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Lipedema is a chronic, progressive disorder of adipose tissue that predominantly affects women, characterized by symmetrical fat accumulation in the extremities, pain, and resistance to caloric restriction. Recent insights suggest that lipedema represents a hormone-driven gynecological fat disorder, in which estrogen receptor (ER) imbalance plays a central role. The predominance of ERβ activity and suppression of ERα signaling are hypothesized to drive adipose hypertrophy, fibrosis, and inflammation, particularly in the context of intracrine estradiol excess. This model aligns lipedema with other estrogen-sensitive conditions, such as endometriosis and uterine fibroids, and provides a novel framework for understanding its pathophysiology. Therapeutically, this reframing opens new perspectives for hormonal modulation using selective progestins (drospirenone, gestrinone) and metabolic adjuncts such as tirzepatide, beyond the current symptomatic or surgical approaches.

Often regarded as the forgotten second circulatory system, the lymphatic system is critical in working with the venous and arterial system to maintain fluid equilibrium, circulate cells and signaling molecules in the immune system, and transport fat molecules and nutrients. When there is an alteration in the flow of lymphatic fluid, lymphedema is the result, usually manifesting as significant swelling of a particular region of the body with protein-rich fluid accumulation in the interstitial spaces. The result of this disease ranges from psychological disturbance to significant disability and morbidity, even leading to aggressive malignancy. The prevalence of lymphedema is in the hundreds of millions worldwide; however, it is routinely under-diagnosed and under-recognized as a disease, especially in the United States. Treatment rates for lymphedema are variable, ranging from low rates of treatment in non-cancer etiologies, to high treatment rates seen in breast cancer related etiologies. Furthermore, treatment modalities are equally notorious for being unsuccessful, either as a result of non-compliance or lack of efficacious therapeutic techniques, or a combination of both. There is no cure for lymphedema and treatment mainly focuses on minimizing limb swelling, maintaining functionality, and preventative treatments to reduce complications.

This chapter sets out the most promising modern directions of research in the field of magnetic resonance imaging. These include multinuclear studies aimed at the exploration of magnetic resonance (MR) image contrast induced by exogeneous (fluorine-19, hyperpolarized noble gases) and “built-in” (phosphorus-31, sodium-23) contrast agents for potential clinical benefits. The chapter covers electrodynamic elements of MR scanners that increase signal-to-noise ratio in low-field magnetic resonance imaging (MRI), hyperpolarization techniques that allow several orders of magnitude improved sensitivity in low-field MRI, as well as MRI methods to study dynamics of pharmaceuticals introduced into the body. Special attention is given to MRI methods based upon magnetization transfer aimed at the detection of myelination defects of axons in the brain and functional MRI characterizing brain dynamic response to external stimuli.

Fluid compartments in the human body are divided between the intracellular and extracellular spaces. The extracellular space constitutes about one-third of total body water, which is further divided into intravascular plasma volume (25%) and the extravascular interstitial space (75%). The fluid balance between these compartments is maintained by hydrostatic pressures and oncotic pressures described by Starling. The other two factors that play an important role in fluid balance are vessel wall permeability and the lymphatic system. The lymphatic system collects fluid and filtered proteins from the interstitial space and returns that back to the vasculature. Any disturbance in this delicate homeostasis that results in net filtration out of the vascular space or impaired return of fluid by lymphatics leads to the accumulation of fluid in the interstitial space that is called edema. Edema can affect any part of the body and ranges from local swelling to full-blown anasarca, depending on the underlying pathology. A classic example of local swelling is an insect bite. An example of anasarca can be seen in nephrotic syndrome.[1] Edema, other than localized edema, does not become clinically apparent until the interstitial volume has increased by 2.5 to 3 liters because the tissues constituting the interstitium can easily accommodate several liters of fluid. Therefore, a patient's weight may increase by nearly 10% before pitting edema is evident.

The thigh lift procedure is one of the 5 most requested procedures associated with skin excess from massive weight loss (MWL). The procedure also has the highest reported complication rate amongst MWL procedures. The complication rate is most commonly associated with regional blood flow, higher bacterial involvement associated with proximity to the perineal region and poor-quality dermal thickness to support closure. Technical aspects of ideal management of the region include proper use of lipoplasty, skin excision, multi-layer tissue approximation and suspension. The following chapter reviews the regional anatomy, analysis, and the range of surgical techniques associated with this challenging procedure.

One of the most common breast malformations is tuberous breast anomaly. Being prevalent in adolescence, few patients know about this condition and the options of treatment.

Dr. Allen and Dr. Hines pioneered and first described lipedema in the 1940s, a common subcutaneous adipose tissue disorder characterized as enlargement of both lower extremities. Lipedema is not edema; it is a genetically determined disturbance in adipose tissue mass and adipose tissue distribution.[1][2][3][4] In 1951 a second seminal paper provided more description of lipedema. Fat distribution involves lower extremities, upper arms, hips, buttocks, thighs sparing trunks, and feet.[2] Lower extremities are characterized by pain, easy bruisability, firm subcutaneous nodules of adipose tissue, and resistance of fat to traditional diet and exercise.[5][6]

Lipedema is an underdiagnosed painful adipose tissue disorder that occurs almost exclusively in women, with onset manifesting at puberty or at times of hormonal change. Unlike many fat disorders, diet and exercise have little to no impact on the prevention or progression of this disease. Estrogens control the distribution of body fat and food intake, regulate leptin expression, increase insulin sensitivity, and reduce inflammation through signaling pathways mediated by its receptors, estrogen receptor alpha (ERα) and ERβ. This review will focus on understanding the role of estrogen in the pathogenesis of the disease and envisage potential hormonal therapy for lipedema patients.

Lipomas are defined as a common subcutaneous tumor composed of adipose (fat) cells, often encapsulated by a thin layer of fibrous tissue.[1] In fact, these are the frequently encountered neoplasms by the clinicians. [2] Clinically, they often present in the body's cephalic part, specifically in the head, neck, shoulders, and backs of patients. However, they can less commonly be seen elsewhere, for example, the thighs. The tumors typically lie in the subcutaneous tissues of patients. The masses are often benign, and while the age of onset can vary. There is usually no reason for treatment. They pose no threat to the patient unless they are uncomfortable due to being located on joints or rapidly growing, which is uncommon, as the typical lipoma growth is slow. Lipomas can sometimes, though rare, be associated with certain disorders such as multiple hereditary lipomatosis, Gardner syndrome, adiposis dolorosa, and Madelung disease.[3] [4] Some unconventional forms of lipomas include the following: angiolipoma, chondroid lipoma, lipoblastoma, myolipoma, pleomorphic lipoma/spindle cell lipoma, intramuscular and intermuscular lipoma, lipomatosis of nerve, lipoma of the tendon sheath and joint, lipoma arborescens, multiple symmetric lipomatosis, diffuse lipomatosis, adiposis dolorosa, and hibernoma.

Lipedema is a painful fat disease of loose connective tissue usually misdiagnosed as lifestyle-induced obesity that affects ~10% of women of European descent as well as other populations. Lipedema is characterized by symmetric enlargement of the buttocks, hips, and legs due to increased loose connective tissue; arms are also affected in 80% of patients. Lipedema loose connective tissue is characterized by hypertrophic adipocytes, inflammatory cells, and dilated leaky blood and lymphatic vessels. Altered fluid flux through the tissue causes accumulation of fluid, protein, and other constituents in the interstitium resulting in recruitment of inflammatory cells, which in turn stimulates fibrosis and results in difficulty in weight loss. Inflammation and excess interstitial substance may also activate nerve fibers instigating the painful lipedema fat tissue. More research is needed to characterize lipedema loose connective tissue structure in depth, as well as the form and function of blood and lymphatic vessels. Understanding the pathophysiology of the disease will allow healthcare providers to diagnose the disease and develop treatments.

Lipedema is a chronic fat disorder with disproportional fat distribution, especially around the legs, hips, and sometimes arms, and it affects women almost exclusively. The major symptoms and complaints include pain in the soft tissue and the feeling of “heavy legs.” The perception of pain depends to a high degree on the psychological condition of the patient. Obesity is the major comorbidity and can worsen lipedema. In combination with impaired levels of physical activity, there is an increase in interstitial filtration, and noninfectious inflammation with capillary leakage can occur. Eventually, chronic edema develops due to the dynamic insufficiency of the lymphatic system. However, edema is not a pathognomonic aspect of lipedema. There are many controversies and myths about the condition lipedema, and no objective diagnostic tool is available to confirm the diagnosis. Therapeutic approaches in lipedema are multimodal and focus on the biomedical, psychological, and functional aspects involved with the disorder. A lifestyle change is often part of the therapeutic program, along with other therapeutic interventions, such as exercise, compression, weight management, and nutritional and psychological support. Clinimetrics with validated techniques in all fields of human functioning of a lipedema patient are mandatory to objectively evaluate the improvements that are due to the treatment program. Liposuction is a technique to remove fat and is therefore introduced to treat lipedema. Some doctors who offer the procedure state that “liposuction leads to comprehensive and long-term improvements in lipedema and cures the disease.” These statements are often too optimistic and lead to high costs for the patient and disappointment in the end. However, liposuction can lead to improvements in lipedema when offered within a therapeutic program that includes other nonoperative modalities for the correct selection of patients according to their medical criteria. It cannot be emphasized enough that liposuction is not a method that should be used to treat obesity.

Subcutaneous adipose tissue diseases involving adipose tissue and its fascia, also known as adipofascial disorders, represent variations in the spectrum of obesity. The adipofascia diseases discussed in this chapter can be localized or generalized and include a common disorder primarily affecting women, lipedema, and four rare diseases, familial multiple lipomatosis, angiolipomatosis, Dercum disease, and multiple symmetric lipomatosis. The fat in adipofascial disorders is difficult to lose by standard weight loss approaches, including lifestyle (diet, exercise), pharmacologic therapy, and even bariatric surgery, due in part to tissue fibrosis. In the management of obesity, healthcare providers should be aware of this difficulty and be able to provide appropriate counseling and care of these conditions. Endocrinologists and primary care providers alike will encounter these conditions and should consider their occurrence during workup for bariatric surgery or hypothyroidism (lipedema) and in those that manifest, or are referred for, dyslipidemia or diabetes (Dercum disease). People with angiolipomas should be worked up for Cowden’s disease where a mutation in the gene PTEN increases their risk for thyroid and breast cancer. This chapter provides details on the pathophysiology, prevalence, genetics and treatments for these adipofascial disorders along with recommendations for the care of people with these diseases. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

The easiest way to differentiate lipedema from lymphedema is to detect lipedema-associated clinical symptoms (e.g., cuffing sign, retromalleolar fat pads, tenderness of the skin). Physical examinations including the Streeten test, waist-to-height ratio, capillary fragility, and pain measurements can also aid in differential diagnosis. The last two methods can be used to follow and measure therapeutical efficacy. Imaging techniques (ultrasound, computed tomography, magnetic resonance imaging, lymphoscintigraphy, infrared fluoroscopy) and cardiovascular methods (aortic stiffness determination, three-dimensional speckle tracking echocardiography) are sensitive tools to find subtle differences.