Sophia Ish-Shalom

The distal axis of growth hormone (GH) in nutritional disorders: GH-binding protein, insulin-like growth factor-I (IGF-I), and IGF-I receptors in obesity and anorexia nervosa.

The endocrine abnormalities along the growth hormone (GH) axis in anorexia nervosa (AN) and in obesity include hypothalamic, pituitary, and peripheral elements. The present study was undertaken to evaluate the effects of these nutritional extremes on GH-binding protein (BP) levels and on Insulin-like growth factor-I (IGF-I) receptors on red blood cells (RBC). Nine patients with AN and 20 obese subjects were compared with normal control children, adolescents, and adults. GH-BP was measured by a binding assay with dextran-coated charcoal separation. IGF-I binding was measured on enriched RBC. Serum GH-BP levels were markedly reduced in the AN patients, and highly increased in the obese. Scatchard analyses showed linear plots with unaltered binding affinities (Ka). The binding capacity (Bmax) was significantly lower than normal control in the AN patients and higher in the obese. GH-BP levels correlated positively with the body mass index (BMI). RBC [125I]IGF-I binding was significantly elevated in the AN patients and low in the obese. Scatchard analyses showed curvilinear plots. The high-affinity constants (Ka1) were slightly, but significantly, higher in the AN patients and in the obese compared with control. The binding capacity of the first binder (Bmax1) was lower in obesity than in AN or control. The low-affinity constants (Ka2) were similar in the three groups, and its binding capacity (Bmax2) was similar in the AN patients and the controls, but significantly lower in the obese. [125I]IGF-I binding correlated negatively and significantly with the BMI and with the GH-BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin-Receptor Scintigraphy in the Management of Gastroenteropancreatic Tumors

Objective:This study evaluates the diagnostic and therapeutic implications of somatostatin-receptor scintigraphy in the management of patients with proven or high clinical suspicion of gastroenteropancreatic endocrine tumors.Methods:Forty-one patients were studied by planar and tomographic imaging at 4 h and 24 h after 111In-pentetreotide injection. Scintigraphic findings were compared with computed tomography, and in several patients also with ultrasound, angiography, biopsy, and/or surgery, when performed.Results:Among 23 patients with carcinoid tumor, three of nine primary tumors were initially identified by scintigraphy. Unsuspected mesenteric metastases found on scintigraphy in three patients led to octreotide treatment. Scintigraphic detection of multiple metastases in a patient with thyroid metastasis of bronchial carcinoid spared her an unnecessary total thyroidectomy. Among 18 patients with 19 islet-cell tumors, scintigraphy detected three of five insulinomas, whereas computed tomography identified only one. Receptor positivity in an islet-cell tumor (vipoma?) with no metastases on the scan led to surgical removal of the primary tumor. Receptor-positive metastases of gastrinoma (two of three patients), glucagonoma (two of three patients), and parathyroid hormone-related peptide-producing tumor (one patient) led to octreotide treatment. Nonvisualization of metastases of a glucovipoma led to chemotherapy.Conclusions:Somatostatin-receptor scintigraphy contributes to the management of patients with gastroenteropancreatic tumors in the following ways: 1) localization of a primary occult tumor, allowing surgical removal; 2) staging of the disease for optimal therapy—surgical excision or systemic treatment; and 3) identification of receptor status of the metastases for octreotide treatment or chemotherapy.

Choosing an oestrogen replacement therapy in young adult women with Turner syndrome

OBJECTIVE Hormone replacement therapy (HRT) is prescribed to most patients with Turner syndrome (TS) although its use in adult TS patients has not been scientifically evaluated. The present study was performed to compare the short‐term effects in adult women with Turner syndrome of low‐dose oral conjugated oestrogen (0·625 mg, CE) with relatively high dose ethinyl oestradiol (30 µg, EE2); both combined with an oral progestin.

Somatostatin receptor scintigraphy for early detection of regional and distant metastases of medullary carcinoma of the thyroid.

Three patients are described who had regional and distant metastases of medullary thyroid cancer detected by somatostatin receptor scintigraphy but not by CT; two had minimal disease that was amenable to surgery. The first patient had been followed for 2 years before having a repeated scan and positive CT, with subsequent surgical removal of metastatic paratracheal nodes. The plasma calcitonin level, however, did not approach normal values after surgery, and a third scan showed persistence of focal uptake in the left paratracheal area of the lower neck, whereas CT was negative. At repeated exploration, a tumor mass of medullary carcinoma, embedded in lymphatic tissue, was removed. Nine months after the last surgical procedure, calcitonin and carcinoembryonic antigen levels were normal. The second patient underwent microdissection of the mediastinum and removal of two metastatic nodes that were demonstrable only by the scintigraphic technique. The plasma calcitonin level subsequently became normal. The third patient, with multiple endocrine neoplasia IIB and associated pheochromocytoma, had bony metastatic involvement of the left shoulder, demonstrable initially on somatostatin receptor scintigraphy and subsequently with radioiodinated metaiodobenzylguanidine but not on CT.

Treatment preference and tolerability with alendronate once weekly over a 3-month period: an Israeli multi-center study

Background and aims: Osteoporosis is a chronic condition requiring long-term treatment, for which compliance is not easy to achieve. 70 mg of alendronate once weekly (alendronate OW) provides equivalent efficacy to treatment with 10 mg of alendronate once a day (alendronate OD); however, there are relatively few data regarding patient and physician preferences for once-weekly vs daily dosing. The aim of this study was to measure compliance, convenience, tolerance and relative preference of alendronate OW treatment among post-menopausal women with osteoporosis and physician satisfaction, compared with previous treatment with alendronate OD. Methods: This open-label, prospective multi-center trial was conducted at 14 hospitals and 150 primary-care community clinics in Israel. Post-menopausal osteoporotic women (n=3710), who had been treated for at least 1 month with alendronate OD during the preceding year, were treated with alendronate OW for 12 weeks. Convenience, satisfaction, tolerance and relative preference of alendronate OW during the trial, compared with past experience with alendronate OD, were recorded. Results: Overall, 96% of the patients preferred the alendronate OW regimen to the 10-mg daily dosage. Nearly all (98%) the patients who completed 12 weeks of treatment, including 77% of patients who had previously discontinued daily treatment due to intolerance, were willing to continue the alendronate OW regimen. Patient-reported compliance with dosing instructions was over 98%. Alendronate OW was well tolerated; only 2.8% of patients discontinued, due to adverse events. Physicians were highly satisfied with the once-weekly dosing regimen, and recommended continued treatment with alendronate OW for 99% of the patients. Conclusions: The majority of post-menopausal women with osteoporosis, including those who were previously intolerant to alendronate OD, preferred alendronate OW to the once-daily dosing regimen. It is important to consider patient preference when selecting the appropriate treatment for osteoporosis.

Predominant factors associated with bone loss in liver transplant patients: after prolonged post-transplantation period

Abstract: Introduction: Osteoporosis is a major cause of morbidity in liver transplant recipients and is associated with multiple factors.

Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation

A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.

Growth-Hormone-Binding Protein in Patients with Acromegaly

The present study was undertaken to investigate the possible regulatory effect of chronic exposure to human growth hormone (hGH), in patients with acromegaly, on growth-hormone-binding protein (GH-BP). Nineteen patients with active acromegaly, before, during or after treatment, comprised the subjects of this study. Serum GH was measured by radioimmunoassay and GH-BP by a binding assay with dextran-coated charcoal separation. The specific binding of [125I]hGH (1 ng) obtained with 50 microliters serum was expressed as a percentage of total cpm. To evaluate the impact of the lower GH-BP on GH activity, we studied the effect of acromegalic serum on hGH displacement of [125I]hGH binding to GH receptors in rabbit liver membranes. Compared to normal controls (11.43 +/- 0.37%), the acromegalic patients had low serum levels of GH-BP (5.45 +/- 0.40%; p < 0.001), which correlated negatively with serum GH levels (p < 0.01). In 7 patients, GH-BP normalized within 2-3 months of successful therapy. The lower GH-BP was due to a reduction in binding capacity, whereas binding affinity remained unchanged. Acromegalic serum, with its low GH-BP, resulted in a shift to the left of the GH displacement curve when compared with normal human sera: IC50 values were 7.47 +/- 0.29 and 11.19 +/- 0.84 ng (p < 0.02) for acromegalic and normal human sera, respectively. We conclude that acromegaly is characterized by low levels of GH-BP due to a decrease in serum-binding capacity. The decrease in GH-BP may render the acromegalic serum GH relatively more active in the GH receptor assay.

Somatostatin-receptor imaging of medullary thyroid carcinoma.

ln-111 pentetreotide scintigraphy of 10 patients with residual or metastatic medullary thyroid carcinoma is described. Six patients had sporadic tumor and 4 had MEN IIB. Foci of increased tracer uptake were observed in 9 patients: in the thyroid bed (4 patients), the mediastinum (3 patients.), the shoulder area and left lower abdomen (1 patient), and the left upper abdomen (1 patient). The 10th patient had no abnormal uptake. CT confirmed 2 mediastinal lesions and 2 out of 3 thyroid masses, but did not detect the thyroid remnants or the lesions in the shoulder area and abdomen. Lung lesions ≤1 cm in diameter and ill-defined liver foci (2 patients) were seen on CT, but not on scintigraphy. Small liver metastases not demonstrated on CT or on scintigraphy were identified at surgery in a MEN IIB patient. Elevated urinary epinephrine was found in 2 out of 4 MEN IIB patients. In one, tracer uptake in the left adrenal corresponded to a mass on CT, to pathological uptake of MIBG and DMSA, and to a tumor removed at surgery. The second patient had peritoneal spread of malignant pheochromocytoma (at surgery), but negative CT and only a single focus in the left lower abdomen on scintigraphy. Somatostatin-receptor imaging is useful for the detection of residual and recurrent medullary thyroid carcinoma, and may identify pheochromocytoma in MEN IIB patients.

Effects of hypo or hyper-thyroidism on growth hormone-binding protein.

Summary. objective Growth hormone (GH) receptors are Influenced by the thyroidal state of experimental animals. It has been suggested that GH‐binding protein (BP) might serve as an Indirect measure of the GH receptors. The present study was undertaken to investigate the growth hormone binding protein in patients with hypo or hyperthyroidism.