Short-Term Decline in Prolactin Concentrations Can Predict Future Prolactin Normalization,Tumor Shrinkage,and Time to Remission in Men with Macroprolactinomas

Objective: To identify early follow-up measures that will predict the dynamics of prolactin (PRL) decrease and adenoma shrinkage in men harboring macroprolactinomas.Methods: A single-center historical prospective study including a consecutive group of 71 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (PRL >7 times the upper limit of normal &lsqb;ULN]) treated medically with cabergoline. Comparisons of PRL normalization rates were performed according to PRL levels achieved at 6 months, maximal adenoma shrinkage during follow-up, and other patient characteristics. Correlations were analyzed to identify characteristics of PRL suppression dynamics.Results: PRL levels after 6 months of treatment correlated positively with current PRL levels (r = 0.74; P<.001), with time to PRL normalization (r = 0.75; P<.001), and with adenoma diameter following treatment (r = 0.38; P = .01). Adenoma shrinkage depicted by first magnetic resonance imaging on treatment correlated with maximal adenoma shrinkage during follow-up (r = 0.56; P = .006). Five patients had nadir PRL levels ≥3 times the ULN (51 ng/mL) and showed slower response to cabergoline treatment, with consistently higher PRL levels compared with responding patients throughout follow-up (mean 6-month PRL levels, 519 ± 403 ng/mL versus 59 ± 118 ng/mL; P<.001).Conclusion: Six-month PRL level might serve as a surrogate marker for PRL normalization and adenoma shrinkage dynamics among men harboring macroprolactinomas.Abbreviations: CAB = cabergoline MRI = magnetic resonance imaging PRL = prolactin RMC = Rabin Medical Centre ULN = upper limit of normal     

The Effect of Raloxifene on Serum Prolactin Level in Patients with Prolactinoma

Objective: To evaluate the effect of raloxifene on prolactin (PRL) levels in addition to dopamine agonist (DA) therapy in patients with prolactinoma.Methods: We conducted a retrospective chart review of 14 patients with prolactinoma on stable dose of DA for 6 months who received raloxifene 60 mg daily, as PRL could not be normalized despite being on fairly high doses of DA. Patients were informed that raloxifene is not approved by the Food and Drug Administration for prolactinoma treatment. PRL level was measured at 1 to 6 months after starting raloxifene and at 1 to 3 months following its discontinuation. Raloxifene was stopped in 8 out of 14 patients after 2 (1 to 6) months of treatment as the absolute change in PRL level was felt to be small.Results: The median age and female/male sex ratios were 50 years (range 18 to 63 years), 6/8 respectively. The baseline DA dose was 3 mg/week (0.5 to 7 mg/week) for cabergoline and 15 mg/day for bromocriptine. Ten patients had an absolute and percentage decrease in PRL of 8.3 ng/mL (1.5 to 54.2 ng/mL) and 25.9% (8 to 55%) from baseline, respectively, after 1 to 6 months on raloxifene treatment. Among 10 patients with a decrease in PRL level, 2 (20%) achieved PRL normalization. Two patients had no change in PRL and two patients had an increase in PRL level by 22.8 ng/mL and 8.8 ng/mL (47% and 23.6%), respectively.Conclusion: Raloxifene was associated with a 25.9% (8 to 55%) decrease in PRL level in 10/14 (71%) patients with prolactinoma who were on stable doses of DA including 2 patients (14%) who achieved normoprolactinemia.Abbreviations: CV = coefficient of variation; DA = dopamine agonist; FSH = follicule-stimulating hormone; LH = luteinizing hormone; PRL = prolactin; PTTG = pituitary tumor transforming gene     

Prolactin Levels Do Not Rise Among Transgender Women Treated With Estradiol and Spironolactone

Objective: Existing transgender treatment guidelines suggest that there is a need to monitor prolactin levels in patients receiving transfeminine hormone treatment. Also, recent studies suggest that use of cyproterone acetate as an adjunctive anti-androgen during transgender hormone treatment may elevate serum prolactin. We sought to determine whether the reported relationship between transfeminine estradiol treatment and hyperprolactinemia would be evident when the regimen used spironolactone as the adjunctive anti-androgen.Methods: Estradiol levels, testosterone levels, prolactin levels, body mass index (BMI), and prescribed spironolactone dosage were extracted from the electronic medical records of 98 de-identified transgender women treated with estrogen therapy at the Endocrinology Clinic at Boston Medical Center (BMC). Up to 6 years of data were available for some patients.Results: We found no statistically significant relationship between prolactin and any of the other measures. No estrogen dose-associated elevations in prolactin were found. None of the patients were diagnosed with prolactinoma.Conclusion: Our data suggest that there may be no significant rise in prolactin when transgender women are treated with estrogen along with spironolactone as the adjunct anti-androgen. It may be unnecessary to monitor prolactin in patients on this treatment combination.Abbreviations: BMI = body mass index; BMC = Boston Medical Center; HT = hormone therapy     

Hyperthyroidism and Hyperprolactinemia: Is There any Association?

Objective: To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism.Methods: Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age.Results: The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001).Conclusion: The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism.Abbreviations:PRL = prolactinT4 = thyroxineTRH = thyrotropin-releasing hormoneTSH = thyroid-stimulating hormone     

Serial Changes of Liver Function Tests before and during Methimazole Treatment in Thyrotoxic Patients

Objective: Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients.Methods: We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment.Results: At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation.Conclusion: MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated.Abbreviations:ALT = alanine aminotransferaseAST = aspartate aminotransferasefT4 = free thyroxineHCV = hepatitis C virusLFT = liver function testLOCF = last observation carried forwardMMI = methimazolePTU = propylthiouracilTSH = thyroid-stimulating hormoneULN = upper limit of normal     

American Association of Clinical Endocrinologists,American College of Endocrinology Disease State Clinical Review: Clinical Relevance of Macroprolactin in the Absence or Presence of True Hyperprolactinemia

Objective: To review the current literature regarding the prevalence of macroprolactin (macroPRL) in hyperprolactinemic patients and determine recommendations for testing.Methods: An electronic United States National Library of Medicine PubMed search was conducted for search term “macroprolactin.” Only English-language articles were considered.Results: MacroPRL is an under-recognized cause of elevated prolactin (PRL) and is present in approximately 4% to 40% of hyperprolactinemic patients depending on the referral population. Clinical findings which could be due to hyperprolactinemia are the impetus for testing for PRL. Because of this there is significant overlap in the clinical presentation of patients with true hyperprolactinemia and those with macroPRL, differentiation cannot always be made on the basis of symptoms. A lack of recognition of the presence of macroPRL can lead to unnecessary laboratory investigations, imaging, and pharmacologic or surgical treatment.Conclusion: Until there is a commercially available PRL assay that is not subject to interference by macroPRL, clinicians should consider the possibility of macroPRL, especially if the clinical presentation, imaging findings, and/or response to therapy reveal inconsistenciesAbbreviations:DA = dopamine agonistGFC = gel filtration chromatographyIgG = immunoglobulin GmacroPRL = macroprolactinMMP3 = matrix metalloproteinase-3NS = nonsignificantPEG = polyethylene glycolPRL = prolactinRA = rheumatoid arthritisSLE = systemic lupus erythematosus     

Medical Treatment Landscape for Active Acromegaly in A Pituitary Center in Israel

Objective: To evaluate current real-life experience with medical treatment for active acromegaly in a large cohort.Methods: Data on demographic parameters, blood tests, imaging studies, and treatments were extracted from the medical records.Results: The cohort included 87 patients (43 male) with active acromegaly. The mean age at diagnosis was 40.2 ± 11.4 years, and the mean duration of follow-up was 7.9 ± 5.8 years. Seventy patients presented with a macroadenoma. Mean baseline insulin growth factor 1 (IGF-1) (n = 67) was 3.2 ± 1.9 × upper limit of normal (ULN). Surgery and radiotherapy were performed in 75 and 10 patients, respectively. Currently, 38 subjects receive somatostatin analogues, pegvisomant as a monotherapy is given to 8 patients, pasireotide is given to 17 patients, cabegoline to 4 patients, estrogen to 2 females, and SSAs combined with pegvisomant to 10 patients. Eight patients are not being actively treated, including 4 following radiotherapy. Good biochemical control (IGF-1 <1.3 × ULN) was achieved in 76 patients (87%), and 11 patients (13%) are currently uncontrolled (IGF-1 >1.3 × ULN). Seventy-eight percent of controlled patients are being given 1 medication; 11% are on combination therapy; 4 patients are well controlled after radiotherapy and 2 are partially controlled without any treatment. The main adverse effects of treatment were diabetes mellitus in 7 patients (on pasireotide) and symptomatic cholelithiasis in 5 patients.Conclusion: Active acromegaly can be controlled medically in most patients, with a low rate of adverse effects. This study displays the characteristic variety of treatment options available for active acromegaly.     

Pituitary Mri Findings in Patients With Pituitary and Ectopic Acth-Dependent Cushing Syndrome: Does A 6-Mm Pituitary Tumor Size Cut-Off Value Exclude Ectopic Acth Syndrome?

Objective: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS).Methods: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS.Results: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3–14) and 8 mm (2–31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN)Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.Abbreviations: ACTH = adrenocorticotropic hormone CD = Cushing disease CRH = corticotropin-releasing hormone CS = Cushing syndrome EAS = ectopic ACTH secretion IPSS = inferior petrosal sinus sampling HDDST = high-dose dexamethasone suppression test LDDST = low-dose dexamethasone suppression test MRI = magnetic resonance imaging UFC = urine free cortisol ULN = upper limit of normal     

Biochemical Responses in Symptomatic and Asymptomatic Patients with Neuroendocrine Tumors: Pooled Analysis of Two Phase 3 Trials

Objective: Neuroendocrine tumors (NETs) are associated with elevated 5-hydroxyindoleacetic acid (5-HIAA) and chromogranin A (CgA) levels. This study aimed to analyze relationships between urinary 5-HIAA and plasma CgA levels and clinical outcomes.Methods: Centrally assessed biomarker levels and correlations with progression-free survival (PFS) and carcinoid syndrome (CS) symptom control were evaluated in a pooled analysis of CLARINET (96-week randomized, double-blind, placebo-controlled) and ELECT (16-week randomized, double-blind, placebo-controlled, 32-week initial open label and ≥2 year long-term extension open label) studies of adults with NETs, with (ELECT) or without (CLARINET) CS at 97 institutions. Patients were treated with subcutaneous lanreotide depot 120 mg monthly.Results: Of 319 pooled patients, 86% and 95% had baseline 5-HIAA and CgA data, respectively, with 47% and 74% having levels greater than the upper limit of normal (ULN). PFS was longer among patients who experienced a decrease in biomarker levels at week 12, with statistical significance reached in the CgA cohort (not reached vs. 14.4 months; P<.0001). A large proportion (87%) of patients without symptoms of CS in the CLARINET study had detectable levels of 5-HIAA (48% >ULN). In ELECT, patients with CS who received lanreotide and experienced a biochemical response (≥50% decrease from baseline) achieved greater symptom control.Conclusion: This pooled analysis of two randomized, placebo-controlled trials demonstrated that 5-HIAA and CgA are secreted as biochemical biomarkers in many patients with NETs, regardless of clinical syndromes. Significant biochemical response was associated with improved clinical outcomes, as measured by improved PFS or improved CS symptom control.Abbreviations: 5-HIAA = 5-hydroxyindoleacetic acid; CgA = chromogranin A; CI = confidence interval; CLARINET = Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors; CS = carcinoid syndrome; ELECT = Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment; HR = hazard ratio; ITT = intention-to-treat; NET = neuroendocrine tumor; PanNET = pancreatic NET; PFS = progression-free survival; PPI = proton pump inhibitor; SSA = somatostatin analogue; ULN = upper limit of normal     

Pituitary Dysfunction in Patients with Intracranial Germ Cell Tumors Treated with Radiotherapy

Objective:To evaluate the endocrine abnormalities in intracranial germ cell tumors (iGCTs) treated with radio-therapy (RT), and to discuss the effects of RT on pituitary functions.Methods: Seventy-seven patients diagnosed with iGCTs who had received RT and endocrine follow-up in Huashan Hospital between January 2010 and July 2017 were retrospectively analyzed, consisting of 49 germinomas and 28 NGGCTs. The median follow-up period was 50.0 months. Fifty-one patients had radiologically proved suprasellar/sellar lesions.Results: The male to female ratio was 62/15. The median endocrine follow-up period was 19 (4, 42) months. The median age at the last endocrine visit was 18 (16, 20) years old. The 5-year overall and recurrence-free survival were both 98.7%. The overall prevalence of central adrenal insufficiency (CAI), central hypothyroidism (CHT), central hypogonadism (CHG), hyperprolactinemia, and central diabetes insipidus (CDI) was 57.3%, 56%, 56.6%, 35.3%, and 52.1%, respectively, after RT. Patients having suprasellar/sellar lesions showed significantly higher post-therapeutic prevalence of hypopituitarism than those who didn’t. Compared to that before RT, CAI, CHT, and CHG weren’t significantly improved while the levels of prolactin and the prevalence of CDI declined significantly (P =.03 and.001). The radiation doses to pituitary and hypothalamus between those with and without CAI, CHT, and CHG weren’t significantly different.Conclusion: The prevalence of hypopituitarism was high in iGCTs, especially in those with suprasellar/sellar involvement. The levels of prolactin and the prevalence of CDI declined significantly after RT. The hypopituitarism in iGCTs was mainly induced by tumor effects, and RT showed no additional damage to pituitary functions in our study.Abbreviations: AFP = alpha-fetoprotein; CAI = central adrenal insufficiency; CDI = central diabetes insipidus; CHG = central hypogonadism; CHT = central hypothyroidism; CT = computed tomography; DA = dopamine; GH = growth hormone; βHCG = beta-human chorionic gonadotropin; HPA = hypothalamus-pituitary-adrenal; HPG = hypothalamus-pituitary-gonadal; HPL = hyperprolactinemia; HPT = hypothalamus-pituitary-thyroid; iGCT = intracranial germ cell tumor; IGF-1 = insulin-like growth factor 1; NGGCT = nongerminomatous germ cell tumors; OS = overall survival; PFS = progression-free survival; PRL = hypothalamus-pituitary-prolactin; RT = radiotherapy     

Serum Prolactin and Macroprolactin Levels among Outpatients with Major Depressive Disorder Following the Administration of Selective Serotonin-Reuptake Inhibitors: A Cross-Sectional Pilot Study

Clinical trials evaluating the rate of short-term selective serotonin-reuptake inhibitor (SSRI)-induced hyperprolactinemia have produced conflicting results. Thus, the aim of this study was to clarify whether SSRI therapy can induce hyperprolactinemia and macroprolactinemia. Fifty-five patients with major depressive disorder (MDD) were enrolled in this study. Serum prolactin and macroprolactin levels were measured at a single time point (i.e., in a cross-sectional design). All patients had received SSRI monotherapy (escitalopram, paroxetine, or sertraline) for a mean of 14.75 months. Their mean prolactin level was 15.26 ng/ml. The prevalence of patients with hyperprolactinemia was 10.9% for 6/55, while that of patients with macroprolactinemia was 3.6% for 2/55. The mean prolactin levels were 51.36 and 10.84 ng/ml among those with hyperprolactinemia and a normal prolactin level, respectively. The prolactin level and prevalence of hyperprolactinemia did not differ significantly within each SSRI group. Correlation analysis revealed that there was no correlation between the dosage of each SSRI and prolactin level. These findings suggest that SSRI therapy can induce hyperprolactinemia in patients with MDD. Clinicians should measure and monitor serum prolactin levels, even when both SSRIs and antipsychotics are administered.     

The Efficacy and Safety of Co-Administration of Sitagliptin With Metformin in Patients With Type 2 Diabetes at Hospital Discharge

Objective: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D.Methods: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53–75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge.Results: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months (P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups.Conclusion: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D.Abbreviations: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes     

Impaired Awareness of Hypoglycemia Continues to be a Risk Factor for Severe Hypoglycemia Despite the Use of Continuous Glucose Monitoring System in Type 1 Diabetes

Objective: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in patients with type 1 diabetes (T1D) not using a continuous glucose monitoring (CGM) system. The current study investigated the prevalence of IAH and its relationship with severe hypoglycemia in T1D patients using CGM systems.Methods: This cross-sectional observational study enrolled 135 patients with T1D and ongoing real-time CGM use. A survey was conducted to assess hypoglycemia awareness with the Gold, Clarke, and Pedersen-Bjergaard questionnaires and the 6-month history of severe hypoglycemia. Other diabetes histories and the CGM glucose data were collected.Results: The Gold, Clarke, and Pedersen-Bjergaard questionnaires demonstrated the overall prevalence of IAH/abnormal awareness to be 33.3%, 43.7%, and 77.0%, respectively. Participant age and duration of T1D were consistently related to IAH or hypoglycemia unawareness with all three questionnaires (P<.05). Amongst the patients using CGM for >6 months, 24.5% were found to have at least one episode of severe hypoglycemia in the preceding 6 months. IAH identified by the Gold and Clarke questionnaires and hypoglycemia unawareness identified by the Pedersen-Bjergaard questionnaire were related to 6-, 4.63-, and 5.83-fold increased risk of severe hypoglycemia (P = .001, .004, and .013), respectively. IAH identified by the Gold/Clarke questionnaires was associated with a longer duration of CGM glucose <54 mg/dL and higher glucose coefficients of variation (P<.05).Conclusion: IAH is highly prevalent and related to a higher risk for severe hypoglycemia in T1D patients using CGM.Abbreviations: CGM = continuous glucose monitoring; CI = confidence interval; HAAF = hypoglycemia-associated autonomic failure; HbA1c = hemoglobin A1C; IAH = impaired awareness of hypoglycemia; T1D = type 1 diabetes     

Endocrine Dysfunction and Follow-Up Outcomes in Patients With Pituitary Abscess

Objective: Endocrine dysfunction caused by pituitary abscess (PA) and its outcomes have not been fully studied. This study aims to investigate endocrine dysfunction and outcomes in patients with PA.Methods: Eight patients (3 males and 5 females) with PA were identified for collecting clinical, hormone, and therapeutic data before and after long-term follow-up lasting 12 to 116 months (median, 25 months) since the first hospitalization, which was regarded as the baseline time. All patients' pituitary and respective target gland functions were evaluated. Six patients had acute onset (less than 1 month), and the other 2 patients had chronic onset (more than 6 months). Five patients underwent surgical therapy, and the other 3 patients underwent conservative therapy. The factors associated with endocrine outcome were analyzed as well.Results: At baseline, the release of 91.7% (22 of 24 total) of pituitary tropic hormones was impaired, but 59.1% (13 of 22) had normalized by the last follow-up. Male gender, acute onset mode, and normal baseline prolactin level seemed to be the factors that favored tropic hormone normalization, whereas surgical operation was not. Two patients received provocative test suggesting decreased reserves of both somatotrophin and prolactin or only somatotrophin. Only 1 patient suffered from permanent diabetes insipidus.Conclusion: The production of almost all pituitary tropic hormones was impaired with PA in the present study, but production of nearly 60% percent of the hormones normalized during follow-up of >1 year. A chronic abscess state may be the most important factor associated with permanent hormone deficiency.Abbreviations: ACTH = adrenocorticotropic hormone GnH = gonadotrophin MRI = magnetic resonance imaging PA = pituitary abscess TSH = thyroid-stimulating hormone     

Performance of A1C Versus Ogtt for the Diagnosis of Prediabetes in a Community-Based Screening

Objective: Reliable identification of individuals at risk for developing diabetes is critical to instituting preventative strategies. Studies suggest that the accuracy of using hemoglobin A1c as a sole diagnostic criterion for diabetes may be variable across different ethnic groups. We postulate that there will be lack of concordance between A1c and the oral glucose tolerance test (OGTT) for diagnosing prediabetes across Hispanic and non-Hispanic white (NHW) populations.Methods: A total of 218 asymptomatic adults at risk for type 2 diabetes (T2D) were assessed with A1c and OGTT for the diagnosis of prediabetes. Glucose homeostasis status was assigned as no diabetes (A1c <5.7% [39 mmol/mol]), prediabetes (A1c 5.7 to 6.4% [46 mmol/mol]), and T2D (A1c >6.4% [46 mmol/mol]). Inclusion criteria were age >18 years and at least one of the following: a family history of diabetes, a history of gestational diabetes, Hispanic ethnicity, non-Caucasian race, or obesity. Subjects received a fasting 75-g OGTT and A1c on the same day. Bowker's test of symmetry was employed to determine agreement between the tests.Results: Data from 99 Hispanic patients and 79 NHW patients were analyzed. There was no concordance between A1c and OGTT for Hispanic (P =.002) or NHW individuals (P =.003) with prediabetes.Conclusion: A1c is discordant with OGTT among Hispanic and NHW subjects for the diagnosis of prediabetes. Sole use of A1c to designate glycemic status will result in a greater prevalence of prediabetes among Hispanic and NHW New Mexicans.Abbreviations:A1c = hemoglobin A1cBMI = body mass indexCDC = Centers for Disease ControlCI = confidence intervalFPG = fasting plasma glucoseNHW = non-Hispanic whiteOGTT = oral glucose tolerance testT2D = type 2 diabetesWHO = World Health Organization     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio &lsqb;OR], 3.45; 95% confidence interval &lsqb;CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Comparison of Cabergoline Versus Raloxifene Add-On Therapy to Long-Acting Somatostatin Analogue in Patients With Inadequately Controlled Acromegaly: A Randomized Open Label Clinical Trial

Objective: The present study aimed to evaluate the efficacy of add-on therapy of cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in patients with inadequately controlled acromegaly.Methods: This was a prospective, randomized open label clinical trial. Forty-four patients (22 per group) completed the study; where participants received either cabergoline (3 mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a parallel manner. The primary outcome was the rate of reduction in serum insulin-like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised normalization of serum IGF-1 for age and sex.Results: Serum IGF-1 was significantly decreased in both the cabergoline (40.3 ± 25.6%, P<.001) and raloxifene (31.5 ± 24.6%, P<.001) groups, with no significant difference between arms (P>.05). Normalization in serum IGF-1 values occurred in 40.9% of patients who were on cabergoline compared to 45.5% of those receiving raloxifene (P = .76). The subsequent logistic regression analysis highlighted baseline IGF-1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95% confidence interval, 0.990–0.999; P = .02). Using the receiver operating characteristic (ROC) curve analysis for the entire group, the baseline IGF-1 value of 1.47 the upper limit of normal (ULN) was the best cut-off point to identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%, specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of those in the raloxifene group (P = .43).Conclusion: Cabergoline and raloxifene add-on therapy could effectively decrease serum IGF-1 level in patients with inadequately controlled acromegaly. The efficacy profiles of both drugs are comparable.Abbreviations: DA = dopamine agonist; FBG = fasting blood glucose; GH = growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range; OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of normal     

Pituitary Evaluation in Patients with Low Prostate-Specific Antigen

Objective: To evaluate pituitary function in men with a low screening prostate-specific antigen (PSA) of ≤0.1 ng/mL and test the hypothesis that low PSA is associated with hypogonadism alone or other hormone deficiency.Methods: This was a case-control study evaluating the rates of hypogonadism and low insulin-like growth factor (IGF)-1 in a cohort of men with low or normal screening PSA level. Sixty-four men >40 years old without known prostate disease were divided into a low-PSA group (PSA ≤0.1 ng/mL) and normal-PSA group (PSA 1 to 4 ng/mL). Hormonal evaluation included total testosterone, prolactin, luteinizing hormone, follicle-stimulating hormone, IGF-1, growth hormone, thyroid-stimulating hormone, free thyroxine, morning cortisol, and adrenocorticotropic hormone. The difference between each patient's observed IGF-1 and the IGF-1 age-specific lower limit was calculated. The odds ratios (ORs) for having hypogonadism and associated 95% confidence intervals (CIs) were calculated using the Cochran-Mantel-Haenszel test.Results: The rate of hypogonadism was significantly higher in the low-PSA group (n = 44) compared with the normal-PSA control group (n = 20) (45.5% vs. 15.0%; OR, 4.7; 95% CI, 1.2 to 18.4; P = .027). The total testosterone in the low-PSA group was significantly lower compared with the control group (181.7 ng/dL vs. 263.7 ng/dL; P = .008). IGF-1 values were below their lower bound in 18.6% of subjects in the low-PSA group, compared with 0% in the control group.Conclusion: Men with low PSA have significantly higher rates of hypogonadism and low IGF-1 compared with those with normal PSA. In such men, we recommend hormonal evaluation to exclude associated pituitary dysfunction.Abbreviations: BMI = body mass index; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; PSA = prostate-specific antigen; T2DM = type 2 diabetes mellitus; VA-NWIHCS = VA-Nebraska Western Iowa Health Care System     

Prevalence of Valvular Heart Disease in A Cohort of Patients Taking Cabergoline for Management of Hyperprolactinemia

ObjectiveTo determine the prevalence of valvular heart disease in a cohort of patients taking cabergoline for the management of hyperprolactinemia.MethodsA retrospective review of medical records identified patients with hyperprolactinemia who underwent evaluation at Vanderbilt University Medical Center between January and June 2007. The medical records of those patients who were prescribed cabergoline and who underwent elective echocardiography were reviewed for details pertaining to cardiac valvular abnormalities and cabergoline use.ResultsForty-five patients (mean age, 41 ± 10 years [SD]) taking 0.91 ± 0.96 mg of cabergoline per week for a mean duration of 39 ± 29 months underwent echocardiography. Abnormalities of the cardiac valves were present in 3 patients (7%): 1 patient exhibited mild mitral regurgitation, 1 patient had focal aortic valve thickening, and 1 patient demonstrated mitral valve thickening. We found no significant difference in either the cumulative dose of cabergoline (P = .800) or the duration of cabergoline therapy (P = .745) between those patients with and those without these echocardiographic abnormalities.ConclusionWe found echocardiographic valve abnormalities in 3 of 45 patients (7 %) who had been prescribed cabergoline for the management of hyperprolactinemia. This prevalence of valvular heart disease after approximately 3 years of cabergoline treatment is no different from that previously reported in normal populations as determined by echocardiography. (Endocr Pract. 2008;14:672-677)     

Venous Sampling for Cushing Disease: Comparison of Internal Jugular Vein and Inferior Petrosal Sinus Sampling

Objective: Because magnetic resonance imaging (MRI) fails to detect many adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, inferior petrosal sinus sampling (IPSS) is considered the gold standard to differentiate Cushing disease (CD) from ectopic ACTH secretion syndrome (EAS). Some authors have suggested internal jugular vein sampling (IJVS) as an alternative to IPSS.Methods: We simultaneously compared IJVS to IPSS in 30 consecutive patients referred for ACTH-dependent Cushing syndrome and equivocal MRI exams. Five sites were simultaneously sampled in each patient (right and left IPS, right and left IJV, and femoral vein) before and after the administration of corticotrophin-releasing hormone or desmopressin. The test was considered consistent with CD when the IPS to peripheral ratio was >2 at baseline or >3 after stimulus and the IJV to peripheral ratio was >1.7 at baseline or >2 after stimulus.Results: In 27 of 30 patients, IPSS results were consistent with a central source of ACTH. Two of the other 3 patients had EAS (one lung carcinoid and one occult), and 1 patient had pathology-proven CD. The sensitivity of IPSS was 96.4%. Only 64.2% of these patients had results meeting criteria for a central source of ACTH by IJVS criteria. Twenty patients with centralizing IPPS have undergone pituitary surgery. Of these, the central origin of excessive ACTH was confirmed with certainty in 16 patients. Among these 16 patients, the IPSS sensitivity was 93.8%, whereas 5 patients had false-negative IJVS (68.7% sensitivity).Conclusion: These results do not support the routine use of IJVS in establishing if the pituitary is the source of excessive ACTH.Abbreviations:ACTH = adrenocorticotropic hormoneCD = Cushing diseaseCRH = corticotrophin-releasing hormoneCS = Cushing syndromeDDAVP = desmopressinEAS = ectopic ACTH secretionIJVS = internal jugular vein samplingIPSS = inferior petrosal sinus samplingJVS = jugular venous samplingMRI = magnetic resonance imaging