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1.
J Clin Endocrinol Metab ; 88(4): 1433-41, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12679418

ABSTRACT

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.


Subject(s)
Carcinoma, Papillary/blood , Thyroglobulin/blood , Thyroid Neoplasms/blood , Carcinoma, Papillary/therapy , Humans , Iodine Radioisotopes/therapeutic use , Neoplasm Metastasis/diagnosis , Neoplasm, Residual/diagnosis , Recombinant Proteins/administration & dosage , Risk Factors , Sensitivity and Specificity , Thyroid Neoplasms/therapy , Thyroidectomy , Thyrotropin/administration & dosage
2.
Endocr Relat Cancer ; 8(4): 287-305, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733226

ABSTRACT

Pituitary tumors are frequently encountered intracranial neoplasms. They present with a variety of clinical manifestations that include symptoms and signs of excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others related to expansion of the tumor mass and the resulting compression of surrounding structures such as the optic chiasm and cranial nerves. Advances in molecular biology, immunocytochemical staining and imaging, and the introduction of new treatment options have improved our understanding of the natural history of these adenomas and their management. Available treatments include surgical, medical and radiation therapy. Although the primary treatment for each tumor type may vary, it is important to consider all available options and select the most applicable for that patient. The interaction of all members of management team, including the primary care provider, the endocrinologist and the neurosurgeon in selecting the treatment course can only improve therapeutic outcome. Regardless of the initial choice of treatment,follow-up of all patients should be maintained indefinitely. The managing physician should be familiar with the natural history and long-term complications of pituitary adenomas, and with the side effects of treatments given over the years.


Subject(s)
Pituitary Neoplasms , Acromegaly/etiology , Adenoma/classification , Adenoma/diagnosis , Adenoma/drug therapy , Adenoma/epidemiology , Adenoma/physiopathology , Adenoma/surgery , Adrenocorticotropic Hormone/metabolism , Adult , Case Management , Child , Clone Cells/pathology , Combined Modality Therapy , Diabetes Insipidus, Neurogenic/drug therapy , Diabetes Insipidus, Neurogenic/etiology , Dopamine Agonists/therapeutic use , False Negative Reactions , Female , Human Growth Hormone/metabolism , Humans , Hydrocortisone/metabolism , Hypophysectomy/adverse effects , Hypophysectomy/methods , Hypopituitarism/drug therapy , Hypopituitarism/etiology , Hypothalamo-Hypophyseal System/physiopathology , Incidence , Male , Middle Aged , Nelson Syndrome/etiology , Octreotide/therapeutic use , Pituitary Function Tests , Pituitary Hormones/analysis , Pituitary Hormones/metabolism , Pituitary Hormones/therapeutic use , Pituitary Neoplasms/classification , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/physiopathology , Pituitary Neoplasms/therapy , Pituitary-Adrenal System/metabolism , Pregnancy , Pregnancy Complications, Neoplastic/therapy , Prevalence , Prolactin/blood , Prolactin/metabolism , Prolactinoma/blood , Prolactinoma/complications , Prolactinoma/diagnosis
3.
N Engl J Med ; 344(23): 1743-9, 2001 Jun 07.
Article in English | MEDLINE | ID: mdl-11396440

ABSTRACT

BACKGROUND: Women with hypothyroidism that is being treated with thyroxine often need higher doses when they are pregnant. Whether this need can be attributed solely to estrogen-induced increases in serum thyroxine-binding globulin or whether other factors are involved is not known. METHODS: In 11 postmenopausal women with normal thyroid function and 25 postmenopausal women with hypothyroidism treated with thyroxine, I assessed thyroid function before they started estrogen therapy and every 6 weeks for 48 weeks thereafter. The women with hypothyroidism included 18 women receiving thyroxine-replacement therapy and 7 women receiving thyrotropin-suppressive thyroxine therapy. On each occasion, serum thyroxine, free thyroxine, thyrotropin, and thyroxine-binding globulin were measured. RESULTS: In the women with normal thyroid function, the serum free thyroxine and thyrotropin concentrations did not change, whereas at 12 weeks the mean (+/-SD) serum thyroxine concentration had increased from 8.0+/-0.9 microg per deciliter (103+/-12 nmol per liter) to 10.4+/-1.5 microg per deciliter (134+/-19 nmol per liter, P<0.001) and the serum thyroxine-binding globulin concentration had increased from 20.3+/-3.5 mg per liter to 31.3+/-3.2 mg per liter, P<0.001). The women with hypothyroidism had similar increases in serum thyroxine and thyroxine-binding globulin concentrations during estrogen therapy, but their serum free thyroxine concentration decreased from 1.7+/-0.4 ng per deciliter (22+/-5 pmol per liter) to 1.4+/-0.3 ng per deciliter (18+/-4 pmol per liter, P<0.001) and their serum thyrotropin concentration increased from 0.9+/-1.1 to 3.2+/-3.1 microU per milliliter (P<0.001). The serum thyrotropin concentrations increased to more than 7 microU per milliliter in 7 of the 18 women in the thyroxine-replacement group and to more than 1 microU per milliliter in 3 of the 7 women in the thyrotropin-suppression group. CONCLUSIONS: In women with hypothyroidism treated with thyroxine, estrogen therapy may increase the need for thyroxine.


Subject(s)
Estrogens, Conjugated (USP)/therapeutic use , Hypothyroidism/drug therapy , Thyroxine-Binding Proteins/metabolism , Thyroxine/administration & dosage , Adult , Estrogens, Conjugated (USP)/pharmacology , Female , Hormone Replacement Therapy , Humans , Hypothyroidism/blood , Medroxyprogesterone/therapeutic use , Middle Aged , Postmenopause/blood , Reference Values , Thyroid Function Tests , Thyroid Gland/drug effects , Thyroid Gland/physiology , Thyroid Neoplasms/drug therapy , Thyrotropin/blood , Thyroxine/blood , Thyroxine/therapeutic use
4.
J Clin Endocrinol Metab ; 85(5): 1789-93, 2000 May.
Article in English | MEDLINE | ID: mdl-10843153

ABSTRACT

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this setting are largely due to compression of pituitary stalk and portal vessels. Headaches (HAs) are frequently seen in patients with large adenomas and at times in those with microadenomas. Because the walls of the sella turcica are relatively rigid, we postulate that tumor growth within the sella increases intrasellar pressure (ISP), which in turn impairs portal blood flow, resulting in mild hyperprolactinemia and hypopituitarism. We also postulate that increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pituitary adenomas. MISP was measured using a commonly available intracranial monitoring kit where a fiberoptic transducer was inserted through a 2-mm dural incision at the time of adenomectomy. Patients with deficient FSH, LH, ACTH, or TSH secretion were considered hypopituitary. Data on serum PRL levels were included for analysis only in patients whose adenomas had negative immunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 13.5 and a median of 26 mm Hg. The pressure measurements were higher in patients with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involved in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pituitary function, suggest that increased ISP is a major mechanism involved in the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contributing to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased ISP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.


Subject(s)
Adenoma/complications , Headache/etiology , Hyperprolactinemia/etiology , Hypopituitarism/etiology , Intracranial Hypertension/complications , Pituitary Neoplasms/complications , Adenoma/pathology , Adenoma/surgery , Female , Humans , Intracranial Pressure , Male , Middle Aged , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Prolactin/blood
6.
Mayo Clin Proc ; 74(2): 150-4, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10069353

ABSTRACT

Of the 128 previously reported cases of lymphocytic hypophysitis, the diagnosis was histologically proven in 6 patients in whom the pituitary mass regressed spontaneously; only 1 subsequently became pregnant. Among six additional patients who became pregnant after a diagnosis of presumed lymphocytic hypophysitis, the disease was confirmed histologically in only three, two of whom underwent surgical debulking and one who had no follow-up imaging. To our knowledge, we describe the second patient with histologically proven lymphocytic hypophysitis, associated with adrenocorticotropic hormone (corticotropin) and prolactin deficiencies, in whom the pituitary mass regressed completely with physiologic hydrocortisone therapy only and in whom a spontaneous pregnancy occurred subsequently with no postpartum recurrence of the pituitary mass. This information lends credence to previous recommendations that, in the absence of visual field defects, surgical and corticosteroid therapy may be safely withheld, with periodic reassessment.


Subject(s)
Endocrine System Diseases/diagnosis , Lymphocytes , Pituitary Gland/pathology , Pituitary Hormones/blood , Pregnancy Complications/blood , Adrenocorticotropic Hormone/deficiency , Adult , Endocrine System Diseases/blood , Endocrine System Diseases/pathology , Female , Humans , Inflammation , Magnetic Resonance Imaging , Pregnancy , Pregnancy Outcome , Prolactin/deficiency
7.
Ann Emerg Med ; 33(3): 291-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10036343

ABSTRACT

STUDY OBJECTIVE: To assess the value of plasma glucose concentration alone as a predictor of neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examination and electroencephalographic (EEG) findings. METHODS: Neurologic function and EEG results were evaluated in 17 subjects before and during insulin-induced hypoglycemia using relevant and reliable clinical tools for bedside use. RESULTS: Hypoglycemia (mean nadir concentration, 30 mg/dL) was without effect on level of consciousness or cranial nerve, motor, sensory, vestibulocerebellar, language, or simple visuospatial functions. Attention was minimally impaired in all subjects, but memory in only 3. EEG results remained normal in 5 subjects; minimal to moderate nonspecific changes occurred in the rest. All patients manifested signs of sympathetic stimulation from hypoglycemia, including tremor, tachycardia, and diaphoresis. The manifestations of neuroglycopenia did not correlate significantly with nadir plasma glucose or duration of hypoglycemia. CONCLUSION: Moderately severe hypoglycemia of short duration can be neurologically occult, or subtle inattention can be its first and only clinical manifestation. Our findings are at variance with reports in the emergency medicine literature in which marked deficits are universally present at glucose concentrations equal to those attained in this study. This discrepancy suggests that the expression of neuroglycopenia is multifactorially determined and that plasma glucose concentration alone does not predict neurologic dysfunction in nondiabetic subjects with normal baseline neurologic examinations.


Subject(s)
Blood Glucose , Hypoglycemia/complications , Nervous System Diseases/etiology , Adult , Aged , Cognition , Electroencephalography , Female , Humans , Hypoglycemia/blood , Hypoglycemia/chemically induced , Hypoglycemia/physiopathology , Insulin , Male , Memory , Middle Aged , Nervous System Diseases/classification , Neurologic Examination , Predictive Value of Tests
8.
Gynecol Oncol ; 70(3): 425-7, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9790800

ABSTRACT

A patient with malignant struma ovarii who had elevated thyroglobulin levels at the time of her original surgery was diagnosed with recurrence on the basis of progressive thyroglobulin level elevation while on thyroid suppressive therapy. Subsequent treatment with therapeutic doses of iodine-137 resulted in normalization of the elevated thyroglobulin level. The patient remains disease free on thyroid replacement.


Subject(s)
Carcinoma, Papillary/pathology , Ovarian Neoplasms/secondary , Struma Ovarii/secondary , Thyroglobulin/blood , Thyroid Neoplasms/pathology , Adult , Carcinoma, Papillary/blood , Diagnosis, Differential , Female , Humans , Ovarian Neoplasms/blood , Recurrence , Struma Ovarii/blood , Thyroid Neoplasms/blood , Treatment Outcome
9.
J Clin Endocrinol Metab ; 80(12): 3507-12, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8530591

ABSTRACT

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. We postulated that hypopituitarism in this setting, is primarily caused by compression of the portal vessels and/or pituitary stalk. If this were the case, the dynamics of PRL secretion in this instance would be similar to those in patients with stalk section, dopamine deficiency, or hypothalamic disease. Furthermore, as hypopituitarism in this setting is largely reversible, we postulate that PRL dynamics should also normalize after adenomectomy as a result of the resumption of hypothalamic regulation of pituitary hormone secretion. To test these hypotheses, we examined PRL responsiveness to TRH and the dopamine antagonist, perphenazine (PZ), in patients with pituitary macroadenomas who had hypopituitarism and others with intact pituitary function (controls). Dynamic studies were performed before and 2-3 months after total or subtotal adenomectomy, and the results were correlated with alterations in other pituitary function. In addition, plasma ACTH, cortisol, and PRL levels were measured hours to days after surgery to investigate immediate alterations in pituitary function following surgical decompression. Before surgery, hypopituitary patients had higher serum PRL level than controls (25.5 +/- 12 vs. 11 +/- 3 micrograms/L; P < 0.001). Preoperative dynamic testing of PRL secretion in hypopituitary patients demonstrated an increase in PRL levels after TRH, but not after PZ, administration. In contrast, PRL levels increased appropriately when either stimulus was given to controls. Hours after adenomectomy, PRL levels decreased by 50% in hypopituitary patients (P < 0.0001) and remained so until discharge. In contrast, controls had a transient increase in serum PRL levels after adenomectomy. After surgery, 25 of 43 previously hypopituitary patients recovered part or all pituitary function. Serum PRL levels in the latter subgroup became normal and increased appropriately after stimulation with either TRH or PZ. In contrast, patients who did not recover pituitary function had lower PRL levels that increased minimally after TRH or PZ. The mild increase in serum PRL levels in hypopituitary patients and the discordant responses to stimulation with TRH and PZ suggest dopamine deficiency as a cause of hyperprolactinemia. The drop in serum PRL levels immediately after surgery, at a time when other pituitary hormones (e.g. ACTH), were documented to rise suggests restoration of hypothalamic control over pituitary hormone secretion. The pattern of PRL responses to stimulation in patients recovering function postoperatively was similar to that in controls, although the incremental rise was subnormal.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Adenoma/metabolism , Hypopituitarism/metabolism , Pituitary Neoplasms/metabolism , Prolactin/metabolism , Adenoma/physiopathology , Adenoma/surgery , Adult , Female , Humans , Male , Middle Aged , Phenothiazines/pharmacology , Pituitary Gland/physiopathology , Pituitary Neoplasms/physiopathology , Pituitary Neoplasms/surgery , Postoperative Period , Prolactin/blood , Thyrotropin-Releasing Hormone/pharmacology , Time Factors
10.
J Clin Endocrinol Metab ; 79(2): 348-54, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8045946

ABSTRACT

Mild hyperprolactinemia frequently accompanies the hypopituitarism associated with pituitary macroadenomas not secreting PRL. Because of this association, hypopituitarism was postulated to be due to compression of portal vessels. We postulate that resumption of hypothalamic control over pituitary function occurs immediately after adenomectomy. To test this hypothesis, we examined pituitary function before and after transsphenoidal adenomectomy in 26 ACTH-deficient patients and 23 subjects with normal adrenal and thyroidal functions (control group). Glucocorticoids, given only to ACTH-deficient subjects, were withdrawn 36 h after surgery. ACTH, cortisol, and PRL levels were measured twice daily in all patients. Both ACTH and PRL levels increased hours after surgery in controls and returned to baseline over 4 days. In all hypopituitary subjects, PRL levels decreased by 50% within hours of adenomectomy and remained so until discharge. ACTH levels, measured simultaneously, increased within hours in 17 of 26 hypopituitary patients, all of whom recovered normal adrenal function before discharge. Nine additional patients had low ACTH levels and required cortisol replacement. The reciprocal changes in PRL and ACTH levels measured simultaneously, hours after surgery, support the hypothesis that hypopituitarism is reversible and largely caused by compression of the protal vessels and the resulting interruption of delivery of hypothalamic hormones. The persistence of hypopituitarism in some patients suggests that ischemic necrosis of the anterior pituitary could limit recovery.


Subject(s)
Adenoma/surgery , Pituitary Gland/physiopathology , Pituitary Neoplasms/surgery , Adenoma/physiopathology , Adrenal Glands/physiopathology , Adrenocorticotropic Hormone/blood , Female , Follicle Stimulating Hormone/blood , Humans , Hydrocortisone/blood , Kinetics , Luteinizing Hormone/blood , Male , Ovary/physiopathology , Pituitary Neoplasms/physiopathology , Prolactin/blood , Testis/physiopathology , Testosterone/blood , Thyroid Gland/physiopathology
11.
Ann Intern Med ; 121(4): 247-51, 1994 Aug 15.
Article in English | MEDLINE | ID: mdl-7518657

ABSTRACT

OBJECTIVE: To determine the effects of androgen administration on measures of thyroid function and thyroid hormone replacement doses in women with breast cancer. DESIGN: Consecutive patients with metastatic, hormone-dependent breast cancer who were eligible for androgen treatment. INTERVENTIONS: Androgen therapy (fluoxymesterone, 10 mg orally twice daily) was continued for as long as it was effective in controlling tumor growth. PATIENTS: 7 patients with no known thyroid disease and 4 others receiving long-term treatment for hypothyroidism. MEASUREMENTS: Serum levels of total and free thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin were determined before and every 4 weeks after androgen therapy was initiated. RESULTS: Within 4 weeks of androgen administration to the seven patients without thyroid disease, serum levels of total T4 and T4-binding globulin decreased (P < 0.001), whereas the calculated free thyroxine index and measured free hormone levels remained unchanged. Six to 12 weeks after androgen therapy was discontinued, all seven patients remained clinically euthyroid, and serum levels returned to baseline values. In contrast, clinical hyperthyroidism developed shortly after androgen was administered to four patients who received long-term thyroid hormone replacement therapy. Within 4 weeks of treatment, the serum free T4 level increased in each of the four patients, whereas the TSH level decreased. Thyroid hormone doses had to be reduced by 25% to 50% to maintain euthyroidism. CONCLUSIONS: The study documents the reversible effects of androgens on thyroid hormone levels and indicates the need to reduce thyroid replacement doses in women during androgen therapy. Monitoring thyroid hormone levels in patients receiving replacement therapy and perhaps in those with autonomous thyroid function is necessary after androgen therapy.


Subject(s)
Breast Neoplasms/drug therapy , Fluoxymesterone/pharmacology , Hypothyroidism/drug therapy , Thyroxine/administration & dosage , Aged , Breast Neoplasms/blood , Breast Neoplasms/complications , Female , Fluoxymesterone/therapeutic use , Humans , Hypothyroidism/blood , Hypothyroidism/complications , Middle Aged , Palliative Care , Thyrotropin/drug effects , Thyroxine/blood , Thyroxine/drug effects , Thyroxine/therapeutic use , Thyroxine-Binding Proteins/drug effects
12.
Acta Cytol ; 38(1): 101-6, 1994.
Article in English | MEDLINE | ID: mdl-8291346

ABSTRACT

We present an unusual case of Langerhans cell histiocytosis (LCH) involving the thyroid gland initially diagnosed by fine needle aspiration biopsy in a 16-year-old boy. The cytologic findings in LCH involving the thyroid include high cellularity, isolated Langerhans cells with prominent nuclear grooves, multinucleate Langerhans cells, eosinophils, lymphocytes and rare benign follicular cells. Confirmation of LCH was obtained by core biopsy, positive S-100 protein immunohistochemical staining and the demonstration of Birbeck granules on electron microscopy. We present the complete clinicopathologic features of this case with a review of the literature and discussion of the differential diagnosis.


Subject(s)
Histiocytosis, Langerhans-Cell/pathology , Thyroid Diseases/pathology , Adolescent , Biopsy, Needle , Diagnosis, Differential , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/metabolism , Humans , Male , Microscopy, Electron , S100 Proteins/analysis , Thyroid Diseases/diagnosis , Thyroid Diseases/metabolism
13.
South Med J ; 85(2): 204-6, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1738892

ABSTRACT

This report describes two cases of Cushing's syndrome associated with radiologic abnormalities in the lung and brain. In both cases, the pathologic diagnosis of the intracranial lesion was unsuspected and prompted changes in management. These cases illustrate that the etiology of pulmonary and central nervous system mass lesions in patients with Cushing's syndrome may not be predicted on clinical grounds or by conventional radiologic methods. A tissue diagnosis is essential as a guide to appropriate management, and biopsies of such lesions are indicated.


Subject(s)
Brain Abscess/diagnosis , Brain Neoplasms/diagnosis , Carcinoid Tumor/diagnosis , Cushing Syndrome/diagnosis , Lung Neoplasms/diagnosis , Nocardia Infections/diagnosis , Aged , Biopsy , Brain/pathology , Brain Abscess/pathology , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Carcinoid Tumor/pathology , Carcinoid Tumor/secondary , Cushing Syndrome/pathology , Diagnosis, Differential , Female , Humans , Lung/pathology , Lung Neoplasms/pathology , Middle Aged , Nocardia Infections/pathology
14.
J Lab Clin Med ; 118(6): 531-7, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1660511

ABSTRACT

This study investigated the binding characteristics of insulin-like growth factor-I (IGF-I) to rat adrenal cells. The binding constants in two regions of the adrenal glands (glomerulosa and fasciculata-reticularis-medulla) were studied separately. In membrane fractions prepared from either region, the binding of iodine 125-labeled IGF-I was demonstrated to be protein and temperature dependent, saturable, and specific. Unlabeled IGF-I was more effective than IGF-II or insulin in displacing 125I-labeled IGF-I binding to the receptor. Fifty percent of the binding was displaced when 2.2, 77.2, or 433.2 nmol/L IGF-I, IGF-II, or insulin, respectively, were added. Receptor numbers and affinity in membrane fractions obtained from either region of the adrenal glands were similar (1821 +/- 188 fmol/mg 1689 +/- 211 fmol/mg protein and a dissociation constant of 1.54 +/- 0.16 nmol/L versus 1.61 +/- 0.13 nmol/L for the glomerulosa and fasciculata-reticularis-medulla regions, respectively). When labeled IGF-I was cross-linked to the binding subunit under reducing conditions, a predominant band with a molecular weight of 135 kd was noted in either region of the adrenal glands. The data indicate that both regions of the rat adrenal glands have specific IGF-I receptors. The binding and the molecular weight characteristics are similar to the "classical" type I IGF receptor. The data are consistent with recent reports suggesting a modulating role for IGF-I in regulating adrenal cell growth and function.


Subject(s)
Adrenal Glands/metabolism , Insulin-Like Growth Factor I/metabolism , Receptors, Cell Surface/metabolism , Affinity Labels , Animals , Cell Membrane/metabolism , Cross-Linking Reagents , Insulin-Like Growth Factor I/chemistry , Molecular Weight , Rats , Receptors, Cell Surface/chemistry , Receptors, Somatomedin
15.
J Clin Endocrinol Metab ; 72(4): 814-8, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2005206

ABSTRACT

We investigated the effect of chronic hyperglycemia on glucose transporters in erythrocytes of subjects with and without diabetes mellitus. We found a 22% increase in D-glucose-displaceable cytochalasin-B binding in erythrocyte membranes of diabetic subjects over those of controls (311 +/- 13 vs. 254 +/- 8 pmol/mg protein; P less than 0.001). This increased binding was due to a higher density of binding sites without a significant change in binding affinity. Cytochalasin-B binding to erythrocyte membrane correlated positively with both erythrocyte glycohemoglobin and serum glucose levels, but not with plasma C-peptide levels. The data are compatible with up-regulation of glucose transporters in the erythrocytes of subjects with chronic hyperglycemia. We suspect that this is brought about by increased synthesis and membrane incorporation of the glucose transporter during erythropoiesis.


Subject(s)
Diabetes Mellitus/blood , Erythrocyte Membrane/metabolism , Hyperglycemia/blood , Monosaccharide Transport Proteins/blood , Adult , Aged , Blood Glucose/analysis , C-Peptide/blood , Chronic Disease , Cytochalasin B/metabolism , Female , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Reference Values
16.
J Biol Chem ; 265(36): 22371-9, 1990 Dec 25.
Article in English | MEDLINE | ID: mdl-1702419

ABSTRACT

Transgenic mice were used to investigate sequences within the promoter of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the rat (EC 4.1.1.32) (PEPCK) which are involved in tissue-specific and developmental regulation of gene expression. Segments of the PEPCK promoter between -2000 and -109 were linked to the structural gene for bovine growth hormone (bGH) and introduced into the germ line of mice by microinjection. Bovine growth hormone mRNA was found in tissues that express the endogenous PEPCK gene, mainly in the liver but to a lesser extent in the kidney, adipose tissue, small intestine, and mammary gland. In the liver the chimeric PEPCK/bGH(460) gene was expressed in periportal cells, which is consistent with the zonation of endogenous PEPCK. The PEPCK/bGH gene was not transcribed in the livers of fetal mice until immediately before birth; at birth the concentration of bGH mRNA increased 200-fold. Our results indicate that the region of the PEPCK promoter from -460 to +73 base pairs contains regulatory sequences required for tissue-specific and developmental regulation of PEPCK gene expression. Mice transgenic for PEPCK/bGH(460) were not hyperglycemic or hyperinsulinemic in response to elevated bGH, as were transgenic mice with the MT/bGH gene. The number of insulin receptors in skeletal muscle was no different in mice transgenic for MT/bGH when compared with mice transgenic for PEPCK/bGH(460) and control animals. However, mRNA abundance for the insulin-sensitive glucose transporter in skeletal muscle was decreased in mice transgenic for the MT/bGH gene. The differences in glucose homeostasis noted with the two types of transgenic mice may be the result of the relative site of expression, the different developmental pattern, or hormonal regulation of expression of the bGH gene.


Subject(s)
Growth Hormone/genetics , Monosaccharide Transport Proteins/metabolism , Phosphoenolpyruvate Carboxykinase (GTP)/genetics , Receptor, Insulin/metabolism , Animals , Cattle , Chimera , DNA Probes , DNA, Recombinant/metabolism , Gene Expression Regulation , Genes , Mice , Mice, Inbred C57BL , Mice, Transgenic , Organ Specificity , Plasmids , Promoter Regions, Genetic , RNA/genetics , RNA/isolation & purification , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Rats , Reference Values , Restriction Mapping
17.
Surgery ; 108(4): 619-27; discussion 627-8, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2218871

ABSTRACT

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Lymph Nodes/pathology , Tamoxifen/administration & dosage , BCG Vaccine/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Cyclophosphamide/therapeutic use , Follow-Up Studies , Humans , Methotrexate/therapeutic use , Statistics as Topic , Survival Analysis , Tamoxifen/therapeutic use , Time Factors
18.
J Clin Endocrinol Metab ; 71(2): 323-8, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2166068

ABSTRACT

Hypopituitarism is a major manifestation of pituitary adenoma apoplexy. We postulated that the acute deterioration in pituitary function may be caused by compression of portal vessels and the pituitary stalk, secondary to a sudden increase in intrasellar contents. If this were the case, one would predict improvement in pituitary function to occur after surgical decompression. We studied pituitary function in eight patients presenting with the clinical syndrome of pituitary adenoma apoplexy before and on multiple occasions after urgent surgical decompression. Partial or complete hypopituitarism was seen in all subjects at the time of presentation. Serum cortisol levels were inappropriately low (5.9 +/- 1.4 micrograms/dL; 162.8 +/- 38 nmol/L) for the degree of stress in seven patients and appropriately elevated in only one subject (55.3 micrograms/dL; 1525.7 nmol/L). High normal increments in cortisol levels were noted in three subjects given test doses of cosyntropin. Patients were given glucocorticoids before, during, and for 2 days after surgery. Serum cortisol concentrations measured on or after the third day when glucocorticoids had already been stopped were normal in seven subjects and consistently low in one. These seven subjects were discharged on no replacement and were subsequently documented by dynamic testing to have normal pituitary-adrenal function. Gonadal function improved in two of four men and in one of two women who had hypogonadism on presentation. Improvement in thyroid function was documented in two of three subjects with preoperative hypothyroidism. Gradual improvement and almost complete resolution of the neuroophthalmological abnormalities occurred days to weeks after decompression. These observations demonstrate that urgent surgical decompression after pituitary tumor apoplexy was associated with improvement not only in neurological defects but also in pituitary function. The rapid improvement in pituitary function indicates not only that the hypopituitarism was reversible, but also that it might be caused by compression of the portal circulation and pituitary stalk by the sudden increase in intrasellar contents.


Subject(s)
Cerebrovascular Disorders/etiology , Hypopituitarism/physiopathology , Pituitary Neoplasms/surgery , Adrenocorticotropic Hormone/analysis , Adult , Cerebrovascular Disorders/surgery , Female , Follicle Stimulating Hormone/analysis , Growth Hormone/analysis , Humans , Hypopituitarism/etiology , Immunoenzyme Techniques , Luteinizing Hormone/analysis , Male , Middle Aged , Pituitary Neoplasms/complications , Pituitary Neoplasms/physiopathology , Prolactin/analysis , Testosterone/blood , Thyrotropin/analysis
19.
J Clin Endocrinol Metab ; 71(1): 60-6, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2370301

ABSTRACT

The present studies were designed to test the hypothesis that hyperprolactinemia modulates target tissue responsiveness to angiotensin-II (AII). Adrenal and pressor responses to AII infusions were determined in six patients with PRL-secreting pituitary microadenomas and in five normal controls during defined electrolyte balance. Hyperprolactinemic and normal subjects had similar mean blood pressures while on a regular Na intake (82.5 +/- 0.5 vs. 81.2 +/- 0.3 mm Hg). However, after 4 days of Na loading (200 meq/day), the mean blood pressure in hyperprolactinemic subjects was higher than that in normal (86.6 +/- 1 vs. 83.4 +/- 0.8 mm Hg; P less than 0.05). In addition, enhancement of the mean blood pressure response to three doses of AII was noted in hyperprolactinemic subjects (P less than 0.05) compared to that in normal subjects. After 4 days of Na restriction (10 meq/day), the mean blood pressure in hyperprolactinemic subjects was similar to that in normal subjects (79.7 +/- 0.6 vs. 78.9 +/- 1 mm Hg). However, despite adequate Na restriction, the pressor response to AII continued to be enhanced (P less than 0.05) in hyperprolactinemic subjects. There were no differences in plasma or urinary electrolytes or in PRA between hyperprolactinemic and normal subjects. Hyperprolactinemic subjects had higher basal (P less than 0.01), AII-stimulated (P less than 0.05), and ACTH-stimulated (P less than 0.02) aldosterone levels during Na loading, but not during Na restriction. The differences disappeared after the correction of the hyperprolactinemia. The data demonstrate significant alterations in adrenal and pressor responsiveness in hyperprolactinemic subjects and suggest a modulating role for PRL on vascular reactivity and steroid biosynthesis. The precise mechanism has not been determined, but may be secondary to PRL-induced up-regulation of adrenal and vascular AII receptors.


Subject(s)
Adrenal Glands/drug effects , Angiotensin II/pharmacology , Hyperprolactinemia/metabolism , Prolactin/metabolism , Adenoma/metabolism , Adrenal Glands/metabolism , Adult , Blood Pressure/drug effects , Female , Humans , Infusions, Intravenous , Male , Pituitary Neoplasms/metabolism , Potassium/metabolism , Sodium/metabolism , Steroids/biosynthesis , Water-Electrolyte Balance/drug effects , Water-Electrolyte Balance/physiology
20.
Cancer ; 64(9): 1819-23, 1989 Nov 01.
Article in English | MEDLINE | ID: mdl-2790695

ABSTRACT

Postmenopausal women who underwent modified radical mastectomy for Stage II, estrogen receptor (ER)-positive breast cancer were randomized to receive endocrine treatment (tamoxifen [T], 40 mg daily for 3 years) alone versus endocrine treatment plus five-drug chemotherapy (Cytoxan [cyclophosphamide, C], methotrexate [M], 5-fluorouracil [F], vincristine [V], and prednisone [P], CMFVP, for 1 year). Chemotherapy consisted of oral P (1 month), oral C (12 months), and intravenous MFV weekly for the first 3 months, biweekly for 3 months, and triweekly for 6 months. Patients were entered into the study from October 1979, to October 1985, and the median follow-up is 55 months. Results show that with 94 postmenopausal women, disease-free survival (DFS) is significantly greater (P = 0.04, log-rank test; P = 0.03, multivariate analysis) in patients receiving CMFVPT as compared to those receiving T alone. These results suggest that intensive chemotherapy combined with T is more effective in delaying recurrence than T alone in postmenopausal patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Menopause , Receptors, Estrogen/analysis , Tamoxifen/therapeutic use , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Mastectomy, Modified Radical , Methotrexate/administration & dosage , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Prednisone/administration & dosage , Survival Analysis , Tamoxifen/administration & dosage , Vincristine/administration & dosage
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