Aline Barbosa Moraes

Dopamine receptor subtype 2 expression profile in nonfunctioning pituitary adenomas and in vivo response to cabergoline therapy

To determine the dopamine receptor subtype 2 (DR2) mRNA levels and protein expression and to evaluate the effect of adjuvant cabergoline therapy on tumour volume (TV) in patients with postoperative residual nonfunctioning pituitary adenoma (NFPA).

ZAC1 and SSTR2 Are Downregulated in Non-Functioning Pituitary Adenomas but Not in somatotropinomas

Introduction There are few data regarding ZAC1 expression in clinically non-functioning pituitary adenomas (NFPA). Because somatotropinomas and NFPA behave differently with respect to tumor shrinkage during somatostatin analogs (SA) therapy, we sought to compare the ZAC1 and somatostatin receptor (sstr) types 1, 2, 3 and 5 mRNA expression in these two pituitary adenoma subtypes and in normal human pituitaries. Methods ZAC1 and SSTR mRNA expression levels were evaluated using real-time RT-PCR (TaqMan) in 20 NFPA and compared with the expression levels in 23 somatotropinomas and five normal pituitaries. The NFPA invasiveness was evaluated using magnetic resonance imaging with Hardy’s modified criteria. Ki-67 and p53 were evaluated using immunohistochemistry. Results A total of 20 patients with NFPA [6 males, median age 56 years (range: 30-78)], 23 with acromegaly [12 males, median age 43 years (range: 24–57)] and five normal pituitaries [4 males, median age 48 years (range: 36–54)] were included. Four of the patients (20%) had Hardy’s grade 2 tumors; all of the others had Hardy’s grade 3 tumors. The Ki-67 median expression was 2.35 (range: 0.2–9.23), and only four of the tumors (20%) were positive for p53. The ZAC1 mRNA expression was significantly lower in NFPA than in somatotropinomas and in normal pituitaries (p<0.001 for both), as well as the SSTR2 (p=0.001 and 0.01, respectively). The SSTR3 expression was higher in the NFPA than in the somatotropinomas and in the normal pituitaries (p=0.03 and 0.02, respectively). No correlation was found between the ZAC1 mRNA expression and the tumor invasiveness, Ki-67 and p53. Conclusion ZAC1 and SSTR2 are underexpressed and SSTR3 is overexpressed in NFPA compared to those in somatotropinomas and in normal pituitaries, which might explain the lack of tumor shrinkage that is observed in response to commercially available SA therapy in patients with NFPA.

Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

We present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome.

Bone Mineral Density and Microarchitecture in Patients With Autosomal Dominant Osteopetrosis: A Report of Two Cases

The aim of this case study is to describe changes in areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) scan, as well as volumetric bone density and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) in two patients with autosomal dominant osteopetrosis (ADO) and compare with 20 healthy subjects. We describe a 44-year-old male patient with six low-impact fractures since he was age 16 years, and a 32-year-old female patient with four low-impact fractures on her past history. Radiographic changes were typical of ADO. Consistent with the much higher aBMD, total volumetric BMD (average bone density of the whole bone, including trabecular and cortical compartments) at distal radius and tibia (HR-pQCT) was more than twice the mean values found in healthy subjects in both patients. Trabecular number and thickness were higher, leading to an evident increase in trabecular bone volume to tissue volume. Also, an enormous increase in cortical thickness was found. Most important, a great heterogeneity in bone microstructure of the affected patients was evident on HR-pQCT images: islets of very dense bone were interposed with areas with apparent normal density. The increase in aBMD, volumetric BMD, and most indices of trabecular and cortical bone, associated with the great heterogeneity on bone tridimensional microarchitecture, reflect the accumulation of old and fragile bone randomly distributed along the skeleton. These alterations in bone microstructure probably compromise bone quality, which might justify the high prevalence of low-impact fractures in patients with ADO, despite abnormally elevated BMD.

Sellar and suprasellar mixed germ cell tumor mimicking a pituitary adenoma

Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not well established. Several cases of primary intrasellar germinomas have been reported, however non-germinomatous GCT have rarely been described. We report the case of a young adult male patient with a mixed GCT that presented with a sellar tumor with suprasellar extension. The patient seeked medical attention because of seizures and magnetic resonance imaging evidenced a tumor of the sellar region. Hyperprolactinemia was also present and dopamine agonist therapy was started. As there was a rapid tumor growth and the patient had concomitant central diabetes insipidus and elevated testosterone levels, a GCT was suspected and confirmed by elevated serum concentration of β-human chorionic gonadotrophin. Patient underwent surgical resection of the tumor and histopathological examination confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by conventional radiotherapy. In conclusion, although pituitary adenomas respond for the vast majority of sellar tumors, concomitant symptoms such as central diabetes insipidus and rapid tumor growth should raise the suspicion of a diverse diagnosis. The present report intend not only to show a rare case of sellar and suprasellar mixed GCT but also to remind clinicians that if laboratory findings do not fit into patient’s diagnosis (such as high testosterone levels in our patient), then the diagnosis should be reviewed.

The presence of nonfunctioning adrenal incidentalomas increases arterial hypertension frequency and severity, and is associated with cortisol levels after dexamethasone suppression test

There are limited data regarding the frequency of hypertension in nonfunctioning adrenal incidentaloma (NFAI). Our objectives were to investigate rates of hypertension and resistant hypertension in NFAI patients, and compare them to a control group without adrenal adenoma. We also aimed to evaluate the relationship between cortisol levels after 1 mg-dexamethasone suppression test (DST) and hypertension in NFAI patients. We selected 40 patients with NFAI and 40 control patients over the age of 18 without adrenal lesions on abdominal imaging. Data regarding hypertension, resistant hypertension, number, and type of antihypertensive drugs were collected from each subject. Blood samples for C-reactive protein (CRP), plasma adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were also collected from the patients. Age, gender, race, smoking status, menopause status and BMI were comparable between patient and control groups. Patients with NFAI had a higher frequency of hypertension (72.5 vs. 47.5%; p = 0.04), resistant hypertension (37.9 vs. 11.1%; p = 0.04) and took three or more antihypertensive drugs (33.3 vs. 5.2%; p = 0.002) when compared to the controls, respectively. NFAI patients with hypertension had higher mean cortisol levels after 1 mg-DST when compared to NFAI patients without hypertension (1.3 ± 0.3 vs. 1.0 ± 0.4; p = 0.03, respectively). We found a negative correlation between cortisol levels after 1 mg-DST DHEA-S levels (r = −0.61; p < 0.001) and a positive correlation with CRP levels (r = 0.44; p = 0.02). In conclusion, NFAI patients presented a higher frequency of hypertension, resistant hypertension and used more antihypertensive medications when compared to the control group. We found an association between hypertension in NFAI patients and cortisol levels after 1 mg-DST.

Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome

Although metabolic syndrome has been studied in patients with autonomous cortisol secretion, there are limited data for those with nonfunctioning adrenal incidentaloma (NFAI).

Endocrine abnormalities in ring chromosome 11: a case report and review of the literature

Summary Ring chromosomes (RCs) are uncommon cytogenetic findings, and RC11 has only been described in 19 cases in the literature. Endocrine abnormalities associated with RC11 were reported for two of these cases. The clinical features of RC11 can result from an alteration in the structure of the genetic material, ring instability, mosaicism, and various extents of genetic material loss. We herein describe a case of RC11 with clinical features of 11q-syndrome and endocrine abnormalities that have not yet been reported. A 20-year-old female patient had facial dysmorphism, short stature, psychomotor developmental delays, a ventricular septal defect, and thrombocytopenia. Karyotyping demonstrated RC11 (46,XX,r(11)(p15q25)). This patient presented with clinical features that may be related to Jacobsen syndrome, which is caused by partial deletion of the long arm of chromosome 11. Regarding endocrine abnormalities, our patient presented with precocious puberty followed by severe hirsutism, androgenic alopecia, clitoromegaly, and amenorrhea, which were associated with overweight, type 2 diabetes mellitus (T2DM), and hyperinsulinemia; therefore, this case meets the diagnostic criteria for polycystic ovary syndrome. Endocrine abnormalities are rare in patients with RC11, and the association of RC11 with precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM has not been reported previously. We speculate that gene(s) located on chromosome 11 might be involved in the pathogenesis of these conditions. Despite the rarity of RCs, studies to correlate the genes located on the chromosomes with the phenotypes observed could lead to major advances in the understanding and treatment of more prevalent diseases. Learning points We hypothesize that the endocrine features of precocious puberty, severe clinical hyperandrogenism, insulin resistance, and T2DM might be associated with 11q-syndrome. A karyotype study should be performed in patients with short stature and facial dysmorphism. Early diagnosis and adequate management of these endocrine abnormalities are essential to improve the quality of life of the patient and to prevent other chronic diseases, such as diabetes and its complications.