Dopamine Agonists for Pituitary Adenomas

Dopamine agonists (DA) are well established as first-line therapy for prolactinomas. These tumors express high levels of dopamine 2 receptors (D2R), leading to the strong efficacy of DA in reducing tumor size and hormonal secretion. Other pituitary tumor subtypes express D2R to varying degrees, leading to an extensive body of research into potential off-label use of DA in non-prolactinoma pituitary tumors. Preclinical models of Cushing's disease, acromegaly, and nonfunctioning pituitary tumors (NFPT) demonstrate D2R expression in cell lines and cultured tumors as well as effectiveness of DA in reducing hormonal secretion in functioning tumors and arresting tumor proliferation. Clinical studies have shown some efficacy of DA in treatment of these tumors. In Cushing's disease, DA therapy results in normalization of urinary cortisol levels in approximately 25% of patients, but reported rates of tumor shrinkage are very low; in acromegaly, DA therapy leads to normalization of insulin-like growth factor I and tumor shrinkage in approximately one-third of patients, and improved responses when used in combination with somatostatin receptor ligands. Among patients with NFPT, pooled results show 30% experience reduction of tumor size and 58% show stabilization of disease. DA therapy appears to have some clinical benefit in patients with non-prolactinoma pituitary tumors, and may be an option for medical therapy in some clinical scenarios

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies

Thyroid cysts: a new extra-adrenal site of aldosterone synthase expression and increased aldosterone content

Abstract Background The rapid re-accumulation of fluid following aspiration of thyroid cystic lesions suggests that active transport of sodium and water may be involved in volume regulation of these lesions. In this study we address the possibility that aldosterone may take part in this process. Subjects and methods Thirty-one patients (29 women and two men), with a mean age of 52·7 ± 13·2 years (range: 27-77 years) underwent evaluation for thyroid nodules that had a sonographic cystic component. Cystic fluid obtained by FNA biopsy was sent for cytological examination and biochemical measurements. In 10 patients, material was collected for RNA extraction and determination of aldosterone synthase expression by RT-PCR amplification. Results All lesions were benign, cystic, colloid nodules. Cyst fluid aldosterone levels as measured by routine radioimmunoassay (RIA) were elevated above the normal plasma levels in all but five patients. Mean aldosterone levels were 27·1 ± 22·9 ng /dl (SD) (range: 5·9-117·5 ng/dl). In contrast, cyst cortisol values were in the low, low normal serum range (6·2 ± 2·9 µ g/dl, range: 0·2-10·2 µ g/dl). Sodium, chloride and potassium levels were 137 ± 4·7 mEq/l, 98 ± 5 mEq/l and 4·9 ± 1·4 mEq/l, respectively. Plasma aldosterone levels were normal in all patients tested. To confirm these results, 12 samples were assayed after extraction and chromatography using a highly specific antibody. Cyst aldosterone levels in this group were elevated above the normal serum range in all but one patient (mean concentration: 24·5 ± 14·6 ng/dl, range: 8·72-40·1 ng /dl). In this group, 18(OH)B levels were within the normal plasma range (12-55 ng /dl) in all but one patient (34·9 ± 17 ng/dl). Furthermore, aldosterone synthase mRNA expression was found in aspirates of four of 10 patients. Conclusions The increased aldosterone concentration and the presence of aldosterone synthase expression suggest that aldosterone may be locally produced and secreted in thyroid tissue. The pathophysiological implications of this finding remain to be established

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges

Hypogonadotropic hypogonadism in women: treatment options

Treatment of female hypogonadotropic hypogonadism is geared to mimic normal physiology, allowing for age appropriate development, while preventing complications secondary to sex hormone deprivation. In this paper we review data concerning efficacy and safety of sex hormone replacement therapy at the various stages of female reproduction, taking into account safety profiles of different types of estrogen and progesterone formulations, and their interactions with other components of the pituitary substitutive therapy

Validation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes

10.1038/s41387-022-00223-1NUTRITION & DIABETES12

The ENIGI (European Network for the Investigation of Gender Incongruence) Study: Overview of Acquired Endocrine Knowledge and Future Perspectives

Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on mortality rates, oncological risk, and cardiovascular, cerebrovascular and thromboembolic events are lacking. With this aim, we decided to extend the observation of the ENIGI study to 10 years in order to study all these aspects in depth and to answer these questions