Reviews in Endocrine & Metabolic Disorders最新文献

Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited. There is currently no consensus on the definition of androgen deficiency in women and it is still controversial whether androgen substitution should be used in women with hypopituitarism and coexisting androgen deficiency. Some studies suggest beneficial clinical effects of androgen replacement but data on long-term benefits and risk are not available. Transdermal testosterone replacement therapy in hypopituitary women has shown some positive effects on bone metabolism and body composition. Studies of treatment with oral dehydroepiandrosterone have yielded mixed results, with some studies suggesting improvements in quality of life and sexual function. Further research is required to elucidate the impact of androgen deficiency and its replacement treatment on long-term outcomes in women with hypopituitarism. The lack of transdermal androgens for replacement in this patient population and limited outcome data limit its use. A cautious and personalized treatment approach in the clinical management of androgen deficiency in women with hypopituitarism is recommended while awaiting more efficacy and safety data.

Growth hormone (GH) is secreted by somatotropic cells of the anterior pituitary gland. The classical effects of GH comprise the stimulation of cell proliferation, tissue and body growth, lipolysis, and insulin resistance. The GH receptor (GHR) is expressed in numerous brain regions. Notably, a growing body of evidence indicates that GH-induced GHR signaling in specific neuronal populations regulates multiple physiological functions, including energy balance, glucose homeostasis, stress response, behavior, and several neurological/cognitive aspects. The importance of central GHR signaling is particularly evident when the organism is under metabolic stress, such as pregnancy, chronic food deprivation, hypoglycemia, and prolonged exercise. These particular situations are associated with elevated GH secretion. Thus, central GH action represents an internal signal that coordinates metabolic, neurological, neuroendocrine, and behavioral adaptations that are evolutionarily advantageous to increase the chances of survival. This review summarizes and discusses recent findings indicating that the brain is an important target of GH, and GHR signaling in different neuronal populations regulates essential physiological functions.

Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism.

Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.

Adrenal crisis (AC) is a life threatening acute adrenal insufficiency (AI) episode which can occur in patients with primary AI but also secondary AI (SAI), tertiary AI (TAI) and iatrogenic AI (IAI). In SAI, TAI and IAI, AC may develop when the HPA axis is unable to mount an adequate glucocorticoid response to severe stress due to pituitary or hypothalamic disruption. It manifests as an acute deterioration in multi-organ homeostasis that, if untreated, leads to shock and death. Despite the availability of effective preventive strategies, its prevalence is increasing in patients with SAI, TAI and IAI due to more frequent exogenous steroid administration, pituitary immune-related effects of immune checkpoint inhibitors and opioid use in pain management. The delayed diagnosis of acute AI which remains infrequently suspected increases the risk of AC. Its main precipitating factors are infections, emotional distress, surgery, cessation or reduction in GC doses, pituitary infarction or surgical cure of endogenous Cushing's syndrome. In patients not known previously to have SAI/TAI/IAI, recognition of its symptoms, signs, and biochemical abnormalities can be challenging and cause delay in proper diagnosis and therapy. Effective therapy of AC is rapid intravenous administration of hydrocortisone (initial bolus of 100 mg followed by 200 mg/24 h as continuous infusion or bolus of 50 mg every 6 h) and 0.9% saline. In diagnosed patients, preventive education in sick-day rules adjustment of glucocorticoid replacement and hydrocortisone parenteral self-administration must be performed repeatedly by trained health care providers. Strategies to improve the adequate preventive education in patients at risk for secondary AI should be promoted in collaboration with various medical specialist societies and patients support associations.

Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.

Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.

Central hypothyroidism (CH) is characterized by decreased thyroid hormone production due to insufficient stimulation of an otherwise normal thyroid gland by TSH. In patients with established hypothalamic-pituitary disease, a low FT4 concentration is considered highly specific, although poorly sensitive, for the diagnosis of CH. That would be comparable to diagnosing primary hypothyroidism in patients at risk only when serum FT4 concentrations are below the reference range, missing all patients with subclinical primary hypothyroidism and preventing proper therapy in patients in which thyroxine replacement is clearly beneficial. Cardiac time intervals, especially the isovolumic contraction time (ICT), have been considered the gold standard of peripheral thyroid hormone action. Using Doppler echocardiography, we have previously shown a very high proportion of prolonged ICT in patients with hypothalamic-pituitary disease and serum FT4 levels indistinguishable from controls. As ICT decreased/normalized after thyroxine-induced increases in FT4 concentrations within the normal reference range, prolonged ICT was considered a bona fide diagnostic biomarker of subclinical CH. Those findings challenge the usual interpretation that FT4 concentrations in the mid-reference range exclude hypothyroidism in patients with hypothalamic-pituitary disease. Rather, subclinical central hypothyroidism, a state analogous to subclinical primary hypothyroidism, seems to be frequent in patients with hypothalamic-pituitary disease and normal FT4 levels. They also challenge the notion that thyroid function is usually the least or the last affected in acquired hypopituitarism. The relevance of Doppler echocardiography to correctly diagnose and monitor replacement therapy in both clinical and subclinical forms of CH should improve quality of life and decrease cardiovascular risk, as already demonstrated in patients with clinical and subclinical primary hypothyroidism.

Hypopituitarism (HP) frequently occurs in patients presenting with sellar masses and despite recent advances in therapeutic options, HP patients consistently suffer from impaired quality of life due to psychological distress and cognitive dysfunction. These neurocognitive complications tend to persist in spite of surgical or biochemical remission of the disease making it especially challenging to segregate the effect of HP per se from other comorbidities such as the effect of tumour, surgery, radiation therapy, or complications caused by excess hormone production. Regardless, there is ample evidence to suggest that receptors for various pituitary hormones are abundantly expressed in key areas of central nervous system that are associated with memory and behaviour function and HP is also associated with poor sleep which can further exacerbate neurocognitive dysfunction. There is also evidence that hormonal replacement in HP patients partially restores these neurocognitive functions and improves sleep disorders. However, there is a need for creating better awareness among healthcare providers interacting with HP patients to enhance an earlier recognition of these disorder and their impact on quality of life despite initial remission. Importantly, there is a need to not only develop better and more cost-effective replacement therapies that would closely mimic the physiological hormonal release patterns, but also develop coping strategies for HP patients suffering from these complications.

Hypopituitarism in the elderly is an underestimated condition mainly due to the non-specific presentation that can be attributed to the effects of aging and the presence of comorbidities. Diagnosis and treatment of hypopituitarism often represent a challenging task and this is even more significant in the elderly. Diagnosis can be insidious due to the physiological changes occurring with aging that complicate the interpretation of hormonal investigations, and the need to avoid some provocative tests that carry higher risks of side effects in this population. Treatment of hypopituitarism has generally the goal to replace the hormonal deficiencies to restore a physiological balance as close as possible to that of healthy individuals but in the elderly this must be balanced with the risks of over-replacement and worsening of comorbidities. Moreover, the benefit of some hormonal replacement therapies in the elderly, including sex hormones and growth hormone, remains controversial.