Best practice & research. Clinical endocrinology & metabolism最新文献

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.

Preserving bone health is an important goal of care of patients with acromegaly and growth hormone deficiency (GHD). Both disorders are associated with compromised bone health and an increased risk of fracture. However, parameters of bone health that are routinely used to predict fractures in other populations, such as aBMD measured by DXA, are unreliable for this in acromegaly and GHD. Additional methodologies need to be employed to assess bone health in these patients. This review summarizes available data on the effects of acromegaly and GHD on parameters of bone health such as aBMD, volumetric bone mineral density (vBMD) and microarchitecture assessed by HRpQCT and other techniques, trabecular bone score (TBS) and fracture assessment. More research is needed to identify reliable predictors of fracture risk and to determine how best to screen for and treat those patients at risk so that bone health is optimized in these patients.

The gut microbiome has been implicated in a variety of neuropathologies with recent data suggesting direct effects of the microbiome on host metabolism, hormonal regulation, and pathophysiology. Studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, no study to date has examined the specific role of GH on the fecal microbiome (FMB) or the changes in this relationship following a traumatic brain injury (TBI). Current literature has demonstrated that TBI can lead to either temporary or sustained abnormal GH secretion (aGHS). More recent literature has suggested that gut dysbiosis may contribute to aGHS leading to long-term sequelae now known as brain injury associated fatigue and cognition (BIAFAC). The aGHS observed in some TBI patients presents with a symptom complex including profound fatigue and cognitive dysfunction that improves significantly with exogenous recombinant human GH treatment. Notably, GH treatment is not curative as fatigue and cognitive decline typically recur upon treatment cessation, indicating the need for additional studies to address the underlying mechanistic cause.

Growth hormone (GH) plays an essential role not only in promoting growth in children, but also in many important metabolic processes in adults. One of the major metabolic functions of GH is its stimulatory effects on the liver in generating approximately 80% of circulating insulin-like growth factor 1 (IGF-1). Adult growth hormone deficiency (GHD) is an established clinical entity defined as a defect in endogenous GH secretion that is frequently associated with central obesity, loss of muscle mass, decreased bone mass, and impaired quality of life. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions that are often under-recognized in adults with GHD, and accordingly some studies have shown that GH and IGF-1 levels are decreased in patients with NAFLD. Furthermore, it has been reported that it can progress to end-stage liver cirrhosis in some adults and children with GHD. Due to their underlying mechanisms of action, GH and IGF-1 can act on hepatocytes, macrophages, and hepatic stellate cells to mitigate progression to steatosis and fibrosis. It is, thus, important to recognize NAFLD/NASH as important complications in adult and childhood GHD. Therefore, careful and thorough evaluation of NAFLD/NASH in adults with GHD and the consideration for GH replacement therapy is crucial in these patients, together with management of other metabolic risk factors, such as obesity and dyslipidemia. This review will focus on recent reports on the role of GH and IGF-1 in the liver and its clinical significance in the regulation of hepatic function.

The predominant features of the adult growth hormone deficiency (GHD) syndrome may vary between patients of different age and age of onset of GHD. Evidence from clinical trials and long-term observational studies has informed our ability to understand the unique considerations regarding risks and benefits of daily growth hormone replacement therapy (GHRT) and specific dosing and monitoring strategies for these patient subgroups. High rates of nonadherence with daily GHRT presents a challenge to achieving optimal treatment outcomes and long-acting growth hormone (LAGH) formulations have been developed with the promise of improving treatment adherence resulting in improved therapeutic outcomes. While existing data from short-term studies have demonstrated noninferiority of efficacy and safety of LAGH compared to daily GHRT, long-term studies are needed to assess the full spectrum of outcomes of interest and long-term safety considerations specific to patients in adolescence, adulthood and the elderly GHD population. Since each LAGH formulation has a unique pharmacodynamic and pharmacokinetic profile optimal dosing and monitoring strategies will need to be developed to allow for the provision of individualized patient treatment.

The SARS-CoV-2 pandemic created a multitude of medical crossroads requiring real time adaptations of best practice covering preventative and interventional aspects of care. Among the many discoveries borne from efforts to address the myriad clinical presentations across multiple organ systems was a common impact on tissues with cells that express the ACE-2 receptor. The vast majority of acute infections began and often ended in the respiratory tract, but more recent evaluations have confirmed significant extrapulmonary manifestations including symptom clusters that extend beyond the acute phase of infection collectively referred to as “post-acute sequelae SARS-CoV-2 infection” (PASC) or more commonly as “long (-haul) COVID”. Both acute SARS-CoV-2 infection and PASC are associated with gut microbiome dysbiosis and alterations in the gut-brain and HPA-axis in a subset of the infected. Mounting evidence suggests these extrapulmonary manifestations may ultimately lead to reduced growth hormone (GH) secretion as demonstrated following stimulation tests. Disrupted GH secretion could cause or exacerbate long lasting neuropsychological symptoms as seen in other similar manifesting conditions. Ongoing clinical research has shown promising improvement in PASC patients with fatigue and cognition complaints can be achieved via GH replacement therapy. GH stimulation testing should be considered in PASC workups and future research should delve deeper into the mechanistic effects of GH on acute COVID and PASC.

Growth hormone is among the most common hormones to be deficient in pituitary insult. It can occur either in isolation or combined with other hormone deficiencies. Growth hormone deficiency in adults (AGHD) can be due to causes acquired in adulthood or have a childhood-onset etiology, but the former is about three times more common. Usual causes of AGHD include mass effects due to a pituitary tumour, and/or its treatment (surgery, medical therapy, or radiotherapy), or radiotherapy to the head and neck region for non-pituitary lesions. The unusual or lesser-known causes of AGHD, are usually due to non-tumoral etiology and range from vascular and infective to inflammatory and miscellaneous causes. These not only expand the spectrum of AGHD but may also contribute to increased morbidity, adverse metabolic consequences, and mortality due to the primary condition, if unrecognised. The review features these lesser-known and rare causes of AGHD and highlights their clinical and diagnostic implications.

Growth hormone deficiency (GHD) is a common complication of several pituitary and hypothalamic disorders and dependent on the onset of disease. It may have severe clinical implications ranging from growth retardation in childhood-onset, to impaired lipid metabolism and increased cardiovascular risk and mortality in adults. GH effectively modulates lipid metabolism at multiple levels and GHD has been associated with an atherogenic lipid profile, that can be reversed by GH replacement therapy. Despite increasing knowledge on the effects of GH on several key enzymes regulating lipid metabolism and recent breakthroughs in the development and wider availability of recombinant GH preparations, several questions remain regarding the replacement therapy in adults with GHD. This review aims to comprehensively summarize the current knowledge on (i) lipid profile abnormalities in individuals with GHD, (ii) proposed mechanisms of action of GH on lipid and lipoprotein metabolism, and (iii) clinical implications of GH replacement therapy in individuals diagnosed with GHD.

In recent years, mild traumatic brain injury (mTBI) has been recognized as a cause of acquired growth hormone deficiency (AGHD) and is likely much more prevalent than previous estimates. There is great overlap between persistent symptoms following mTBI and those of AGHD and it is possible that these persistent symptoms of mTBI are, at least in part, due to or aggravated by AGHD. This article reviews the current literature of AGHD following mTBI, and proposes practice recommendations for the screening, diagnosis, and management of patients with AGHD following mTBI.