 ± 1.2 nmol/1; day 15:11.0 ± 1.5 nmol/1, /)<0.001;E2: day 0: 110.5 ± 7.1 pmol/1; day 15:86.79 ± 9.4 pmol/1, P < 0.01). The T/E2 ratio decreased from 231 ± 20 to 164 ± 27 (P < 0.05) while the T + DHT/E2 ratio increased significantly (P < 0.02) to a normal mean value (day 15: 354 + 57). Identical hormonal changes were observed in group B. Furthermore it was observed that LH plasma levels decreased (day 0: 7.8 ± 1.0 mU/ml; day 10: 4.2 ± 0.8 mU/ml, P < 0.05), while there was no significant variation of hormonal parameters in group C.

Chronic percutaneous DHT administration appears to be an efficient treatment for persistent idiopathic gynaecomastia since it caused a reduction in 29 out of 40 cases. The effectiveness seems to be due principally to systemic effects which include an increase in DHT levels and a decrease in testicular E2 and T secretion following a reduction in LH secretion.
LACK OF RISE IN SERUM PROLACTIN FOLLOWING YTTRIUM‐90 INTERSTITIAL IRRADIATION FOR ACROMEGALY
Authors: CLARK A. J. L. , CHAHAL P. , MASHITER K. , JOPLIN G. F.
Published: March 2008

We have investigated the possibility that the increase in serum PRL levels observed in patients with acromegaly treated with external irradiation could be due to damage to the hypothalamus or portal vessels, by comparing the effects of yttrium‐90 interstitial irradiation, which is highly localised and does not normally extend to the hypothalamus, in a similar series of patients.

Sixteen acromegalic patients treated by interstitial irradiation with yttrium‐90 are described; GH fell from a mean of 131 mU/1 (median 113 mU/1) to 17 mU/1 (median 8 mU/1) after one year (P< 0·001). PRL fell in the five initially hyperprolactinaemic patients (mean fall ± SD: 39 ± 17 μg/1 at one year), but remained unchanged in the normoprolactinaemic group; PRL responsiveness to TRH was retained. Five, out of the seven normoprolactinaemic patients examined, were shown by in vitro studies of their pituitary biopsies, to have tumours that also synthesised or secreted PRL.

These results are consistent with the hypothesis that the rise in PRL following external irradiation is the result of damage to the hypothalamus or portal vessels. A less likely explanation is that an overgrowth of radio‐resistant PRL‐secreting tumour cells is occurring after external irradiation, but not after yttrium‐90 implantation.
INCOMPLETE ANDROGEN INSENSITIVITY SYNDROME: PARTIALLY MASCULINIZED GENITALIA IN TWO PATIENTS WITH ABSENCE OF ANDROGEN RECEPTOR IN CULTURED FIBROBLASTS
Authors: SULTAN C. , PICARD J.‐Y. , JOSSO NATHALIE , MIGEON C. J.
Published: March 2008

In male pseudo‐hermaphroditism due to end organ unresponsiveness, partial androgen insensitivity can usually be related to low but detectable dihydrotestosterone (DHT) binding activity in cultured sexual skin fibroblasts. We have studied two patients with partial virilization and total absence of androgen receptors in cultured fibroblasts. A lack of DHT binding could be related to a selection of a fibroblast strain with no androgen receptor activity, to insufficient sensitivity of the method in detecting very low receptor concentrations or to an instability of the receptor or the androgen‐receptor complex. However, these observations raise the question of masculinization of external genitalia with undetectable androgen receptor.
DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [3H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES
Authors: CHIOVATO L. , HAMMOND L. J. , HANAFUSA T. , PUJOL‐BORRELL R. , DONIACH D. , BOTTAZZO G. F.
Published: March 2008

A new bioassay is described for detecting the growth stimulating immunoglobulins (TGI)* that contribute to goitre formation in human thyroid autoimmune diseases. It measures the incorporation of tritiated thymidine into intact rat thyroid follicles grown in tissue culture. This radiometric assay demands much less technical skill than the cytochemical bioassays (CBA) previously employed. It has good reproducibility and the techniques and apparatus are available in many clinical laboratories.

Immunoglobulins (Igs) from 68% of patients with goitrous GRAVES' disease were positive, in proportion with goitre size, and this showed no correlation with T3 levels, or three accepted methods for conventional thyroid stimulating antibodies. Non‐toxic nodular goitre cases gave positive results in 3/9 who had recurrences after one or more thyroidectomies and in 1/10 cases of familial simple goitre. All normal subjects and all endemic goitre cases were negative as well as 21 cases of sporadic non‐toxic nodular goitre. Although it is less sensitive than the ‘growth CBA’ it clearly emphasizes the essential difference between the intensity of growth stimulus which leads to the regular hyperplasia of thyroid epithelium seen in GRAVES' thyrotoxicosis and the disorganized and metabolically uncoordinated hyperplasia typical of non‐toxic nodular goitre.
EFFECT OF HEPARIN ON SERUM FREE THYROXINE LINKED TO POST‐HEPARIN LIPOLYTIC ACTIVITY
Authors: BAYER MONIKA F.
Published: March 2008

A possible association between free T4 (fT4) changes, occuring after heparin administration, and the post‐heparin lipolytic activity, i.e., the release of lipases and the lipolysis of triglycerides to non‐esterified fatty acids (NEFAs) was studied. In 19 patients heparin increased mean fT4 values obtained by equilibrium dialysis from 23·4 to 38·6 pmol/l (P<0·01) and mean fT4 values measured by GammaCoat two‐step RIA from 17·0 to 24·1 pmol/l (P < 0·01), the results of the two methods agreeing well (rS= 0·88). Concurrently, NEFAs increased from a mean of 0·55 to 2·20 mmol/l (P < 0·01) and fT4 increases were significantly correlated with post‐heparin NEFAs (rS= 0·69, P < 0·001). In vitro addition of palmitic acid to sera increased fT4 concentrations to values similar to those observed in vivo. Post‐heparin fT4 increases were also strongly correlated to the concentrations of triglycerides (rS= 0·63, P < 0·01). Hypertrig‐lyceridaemia was associated with pronounced fT4 increases after heparin administration, and normolipidaemia with moderate or no changes. These results suggest that the effect of heparin on fT4 is linked to the activation of lipases by heparin and is mediated by NEFAs, which, at high concentrations, compete with thyroxine for binding proteins.
HIGH INCIDENCE OF NORMAL THYROID GLAND VOLUME IN PATIENTS WITH GRAVES' DISEASE
Authors: HEGEDÜS L. , HANSEN J. MØCSLHOLM , KARSTRUP S.
Published: March 2008

Thyroid function and thyroid gland volume, ultrasonically determined, were investigated in ninety consecutive untreated patients with GRAVES' disease.

Twenty‐eight patients (31%) had no clinically detectable goitre. Median thyroid gland volume was 31 ml (range 12–99 ml). Twenty‐one patients (23%) had a normal calculated thyroid volume. Thyroid volume did not correlate with any measure of thyroid function. The lack of a goitre in a large portion of patients with GRAVES' disease could be responsible for delayed diagnosis and subsequent treatment of these patients.
AFFINITY OF LIQUORICE DERIVATIVES FOR MINERALOCORTICOID AND GLUCOCORTICOID RECEPTORS
Authors: ARMANINI D. , KARBOWIAK I. , FUNDER J. W.
Published: March 2008

Liquorice abuse causes a syndrome of pseudohyperaldosteronism. Much less commonly, glucocorticoid‐like effects have been reported. The electrolyte‐active principle of liquorice is glycyrrhizic acid (GI), which can be hydrolyzed to glycyrrhetinic acid (GE). Previous studies have reported that GE, but not GI, may occupy mineralocorticoid and glucocorticoid receptors. We here report that both GE and GI can bind to both mineralocorticoid and glucocorticoid receptors. The affinity of GI for mineralocorticoid receptors is four orders of magnitude lower than aldosterone and for glucocorticoid receptors five orders of magnitude lower than dexamethasone. The affinity, though low, is sufficient to explain the mineralocorticoid‐like side effects, given the large amount of liquorice required to produce such a syndrome.
LONG TERM RESULTS OF RADICAL HYPOPHYSECTOMY FOR CUSHING'S DISEASE
Authors: THOMAS J. P. , RICHARDS S. H.
Published: March 2008

Sixteen consecutive cases of Cushing's disease were treated by radical transsphenoidal hypophysectomy. Surgical removal was not possible in two cases. Of the other 14, there was total clinical and biochemical remission of the disease in 13 and partial remission in one. Some form of replacement therapy has been necessary in 11 out of the 14 cases. During a long period of postoperative clinical and biochemical assessment extending over 5–14 years (average 8 years) there have been no recurrences.
EFFECTS OF AMINOGLUTETHIMIDE ON ADRENAL STEROID SECRETION
Authors: VERMEULEN A. , PARIDAENS R. , HEUSON J. C.
Published: March 2008

Effects of various doses of aminoglutethimide (AG) alone upon adrenal steroidogenesis were studied in normal postmenopausal women, whereas the effects of combined treatment with aminoglutethimide in variable doses together with 40 mg of hydrocortisone were studied in postmenopausal women with advanced mammary concer and compared to effects of treatment with cortisol alone. Despite the well known inhibitory effect of AG on cortisol biosynthesis, plasma cortisol levels were unaffected by AG in doses of 150–1000 mg/d, probably due to a compensatory increase in ACTH in subjects with an intact pituitary‐adrenal axis. The aromatase system appeared to be very sensitive to inhibition by AG, a clearcut inhibition being shown at doses as low as 150 mg/d. Evaluated from the ratio of plasma oestrone (E1) to plasma androstenedione (AN), treatment with AG at a dose of 150 mg/d appeared to reduce the aromatase activity to 33% of the basal value; 250 mg/d resulted in a reduction to 20% and 1 g/d to 5% of basal values. Whereas AG at 150 mg/d did not appear to affect 11β‐hydroxylase, the latter was clearly inhibited by 250 mg/d and even more so by 1000 mg/d, as indicated by the increase in plasma 11‐desoxycortisol and 17‐OH progesterone (17‐OHP) levels. Due to the increase of the latter, their biosynthetic precursor, AN and to a lesser degree testosterone (TS) levels increased significantly during AG treatment at a dose of 250 or 1000 mg/d. Δ5 steroid levels remained practically unchanged, probably because 11‐(as well as the 21‐) hydroxylation concerns essentially the Δ4 pathway. During combined treatment with 500–1000 mg/d of AG and cortisol 40 mg/d, AN and TS were significantly higher than during treatment with cortisol alone, suggesting that cortisol had not completely blocked ACTH secretion. E1 and E2 levels were however lower than during treatment with cortisol alone, a consequence of the inhibition of the aromatase activity. Although at a dose of
NELSON'S SYNDROME: INCIDENCE AND PROGNOSIS
Authors: KASPERLIK‐ZAŁUSKA A. A. , NIELUBOWICZ J. , WISŁAWSKI J. , HARTWIG W. , ZAŁUSKA J. , JESKE W. , MIGDALSKA B.
Published: March 2008

Fifty patients bilaterally adrenalectomized for Cushing's disease were followed for 1 to 22 (mean, 12) years. In 14 of them (28%) Nelson's syndrome appeared within 1·5 to 12 (mean, 4·8) years after adrenalectomy. All the patients were deeply pigmented, 12 had a radiologically demonstrable tumour and six had visual defects. Plasma ACTH levels ranged from 450 to 8000 ng/1. However in every case at least one estimation during circadian studies equalled 2000 ng/1. One patient with an anaplastic pituitary tumour died 3 years after the discovery of the tumour. Anaplasia was also diagnosed in another patient with recurrence of pituitary tumour after a transsphenoidal operation. Symptoms of tumour infarction occurred in two patients, followed by clinical remission of Nelson's syndrome. In the majority of cases the course was benign. We conclude that all cases, however, should be followed indefinitely because Nelson's tumours are not infrequently aggressive.
EVIDENCE FOR DOPAMINERGIC CONTROL OF ALDOSTERONE IN MAN
Authors: FRISINA N. , COSTA G. , BUEMI M.
Published: March 2008

The effect of L‐dopa (0·50 g, orally) on serum aldosterone, cortisol and potassium levels, plasma renin activity, and on urinary aldosterone excretion has been studied in normotensive subjects, before and after dexamethasone‐induced ACTH suppression. L‐dopa caused a further reduction in the levels of aldosterone but not cortisol, in the dexamethasone treated subjects. It is therefore suggested that the inhibitory action of L‐dopa on aldosterone secretion is mediated by the dopaminergic system.
NYCTOHEMERAL PATTERN OF SERUM LH, FSH AND PRL IN PATIENTS WITH MYOTONIC DYSTROPHY
Authors: BARRECA T. , ROSSI B. , MAGNANI G. , SARTUCCI F. , ARENA R. , ROLANDI E.
Published: March 2008

The nycotohemeral pattern of serum luteinizing (LH), follicle‐stimulating hormone (FSH) and prolactin (PRL) in eight patients with myotonic dystrophy (MD) was studied. Gonadotropin patterns were classified as adult, pubertal or infantile. Six patients showed an adult pattern, whereas two had a pubertal or infantile pattern. A normal pattern of PRL secretion was found in seven patients and a blunted sleep‐related hormonal increase was observed in one. Impaired hypothalamic control of pituitary secretion in MD is proposed as the cause for these findings.
SUPPRESSIVE EFFECT OF METYRAPONE ON PLASMA CORTICOTROPHIN IMMUNOREACTIVITY IN NORMAL MAN
Authors: SCHÖNESHÖFER M. , FENNER A. , CLAUS M.
Published: March 2008

Short term alterations of plasma corticotrophin immunoreactivity (ACTH) and cortisol were studied in healthy men under basal conditions and during intravenous administration of metyrapone. In the intravenous experiment, a low dose (1 g/5 h) and a high dose (4 g/5 h) of metyrapone ditartrate were infused. In the early phase of the metyrapone experiments, plasma ACTH fell from 9.46 ± 0.95 (se) pmol/l at 08.00 h to 7.7 ± 1.1 pmol/l at 09.00 h (P > 0.05) in the low‐dose experiment, and from 7.0 ± 1.6 pmol/l to 4.6 ± 0.9 pmol/1 (P < 0.05) in the high‐dose experiment. A significant delayed increase of plasma ACTH secondary to the hypocortisolaemic stimulus was apparent in the high‐dose experiment, in which plasma cortisol was maximally suppressed to 14 ± 3 nmol/l at 13.00 h. No significant increase was observed in the low‐dose experiment, the maximal suppression of plasma cortisol being 46 ± 9 nmol/1 at 14.00 h.

The present data suggest dual effects of metyrapone on plasma ACTH: 1) a suppressive effect, the mechanism of which is not yet understood, and 2) the known increasing effect of ‘feed‐back’ stimulation, which seems to be very sensitive to alterations of plasma cortisol only at cortisol levels lower than about 50 nmol/l. The suppressive effect of metyrapone may account for the frequently described inadequate response of plasma ACTH to metyrapone‐induced hypocortisolaemia. Particularly, the diagnostic validity of the very short versions of the metyrapone test would seem to be seriously questioned.
CRITICAL STUDY OF THE GROWTH HORMONE RESPONSE TO DYNAMIC TESTS AND THE INSULIN GROWTH FACTOR ASSAY IN ACROMEGALY AFTER MICROSURGERY
Authors: SCHAISON G. , COUZINET B. , MOATTI N. , PERTUISET B.
Published: March 2008

Eighteen acromegalic patients were studied 8 months to 5 years after transsphenoidal selective adenomectomy in order to evaluate the most reliable criteria for assessing the efficacy of treatment. Dynamic growth hormone (GH) studies were performed after administration of oral glucose (OGTT), thyrotro‐phin‐releasing‐hormone (TRH) or l‐dopa, and after insulin‐induced hypogly‐caemia. Insulin‐like growth factor (IGF) was measured by means of a competitive protein‐binding assay which detects all somatomedins, particularly those which are GH‐dependent.

Of the 18 subjects reported in our study, five showed clinical symptoms of persistent acromegaly. After oral glucose, seven patients had minimum plasma GH levels above 5 ng/ml, five had GH levels between 5 and 2 ng/ml (three of whom maintained a positive GH response to TRH), and six had minimum plasma GH values below 2 ng/ml. Only the latter six patients had normal IGF levels; however, one was still responsive to TRH and three did not increase their GH plasma levels after insulin or l‐dopa administration.

Thus, our data suggest that the criteria used to assess the cure of acromegaly should be more rigorous than those generally applied. When plasma GH levels remain above 2 ng/ml after OGTT, it is doubtful that the cure is complete. A positive GH response to TRH after neurosurgery indicates incomplete removal of the adenoma. The lack of a GH response following insulin‐induced hypoglycaemia and l‐dopa administration suggests that the initial somatotroph dysfunction persists. Finally, high plasma IGF levels point to residual GH overproduction. The definition of cure in acromegaly should involve stricter biochemical criteria than those currently in use.
SINGLE DAILY DOSE SHORT TERM CARBIMAZOLE THERAPY FOR HYPERTHYROID GRAVES’DISEASE
Authors: MACFARLANE I. A. , DAVIES D. , LONGSON D. , SHALET S. M. , BEARDWELL C. G.
Published: March 2008

Twenty‐one patients with hyperthyroid Graves’disease were treated with carbimazole 30 mg daily, given as a single dose. Propranolol was also given for the first 3 weeks. All became clinically euthyroid with normal serum thyroxine (T4) levels, usually within 1–3 months. Patients with large goitres and raised serum alkaline phosphatase concentrations took longer to respond. In 19 patients a positive thyroid stimulating hormone (TSH) response to intravenous thyrotrophin releasing hormone (TRH) developed. Carbimazole was stopped soon after (median time of treatment 18 weeks, range 9–41 weeks) and 18 patients have been followed. Seven of these (39%) have remained in remission from hyperthyroidism for more than one year (median 77 weeks).

Carbimazole 30 mg once daily is a convenient and effective treatment for hyperthyroid Graves’disease. Many patients will achieve prolonged remissions if treatment is stopped when serum T3 and T4 levels are in the low‐normal range, usually 2–4 months after clinical euthyroidism has been reached.
PITUITARY FUNCTION IN PATIENTS WITH EVIDENCE OF SPONTANEOUS DISAPPEARANCE OF A PITUITARY ADENOMA
Authors: LINDHOLM J. , BJERRE P. , RIISHEDE J. , GYLDENSTED C. , HAGEN C.
Published: March 2008

Forty‐four untreated patients with an enlarged sella were studied (excluding patients with acromegaly, Cushing's disease, and those with radiological evidence of suprasellar extension). In 20 patients CT revealed a completely or partially empty sella. Based on recent studies we take this finding to signify the previous presence of a pituitary adenoma which has undergone complete or partial necrosis. Ten of the 20 patients had in fact experienced symptoms typical of a pituitary apoplexy compared with only one out of the other 24 patients. Adrenal, thyroid, and growth‐hormone insufficiency occurred as often in patients with an empty sella as in those with a solid pituitary tumour. In contrast, plasma prolactin levels were much lower in patients with an empty sella than in patients with a solid tumour (11 vs 166 ng/ml). It is assumed that this discrepancy reflects previous necrosis occurring in an adenoma hyper‐secreting prolactin. These results emphasize the importance of taking the spontaneous course of pituitary adenomas into account when assessing the effect of various treatment protocols.
HEPATIC OSTEODYSTROPHY IN PRIMARY BILIARY CIRRHOSIS: A POSSIBLE DEFECT IN KUPFFER CELL MEDIATED CLEAVAGE OF PARATHYROID HORMONE
Authors: ATKINSON M. J. , VIDO I. , KECK E. , HESCH R.‐D.
Published: March 2008

Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25‐hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25‐dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl‐regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl‐regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.
BINDING OF IMMUNOGLOBULIN‐G FROM PATIENTS WITH THYROID AUTOIMMUNE DISEASE TO NORMAL T LYMPHOCYTES
Authors: PACINI F. , SRIDAMA V. , PRESSENDO J. , DEGROOT L. J. , MEDOF M. E.
Published: March 2008

Sera from patients with Graves' disease and Hashimoto's thyroiditis were reacted with normal T lymphocyte preparations in an attempt to detect binding of immunoglobulin G (IgG) to T cells. Sera from normal subjects and patients with toxic adenomas served as controls. Each serum was reacted with at least three different preparations of normal T cells. Bound IgG was identified using a fluoresceinated second antibody, antihuman IgG. Positive cells were enumerated by means of epifluorescent microscopy. IgG from 57·8% of toxic Graves' patients, 30·7% of Graves' patients who were euthyroid after treatment, and 41·6% of Hashimoto's patients bound to normal T cells more than did IgG from normal controls.

Reactivity of toxic adenoma sera was similar to that of normal sera. When the positive sera were reacted with helper or suppressor/cytotoxic T cell preparations (separated by negative selection technique), the binding was shown to be directed against suppressor/cytotoxic T cells but not against helper cells. These data indicate that a significant proportion of patients with autoimmune thyroid disease have IgG in their serum which react with a subset of normal T suppressor/cytotoxic cells. This phenomenon could be the expression of anti‐lymphocyte antibodies, which may relate to previously recognized reductions in number and function of suppressor T cells in autoimmune thyroid disease.
PLASMA AMINE AND HORMONE CHANGES IN ‘POST‐PARTUM BLUEs'
Authors: KUEVI V. , CAUSON R. , DIXSON A. F. , EVERARD D. M. , HALL J. M. , HOLE D. , WHITEHEAD S. A. , WILSON C. A. , WISE J. C. M.
Published: March 2008

The relationship between hormone levels, plasma catecholamines, and mood disturbances has been investigated in 44 patients during days 2 to 5 of the immediate post‐partum period. Fifty‐two per cent of the mothers showed periods of emotional lability although there was no significant correlation between plasma concentrations of FSH, prolactin, oestrone, oestradiol, cortisol, or progesterone and the incidence of post‐partum blues. In contrast there was a significant reduction of circulating catecholamines which correlated with mood disturbances. Women who experienced only a single day of post‐partum blues had significantly lower levels of noradrenaline and adrenaline on that day compared with preceding or subsequent days.
PLASMA SOMATOMEDIN ACTIVITY AND DIABETIC RETINOPATHY
Authors: ASHTON I. K. , DORNAN T. L. , POCOCK A. E. , TURNER R. C. , BRON A. J.
Published: March 2008

Somatomedin activity was measured by a rabbit chondrocyte bioassay in plasma of adult patients with insulin‐dependent diabetes of 11–28 years duration. Mean somatomedin activity in patients with background or proliferative retinopathy, assessed by ophthalmoscopy or fluorescein angiography, was 1·42 ± 0·65 U/ml (n= 20) which was significantly greater than in age‐ and weight‐matched control subjects (1·05 ± 0·22 U/ml, n= 9). In contrast, somatomedin activity was not raised in patients who had no retinopathy (1·16 ± 0·33 U/ml, n= 10).

Diabetic patients with retinopathy also showed the greatest differences between repeat samples suggesting wider fluctuations in plasma somatomedin levels. Plasma growth hormone and glucose measured either simultaneously with somatomedin or during a 12–24 h profile were not different when diabetics with or without retinopathy were compared.

The somatomedins have mitogenic actions in vivo on a variety of connective tissues. The possibility that this may extend to retinal vessels should be further evaluated.
ENDOGENOUS CORTISOL AND THYROID HORMONE LEVELS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: KAHANA LUNA , KEIDAR SHLOMO , SHEINFELD MAXIM , PALANT AVRAHAM
Published: March 2008

Thyroid hormones and cortisol levels were serially measured over seven mornings and evenings in 23 consecutive patients with acute myocardial infarction (AMI) or acute coronary insufficiency (ACI). The patients were divided into two groups, high level cortisol (HLC) and low level cortisol (LLC) groups, according to mean morning and evening cortisol levels. The transient increase in plasma rT3, decrease in T3 and TSH was significantly greater in the HLC group. A diurnal variation in cortisol levels was observed in the LLC group 48 h and in the HLC group 72 h after admission. Taking the 23 patients together, no significant correlation was observed between infarct size (peak CPK levels) and the altered rT3, T4 or TSH levels. However, a significant correlation was obtained between the maximal change in T3, rT3 or TSH and the mean cortisol levels preceding these alterations, as well as between cortisol levels and infarct size. It is suggested that cortisol rather than infarct size may be the dominant factor involved in the alteration of thyroidal levels in AMI patients.
PLASMA IMMUNOREACTIVE β‐ENDORPHIN IS ELEVATED IN URAEMIA
Authors: ARONIN N. , KRIEGER DOROTHY T.
Published: March 2008

Plasma immunoreactive‐(IR) β‐endorphin (β‐EP) and β‐lipotrophin (β‐LPH) levels were measured in 15 adult uraemic patients on chronic haemodialysis. The presence of immunoreactivity eluting in the position of β‐EP was demonstrated following submission of pooled extracts of uraemic plasma to gel permeation chromatography on Sephadex G‐50. To separate β‐EP from β‐LPH, pre‐dialysis plasma extracts from six individual patients, and three pools of three patients each, were submitted to sequential immune‐affinity chromatography and levels were measured by radioimmunoassay. In all cases, plasma IR β‐EP concentrations were markedly increased compared with normal subjects (m± SEM fmol/ml; 64·4 ± 13·7 vs. 2·3 ± 0·2). IR β‐LPH concentrations were also increased (m± SEM fmol/ml; 55·7 ± 13·2 vs. normal 6·1 ± 0·8). In addition, post‐dialysis concentrations of plasma IR β‐EP and β‐LPH were lower than pre‐dialysis levels (n= 4).
TESTICULAR DAMAGE AFTER RADIOACTIVE IODINE (I‐131) THERAPY FOR THYROID CANCER
Authors: HANDELSMAN D. J. , TURTLE J. R.
Published: March 2008

Testicular damage was evaluated in twelve men by determination of sperm counts, serum FSH, LH, and testosterone up to 3½ years after treatment with radioactive iodine (131I) therapy for thyroid cancer. Dose‐dependent spermatogenic damage with elevation of serum FSH was evident. Full recovery in one and partial recovery in another patient was documented during 2½ years of follow‐up. Serial study in two patients documented a small but significant effect of 50 mCi 131I on serum FSH levels and clinically important effects appear to be restricted to men having multiple doses totalling over 100 mCi.
HYPERTHYROIDISM DUE TO A TSH SECRETING PITUITARY ADENOMA: CASE REPORT, TREATMENT AND EVIDENCE FOR ADENOMA TSH BY MORPHOLOGICAL AND CELL CULTURE STUDIES
Authors: MASHITER K. , VAN NOORDEN SUSAN , FAHLBUSCH R. , FILL H. , SKRABAL K.
Published: March 2008

A 36‐year‐old woman with recurrent hyperthyroidism, inappropriately elevated serum TSH, and an 8 mm pituitary microadenoma is described. Transsphenoidal adenomectomy rapidly reduced serum TSH to normal and restored the euthyroid state with retention of other anterior pituitary functions. Tissue removed at operation was examined by light and electron microscopy and cell culture. The tissue was neoplastic, composed of irregular often elongated cells which immunostrained positively only with antisera to β‐TSH. The cells contained small granules (100–170 nm) usually along the cell membrane. In cell culture TSH alone was secreted and the rate of secretion declined with time. We conclude that the patient had a TSH secreting microadenoma as a cause of her hyperthyroidism.
AN EVALUATION OF PLASMA EXCHANGE FOR GRAVES' OPHTHALMOPATHY
Authors: KELLY W. , LONGSON D. , SMITHARD D. , FAWCITT R. , WENSLEY R. , NOBLE JOAN , KEELEY JANE
Published: March 2008

Eighteen patients with ocular manifestations of Graves' disease were treated by plasma exchange. Detailed clinical, ophthalmological and orthoptic assessments were made including computerized axial tomography and A + B scan ultrasound of the orbits. Seventeen different ocular parameters were separately rated for each patient. The changes recorded were small, statistically insignificant, and no patient was cured of ocular disease. There were no significant correlations between the ocular changes recorded and age, sex, duration of ophthalmic symptoms, the presence of thyroid antibodies, the number of exchanges, or the concurrent administration of azathioprine.
BIOASSAY OF THYROID‐STIMULATING IMMUNOGLOBULINS USING HUMAN THYROID CELL CULTURES: OPTIMIZATION AND CLINICAL ASSESSMENT
Authors: BIDEY S. P. , MARSHALL N. J. , EKINS R. P.
Published: March 2008

Primary monolayer cultures of human thyroid cells have been used to investigate the intracellular cyclic AMP response to thyroid‐stimulating immunoglobulins (TSIg) prepared from the sera of patients with Graves' disease. In particular, attention was directed towards dose‐response characteristics obtained under differing incubation conditions, and an optimized incubation procedure based upon conditions consistent with the maximal precision of TSIg measurement was developed.

The magnitude of the cyclic AMP response to a tested TSIg preparation was shown to be greatest after the longest incubation period investigated, 16 h, for all doses of TSIg investigated. The greatest precision of TSIg measurement, as determined by the lowest relative error, was obtained at an immunoglobulin (Ig) dose of 1 mg/ml, and when incubated at this dose level for 16 h, all Ig‐enriched fractions prepared from the sera of 28 newly‐diagnosed patients with Graves' disease significantly (P<0.05) raised the intracellular cyclic AMP level of thyroid cell monolayers. After thionamide drug therapy, the incidence of TSIg detection declined to 42% (5 of 12 patients). TSIg bioactivity was also found in 9 of 14 (64%) patients with euthyroid exophthalmos and in 4 of 11 (36%) cases of non‐toxic goitre. In contrast, Ig's prepared from the sera of normal euthyroid volunteers were devoid of TSIg bioactivity.
EFFECT OF MECLASTINE, A SELECTIVE H1 RECEPTOR ANTAGONIST, UPON ACTH RELEASE
Authors: ALLOLIO B. , DEUSS U. , KAULEN D. , WINKELMANN W.
Published: March 2008

To elucidate further the role of histamine in the control of ACTH secretion we investigated the effect of the selective H1 receptor antagonist meclastine on the ACTH response to insulin hypoglycaemia and to metyrapone‐induced hypocortisolaemia in normal subjects. Intravenous meclastine (4·8 mg/90 min) significantly inhibited the hypoglycaemia‐induced ACTH and Cortisol increase whereas serum GH and PRL concentrations were unaffected. Orally administered meclastine (3 × 2 mg) also reduced the ACTH feedback response to cortisol deficiency in a modified metyrapone test, compared to a placebo. Our findings support the concept of an excitatory influence of histamine upon ACTH secretion via H1 receptors, possibly by stimulation of CRF release.
HYPERTHYROXINAEMIA: ABNORMAL BINDING OF T4 BY AN INHERITED ALBUMIN VARIANT
Authors: LALLOZ M. R. A. , BYFIELD P. G. H. , HIMSWORTH R. L.
Published: March 2008

Two euthyroid subjects with high total concentrations of T4 in their sera have been studied (J.D.: T4, 170; T3, 1·90; rT3, 0·54 nmol/1. E.T.: T4, 185; T3, 1·63; rT3, 0·37 nmol/1). Concentrations of all three T4‐binding proteins were within normal limits in both cases. However, on reverse‐flow electrophoresis an abnormally large amount of thyroxine was found to travel with albumin. The three T4‐binding proteins in the sera of both patients were separated from each other by a novel affinity chromatographic method using dye‐Sepharose conjugates. Affinity constants for T4 binding to TBG and to prealbumin from both patients were normal. The albumin preparations were further purified and shown by physical and immunochemical techniques to be uncontaminated by other proteins. Scatchard plots of the binding of T4 to each of these pure albumins revealed two components, one having a normal affinity constant (J.D., 1·8 ± 105 lmol−1 and E.T., 2·3 × 105 lmol−1), the other having a raised affinity constant (J.D., 5·4 × 106 lmol−6 and E.T., 5·8 × 106 lmol−1). Extrapolation of the plots showed that the high affinity components comprised 66% (J.D.) and 54% (E.T.) of the total purified albumin. The raised affinity and high concentrations of the variants thus account for the raised total T4 concentrations in the patients. The presumed amino acid substitution in the albumins may be different in the two patients since the affinities for rT3 differ. Some methods for the estimation of free T4 levels give misleading results in the presence of these albumin variants. In the course of two episodes of illness, patient J.D. manifested large falls in serum T4 levels which could only be accounted for by reduced carriage of T4 by the abnormal and conventional binding proteins. Many cases reported in the literature as partial peripheral resistance to thyroid hormone may be examples of similar albumin variants.
CORTICOSTEROID MYOPATHY: A CLINICAL AND PATHOLOGICAL STUDY
Authors: KHALEELI A. A. , EDWARDS R. H. T. , GOHIL K. , McPHAIL G. , RENNIE M. J. , ROUND J. , ROSS E. J.
Published: March 2008

In six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24‐h urinary 3‐methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.
STUDIES OF IMMUNOGLOBULIN SYNTHESIS IN CULTURES OF PERIPHERAL T AND B LYMPHOCYTES: REDUCED T‐SUPPRESSOR CELL ACTIVITY IN GRAVES’DISEASE
Authors: PACINI FURIO , DeGROOT LESLIE J.
Published: March 2008

Cellular interactions involved in Graves’disease were studied in patients in different stages of the disease and in normal controls. Synthesis and secretion of immunoglobulin G (IgG) in the supernate of pokeweed mitogen (PWM)‐stimulated cultures of constant numbers of non E rosette forming cells (E− cells) and of increasing numbers of autologous E rosette forming cells (E+ cells) (E+/E− ratios = 1:1, 2:1, 4:1, 8:1, 10:1) were measured by a specific solid‐phase radioimmunoassay. In the normal group, the mean IgG production increased with increasing E+/E‐ ratio (T helper effect), reaching a maximum at a T/B ratio of 4:1, then decreased at higher E+/E− ratios (T suppressor effect). At a E+/E− ratio of 10:1 the IgG synthesis was 39% of the peak value. In the Graves’patients the mean IgG synthesis increased with increasing numbers of E+ cells at every ratio with a peak value found at E+/E− ratio = 10:1. There was no detectable suppressor effect. In three experiments performed with allogeneic combinations of cells, it was observed that the Graves’E− cells were able to respond both to helper and suppressor signals from normal E+ cells, while the Graves’E+ were not able to suppress IgG synthesis by normal E− cells. Treatment of E+ cells with 3,000 cGy of irradiation before adding them to E− cells abolished the suppressor effect seen at the higher E+/E− ratios in the normal controls because of inactivation of the T suppressor lymphocytes. In contrast, the same procedure was without effect on the IgG synthesis by E− cells in Graves’patients. When peripheral blood mononuclear cells (PBMC) were cultured in the presence of PWM and of PWM + Concanavalin‐A (Con‐A), the PWM‐induced synthesis of IgG was suppressed in the presence of Con‐A by 75% (using unfractionated PBMC) and 74% (using E+/E− cells) at 1:1 ratio in normal controls, while Graves’patients’cells caused lower suppression of 66 and 48%, respectively. This latter value was significantly different from that found in the normal group (P < 0·05).
COMPARISON OF PREOPERATIVE AND POSTOPERATIVE ACTH CONCENTRATIONS AFTER BILATERAL ADRENALECTOMY IN CUSHING'S DISEASE
Authors: BARNETT A. H. , LIVESEY J. H. , FRIDAY KAREN , DONALD R. A. , ESPINER E. A.
Published: March 2008

Up to one‐third of subjects who have had bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. To examine the value of pre‐operative ACTH assays in predicting outcome, we have studied fifteen cases of Cushing's disease treated by bilateral adrenalectomy and pituitary irradiation. Three patients developed Nelson's syndrome. There was no significant correlation between preoperative ACTH level, either 8 am ‘basal’or during metyrapone testing, and ACTH concentration post‐treatment. Plasma ACTH concentration in the first year after treatment, however, showed a highly significant correlation with the latest postoperative value (n= 14, r= 0·684, P < 0·01), even more marked when subjects with duration of follow‐up < 3 years were excluded (n= 11, r= 0·836, P < 0·002). In nine of fifteen patients, plasma ACTH showed either no change or a definite fall during subsequent follow‐up. We conclude that plasma ACTH measurement in the first post‐operative year is a good indicator of eventual outcome. The continued fall in plasma ACTH shown in many patients after the first year of treatment suggests an effect of irradiation on the pituitary.
DOPAMINERGIC CONTROL OF GONADOTROPHIN SECRETION IN NORMAL WOMEN AND IN PATIENTS WITH PATHOLOGICAL HYPERPROLACTINAEMIA
Authors: HO K. Y. , SMYTHE G. A. , LAZARUS L.
Published: March 2008

The role of dopaminergic mechanisms in the control of gonadotrophin secretion in normal and hyperprolactinaemic subjects is controversial. Whilst bromocriptine, a potent dopamine agonist, has been used to restore normal gonadotrophin secretion in subjects with pathological hyperprolactinaemia (PHP), dopamine and dopamine agonists have been reported to suppress basal and stimulated gonadotrophin release. We therefore investigated the importance of dopaminergic control of gonadotrophin secretion by studying LH, FSH and PRL responses in normal and PHP subjects to central dopamine synthesis inhibition using monoiodotyrosine (MIT) and to a 4 h dopamine infusion designed to elevate peripheral plasma dopamine concentration to levels reported for pituitary portal plasma (1–6 ng/ml). MIT administration resulted in a significant release of PRL (peak increment 520 ± 84% above basal) but not of LH or FSH in normal subjects. In PHP subjects there was a blunted PRL response (peak 13·3 ± 3·5%) to MIT administration and significant LH (P<0·05) but not FSH release. Dopamine infusion (0·5 μg/kg/min) resulted in suppression of PRL (min 19 ± 3% of basal) but not of LH or FSH. A rebound of PRL (peak 188 ± 68% of basal) but not LH or FSH occurred on cessation of dopamine. There was an apparent rise in LH (P < 0·02 vs. normals) but not FSH in PHP patients during dopamine infusion. Plateau dopamine levels achieved during the infusion were 2·9 ± 0·3 ng/ml and 5·9 ± 0·8 ng/ml in normal and PHP subjects respectively. The responses to MIT show that dopamine functions as an inhibitor of PRL but not of LH or FSH in normal subjects. In PHP patients the responses suggest increased dopaminergic inhibition of LH release but loss of inhibitory control of PRL release. Physiological concentrations of plasma dopamine do not significantly inhibit LH or FSH release in normal subjects but paradoxically results in an apparent release of LH in PHP patients. We conclude that dopamine mechanisms do not play a significant role in modulating gonadotrophin release in normal subjects. In PHP patients, PRL feedback
THE EFFECT OF DYDROGESTERONE ON THE MID‐CYCLE GONADOTROPHIN SURGE IN REGULARLY CYCLING WOMEN
Authors: LENTON ELIZABETH A.
Published: March 2008

The effect of dydrogesterone, a retro‐progesterone on the spontaneous mid‐cycle surge of gonadotrophin in regularly cycling women, was investigated. Blood samples were collected through two complete cycles in six subjects. The first untreated cycle acted as a control for the second cycle during which dydrogesterone (10 mg twice daily) was administered. The start of treatment ranged from day 1 (one subject), mid follicular phase (three subjects) to post‐ovulation (two subjects). In all subjects where dydrogesterone was given before ovulation, the mid‐cycle gonadotrophin surge was either abolished or markedly diminished. Despite this follicular growth occurred in all four subjects and subsequently luteinisation was observed in three. Dydrogesterone given after ovulation did not produce any alteration in endocrine profiles but menses was postponed in both subjects.

Thus dydrogesterone can mimic the known blocking actions of progesterone on the mid‐cycle gonadotrophin surge and can support a secretory fehdometrium for a limited period in the absence of endogenous progesterone.
SCREENING FOR MULTIPLE ENDOCRINE NEOPLASIA SYNDROME (TYPE 1) IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM
Authors: MUHR C. , LJUNGHALL S. , ÅKERSTROM G. , PALMÉR M. , BERGSTRÖM K. , ENOKSSON P. , LUNDQVIST G. , WIDE L.
Published: March 2008

In 63 consecutive patients with primary hyperparathyroidism (HPT) a prospective screening study was undertaken for coexistent multiple endocrine neoplasma‐(MEN)‐syndrome type 1. The screening consisted of a clinical examination, a radiological examination of the sella turcica with skeletal tomography (and in equivocal cases computed tomography), visual field examination by perimetry and a hormonal evaluation including measurements of the serum levels of prolactin, gastrin, pancreatic polypeptide (PP) and subunits of human chorionic gonadotrophin (HCG‐α and β). Clinical examination did not reveal any signs of endocrine disease suggestive of a MEN‐1 syndrome. In only one case there was a radiological abnormality of the sella turcica; this patient had an empty sella syndrome and a raised serum prolactin value. All other prolactin values were within the normal range. In 41% of the patients raised serum gastrin levels were found; these tended to normalize after parathyroidectomy. As a group, patients with raised gastrin values were older than the others and generally they had hypo‐ or achlorhydria. The serum PP levels were raised in 28% of the patients but there was no clinical evidence of a pancreatic tumour in any of these cases, and the serum HCG‐α and β levels were within the normal range in all patients but two. We conclude that the incidence of MEN‐1 syndrome in unselected patients with primary HPT must be low, and that investigations for this syndrome are justified only in HPT patients with specific symptoms or with a positive family history.
PITUITARY RESPONSIVENESS TO GONADOTROPHIN‐RELEASING AND THYROTROPHIN‐RELEASING HORMONES IN EPILEPTIC PATIENTS RECEIVING CARBAMAZEPINE OR PHENYTOIN
Authors: DANA‐HAERI J. , OXLEY J. , RICHENS A.
Published: March 2008

Pituitary responsiveness to gonadotrophin‐releasing (LHRH) and thyrotrophin‐releasing (TRH) hormones was studied in 19 epileptic patients receiving long‐term carbamazepine or phenytoin therapy and 14 normal control subjects. Baseline prolactin levels were normal in the patients; 2 h after LHRH‐TRH the prolactin levels in women on carbamazepine were significantly higher than in the controls, but apart from this, no other differences were found. Baseline LH levels were raised in male patients and the response to LHRH‐TRH was exaggerated in all patients on carbamazepine. FSH levels were normal throughout. The exaggerated LH response is consistent with primary hypogonadism caused by enhanced sex hormone metabolism, secondary to hepatic enzyme induction by the antiepileptic drugs.
A STUDY OF THE RELATIONSHIP BETWEEN CIRCULATING β‐ENDORPHIN‐LIKE IMMUNOREACTIVITY AND POST PARTUM ‘BLUES’
Authors: NEWNHAM J. P. , DENNETT PATRICIA M. , FERRON SUZANNE A. , TOMLIN SUSAN , LEGG C. , BOURNE G. L. , REES LESLEY H.
Published: March 2008

Plasma β‐endorphin‐like immunoreactivity was studied in 43 pregnant women at 36 weeks gestation and in 23 of these at delivery and 24 h post‐partum; an attempt made to correlate changes with various social, psychological and obstetric factors, including the ‘post‐natal blues’. β‐endorphin levels were elevated at 36 weeks gestation and term, increased to very high levels during labour and fell rapidly within 1 h of delivery. A negative correlation was observed between the woman's estimate of her pain in labour and the β‐endorphin levels post‐partum, suggesting an analgesic role for β‐endorphin in labour. A positive correlation was also observed between the levels of β‐endorphin at delivery and the woman's attitude to her pregnancy at 36 weeks and a negative correlation between the ‘post‐natal blues score’ and the β‐endorphin level at 36 weeks. However, the ‘blues’ did not correlate either with the β‐endorphin level at delivery or 24 h post‐partum nor with its rate of fall in the first 24 h. Our general finding that there was no consistent social, psychological or obstetric factor which predisposes women to develop ‘post‐natal blues’ still supports the hypothesis that humoral factors, of which β‐endorphin may be one, rather than psychological factors are important in the genesis of this syndrome.