Secretion Of Multiple Hormones Research Articles

SUN-158 Testosterone and Cortisol Secreting Large Adreno- Cortical Adenoma

Background: Functional adrenal adenomas most commonly secrete cortisol or aldosterone. Secretion of multiple hormones is commonly seen in adrenocortical carcinomas and is rare in benign adrenal adenomas. We present a case of a patient with a 6 cm benign adrenal adenoma that was secreting both cortisol and testosterone.Clinical case: A 44-year-old Caucasian female with past medical history of Grave’s disease, hypertension, prediabetes and hyperlipidemia presented with hirsutism and weight gain. Physical exam was suggestive of cushing’s disease with elevated blood pressure, hirsutism, supraclavicular fullness, moon facies, facial plethora, dorsocervical fat pad and abdominal striae. Further workup revealed elevated testosterone level of 152ng/dL (9-55ng/dl) and elevated androstenedione level of 2.520ng/ml (0.130–0.820 ng/ml). DHEA 0.741 ng/ml (0.630–4.7ng/ml) and DHEAS 65ug/dl (32-240ug/dl) were both within reference range. The 24-hour urine free cortisol was also elevated at 107.1ug/gram of creatinine (< 24 ug/gram of creatinine) with an undetectable ACTH level of < 5 pg/ml indicating adrenal source of Cushing’s syndrome. CT abdomen and pelvis with and without contrast revealed a 6.3 x 5.2 x 5.6 cm left adrenal mass which measured 22 Hounsfield units (HU) on non-contrast imaging, 85 HU on 70 second imaging and 48 HU on 15 min delayed phase. Calculated percent relative washout was 43.5 % and absolute washout was 59.4 %. There was another 1.1 cm low density nodule on left adrenal genu. The right adrenal gland also had a 1.2 cm low density nodule with 0 HU on all phases compatible with a lipid rich adenoma. Patient then underwent left open adrenalectomy. Pathology revealed a 6 cm adrenocortical adenoma. There was no tumor invasion into adjacent sites, no vascular invasion or tumor necrosis noted. MIB1 index was <1 %. Patient had resolution of hypertension and prediabetes after the surgery. Her cortisol and androgen levels also normalized. Biochemical follow up 6 months post-surgery has not demonstrated any increase in cortisol or androgen levels.Conclusion: Both androgen and cortisol hypersecretion can cause severe hyperandrogenism and virilization but these hormones are commonly secreted in isolation in functional adrenal adenomas. Adrenal masses co-secreting androgen and cortisol are usually indicative of adrenocortical cancer. In this rare case report, both of these hormones were secreted by a unilateral adrenal adenoma, with resolution of symptoms and normalizing of androgen and cortisol levels post left adrenalectomy.

Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing\u2019s syndrome

PurposeEctopic Cushing’s syndrome (ECS) caused by an ACTH secreting neuroendocrine neoplasm (NEN) is a rare and challenging condition. We aimed to detect predictive and prognostic parameters for ECS patients identified from a retrospective, comprehensive cohort of NENs treated at a tertiary referral center.MethodsMedical records of 886 patients with NENs were reviewed. We identified 51 patients with ECS (33 females/18 men); mean age 52 ± 15 years (SD). Clinical parameters including symptoms, biochemical markers, and survival were extracted and further analyzed.ResultsThe primary tumor was located in the thorax (n = 28) or pancreas (n = 15) or was of unknown primary origin (n = 8). In 30 patients, tumor and ECS were diagnosed simultaneously. In 12 patients, the NEN diagnosis preceded ECS development, with a median time of 43.5 months (range: 9–96), and 10 of these showed radiological tumor progression at ECS diagnosis. Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p = 0.012 (HR 2.4 (95% CI 1.2–4.9)), as did high morning cortisol, p = 0.037 (HR 2.3 (1.0–5.2)), higher tumor grade, p = 0.044 (HR 2.3 (1.0–5.1)), and diabetes, p = 0.050 (HR 2.4 (1.0–6.0)).ConclusionsMultiple hormone secretion, high morning cortisol, higher tumor grade, and diabetes were correlated with shorter OS. Development of ECS in patients with a non-functioning NEN may indicate tumor progression. Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management.

MECHANISMS OF ENDOCRINOLOGY: Mechanisms of disease: the endocrinology of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a common disorder that is associated with serious comorbidities with a negative impact on quality of life, life expectancy and health costs. As OSA is related to obesity and is associated with sleep disruption, increased inflammation and oxidative stress, it is not surprising that OSA has an impact on the secretion of multiple hormones and is implicated in the development of many endocrine conditions. On the other hand, many endocrine conditions that can affect obesity and/or upper airways anatomy and stability have been implicated in the development or worsening of OSA. This bidirectional relationship between OSA and the endocrine system has been increasingly recognised in experimental and epidemiological studies and there are an increasing number of studies examining the effects of OSA treatment on endocrine conditions and vice versa. In this review article, we will critically appraise and describe the impact of OSA on the endocrine system including obesity, dysglycaemia, the pituitary, the thyroid, the adrenals, the reproductive system and the bones. In each section, we will assess whether a bidirectional relationship exists, and we will describe the potential underlying mechanisms. We have focused more on recent studies and randomised controlled trials where available and attempted to provide the information within clinical context and relevance.

Alpha the versatile: Guardians of the islets.

Recent progress in α-cell research has newly revealed its versatility including secretion of multiple hormones, trans-differentiation, and abundant proliferation. A recent report from the Kushner laboratory further provided direct evidence of active proliferation of α-cells in both T1D and non-diabetic control donors. α-cells are suggested to maintain both quality and quantity of islets by serving as 'guardians' of the islets.

Effect of hormone secretory syndromes on neuroendocrine tumor prognosis.

The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: proton-pump inhibitors decrease acid secretion caused by gastrinomas. Somatostatin analogs can inhibit the secretion of multiple hormones and these are now the cornerstone for treating patients with a gastroenteropancreatic NET. However, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs and everolimus can also decrease symptoms of hypersecretion and increase progression-free survival. Several factors affect the survival in patients with a functioning NET. Complications of hypersecretion negatively impact survival; however, secretion of hormones is also often a sign of a well-differentiated NET and due to the symptoms, functioning NETs can be detected in an earlier stage suggesting a positive effect on prognosis. The effect on survival is also dependent on the type of hormone being secreted. This review aims to study the effect of hormone secretion on the prognosis of NETs with the contemporary treatments options available today.

Different Hormonal Expression Patterns Between Primary Pancreatic Neuroendocrine Tumors and Metastatic Sites

Pancreatic neuroendocrine tumors (PNETs) are known to have heterogeneity in terms of their ability to produce multiple hormones. The aim of this study was to evaluate the heterogeneity of PNETs from the viewpoint of hormonal expression. The expressions of 4 representative hormones, gastrin, insulin, glucagon, and somatostatin, in both primary and metastatic lesions, were analyzed by immunohistochemical staining in 20 patients with metastatic PNETs (6 gastrinomas, 1 insulinoma, 1 glucagonoma, and 12 nonfunctioning PNETs [NF-PNETs]). Metastatic sites included lymph nodes in all 20 patients and liver metastasis in 7 patients (2 gastrinomas and 5 NF-PNETs). There were 6 PNETs with multiple hormone secretion (30%), and positive expression of 1 or more hormones was found in 9 of 12 patients whose primary tumors were diagnosed as NF-PNETs. The positive concordance rate of the hormonal expression pattern between primary tumors and metastatic lymph nodes and between primary tumors and hepatic metastasis were 50% and 11%, respectively. Three patients had metastatic lesions with positive hormonal expression, whereas their primary tumors were negative. Hormonal expressions are often different between the primary tumors and metastatic sites of PNETs.

Nutrient and Stress Management

Stress is a complex phenomenon and each individual has his/her own level of stress tolerance. Exposure to stressors results in a series of coordinated responses often referred to as ‘stress responses’ which are composed of series of reactions in the body including alterations in behaviour, autonomic function, secretion of multiple hormones and various physiological changes in the body. There are several ways to cope up with stress and one good solution is to eat stress fighting and reducing nutrient through food. A nutritious, well balanced diet has powerful stress reducing benefits that improve brain functioning, shore up immune function, lower blood pressure, improve the circulation, and reduce toxins from the body. Some specific nutrients play a very important role in reducing the levels of cortisol and adrenalin in the body and also the stress chemicals that activate fight and flight response. They are complex carbohydrates, proteins (tryptophan, phenylalanine and tyrosine, theanine) Vitamin C, Vitamin B, Magnesium, and Selenium. These nutrients play a very specific and important role in stress management. This review paper aims at eliciting the role of various nutrients and food items in stress reduction and management.

Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours.

As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage. The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients. This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail. In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P < .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively. Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

PurposeTo evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA).Methods and MaterialsBetween March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months.ResultsTumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively.ConclusionsSFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function.

Glucoregulatory Hormones and Choice of Osmotic Agent in Peritoneal Dialysis

The present study was performed to explore the range of effects of amino acid-based peritoneal dialysis (PD) solutions on glucoregulatory hormones in comparison with an osmotically equivalent glucose-based solution. ♢ 13 adult nondiabetic patients on PD underwent 2 peritoneal dwells of 2 hours' duration with either 1.5% dextrose solution or 1.1% amino acid solution. Serial sampling for glucoregulatory hormones was done throughout the duration of the dwell. ♢ Instillation of the 1.5% dextrose solution resulted in a modest change in plasma glucose, paralleled by a small increase in plasma insulin levels and plasma insulin-like growth factor (IGF-1). Plasma glucagon was not changed and plasma growth hormone level declined. Instillation of the 1.1% amino acid solution resulted in an increase in plasma glucose, plasma insulin, plasma glucagon, and plasma IGF-1. Plasma growth hormone level declined. Both solutions led to an increase in plasma norepinephrine but no changes were observed in epinephrine or dopamine. ♢ Our observations suggest that the mere replacement of glucose by amino acids in PD solutions does not necessarily imply "glucose sparing" from the perspective of induction of a glucoregulatory hormonal response because of the aminogenic stimulation of secretion of multiple hormones.

Effects of treadmill exercise on hypoactivity of the hypothalamo-pituitary-adrenal axis induced by chronic administration of corticosterone in rats

The stress response alters behavior, autonomic function and secretion of multiple hormones, including CRF, ACTH, and glucocorticoid, through the HPA axis. Consecutive stress exposures lead to HPA axis dysregulation such as hyperactivity in Alzheimer's disease and depression, and hypoactivity in post-traumatic stress disorder. In the present study, we established a model of hypoactivated HPA axis in rat through chronic administration of corticosterone (40mg/kg, s.c.) for 19 consecutive days. In this model, CRF mRNA expression in the hypothalamus and ACTH levels in serum were significantly decreased by chronic administration of corticosterone. In addition, the effect of treadmill exercise was investigated in our hypoactivated HPA axis rat model. Treadmill exercise recovered the dysregulated hypoactivity of the HPA axis induced by corticosterone administration for 19 days. The results of the present study suggest that treadmill exercise may aid recovery of hypoactivated HPA axis dysregulation in psychological diseases such as post-traumatic stress disorder.

Decreased hippocampal cholinergic neurostimulating peptide precursor protein associated with stress exposure in rat brain by proteomic analysis

The stress response alters behavior, autonomic function, and secretion of multiple hormones, including corticotropin-releasing factor, adrenocorticotropin hormone, and cortisol, through the hypothalamic-pituitary-adrenal axis. Constitutive stress responses lead to a number of psychiatric disorders, including depression, posttraumatic stress disorder, Alzheimer's disease (AD), and other anxiety disorders through increased stress hormones and other unknown factors. Here, we performed a proteomic analysis of rat brain exposed to restraint stress compared with a nonstress group by using 2D-DIGE and MALDI-TOF analysis. Several proteins were identified by peptide mass fingerprint (PMF), including down-regulated hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp). The current study demonstrates that HCNP-pp mRNA and protein expression are decreased in rat hippocampus after stress exposure. The level of HCNP-pp in H19-7, a rat hippocampal cell line, significantly decreases with dexamethasone treatment, a synthetic glucocorticoid. Thus, this finding suggests that HCNP-pp expression may decrease in response to stress exposure. Decreased HCNP-pp from stress exposure may result in lower levels of HCNP that might contribute to a loss of acetylcholine production.

Neuroendocrine adaptations in renal disease.

Chronic renal failure (CRF) disrupts the time-dependent secretion of multiple hormones. The present review focuses on altered pulsatile release of peptide hormones. CRF is marked by impaired tissue actions, disorderly release patterns, and relative [growth hormone (GH)] or absolute [luteinizing hormone (LH)] deficiency of secretion. At the hypothalamo-pituitary level, experimental evidence suggests that CRF reduces the synthesis and/or release of the cognate hypothalamic releasing factors, GHRH and LHRH, and enforces excessive inhibition by somatostatin. Parathyroid hormone (PTH) and insulin are secreted in both basal and pulsatile modes, wherein the latter is putatively coordinated by autonomic innervation. Amplitude and frequency-dependent adaptations of PTH and insulin outflow fail in CRF, as assessed under steady-state conditions and during metabolic drive (i.e., calcium for PTH and glucose for insulin). A common feature in CRF is a diminished mass of hormone released per burst, due in principle to attenuation of feedforward signals and/or accentuation of (unknown) feedback signals. Damping of neuronal control and/or prolonged network response times may contribute to aberrant pulse frequency, disproportionate basal (nonpulsatile) hormone release, and consistent erosion of secretory process regularity in the uremic state. The homeostatic consequences of distorted secretory dynamics, tissue resistance, impaired hormone clearance, and altered mean agonist concentrations are evident in certain therapeutic interventions, such as GH supplementation in CRF.

Neuroendocrine pharmacology of stress

Exposure to hostile conditions initiates responses organized to enhance the probability of survival. These coordinated responses, known as stress responses, are composed of alterations in behavior, autonomic function and the secretion of multiple hormones. The activation of the renin–angiotensin system and the hypothalamic–pituitary–adrenocortical axis plays a pivotal role in the stress response. Neuroendocrine components activated by stressors include the increased secretion of epinephrine and norepinephrine from the sympathetic nervous system and adrenal medulla, the release of corticotropin-releasing factor (CRF) and vasopressin from parvicellular neurons into the portal circulation, and seconds later, the secretion of pituitary adrenocorticotropin (ACTH), leading to secretion of glucocorticoids by the adrenal gland. Corticotropin-releasing factor coordinates the endocrine, autonomic, behavioral and immune responses to stress and also acts as a neurotransmitter or neuromodulator in the amygdala, dorsal raphe nucleus, hippocampus and locus coeruleus, to integrate brain multi-system responses to stress. This review discussed the role of classical mediators of the stress response, such as corticotropin-releasing factor, vasopressin, serotonin (5-hydroxytryptamine or 5-HT) and catecholamines. Also discussed are the roles of other neuropeptides/neuromodulators involved in the stress response that have previously received little attention, such as substance P, vasoactive intestinal polypeptide, neuropeptide Y and cholecystokinin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABA A, histamine and serotonin receptors have been used to attenuate the neuroendocrine response to stressors. The neuroendocrine information for these drugs is still incomplete; however, they are a new class of potential antidepressant and anxiolytic drugs that offer new therapeutic approaches to treating anxiety disorders. The studies described in this review suggest that multiple brain mechanisms are responsible for the regulation of each hormone and that not all hormones are regulated by the same neural circuits. In particular, the renin–angiotensin system seems to be regulated by different brain mechanisms than the hypothalamic–pituitary–adrenal system. This could be an important survival mechanism to ensure that dysfunction of one neurotransmitter system will not endanger the appropriate secretion of hormones during exposure to adverse conditions. The measurement of several hormones to examine the mechanisms underlying the stress response and the effects of drugs and lesions on these responses can provide insight into the nature and location of brain circuits and neurotransmitter receptors involved in anxiety and stress.

Multiple hormone secretion by a human pancreatic glucagonoma in culture

A patient presenting clinically with the glucagonoma syndrome had high plasma glucagon levels (1920 ng/l) and at laparotomy, a pancreatic islet cell tumour was removed. The tumour was dispersed and placed in culture where it remained viable for 63 days. The tumour cells secreted immunoreactive (IR) glucagon at levels up to 2400 ng/l as detected by a C-terminal glucagon specific antibody and 85400 ngequiv./l as measured by an N-terminal glucagon specific antibody. The difference between these two levels was attributed to the presence of different molecular forms of glucagon measured with the N-terminal specific antibody. IR insulin (up to 302 mU/l) and IR somatostatin (up to 2500 ng/l) were also detected. There was no direct or inverse correlation between different hormone levels. Small but significant levels of N-terminal and C-terminal vasoactive intestinal peptide (VIP) were detected in some cultures but there was no evidence of gastrin or ACTH. Glucagon and somatostatin secretion persisted for the duration of the culture (63 days) but insulin concentrations declined. Incubation of cultures with somatostatin (1 ng/ml) caused a 75% decrease in glucagon levels, while insulin (1000 mU/l) produced a 70% inhibition of somatostatin.