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Background Hypercortisolism in Cushing's syndrome (CS) is associated with bone loss, skeletal fragility, and altered bone quality. No studies evaluated bone geometric and strain–stress values in CS patients after remission thus far. Patients and methods Thirty-two women with CS in remission (mean age [±SD] 51 ± 11; body mass index [BMI], 27 ± 4 kg/m2; mean time of remission, 120 ± 90 months) and 32 age-, BMI-, and gonadal status–matched female controls. Quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD) and buckling ratio, cross-sectional area, and average cortical thickness at the level of the proximal femur. Finite element (FE) models were generated from QCT to calculate strain and stress values (maximum principal strain [MPE], maximum strain energy density [SED], maximum Von Mises [VM], and maximum principal stress [MPS]). Areal BMD (aBMD) and trabecular bone score (TBS) were assessed by dual-energy X-ray absorptiometry (2D DXA). Results Trabecular vBMD at total hip and trochanter were lower in CS as compared with controls (P <.05). Average cortical thickness was lower, and buckling ratio was greater in CS vs controls (P <.01). All strain and stress values were higher in CS patients vs controls (P <.05). 2D DXA–derived measures were similar between patients and controls (P >.05). Prior hypercortisolism predicted both VM (β.30, P =.014) and MPS (β.30, P =.015), after adjusting for age, BMI, menopause, delay to diagnosis, and duration of remission. Conclusions Women with prior hypercortisolism have reduced trabecular vBMD and impaired bone geometrical and mechanical properties, which may contribute to an elevated fracture risk despite long-term remission. [ABSTRACT FROM AUTHOR]

There is a well-known controversy among scientific societies regarding the recommendation to screen for thyroid dysfunction (TD) during pregnancy. Although several studies have shown an association between maternal subclinical hypothyroidism and/or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, there is only limited evidence on the possible positive effects of thyroxine (T4) treatment in such cases. Despite the scarcity of this evidence, there is a widespread agreement among clinicians on the need for treatment of clinical hypothyroidism during pregnancy and the risks that could arise due to therapeutic abstention. As maternal TD is a quite prevalent condition, easily diagnosed and for which an effective and safe treatment is available, some scientific societies have proposed to assess thyroid function during the first trimester of pregnancy and ideally before week 10 of gestational age. Given the physiologic changes of thyroid function during pregnancy, hormone assessment should be performed using trimester-specific reference values ideally based on locally generated data as geographic variations have been detected. Screening of TD should be based on an initial determination of TSH performed early during the first trimester and only if abnormal should it be followed by either a free or total T4measurement. Furthermore, adequate iodine supplementation during pregnancy is critical and if feasible it should be initiated before the woman attempts to conceive. [ABSTRACT FROM AUTHOR]

There is a well-known controversy among scientific societies regarding the recommendation to screen for thyroid dysfunction (TD) during pregnancy. Although several studies have shown an association between maternal subclinical hypothyroidism and/or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, there is only limited evidence on the possible positive effects of thyroxine (T4) treatment in such cases. Despite the scarcity of this evidence, there is a widespread agreement among clinicians on the need for treatment of clinical hypothyroidism during pregnancy and the risks that could arise due to therapeutic abstention. As maternal TD is a quite prevalent condition, easily diagnosed and for which an effective and safe treatment is available, some scientific societies have proposed to assess thyroid function during the first trimester of pregnancy and ideally before week 10 of gestational age. Given the physiologic changes of thyroid function during pregnancy, hormone assessment should be performed using trimester-specific reference values ideally based on locally generated data as geographic variations have been detected. Screening of TD should be based on an initial determination of TSH performed early during the first trimester and only if abnormal should it be followed by either a free or total T4 measurement. Furthermore, adequate iodine supplementation during pregnancy is critical and if feasible it should be initiated before the woman attempts to conceive.

Objective: Most cases of familial isolated pituitary adenomas with mutated aryl hydrocarbon receptor-interacting protein (AIP:HGNC:358) gene develop somatotropinomas. They are characterised by an aggressive clinical phenotype including early age at diagnosis, large tumours and frequent invasiveness. There is little information on AIP gene mutations' prevalence in isolated somatotropinomas characterised by poor response to somatostatin analogue treatment. The aim of this study was to investigate the prevalence of AIP mutations in non-familial cases of somatotropinomas with poor response to conventional treatment., Design and Methods: Fifty patients with acromegaly (22 males/28 females, age 51±18 years) and 60 controls were included in this study performed at eight University Hospitals in Spain. None had family history of pituitary adenomas or other endocrine tumors. All patients failed to respond to conventional treatment including surgery and somatostatin analogues. Some patients received adjuvant radiotherapy and most cases required pegvisomant (PEG) treatment for normalisation of IGF1. AIP analysis was performed in DNA extracted from peripheral leucocytes, using standardised PCR protocol in which the coding regions of exons 1, 2, 3, 4, 5 and 6 were amplified. Possible deletions/duplications were studied using multiplex ligation-dependent probe amplification., Results: SEQUENCE CHANGES OF POTENTIAL DIFFERENT SIGNIFICANCE THAT COULD BE CONSIDERED AS MUTATIONS OR VARIATIONS OF UNKNOWN SIGNIFICANCE (VUS) OF THE AIP GENE WERE FOUND IN FOUR PATIENTS (8%). IN TWO CASES, TWO DIFFERENT MUTATIONS PREVIOUSLY DESCRIBED WERE FOUND: p.Arg9Gln and p.Phe269Phe. Two other VUS were also found: c.787+24C>T in intron 5 and c.100-18C>T in intron 1. Age at diagnosis ranged from 21 to 50 years old, and in all patients, the tumor was a macroadenoma depicting IGF1 normalisation under PEG treatment., Conclusions: AIP germline mutations show a low, but non-negligible, prevalence in non-familial acromegaly patients with tumors resistant to treatment with somatostatin analogues.