25 26 Objective: To know the prevalence of the Glu354Gln polymorphism of 27 the GIPR gene, investigate possible associations with arterial hypertension and 28 relationships with cardiometabolic diseases. Method: A total of 311 subjects 29 recruited from the Clinical Hospital of Londrina State University, located in a 30 Brazilian metropolitan area. Random stratification was performed considering 31 gender and geographic regions. Data were collected through interviews 32 including anthropometric, sociodemographic and metabolic diseases related 33diseases. In order to analyze GIPR Glu354Gln gene polymorphism, 34 polymerase chain reaction followed by followed by restriction fragment length 35 polymorphism (PCR-RFLP) was performed. Results: The highest prevalence 36 for the allele C carriers were found in the Caucasian 29.4% (p = 0.043, OR = 37 1,89), hypertensive 37.1% (p < 0.0001), smokers 38.3% (p = 0.014) and 38 dyslipidemic group 41.2% (p = 0.019). In this work 46.9% of the participants (n 39 = 146) presented diseases related to cardiometabolic diseases. The results 40 indicated that 60% of hypertensive patients (p = 0.004) and 64.7% of 41 dyslipidemic patients (p = 0.046) were male. Among participants who presented 42 cardiometabolic diseases, arterial hypertension was the most prevalent disease 43 (71.9%), followed by obesity (43.8%). The family comorbidities history to 44 cardiometabolic diseases (DM2, AH, dyslipidemia and obesity) had no 45 significant association with the GIPR Glu354Gln genetic polymorphism. 46Although there was no difference in the case-control analyses for GIPR 47 3 48 twice associated with arterial hypertension (p<0,001) and dyslipidemia 49 (p<0,03). Conclusion: The prevalence of the GIPR Glu354Gln for the CC 50 genotype and for the C polymorphic allele was 25.7% and 3.2%, respectively. 51This study shows the potential participation of the GIPR Glu354Gln 52 polymorphism with the pathophysiology of arterial hypertension, dyslipidemia 53 in this Brazilian population. Taking into account the rarity of the CC genotype, 54 additional studies with larger numbers of participants could contribute to a 55 better understanding. 56 57 65 adipocytes, pancreas, lung, adrenal, kidney and thyroid (1). Nonpancreatic 66 GIPR function is related to adrenal cell proliferation, GIP-dependent 67 oversecretion of cortisol and aldosterone (4, 5, 6) and neurogenesis in the 68 central nervous system (6). 69 Several GIP receptor polymorphisms have been described. These 70 genetic variations could play a role on gluco-insulin homeostasis and body 4 4 71 composition. Some single nucleotide polymorphisms (SNPs) located in coding 72 regions of the GIPR gene (rs8111428, rs2302382 and rs1800437) were related 73 to obesity (7). The GIPR rs10423928 was associated with high postprandial 74 glucose and insulin levels (8), decreased lean mass (9) and low BMD in early 75 postmenopausal women (10). The GIPR SNP rs1800437 (Glu354Gln) showed 76 a borderline association with cardiovascular disease (CVD) in a study of 200 77 p...

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Background: Pregnancy is unusual in patients with acromegaly due to somatotropinomas or somatoprolactinomas. Fertility is impaired because of hormonal hypersecretion, pituitary damage by tumor compression or both. Managing somatoprolactinomas and fertility issues are often challenging. Clinical Case: A 20-year woman with primary amenorrhea and headache was diagnosed with hypogonadotrophic hypogonadism secondary to hyperprolactinemia (2500 µg/L, n&lt;23 µg/L). No other abnormalities were found on the pituitary function screening tests. MRI revealed an intra and suprasellar adenoma (2.5x1.8x1.8 cm) with optic chiasm compression. The onset of menses occurred after 11 months under dopaminergic treatment, and tumor size diminished (1.9x1.5x1.5 cm), bringing on optic chiasm decompression. She remained under dopamine agonist treatment for 6 years, when she realized extremities enlargement and height increase by 3 cm. Acromegaly was confirmed by blood levels of IGF-1 (3.37xULN), GH (8 µg/L, n&lt;8 µg/L), and GH nadir (4.3 µg/L, n&lt;1 µg/L) during OGTT. Then, octreotide LAR was added to cabergoline treatment while waiting for elective surgical treatment. She underwent to transsphenoidal endonasal neurosurgical microscopy approach guided by neuronavigation, with the removal of a large portion of tumor. However, it was not possible to extract the part of invasive adenoma close to right carotid artery due to the risk of vascular and intracavernous cranial nerves injury. Immunohistochemistry analysis of the adenoma was positive only for GH cells with low Ki67 index (&lt;1%). Due to the poor biochemical control (unsuppressed post-OGTT GH, IGF-1 1.66xULN and PRL 301 µg/L) and the presence of a small stable tumor residue, treatment with cabergoline and somatostatin analogues was maintained (3-year octreotide LAR, transitioned to lanreotide in an attempt to achieve a better biochemical response). After 14 years of the initial diagnosis and 5 years post-surgery, the patient expressed the desire to get pregnant and all medications in use were suspended. In the following 3 years, she had two uneventful gestation without complications or worsen of acromegaly; she only breastfed for few months after her first pregnancy. The second one was a twin pregnancy. After one year, the MRI revealed no increase of tumor mass (1.0x0.3x1.0 cm), and PRL levels withing normal range, IGF-1 slightly elevated, but GH not suppressed by OGTT. Cabergoline was reintroduced and the biochemical control of acromegaly was achieved. Conclusion: We reported the very unusual spontaneous conception and normal course of pregnancies in a woman with acromegaly, who was submitted to successful transsphenoidal neurosurgical microscopy approach in which large part of the tumor was removed and the normal pituitary tissue was preserved, allowing fertility restoration.