A systematic review on outcome reporting in randomised controlled trials on surgical interventions for female stress urinary incontinence: a call to develop a core outcome set.

BACKGROUND: Several meta-analyses have identified methodological limitations in female stress urinary incontinence (SUI) trials, precluding the synthesis of primary studies and high-quality evidence. OBJECTIVES: Evaluation of outcome measure selection and outcome reporting in randomised controlled trials (RCTs) on surgery for SUI. SEARCH STRATEGY: Systematic review of RCTs identified from bibliographical databases, including Medline, Cochrane, and EMBASE. SELECTION CRITERIA: Randomised controlled trials evaluating the efficacy and safety of surgical interventions for the management of female SUI. DATA COLLECTION AND ANALYSIS: Two researchers independently assessed the included studies and documented outcomes. MAIN RESULTS: Overall, 108 studies were identified that included 422 reported outcomes and 119 outcome measures. The three most common outcomes were cure rates (87 studies), quality of life (85 studies), and overactive bladder (78 studies). The median methodological quality rating was 3 (range 0-3) and the outcome reporting quality rating was 3 (range 0-5). Multinomial logistic regression analysis revealed that the methodological quality and use of validated questionnaire were significant predictors of the quality of outcome reporting (ß = 0.538, P < 0.001; ß = 0.218, P = 0.011, respectively). CONCLUSIONS: Outcome reporting in SUI trials is highly variable. Until a core outcome set is developed and implemented, we propose an interim use of three commonly reported outcomes in each domain (treatment success rate - complete cure, partial improvement, or failure of response; urodynamic evaluation outcomes - overactive bladder (OAB), voiding dysfunction, and urodynamic stress incontinence; patient-reported outcomes - quality of life, sexual dysfunction, and patient satisfaction) with the use of validated questionnaires for patient-reported outcomes and subjective success rates. Complications should be also explicitly and comprehensively reported using validated outcome measures. TWEETABLE ABSTRACT: There is significant variation in outcome reporting in SUI trials. Our systematic review findings aim to form the basis for the development of a core outcome set.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis.

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells.

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity.

AME position statement on adrenal incidentaloma.

OBJECTIVE: To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice. DESIGN: A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus. RADIOLOGICAL ASSESSMENT: Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of ≤10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma). HORMONAL ASSESSMENT: Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushing's syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l. MANAGEMENT: Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.

Frequent RET rearrangements in thyroid papillary microcarcinoma detected by interphase fluorescence in situ hybridization.

Papillary thyroid microcarcinomas (measuring 1 cm or less in diameter) are very common thyroid tumors, which are present in 10% to 35% of post-mortem histopathological examinations of individuals whose death was due to a cause other than thyroid cancer. The molecular basis of this tumor is still poorly understood. Somatic mutations are better characterized in clinically evident papillary thyroid carcinomas (PTCs), the most common involving the proto-oncogene RET, which maps to 10q11.2. Molecular alterations of RET always lead to intra- or interchromosomal rearrangements. In this study we have investigated the status of RET in 21 microcarcinomas, by means of interphase fluorescence in situ hybridization (FISH). RET was rearranged in 52% of microcarcinomas, a statistically significant higher frequency than that found previously in clinically evident PTCs using the same technique. Moreover, interphase FISH allowed us to detect a putative novel type of rearrangement in a microcarcinoma, and we observed trisomies of chromosome 10 and other chromosomes in two adenomas surrounding two of the microcarcinomas. The strikingly high frequency of RET rearrangements in microcarcinomas strongly suggests that RET plays a role in the initiation of thyroid tumorigenesis but does not seem to be necessary for the further progression of the tumor.

RET rearrangements in familial papillary thyroid carcinomas.

Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized by a more aggressive phenotype than that of its sporadic counterpart. Its mode of inheritance as well as its genetic and molecular bases are still poorly understood. On the contrary, genetic alterations in sporadic papillary thyroid carcinoma (PTC) are better characterized, the most common one involving the activation of the proto-oncogene RET through somatic rearrangements. In the present study, we investigated by interphase fluorescence in situ hybridization the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC and the adenoma from the same patient carry a RET rearrangement (type PTC1) and that this rearrangement is absent in the germline. Furthermore, we excluded a RET haplotype sharing in two brothers of the same family. These results show that RET rearrangements can indeed be found in FPTC and confirm that RET is not involved in the inherited predisposition to FPTC.

Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.

Exploration of cyclical changes in memory and mood in postmenopausal women taking sequential combined oestrogen and progestogen preparations.

OBJECTIVE: To investigate the effect of progesterone on cognitive function, mood, sleep quality and libido when added to oestrogen in sequential combined hormonal replacement therapy regimens. DESIGN: Observational study over three hormonal replacement therapy cycles. SETTING: Menopause Centre of Ospedale Maternità, Bologna, Italy. POPULATION: Twenty-three postmenopausal women with an average of 70 months of amenorrhoea (range 12 to 234 months) on different sequential combined hormonal replacement therapy regimen for an average of 15 months (range 3-48) months. METHODS: Psychological testing for memory, mood, sleep quality and libido during the oestrogen only part of the cycle compared with the oestrogen-progestogen part of the cycle. RESULTS: Twenty women completed the six visits of the trial. The addition of progestogens to oestrogen appeared to benefit memory (P < 0.01) but worsened mood (P < 0.005). There was no evidence of change in other parameters such as sleep quality or libido. CONCLUSION: The addition of progestogens improved memory above what was obtained with oestrogen alone. This effect did not depend on an improvement of mood since the latter worsened during the progestogenic phase of an hormonal replacement therapy cycle. Progestogen added to oestrogen did not significantly influence sleep or libido.

Detection and diagnosis of parathyroid incidentalomas during thyroid sonography.

PURPOSE: The aim of our study was to evaluate the incidence of incidentally found parathyroid adenomas (incidentalomas) in patients undergoing sonography of the neck for thyroid disease. METHODS: A total of 1,686 patients (305 men and 1,381 women) underwent sonography of the neck; the mean age was 49.6 +/- 21.7 years. In 38 patients (2.3%; 7 men and 31 women) with a mean age of 48.7 +/- 14.7 years, hypoechoic, homogeneous, oval nodules (mean volume, 1.0 +/- 0. 9 cm(3)) adjacent to the thyroid parenchyma were observed. All these lesions, compatible with the shape of an enlarged parathyroid gland, underwent ultrasound-guided fine-needle aspiration biopsy (FNAB), with measurement of parathyroid hormone (PTH) and thyroglobulin (Tg) levels in the needle washings (FNAB-PTH and FNAB-Tg). Biochemical screening for hyperparathyroidism was also performed. RESULTS: Cytologic examination plus FNAB-PTH/FNAB-Tg measurements revealed the presence of cellular material consistent with parathyroid tissue in 9 patients (24%), thyroid tissue in 22 patients (58%), and lymphoid tissue in 4 patients (11%). A tissue diagnosis was not established in 3 patients (8%). Five of 9 patients with parathyroid enlargement had high serum PTH and calcium levels. CONCLUSIONS: Enlarged parathyroid glands may be incidentally discovered during sonography of the thyroid. In patients with thyroid disease, the positive-predictive value of sonography in the identification of parathyroid tissue was low. Ultrasound-guided FNAB-PTH determination should be carried out when parathyroid adenoma is suspected. The incidental finding of an enlarged parathyroid may or may not be associated with yet undiagnosed hyperparathyroidism.

Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer.

The identification of metastatic neck lymph nodes in patients awaiting surgery for differentiated thyroid tumor permits their excision during thyroidectomy. In order to detect thyroid cancer lymphatic metastasis before surgery, we measured thyroglobulin (Tg) in the needle wash-out of fine-needle aspiration biopsy (FNAB). Ultrasound-guided FNAB on enlarged neck nodes was performed in 23 patients awaiting surgery for differentiated thyroid tumor (n = 33 lymph nodes), 47 patients previously thyroidectomized for thyroid tumor (n = 89 lymph nodes), and 60 patients without thyroid disease (n = 94 lymph nodes). Immediately after aspiration biopsy, the needle was rinsed with 1 mL of normal saline solution and Tg levels were measured on the needle wash-out (FNAB-Tg). FNAB-Tg levels were markedly elevated in metastatic lymph nodes both in patients awaiting thyroidectomy (metastatic vs. negative lymph nodes, mean +/- SEM, 16,593 +/- 7,050 ng/mL vs. 4.91 +/- 1.61 ng/mL; p < 0.001) and in thyroidectomized patients (11,541 +/- 7,283 ng/mL vs. 0.45 +/- 0.07 ng/mL; p < 0.001). FNAB-Tg sensitivity, evaluated through histological examination in 69 lymph nodes, was 84.0%. The combination of cytology plus FNAB-Tg increased FNAB sensitivity from 76% to 92.0%. In conclusion, FNAB-Tg measurement is a useful technique for early diagnosis of lymph node metastasis originating from differentiated thyroid cancer.

Pulsatile gonadotrophin secretion in hypothyroid women of reproductive age.

Hypothyroid women may have various disturbances of the reproductive system. Although menstrual cycle disturbances and infertility have been reported in hypothyroidism, gonadotrophin levels have usually been found in the normal range. We have investigated whether female hypothyroid patients of reproductive age have any alteration in the pulsatile secretory pattern of gonadotrophin secretion. LH and FSH were assayed on days 2-5 of the menstrual cycle in blood samples taken every 10 min for 8 h from six hypothyroid women and six age-matched control subjects. Pulsatility was analysed using the Cluster and Detect programs. There was no significant difference in the number of peaks identified (3.7 +/- 0.8 vs 3.7 +/- 0.8 for LH, and 3.7 +/- 0.8 vs 4.2 +/- 0.5 for ESH), the mean duration of peaks (LH: 68.0 +/- 6.9 vs 72.7 +/- 5.1 min; FSH: 81.9 +/- 8.1 vs 71.2 +/- 10.3 min), the area under the peaks (LH: 91.5 +/- 20.4 vs 148.2 +/- 55.1 IU/l per min; FSH: 71.5 +/- 4.5 vs 62.7 +/- 15.0 IU/l per min), and the incremental amplitude from baseline (LH: 2.2 +/- 0.4 vs 3.0 +/- 0.8 IU/l; FSH: 1.4 +/- 0.2 vs 2.1 +/- 0.5 IU/ l). However, the absolute pulse amplitude was greater in hypothyroid patients (LH: 14.5 +/- 1.4 vs 8.3 +/- 1.3 IU/l, P < 0.01; FSH: 9.0 +/- 1.5 vs 5.8 +/- 1.2 IU/l, P = 0.04), as were the integrated concentrations (LH: 6.6 +/- 0.7 vs 3.2 +/- 0.4 IU/l per min, P < 0.01; FSH: 4.3 +/- 0.4 vs 2.1 +/- 0.5 IU/l per min, P < 0.01). Oestradiol values were comparable in the two groups (42.7 +/- 0.4 vs 43.5 +/- 9.7 pg/ml). These results indicate that in hypothyroid women there is an increased baseline level with a normal pulsatility of the gonadotrophin secretion. Similar oestrogen levels in both groups, and normal or near-normal cycles in our patients suggest either a decreased biological potency of the gonadotrophins or a mild ovarian resistance.

Effects of trimetazidine on the calcium transport and oxidative phosphorylation of isolated rat heart mitochondria.

Trimetazidine (TMZ) added in vitro to isolated cardiac mitochondria at concentrations 10-100 microM in the presence of 25-100 nM extramitochondrial Ca2+ increased Ca2+ uptake and matrix Ca2+ concentration. This effect was less evident in the presence of physiologically Na+ and Mg2+ extramitochondrial concentrations since only 100 microM TMZ was able to increase mitochondrial Ca2+ entry in the presence of 100 nM Ca2+. The drug stimulated a Ca(2+)-cooperative effect on mitochondrial Ca2+ transport, but did not modify the rate of Ca2+ egress stimulated by 10 mM NaCl. An increase in mitochondrial Ca2+ level produced by TMZ enhanced oxoglutarate dehydrogenase activity and then ATP synthesis, particularly when 50 nM extramitochondrial Ca2+ was used. These data suggest that a possible cardiac mechanism of action of TMZ at mitochondrial level could support ATP synthesis by elevating the mitochondrial Ca2+ level.

Role of the human CD38 molecule in B cell activation and proliferation.

Human CD38 is a surface molecule which has been attributed the function of a signaling channel leading to cellular activation and proliferation, an ectoenzyme with multiple function as well as an inducer of Ca2+ mobilization from cytoplasmic stores. The effect mediated by CD38 have been studied in different cell populations: the results obtained in human B cells are apparently contradictory, with CD38 simultaneously leading to apoptosis in early B cells while increasing survival in cells derived from lymph node germinal center. Other effects recently reported concern a different potential in terms of signaling in early B cells and derived cell lines or in more detailed disease models of human leukemia, namely B chronic lymphocytic leukemia cells. To complete the picture of the effects mediated by CD38 in the B cell compartment, we have studied the signals elicited by ligation of the human molecule in mature B cells from circulating pool and also from spleen of normal individuals. The information obtained completes the picture of CD38 and mature B cells, where we also studied the contribution of relevant cytokines involved in maintenance and differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6. Our results indicate that human CD38 plays a key role as a co-receptor in mature B cells from normal individuals.

Testicular function in hypercholesterolemic male patients during prolonged simvastatin treatment.

Simvastatin is a very effective hypocholesterolemic drug which, reducing cholesterol biosynthesis, can affect normal steroid hormone production. Testes require a continuous cholesterol supply for testosterone synthesis and this can be derived from low density lipoprotein receptor-mediated uptake or from de novo local synthesis. The aim of the study was to see if prolonged simvastatin treatment compromised endocrine testicular function both in basal conditions and after stimulation by human Chorionic Gonadotropin (hCG) (Profasi 5,000 Ul, i.m. at 8 a.m.). Free testosterone (FT) levels were determined at baseline and after 3, 6 and 12 months of simvastatin treatment (20 mg/day) in eight hypercholesterolemic patients. At the same time we performed a hCG stimulation test to evaluate testicular reserve. A significant reduction of FT, both basal and hCG-stimulated, was observed in the 6th and the 12th month of the study. However, FT levels remained in the normal range and no patient complained of gonadal function related symptoms. No significant change was observed in estradiol response to hCG test. Lastly, there was no variation in LH, FSH, progesterone, 17-OH-progesterone, androstenedione or dehydroepiandrosterone-sulphate levels. Our study concluded that the drug causes a mild decline in FT secretion without any clinical sign of testicular dysfunction.

Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment.

We studied the effects of GH administration on myocardial structure and function in 20 patients with hypopituitarism (14 males and 6 females; mean +/- SE age, 47.2 +/- 2.6 yr; range, 31-59 yr) developed in adulthood because of pituitary or parapituitary tumors. All patients had GH deficiency (GHD), as assessed by a GH response of less than 4 micrograms/L to a standard insulin tolerance test (0.05 U kg, iv) and the combined pyridostigmine (120 mg, orally, at -60 min) plus GHRH (1 microgram/kg, iv, at 0 min) test. Patients received either placebo (n = 10) or GH substitution therapy (n = 10; 0.05 U/kg.day GH for 1 yr; 0.03 U/kg.day during the first month). M- and B-mode echocardiography and pulsed Doppler examination of transmitral flow were performed before treatment, 6 months and 1 yr after starting GH or placebo administration, and 15 days and 3 months after GH or placebo withdrawal. Twenty healthy subjects, matched for age, sex, body mass index, and physical activity, served as controls. Left ventricular dimensions, mass, and systolic function were normal in patients with adult-onset GHD; however, diastolic function, specifically E wave deceleration time, was altered. GH administration markedly increased left ventricular performance and reversed diastolic abnormalities at 6 and even more so at 12 months. On the other hand, a clear increase in left ventricular mass was seen after 12, but not after 6, months of GH administration (P < 0.01 vs. pretreatment values). In addition, although all changes induced by GH treatment disappeared within 3 months after GH withdrawal, at that time the increase in left ventricular mass was still detectable (P < 0.05 vs. pretreatment values). These data indicate that augmented left ventricular contractility is not strictly related to cardiac muscle growth, supporting the hypothesis that GH treatment increases the inotropic activity of myocardial fibers. In conclusion, GH treatment enhances cardiac function, increases cardiac mass, and reverses diastolic abnormalities in adults with hypopituitarism and GHD. However, long term studies are required to demonstrate that GH replacement therapy reduces cardiac death rate in these patients.

Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase.

Mast cell growth factor (MGF) (also called stem cell factor) synergizes with several lymphokines, including interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), to promote proliferation and differentiation of certain hemopoietic progenitor cells. Although similar patterns of tyrosine-phosphorylated proteins characterize cells stimulated by MGF, IL-3, and GM-CSF, only the MGF receptor is a tyrosine kinase, and the heterodimeric receptors for IL-3 and GM-CSF share a common beta subunit that is devoid of enzymatic activity. Here we show that signaling pathways utilized by all three cytokines include the cytoplasmic tyrosine kinase JAK2. Analysis of several factor-dependent myeloid cell lines indicated that JAK2 is physically associated with the common beta subunit and with MGF receptor (c-Kit) even prior to ligand binding. However, each of the ligands induced elevated tyrosine phosphorylation of JAK2 and a consequent increase in its catalytic activity. These results demonstrate for the first time the convergence within the same myeloid cells of signaling pathways originating in two distinct lymphokine receptors and a tyrosine kinase receptor on activation of a cytoplasmic tyrosine kinase.

Disturbances in the production of interleukin-1 and tumor necrosis factor in disseminated murine sporotrichosis.

Production of Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) by adherent peritoneal cells from BALB/c mice was measured at week 2, 4, 6, 8 and 10 after intravenous inoculation with 10(6) Sporothrix schenckii yeasts. As compared with age-matched controls, IL-1 and TNF production by adherent peritoneal cells from S. schenckii-infected mice was reduced severely at week 4 and 6 of infection and greater than normal at week 8 and 10. Moreover, between week 4 and 6 of infection there was a depression of delayed type hypersensitivity response to a specific whole soluble antigen, and an increase in fungal multiplication in the livers and spleens of infected mice. Thus, the deficits of cell-mediated immunity in mice with systemic S. schenckii infection may derive, in part, from impaired amplification of the immune response consequent to abnormal generation of IL-1 and TNF.

Vasoactive intestinal peptide-induced prolactin release in hypothyroid patients.

VIP is an established prolactin-releasing factor. VIP gene expression at the anterior pituitary level and the central nervous system is regulated by thyroid hormones. On the other hand, primary hypothyroidism leads in many cases to amenorrhea, galactorrhea and hyperprolactinemia. In this study we assessed prolactin responses to VIP (75 micrograms iv infusion over 12 min) in a group of six hypothyroid women (mean age +/- SE, 38.8 +/- 3.3 yr; serum TSH levels, mU/L, 116.3 +/- 23.9), before treatment and after normalization of thyroid hormone levels during thyroxine (T4) replacement therapy (100-150 micrograms/day over 12-16 weeks). Furthermore, we assessed if VIP infusion had any effects on serum GH levels in these patients. In hypothyroid women, VIP infusion increased serum prolactin concentrations with peak levels being attained at 15 min (28.8 +/- 3.4 micrograms/L). The Area Under the Curve (AUC) was 1921 +/- 103 micrograms/L/2h. PRL responses to VIP were unchanged after T4 therapy, both in terms of peak levels (28.7 +/- 2.2 micrograms/L, NS) and of AUC (2079 +/- 261 micrograms/L/2h, NS). Serum GH levels were unaffected by VIP administration. In conclusion our study shows that, in hypothyroid patients, restoration of normal thyroid hormone levels by thyroxine replacement therapy does not affect lactotroph responsiveness to VIP. Therefore, our data do not support the hypothesis that VIP might contribute to the hypothyroid-induced hyperprolactinemia seen in man.