Patricia Fainstein Day

Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation

Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina

Objectives The main purpose of this study was to estimate the incidence rate and prevalence of clinically relevant pituitary adenomas (PAs) within the Hospital Italiano Medical Care Program (HIMCP), a well-defined population of 150,000 members living in the urban and suburban area of the city of Buenos Aires. We defined clinically relevant PAs as those associated with endocrine dysfunction and/or mass effect. Subjects and methods A retrospective open cohort study was conducted, including all members of the HIMCP over 18 years old, with active memberships during the period of the study, from January 1st 2003, to January 1, 2014. The incidence rates (IRs) were standardized (SIR) to the World Health Organization (WHO) 2000 standard population and were expressed per 100,000 members/year. Prevalence was estimated at January 1, 2014, and was expressed per 100,000 persons. The clinical records have been electronically managed since 2001. All lab and imaging studies were done in-house. Results The overall SIR was 7.39/100,000/year (95% CI 4.47-10.31). Female patients had a specific IR significantly higher than male patients (5.85 vs.1.54) and represented 73% of the affected members. Regarding tumor size, 61.4% were microadenomas, and the mean age at diagnosis was 46.4 years. Prolactinomas had the highest SIR (5.41), followed by acromegaly (Acro) and non-functioning adenomas (NFAs) with overlapping 95% CIs (0.44-1.41 and 0.31-0.99, respectively). Microprolactinomas were more frequent in female (72.6%) (p < 0.01) and younger members (38 vs.60 years; p < 0.04). The overall prevalence rate was 97.76/100,000. Prolactinomas had the highest prevalence (56.29), followed by NFAs (21.48), Acro (14.07) and CD (5.93). Conclusion Our results demonstrate that clinically relevant PAs are more common than usually suspected, especially prolactinomas and growth-hormone secreting PAs. These data highlight the need to increase the awareness of PAs, thereby enabling early diagnosis and treatment.

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

BackgroundThere is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups.MethodsThe study was approved by the “Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires” with the number “1262” and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable logistic regression was used to determine the relative odds of clinical cardiovascular disease in individuals with compared to those without depression. Differences were considered significant using a two-sided p < 0.05.Results21 patients (34%) had MDD and 40 patients (66%) didn’t have MDD. Diabetic patients with MDD had significantly higher CRP levels (4.1(1.9-7.6) vs 1.5(0.5-4.4) mg/l; p = 0.02) and 24-hour urine free cortisol (71.4 ± 21.3 vs 59.8 ± 29.3 ug/24 h; p = 0.03). The other metabolic and inflammatory parameters were not statistically different between groups. There was a significantly higher prevalence of cardiovascular events in individuals with MDD: 38% for the depressive group vs 15% for non-depressive group, p = 0.04). Patients with MDD had a 3.5-fold greater odd of having cardiovascular disease.ConclusionsDiabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.

Histologically confirmed isolated IgG4-related hypophysitis: two case reports in young women

Summary IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis. Learning points IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis. It is more common in older men, but young women may also present this type of hypophysitis. Although involvement of other organs is frequent, isolated pituitary disease is possible. Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus. The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment. Glucocorticoids are recommended as first-line therapy.

Gender differences in macroprolactinomas: study of clinical features, outcome of patients and ki-67 expression in tumor tissue.

Prolactinomas in men are usually macroprolactinomas and other investigators have attributed bigger size of tumors in men to delay in diagnosis. A retrospective study of 71 macroadenomas (42 men) was carried out. Parameters studied were age, signs and symptoms at presentation, time of onset of symptoms, basal prolactin, estradiol, and total testosterone levels, tumor size and Ki 67 expression in tumor tissue. Male patients were older. Visual defects were significantly more prevalent in men. Hardy 4 stage tumors were found only in men. We found no significant correlation between tumor size and the patients age nor between tumor size and the onset of symptoms. Whereas basal E2 levels (21.2+/-12.9 vs. 33.3+/-43.3 pg/ml, p=n.s.) were very similar in male and female patients, testosterone levels were significantly higher in men (0.6+/-0.5 vs. 1.8+/-1.2 ng/ml, p=0.02). The rate of cell proliferation represented by Ki 67 was significantly higher in tumors in men (3.5+/-1.2 vs. 1.5+/-0.5%, p=0.0001). This is the first study focused in macroprolactinomas that shows that they are clinically and biologically more aggressive in men. Hypogonadism in men could appear later in the progression of prolactinomas and this might explain why men were older at the time of diagnosis. Furthermore, testosterone could be a source for E2 in situ aromatization giving male tumors an advantage in cell proliferation.

Catecholamine-Induced Myocarditis in Pheochromocytoma

A 25-year-old man arrived at the emergency room of his community hospital complaining of abdominal pain, headaches, and palpitations that had appeared suddenly while he was playing soccer. He had no history of hypertension. An abdominal ultrasound revealed a tumor located in the right adrenal gland. He was subsequently transferred to our hospital for further evaluation. On admission, he presented acute pulmonary edema with severe hypertension (blood pressure, 220/120 mm Hg). He was admitted to the coronary care unit. Intravenous vasodilators and loop diuretics were administered, with rapid recovery of clinical status. ECG showed sinus rhythm, a heart rate of 80 bpm, and T-wave inversion in the DI, DII, and AVL leads. Transthoracic echocardiography revealed left …

Prolactinomas: evolution after menopause

OBJETIVE The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. SUBJECTS AND METHODS Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. CONCLUSIONS Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Revisión del complejo de Carney: Aspectos genéticos

Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms. In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex. This review will address the genetic aspects related to Carney complex.

Implementing a screening program for acromegaly in Latin America: necessity versus feasibility.

IntroductionAcromegaly is a rare disease with a large burden due its associated comorbidities and the life-long management required. Since the occurrence and severity of associated complications are related to length of exposure to the excess growth hormone seen in acromegaly, early diagnosis is imperative. The delay in diagnosis, however, can be long, and may be the result of a lack of disease awareness and screening programs. Since acromegaly is an uncommon disease, finding ways to increase recognition and diagnosis that would permit early detection in a logical and cost-effective manner could be a challenge.MethodsWe conducted a retrospective literature review for information relating to the screening and diagnosis of acromegaly using PubMed. The aim was to assess whether an acromegaly-screening program in Latin America (and elsewhere) would be both of use and be feasible.Findings and conclusionsAn earlier diagnosis allows earlier initiation of treatment, such as surgery and/or drugs, which leads to more successful disease management (biochemical control) and better outcomes. Since the delay in diagnosis can be long, we believe that clear opportunities exist for earlier (and increased) detection of acromegaly. This can be achieved by increasing disease awareness for earlier recognition of symptoms and by using targeted screening (rather than mass screening) programs.

Erratum to: Retrospective multicentric study of pituitary incidentalomas

The online version of the original article can be found underdoi:10.1007/s11102-005-0007-x.P. Fainstein Day M. Guitelman R. Artese L. Fiszledjer A. Chervin N. M. Vitale G. Stalldecker V. De Miguel D. Cornalo´ A. Alfieri M. S. Mallea-GilNeuroendocrinology Department of the Argentine Societyof Endocrinology and Metabolism, Buenos Aires (Departamentode Neuroendocrinolog´ia de la Sociedad Argentina deEndocrinolog ´ia y Metabolismo, Buenos Aires), Diaz Velez,3889, 1200 Buenos Aires, ArgentinaP. Fainstein Day (&)Lezica 3954, 1202 Buenos Aires, Argentinae-mail: patricia.fainstein@hospitalitaliano.org.ar