bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of the insulin tolerance/glucagon test with the short ACTH stimulation test in the assessment of the hypothalamo‐pituitary‐adrenal axis in the early post‐operative period after hypophysectomy
Authors: Mukherjee J. J. , Jacome de Castro J. , Kaltsas G. , Afshar F. , Grossman A. B. , Wass J. A. H. , Besser G. M.
Published: November 2003

OBJECTIVE

The insulin tolerance test (ITT) is the established reference test for assessing the hypothalamo‐pituitary‐adrenal (HPA) axis. Various authorities, however, have suggested that the 250 μg short ACTH stimulation test may be used to assess the HPA axis in place of the ITT in suspected hypopituitarism, although a number of other studies have suggested that the test may be unreliable in this setting. In this study, the ITT (or glucagon test) has been compared with the 250 μg short ACTH stimulation test in patients with pituitary tumours pre‐operatively and within 2 weeks of trans‐sphenoidal hypophysectomy.

DESIGN

An ITT, or a glucagon test when the ITT was contraindicated, and the 250 μg short ACTH stimulation test, were performed in all the patients before (an ITT in 18 and a glucagon test in three patients) and within 2 weeks after trans‐sphenoidal hypophysectomy (an ITT in 16 and a glucagon test in five patients).

PATIENTS

Twenty‐one patients with pituitary disorders (15 with acromegaly, one with a prolactinoma and five with non‐functioning tumours) were studied; four had a microadenoma, two a mesoadenoma and 15 a macroadenoma.

MEASUREMENTS

Serum cortisol was measured by radioimmunoassay. A normal response was defined as a rise in serum cortisol to 580 nmol/l or above for all the tests.

RESULTS

Before surgery, three of 18 patients (17%) had a discrepancy between the ITT and the 30 minute short ACTH stimulation test and one of three between the glucagon test and the 30 minute short ACTH stimulation test. Combined together, pre‐operatively, four of 21 patients (19%) had discrepant results. In the early post‐operative period, the discrepancy between ITT and the 30 minute short ACTH stimulation test was higher with four of 16 patients (25%) showing discordant results; one of the five patients tested had a discrepancy between the glucagon test and the 30 minute short ACTH stimulation test. On combining the tests, the post‐operative discrepancy was five of 21 patients (24%).

CONCLUSIONS

The 250 μg short ACTH stimulation test produces discordant results from the ITT in a clinically significant proportion of affected patients when assessing the HPA axis, although the rate of discordance varies according to the criteria used for normality for both the tests. We suggest that the ITT should remain the preferred test for assessing ACTH secretory capacity compared with the standard 250 μg short ACTH stimulation test, both in the pre‐operative and in the early post‐trans‐sphenoidal hypophysectomy period.
Endocrine outcome in long‐term survivors of low‐grade hypothalamic/chiasmatic glioma
Authors: Collett‐Solberg Paulo F. , Sernyak Heidi , Satin‐Smith Marta , Katz Lorraine L. , Sutton Leslie , Molloy Patricia , Moshang Jr Thomas
Published: November 2003

OBJECTIVE

We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy.

DESIGN

Descriptive retrospective study using case note review analysis.

PATIENTS

The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow‐up was 3.6 years. Thirty‐eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment.

MEASUREMENTS

Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic‐pituitary function.

RESULTS

Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). However, 15 children treated with more than 45 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery.

CONCLUSIONS

Nearly all studies assessing the endocrine outcome after tumour therapy evaluate patients with different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different forms of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.
Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause
Authors: Jódar Esteban , Muñoz‐Torres Manuel , Escobar‐Jiménez Fernando , Quesada‐Charneco Miguel , Castillo Juan D. Luna del
Published: November 2003

OBJECTIVE

The effect of hyperthyroidism on osteoporosis risk and its reversal after control of hyperthyroidism remains somewhat controversial. We assessed the values of bone mineral density in hyperthyroid patients and in former hyperthyroid patients euthyroid on medical therapy, as well as the influence of aetiology and menopause upon bone mass.

DESIGN

The values of bone mineral density in hyperthyroid patients (active) and former hyperthyroid patients euthyroid on medical therapy (controlled), were compared, together with data from our control group and from the Spanish reference population. We also compared the values of bone mineral density in patients with Graves' disease with those in patients with toxic nodular goitre and assessed the influence of the menopause.

PATIENTS

We studied 127 consecutive hyperthyroid patients (age 41  ±  16 years; 110 females, 17 males; 102 Graves' disease and 25 toxic nodular goitre); 78 were active (group A) and 49 controlled on medical therapy (carbimazole, mean time of euthyroidism 7.5  ±  9.1 months; group B). We also studied 43 healthy subjects (age 40  ±  14 years; 41 females, two males; group C).

MEASUREMENTS

Bone mineral density was assessed by dual X‐ray absorptiometry at lumbar spine (L2–L4), femoral neck and Ward's triangle. Data were expressed as g/cm2 and as a Z score (SD vs Spanish reference population adjusted by age and sex). Blood was obtained to measure the levels of free T4, TSH and TSH receptor antibody.

RESULTS

Patients with active hyperthyroidism showed a generalized reduction in axial bone mineral density in comparison with both the control group and the reference population, whereas former hyperthyroid patients showed partial recovery of bone mass in lumbar spine and Ward's triangle. Mean Z scores at lumbar spine, femoral neck and Ward's triangle were: −0.92, −0.79 and −0.89 in group A; −0.74, −0.23 and −0.44 in group B and 0.18, 0.09 and 0.36 in group C, respectively. No differences were found between bone mineral density values from patients with Graves' disease and those with toxic nodular goitre, nor between pre‐ and postmenopausal hyperthyroid women once adjusted by age and sex.

CONCLUSIONS

Our data suggest that hyperthyroid patients show a generalized reduction of bone mass in the axial skeleton and that only partial recovery is present in former hyperthyroid patients after a mean of 7.5 months of biochemical euthyroidism. This recovery is insufficient to normalize the bone density in lumbar spine and Ward's triangle, although femoral bone mass was not different from that of the control group. The extent and degree of hyperthyroid bone disease surpass the effects of the menopause on the bone mass. The aetiology of hyperthyroidism does not seem to play any role in the severity of hyperthyroid bone disease.
Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy
Authors: Mourits Maarten Ph. , Prummel Mark F. , Wiersinga Wilmar M. , Koornneef L.
Published: November 2003

OBJECTIVE

Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double‐blind, prospective study.

DESIGN, PATIENTS AND MEASUREMENTS

The CAS was determined by an ophthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade.

RESULTS

Responders (22) and non‐responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non‐responders. Twelve of 22 responders and three of 21 non‐responders had a CAS  ≥  4 (80% vs 36%; P  <  0.01). Using this CAS cut‐off point, the accuracy of CAS in predicting the therapeutic outcome was: specificity 86%, sensitivity 55%, positive predictive value 80%, negative predictive value 64%. Patients with a CAS  ≥  4 had a similar duration of Graves' ophthalmopathy as patients with a CAS  <  4.

CONCLUSIONS

The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.
Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy
Authors: Hardie Laura , Trayhurn Paul , Abramovich David , Fowler Paul
Published: November 2003

OBJECTIVE

To investigate whether leptin is linked to reproduction, circulating levels were measured longitudinally throughout spontaneous menstrual cycles and during pregnancy in normal women.

DESIGN

Longitudinal blood samples were collected from normal volunteers, either during regular menstrual cycles or during successful singleton pregnancies.

PATIENTS

Six healthy, regularly cycling, women volunteers (31.5 ± 3.0 years old, BMI = 21.6 + 0.5) were recruited for serial venous blood sampling throughout one complete menstrual cycle. In addition, five healthy, women (31.8 ± 1.2 years old, pre‐pregnant BMI = 30.0 ± 3.1) provided serial venous blood samples throughout one complete singleton pregnancy.

MEASUREMENTS

Circulating venous oestradiol, progesterone, luteinizing hormone (LH), follicle‐stimulating hormone (FSH), leptin and (pregnant group only) human chorionic gonadotrophin (hCG).

RESULTS

In spontaneously cycling women, changes in circulating leptin levels were associated with menstrual phase (P < 0.001) and correlated with progesterone levels (P < 0.05). Peak leptin concentrations were recorded during the luteal phase (P < 0.01), coincident with maximal progesterone levels (P < 0.05). Leptin concentrations were elevated throughout gestation (P < 0.05), and especially during the second trimester (P < 0.05). Post‐partum, circulating leptin levels fell sharply to below pre‐pregnant values. Leptin correlated with oestradiol (P < 0.05) and human chorionic gonadotrophin (hCG, P < 0.01) levels during pregnancy. First trimester (P < 0.05) and postpartum (P < 0.05) oestradiol concentrations and post‐partum hCG levels exhibited the greatest correlation with circulating leptin.

CONCLUSIONS

We conclude that the relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. This, together with the correlation between circulating oestradiol, hCG and leptin levels during pregnancy, strongly suggests a dynamic relationship between leptin and reproductive events in women.
Thyroid function in very low birth weight infants
Authors: Klein R. Z. , Carlton E. L. , Faix J. D. , Frank J. E. , Hermos R. J. , Mullaney D. , Nelson J. C. , Rojas D. A. , Mitchell M. L.
Published: November 2003

OBJECTIVES

The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof.

DESIGN

Cross‐sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2‐ and 4‐week blood specimens from VLBW infants.

PATIENTS

Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing  2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995–96 in 19 VLBW infants and 21 full term infants (Cohort B).

MEASUREMENTS

T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2‐ and 4‐week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated.

RESULTS

(1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 ± 111 vs 680 ± 172 nmol/l (P < 0.0005). T4 concentrations were 76 ± 22 vs 139 ± 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37–113 pmol/l and T4 concentrations of 13–48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested.

CONCLUSIONS

Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the ‘sick euthyroid syndrome’.
Increased incidence of neoplasia in females with acromegaly
Authors: Cheung N. W. , Boyages S. C.
Published: November 2003

OBJECTIVE

Some studies have indicated an increased incidence of neoplasia, particularly breast and colon, in acromegaly. We have determined the incidence of benign and malignant neoplasms in an Australian population of patients with acromegaly.

DESIGN

Retrospective review, with comparison against cancer data for the local population obtained from a State Cancer Registry.

PATIENTS

Fifty patients with documented acromegaly.

RESULTS

There were 7 cases of malignancy (2 in men, 5 in women) in the period of follow‐up (435 patient years). With logistic regression analysis, there was a relative risk of malignancy, of 1.2 (95% confidence interval 0.31–5.0) for men (P = 0.8) and 4.3 (95% confidence interval 1.7–10.5) for women (P= 0.001), when compared to the local population. There were 2 cases of breast and renal carcinoma, and one each of prostatic, colonic and parotid carcinoma. Of the most common benign tumours 35% of patients had thyroid nodules, 10% had colonic polyps and 6% had nasal polyps.

CONCLUSION

The incidence of malignancy was found to be increased in female patients with acromegaly in this series. Routine screening procedures for malignancy, particularly in female patients, should therefore be considered.
Expression of growth hormone receptor by peripheral blood lymphocytes in children: evaluation in clinical conditions of impaired growth
Authors: Valerio G. , Bond H. M. , Badolato R. , Petrella A. , Di Maio S. , Salerno M. , Waters M. J. , Venuta S. , Tenore A.
Published: November 2003

OBJECTIVE

It is widely accepted that the haematopoietic system is a target of growth hormone action and that GH may act as a lymphokine. The expression of GH receptors (GHR) on human peripheral blood lymphocytes (PBL) has been reported previously in adult donors by dual fluorochrome flow cytometry. The aim of this study was to apply the cytofluorimetric method to the analysis of GHR expression on PBL in various human conditions characterized by different patterns of growth due to age or physiophathological conditions.

SUBJECTS AND DESIGN

PBL from 38 normal (control) subjects (7 newborns, 18 prepubertal children, 13 adults) were studied in order to provide age‐related physiological data. Twenty‐two short children (18 with idiopathic short stature, 4 with Ullrich–Turner syndrome) were studied to determine the expression of GHR in conditions of impaired longitudinal growth which may or may not require GH treatment.

METHODS

Analysis was performed using a fluorescein isothiocyanate (FITC)‐conjugated antibody specific for the GHR (mAb263) and phycoerythrin (PE)‐anti CD2 (T and natural killer cells) or PE‐anti CD20 (B cells) in dual fluorochrome flow cytometric assays. Results were expressed as mean fluorescent intensity (MFI).

RESULTS

Adult CD2+ cells exhibited a significantly higher GHR expression (MFI 347 ± 40) than that expressed in children and newborns (MFI 285 ± 36 and 299 ± 41, respectively, P < 0.001). A significantly increased expression of GHR on CD2+ cells was also found in short children (MFI 330 ± 42 vs 285 ± 36, respectively; P < 0.002), whereas Ullrich–Turner syndrome patients did not show any difference from their age and gender matched controls (254 ± 52 and 288 ± 40, respectively). A negative relationship was found between GHR expression on CD2+ cells and height‐SDS (r−0.54, P < 0.0001) or BMI (r−0.4, P < 0.015) in controls and short children, independent of their GH secretory status. Expression of GHR and CD20+ cells was higher than that expressed on CD2+ cells in all subjects. No appreciable differences were found in the MFI levels of GHR expression on CD20+ cells either among the different age group controls or between short children or Ullrich–Turner syndrome patients. A significant downregulation of GHR expression was shown in CD20+ (P < 0.008) but not CD2+ cells after 6 months of GH treatment in 6 short children who had a poor response to GH provocative tests.

CONCLUSIONS

GH receptor expression on immune cells in non‐syndromic short children appears to be inversely related to the linear growth expression and BMI of the subjects, contrary to findings with hepatic derived serum GHBP. This finding may reflect alternate exon usage in lymphoid cells, and indicates that GH has a distinctive role in the immune system.
Hypothalamic adipsic syndrome: diagnosis and management
Authors: Ball S. G. , Vaidja B. , Baylis P. H.
Published: November 2003

Patients with hypothalamic adipsic syndrome, especially in conjunction with diabetes insipidus, pose management difficulties. They are at risk of both under‐ and over‐hydration. We present 4 patients with hypothalamic adipsic syndromes, due to different causes, illustrating the practical difficulties encountered in this condition. The principles of management, with a sliding scale of water intake related to changes in daily body weight, are discussed.
Adrenal adenoma with bilateral adrenocortical nodular change in a patient with Cushing's syndrome
Authors: Iino Kazumi , Sasano Hironobu , Nagura Hiroshi , Watanabe Fumie , Iwabuchi Masayasu , Ozawa Magumi , Oki Yutaka , Yoshimi Teruya
Published: November 2003

We report a 57‐year‐old male patient with adrenocorticotrophin (ACTH)‐independent Cushing's syndrome and long‐standing hypertension. Both abdominal computed tomographic scan and magnetic resonance imaging revealed bilateral adrenal enlargement with the presence of a tumour in the left adrenal. Marked uptake of 131I‐6β‐iodomethyl‐19‐norcholesterol was observed only in the left adrenal gland. Left adrenalectomy and biopsy of the right adrenal gland were subsequently performed. Histological examination revealed the presence of an adrenocortical adenoma in the left adrenal with multiple adrenocortical nodules in both left and right non‐neoplastic adrenals. Peri‐ and intraadrenal arteries and arterioles demonstrated marked arteriosclerotic vascular changes. Immunoreactivity for several steroidogenic enzymes was present in the tumour and markedly diminished in the non‐neoplastic adrenals. This patient with Cushing's adenoma is considered to have developed adrenocortical nodules in the non‐neoplastic adrenal possibly as a result of localized compensatory overgrowth of adrenocortical cells in response to ischaemic changes due to arteriopathy. When examining patients with Cushing's syndrome and bilateral adrenal enlargement, the possibility of concomitant adenoma and adrenocortical nodule formation should also be considered in the differential diagnosis.
Psychological distress in patients with hyperprolactinaemia
Authors: Reavley Saffron , Fisher Alison D. , Owen David , Creed Francis H. , Davis Julian R. E.
Published: November 2003

OBJECTIVE

In addition to the physical symptoms of galactorrhoea and amenorrhoea, hyperprolactinaemia in women is also reported to be associated with psychological symptoms. Previous studies have found an increased incidence of depression, anxiety and hostility in female patients with hyperprolactinaemia. In this study, psychological symptoms were assessed in a large population of patients and symptom scores were compared between patients with definite evidence of pituitary adenoma on high‐resolution CT scanning and those without, who were presumed to have idiopathic or ‘functional’ hyperprolactinaemia.

DESIGN

Postal survey: population–control study of female patients with hyperprolactinaemia.

PATIENTS

Sixty‐five women with hyperprolactinaemia were compared with a control group of 26 women with normoprolactinaemic pituitary disease (acromegaly or nonfunctioning pituitary adenoma). The hyperprolactinaemic patients were subdivided according to whether a pituitary adenoma was visible on high‐resolution CT scanning (39 patients) or whether they had normal CT scans, in which case they were categorized as having idiopathic or ‘functional’ hyperprolactinaemia (26 patients).

MEASUREMENTS

Patients were sent 2 questionnaires, the Hospital Anxiety and Depression (HAD) Scale and the 90‐item Symptom Checklist (SCL‐90), to assess psychological wellbeing.

RESULTS

Overall, 54% of hyperprolactinaemic patients were found to have definite or borderline anxiety as judged by HAD scores, compared with 27% of normoprolactinaemic control patients. Those with normal CT scans were significantly more likely to have definite or borderline anxiety (73% of patients) than those with CT evidence of a pituitary tumour causing their hyperprolactinaemia (41%, P  <  0.003), despite similar levels of serum prolactin. A similar increased proportion of hyperprolactinaemic patients scored highly on the anxiety component of the SCL‐90, although mean scores were not different from controls. No differences were seen in scores for depression, but both subgroups of hyperprolactinaemic patients scored more highly than controls for hostility on the SCL‐90 questionnaire.

CONCLUSION

These findings confirm the presence of significant anxiety in a proportion of women with hyperprolactinaemia. Hyperprolactinaemic women with no abnormality on CT scans displayed more psychological distress than those with definite pituitary microadenomas. These results may provide insight into the pathogenesis of ‘functional’ hyperprolactinaemia.
Effects of excess iodine administration on thyroid function in euthyroid patients with a previous episode of thyroid dysfunction induced by interferon‐alpha treatment
Authors: Minelli Roberta , Braverman Lewis E. , Giuberti Tiziana , Schianchi Claudia , Gardini Eliana , Salvi Mario , Fiaccadori Franco , Ugolotti Giorgio , Roti Elio
Published: November 2003

OBJECTIVE

To determine the effects of pharmacological quantities of iodide (SSKI) on thyroid function in euthyroid patients previously treated with recombinant interferon‐alpha (rIFN‐α) for chronic viral hepatitis B and C (HCV), a cytokine which may induce thyroid dysfunction.

DESIGN

Thyroid function tests were carried out in 16 euthyroid patients, 8 of whom had previously developed thyroid dysfunction during rIFN‐α therapy for HCV, before, during and after the administration of 10 drops of saturated solution of potassium iodide (SSKI) (∼350 mg iodide).

PATIENTS

All 16 patients had been treated in the past with rIFN‐α for HCV. Eight patients had developed rIFN‐α induced abnormalities in thyroid function (5 inflammatory thyrotoxicosis, 1 Graves' disease, and 2 impaired thyroid organification of iodide) and 8 had not developed thyroid dysfunction.

MEASUREMENTS

After baseline serum free T4 (FT4) and free T3 (FT3) concentrations, basal and TRH stimulated TSH concentrations, and TSH‐receptor (TSH‐R‐Ab) and thyroid peroxidase (TPO‐Ab) antibodies were measured, 10 drops saturated solution of potassium iodide (SSKI, ∼350 mg iodide) were given daily for 60 days and the above parameters assessed during and after SSKI was discontinued.

RESULTS

Five of 8 patients with a previous history of rIFN‐α induced thyroid dysfunction developed mild iodide induced abnormalities of thyroid function (subclinical hypothyroidism (slightly elevated basal and TRH stimulated serum TSH concentrations with normal serum FT4 and FT3 concentrations) or hyperthyroidism) compared with the 8 patients who had no previous evidence of thyroid dysfunction during rIFN‐α therapy.

CONCLUSIONS

In view of the present observations, it is prudent to avoid the administration of excess iodine to euthyroid subjects with a previous episode of thyroid dysfunction during rIFN‐α therapy, adding a new group of patients susceptible to iodine induced thyroid disease.
Does growth hormone treatment increase chromosomal abnormalities?
Authors: Bozzola Mauro , Tettoni Katia , Severi Francesca , Capra Elena , Danesino Cesare , Scappaticci Susi
Published: November 2003

OBJECTIVE

The relationship between growth hormone (GH) therapy and malignancy, including leukaemias, remains controversial. In order to study this possible relationship further, we have investigated whether GH treatment induces chromosomal abnormalities in peripheral blood lymphocytes.

DESIGN

Open, prospective study in a University Hospital to examine peripheral blood mononuclear cells in subjects with GH‐deficiency (GHD) before and during GH treatment.

SUBJECTS

Twelve idiopathic GHD patients, aged 1.8–12.5 years, were evaluated before and after 3, 6 and 12 months of GH therapy (0.6 IU/kg per week subcutaneously). Two additional GHD patients, aged 16.6 and 18 years, were studied 1 year after long‐term GH therapy had been discontinued, and 12 age‐matched healthy subjects were evaluated as controls.

METHODS

We examined the incidence of chromosome and chromatid breaks, fragments, structural rearrangements and aneuploidies in 100 metaphases for each blood sample. A total of 5300 cells was analysed in the 14 patients.

RESULTS

The proportion of cells with chromatid and chromosome breaks ranged from 0% to 6% in patients before treatment and from 1% to 5% in controls. During GH therapy the incidence of aneuploid metaphases ranged from 0% to 7% and was comparable with values observed in controls. Chromosomal loss and gain was random.

CONCLUSIONS

We observed no increase in chromosomal abnormalities in GH‐treated patients when compared with age‐matched healthy controls.
Pheochromocytoma due to unilateral adrenal medullary hyperplasia
Authors: Qupty Ghali , Ishay Avraham , Peretz Hava , Dharan Muralee , Kaufman Nathan , Luboshitzky Rafael
Published: November 2003

We describe two male patients, aged 17 and 47 years, with clinical and biochemical features of pheochromocytoma. Both patients had normal‐sized adrenal glands on abdominal CT scan and abnormal unilateral uptake of I‐123 metaiodobenzylguanidine (MIBG) on scintigraphy. The surgical adrenalectomy revealed normal macroscopic glands in both patients. Histological examination showed adrenal medullary hyperplasia with adrenal cortico‐medullary ratios of 2 : 1 and 4 : 1. Unilateral adrenalectomy resulted in amelioration of symptoms and normalization of catecholamines excretion. DNA examination for RET proto‐oncogene revealed no mutations in exons 10, 11, 13, 14 and 16. Our results suggest that diffuse adrenal medullary hyperplasia may be the initial pathological change in the adrenal gland leading, subsequently, to the development of nodular hyperplasia and adrenal medullary tumor. These results indicate that the syndrome of pheochromocytoma may occur as an unilateral adrenal medullary hyperplasia in patients without evidence for multiple endocrine neoplasia.
Analysis of the retinoblastoma tumour suppressor gene in pancreatic endocrine tumours
Authors: Chung Daniel C. , Smith Alison P. , Louis David N. , Graeme‐Cook Fiona , Warshaw Andrew L. , Arnold Andrew
Published: November 2003

OBJECTIVES

The molecular pathogenesis of human pancreatic endocrine tumours (PETs) is largely unknown. One attractive candidate gene for involvement in pancreatic endocrine neoplasia is the retinoblastoma (Rb) tumour suppressor gene. A deletion of the Rb gene was recently described in a human insulinoma. In addition, mice harbouring a null mutation in the Rb gene bred with p53 mutant mice develop pancreatic endocrine tumours. Therefore, we sought to determine the role that allelic loss of Rb may play in a large series of human pancreatic endocrine tumours.

PATIENTS AND MEASUREMENTS

46 pancreatic endocrine tumours were obtained from 41 patients. Utilizing genomic DNA isolated from the tumour samples and control normal cells, 2 highly polymorphic microsatellite loci (D13S153 and Rb 1.20) located within the Rb gene were PCR amplified and examined for loss of heterozygosity.

RESULTS

2 patients were homozygous at both loci and thus uninformative. The remaining 39 had informative markers at one or both of these loci, and none of the tumours from these patients demonstrated allelic loss of Rb.

CONCLUSIONS

In tumours in which Rb inactivation is pathogenetically important, somatic loss of one Rb allele commonly accompanies a point mutation or microdeletion within the other allele. Thus, the absence of demonstrable allelic loss in this large series strongly suggests that Rb gene inactivation is not frequently involved in the pathogenesis of human pancreatic endocrine tumours.
Abnormal pulsatile secretion of growth hormone in non‐insulin‐dependent diabetes mellitus
Authors: Franek E. , Schaefer F. , Bergis K. , Feneberg R. , Ritz E.
Published: November 2003

OBJECTIVE

Studies of GH secretion in patients with non‐insulin dependent diabetes mellitus (NIDDM) have produced conflicting results. We aimed to differentiate the effects of obesity and metabolic control on pulsatile GH secretion in patients with NIDDM.

DESIGN

Blood sampling every 15 min from 22.00 hours to 08.00 hours after a fasting period of at least 3 h. Patients: 13 male NIDDM patients, 9 healthy control subjects matched for age and BMI, and 6 lean subjects matched for age.

MEASUREMENTS

Measurement of GH by a novel ultrasensitive chemiluminescence assay. Analysis of concentration vs time profiles by a multiparameter deconvolution technique.

RESULTS

GH burst frequency was increased in the NIDDM (0.82 ± 0.28 h−1) compared with both control groups (lean: 0.6 ± 0.11; obese: 0.56 ± 0.19). GH burst mass was decreased in patients (1.57 ± 0.98 μg/l.min) and in obese controls (1.46 ± 1.44) compared to lean controls (3.71 ± 3.88). These differences resulted in a significantly higher nocturnal pulsatile GH secretion rate in the lean compared to the obese controls, whereas in the patient group enhanced GH burst frequency compensated for reduced burst mass. The characteristics of GH secretion were not related to nocturnal or early morning blood glucose concentrations. However, GH secretion rate was correlated positively with HbA1c (r = 0.57; P = 0.04), and negatively with plasma C peptide concentrations.

CONCLUSIONS

The specific increase in GH burst frequency previously described in insulin‐dependent diabetes mellitus is also present in NIDDM. However, GH hypersecretion does not occur because GH burst mass is reduced in proportion to the degree of obesity. The effect of diabetes on the hypothalamic control of GH release appears to be determined by the quality of long‐term glycaemic control.
Immunoreactive endothelin in nodular pathology of the thyroid
Authors: Foppiani Luca , Porcella Ena , Micaela Cuttica Carla , Fazzuoli Laura , Valenti Sandra , Giordano Giulio , Giusti Massimo
Published: November 2003

OBJECTIVES

Endothelins (ETs) can act as autocrine and/or paracrine regulators of thyroid homeostasis and growth. The aim of this study was to evaluate immunoreactive ET (i‐ET) levels in a group of patients with nodular pathology of the thyroid and to correlate them with the cytomorphological features after fine‐needle aspiration (FNA) and with hormonal and immunological status and blood pressure levels.

DESIGN

Plasma and cystic i‐ET were assayed in a group of patients with varying thyroid function, who underwent FNA for solid and cystic nodular pathology.

PATIENTS

47 patients (32–81 years) with nodular pathology of the thyroid and 18 controls (28–70 years) with normal thyroid function and morphology were studied.

MEASUREMENTS

Fasting venous blood samples were collected and the plasma for i‐ET was frozen at −80°C until assayed. Sera were frozen at −20°C for FT3, FT4, TSH, TPO autoantibodies and thyroglobulin autoantibodies assay. Cystic fluid was obtained by FNA, centrifuged, and the supernatant was stored at −20°C until i‐ET assay. FNA cytology was examined by light microscopy.

RESULTS

In patients with cystic nodules, plasma i‐ET levels were significantly (P = 0.002) higher (5.7 ± 1.1 ng/l, ± SEM) than in both patients with solid nodules (2.6 ± 0.4 ng/l) and (P = 0.02) controls (3.0 ± 0.3 ng/l). In patients with cystic nodules, cystic i‐ET levels (12.6 ± 1.9 ng/l) were significantly (P = 0.003) higher than plasma levels (5.7 ± 1.1 ng/l) and did not correlate with the percentage of FNA cellularity. i‐ET levels in cystic fluid (12.6 ± 1.9 ng/l) were significantly (P = 0.0001) higher than plasma i‐ET levels in both patients with solid nodules and controls. No difference in either plasma or cystic i‐ET levels was found in patients with cystic nodules in relation to differences in thyroid function. No difference in plasma i‐ET levels was found between patients with solid nodules and controls. In controls, no significant difference in plasma i‐ET levels was found between males and females. A negative correlation (r  = −0.55, P = 0.02) was found between cystic i‐ET levels and systolic and diastolic blood pressure. No correlation between cystic or plasma i‐ET levels and FT3, FT4 or TSH was found in any of the subjects studied.

CONCLUSIONS

It seems that endothelins do not possess a primary role in determining thyroid function and that the increased levels in cystic fluid found in our subjects could be secondary to cystic nodule development.
Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro
Authors: Arlt W. , Dahia P.L.M. , Callies F. , Nordmeyer J.P. , Allolio B. , Grossman A.B. , Reincke M.
Published: November 2003

A desmopressin‐induced ACTH increase has been recently suggested to be specific for pituitary‐dependent Cushing's disease. We present the case of a 47‐year‐old woman with Cushing's syndrome due to ectopic ACTH production by a bronchial carcinoid. While CRH failed to induce an ACTH or cortisol response, intravenous administration of desmopressin led to a 47% increase in serum ACTH and a 42% increase in serum cortisol concentration. After surgical removal of the tumour, the desmopressin response became negative. In vitro, ACTH production by tumour cells obtained at surgery was also stimulated by desmopressin but not by CRH. Additional receptor mRNA expression studies using RT‐PCR revealed expression of both V2 and V3 vasopressin receptor subtypes in the carcinoid tumour at a level comparable to that recently described in pituitary corticotroph adenomas. This case illustrates that ACTH stimulation by desmopressin is not specific for pituitary‐dependent Cushing's syndrome as vasopressin receptor subtypes known to interact with desmopressin may also be found in ectopic tumours producing ACTH.
Prepubertal and pubertal growth, timing and duration of puberty and attained adult height in patients with congenital hypothyroidism (CH) detected by the neonatal screening programme for CH — a longitudinal study
Authors: Dickerman Zvi , De Vries Liat
Published: November 2003

OBJECTIVE

We have evaluated parameters of growth, the pubertal process and attained adult height in patients with congenital hypothyroidism (CH) of various aetiologies, diagnosed by the neonatal screening programme, and followed up longitudinally. To the best of our knowledge, no such data are available in the published literature. Our aim was to define the most important factors affecting these parameters.

PATIENTS AND MEASUREMENTS

Thirty patients with CH (20 females and 10 males) diagnosed by neonatal screening (dysgenetic (n = 15), ectopic thyroid (n = 11), and enzymatic defect (n = 4)), treated with levo‐thyroxine (L − T4) since the age of ≤ 4 months, and followed up at intervals of 1–6 months for a mean period of 11.4 (range 5–19.6) years were evaluated.

Detailed anthropometric measurements were performed by the same trained nurse, and pubertal stages were evaluated according to Tanner's criteria for breast or genitalia and pubic hair. Serum T4 and TSH levels were measured at each clinic visit using commercial kits. Bone age (BA) was determined at 6–12 month intervals using the Greulich & Pyle method. Seventeen patients attained adult height at the time of the report.

RESULTS

Mean L − T4 dose of 7.9 (range 5.2–14.0) to 2.4 (range 1.3–3.4) μg/kg/day at various ages corrected the serum free T4 (f‐T4) levels to normal (> 10 pmol/l) in 95% of determinations, and the TSH level was reduced to < 10 mIU/l in 54% of the determinations during the follow‐up period. Length at initiation of therapy (mean −0.15, (range −2.5–2.1) SDS), height at onset of puberty (mean −0.4, (range −1.8–1.8) SDS) and adult height (mean 0.2 (range −1.4–2.0) SDS, n = 17) were within the normal range (0.00 ± 2 SDS). Onset and duration of puberty were normal in both sexes, and total pubertal growth contributed 19.1% (M) and 16.4% (F) to adult height. Peak height velocity (mean 10.6 (range 7.3–15.1) (M) and mean 8.0 (range 6.2–15.5) (F) cm/year) was within the normal range and occurred at the expected BA (14y;M and 12y; F). The attained average adult height was in close proximity to the average target height in both males and females. A significant positive correlation was found between the average L − T4 daily dose administered during the first 6 months of treatment and the attained adult height.

CONCLUSIONS

Early detection by neonatal screening and treatment of congenital hypothyroidism enables normal prepubertal and pubertal growth and achievement of normal adult height, following normal puberty. Adult height in congenital hypothyroidism is significantly correlated with parental height and the mean L − T4 daily dose administered over the first 6 months of treatment. A dose of at least 8.5μg/kg/day is recommended during this period. Periodical adjustments of L − T4 daily dose should be guided by clinical observation and serum free T4 levels.
Demonstration of fragments with thyroid stimulating activity from Thyroid stimulation blocking antibodies‐IgG molecules by papain digestion
Authors: Kouki Tsuyoshi , Inui Takehiro , Yamashiro Kei , Hachiya Takashi , Ochi Yukio , Kajita Yoshihiro , Takasu Nobuyuki , Sato Yasushi , Nagata Atsuo
Published: November 2003

OBJECTIVES

Thyroid stimulation blocking antibodies (TSBAb) inhibit TSH action and may have a role in the pathogenesis of hypothyroidism. In order to study the relationship between blocking and stimulating activities we have examined the biologically active fragments in TSBAb‐IgG molecules after papain digestion.

DESIGN

Both thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibitory (TBI) activity (determined by TSH receptor assay) in sera from patients with primary hypothyroidism were examined after digestion with papain‐Sepharose in the presence of cysteine. The digested IgG was separated into unbound (UF) and bound (BF) fractions on a Protein A‐Sepharose column. Each fraction was then gel‐filtrated on a Sephadex G‐100 column.

RESULTS

TS activity was found within one hour after hydrolysis in 5 out of 7 antibodies, then gradually decreased after more prolonged incubation. Both TS and TBI activities in the UF and the BF from Protein A were found in Fab (Mr 50 kD) and the second protein peak (Fc with trace amounts of Fab), respectively. The biological activity in the second protein peak was suggested as being derived from Fab fraction, because the activity bound to the anti‐F(ab′)2 column. However, the first peak (undigested IgG) in the BF had neither TS nor TSB activity. The TS activity in the retarded fraction (less than Mr 20 kD) in the UF gradually increased with prolonged digestion.

CONCLUSIONS

The conversion of Thyroid stimulation blocking antibodies activity to thyroid stimulating activity by papain digestion suggests that the inherent thyroid stimulating activity located in the Fab portion of the IgG molecule is unmasked by papain cleavage. We also suggest that the thyroid stimulating activity in the retarded fraction in the unbound fraction may be released from hydrolysis of the Fab portion of the IgG molecule.
Somatostatin receptor imaging in somatotroph and non‐functioning pituitary adenomas: correlation with hormonal and visual responses to octreotide
Authors: Borson‐Chazot Françoise , Houzard Claire , Ajzenberg Christiane , Nocaudie Marie , Duet Michèle , Mundler Olivier , Marchandise Xavier , Epelbaum Jacques , Gomez De Alzaga Maria , Schäfer Judith , Meyerhof Wolfgang , Sassolas Geneviève , Warnet André
Published: November 2003

OBJECTIVE

A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH‐secreting and non‐functioning pituitary adenomas.

SUBJECTS AND METHODS

Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non‐functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty‐five patients were treated for 1 month with octreotide (300 μg daily). The therapeutic response was assessed on GH and IGF‐I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied.

RESULTS

From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide‐induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non‐functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non‐functioning pituitary adenomas with expression of sst2 only.

CONCLUSION

In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non–functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.