Pathology Of Endocrine System Pdf

[Dunstan Jomphe]

Theendocrine system is a network of glands that produce and release hormones. These hormones help control many important body functions, including the body's ability to change calories into energy that powers cells and organs. The endocrine system affects how your heart beats, how your bones and tissues grow, and even your ability to make a baby.

Disorders of the endocrine system happen if your hormone levels are too high or too low, or if your body doesn't respond to hormones in the expected way. You may develop diabetes, thyroid disease, growth disorders, sexual dysfunction, and a host of other hormone-related disorders.

The endocrine feedback system helps control the balance of hormones in the bloodstream. If your body has too much or too little of a certain hormone, the feedback system signals the proper gland or glands to correct the problem. A hormone imbalance may occur if this feedback system has trouble keeping the right level of hormones in the bloodstream, or if your body doesn't clear them out of the bloodstream properly.

Most endocrine tumors and nodules (lumps) are noncancerous. They usually don't spread to other parts of the body. However, a tumor or nodule on the gland may interfere with the gland's hormone production.

The symptoms of an endocrine disorder vary widely and depend on the specific gland involved. However, most people with endocrine disease complain of fatigue and weakness. Certain symptoms may make you think you have a different disease or disorder. Some symptoms that are worth talking to your doctor about include:

Adrenal insufficiency. The adrenal gland releases too little of the hormone cortisol and sometimes, aldosterone. Symptoms include fatigue, stomach upset, dehydration, and skin changes. Addison's disease is a type of adrenal insufficiency.

Cushing's disease. The overproduction of a pituitary gland hormone leads to an overactive adrenal gland. A similar condition called Cushing's syndrome may occur in people, particularly children, who take high doses of corticosteroid medications.

Hyperthyroidism. The thyroid gland produces too much thyroid hormone, leading to weight loss, fast heart rate, sweating, and nervousness. The most common cause for an overactive thyroid is an autoimmune disorder called Grave's disease.

Hypothyroidism. The thyroid gland does not produce enough thyroid hormone, leading to fatigue, constipation, dry skin, and depression. The underactive gland can cause slowed development in children. Some types of hypothyroidism are present at birth.

Hypopituitarism. In this condition, the pituitary gland releases little or no hormones. It may be caused by several different diseases. Women with this condition may stop getting their periods.

Multiple endocrine neoplasia type 1 and 2 (MEN1 and MEN2). These rare, genetic conditions are passed down through families. They cause tumors of the parathyroid, adrenal, and thyroid glands, leading to overproduction of hormones.

Polycystic ovary syndrome (PCOS). The overproduction of androgens interferes with the development of eggs and their release from the female ovaries. PCOS is a leading cause of infertility.

Treatment of endocrine disorders can be complicated, as a change in one hormone level can throw off another. Your doctor or specialist may order routine blood work to check for problems or to determine if your medication or treatment plan needs to be adjusted.

Your endocrine system releases hormones that affect how your body develops and functions. An endocrine system malfunction, caused by genetics, infection, or other factors, can result in various disorders such as diabetes, hyperthyroidism, and polycystic ovarian syndrome (PCOS). If you have fatigue or weakness regularly, it could be a sign of an endocrine disorder, so consult your doctor so that they can diagnose and treat your condition.

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The concept of precursor lesions of endocrine neoplasms is a new and interesting topic in endocrine pathology. A variety of clinicopathological conditions are associated with a sequence of cellular changes from hyperplasia to neoplasia; dysplasia is, in contrast, quite rare. The majority of precursor lesions is associated with familial genetic syndromes. These include C-cell hyperplasia in thyroid that is associated with familial medullary thyroid carcinoma, adrenal medullary hyperplasia as a precursor of phaeochromocytomas in MEN2 syndrome, rare pituitary adenohypophyseal cell hyperplasia in familial syndromes associated with pituitary adenomas, MEN1-related precursor gastric enterochromaffin-like cell (ECL) hyperplasia, and duodenal gastrin producing (G) and/or somatostatin producing (D) cell hyperplasia that give rise to type II gastric neuroendocrine tumours (NETs) and duodenal NETs, respectively, and MEN1- or VHL-related islet hyperplasia, islet dysplasia and ductulo-insular complexes that are associated with pancreatic NETs. Other hyperplasias are not thought to be associated with genetic predisposition. Some are attributed to inflammation; autoimmune chronic atrophic gastritis-related ECL hyperplasia can progress to type I gastric NETs, and EC (enterochromaffin) cell or L cell hyperplasia associated with inflammatory bowel diseases can progress to colorectal NETs. In the lung, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia can give rise to peripherally-located low grade pulmonary NETs and tumourlets (neuroendocrine microtumours

Tumors of the endocrine glands are common. Knowledge of their molecular pathology has greatly advanced in the recent past. This review covers the main molecular alterations of tumors of the anterior pituitary, thyroid and parathyroid glands, adrenal cortex, and adrenal medulla and paraganglia. All endocrine gland tumors enjoy a robust correlation between genotype and phenotype. High-throughput molecular analysis demonstrates that endocrine gland tumors can be grouped into molecular groups that are relevant from both pathologic and clinical point of views. In this review, genetic alterations have been discussed and tabulated with respect to their molecular pathogenetic role and clinicopathologic implications, addressing the use of molecular biomarkers for the purpose of diagnosis and prognosis and predicting response to molecular therapy. Hereditary conditions that play a key role in determining predisposition to many types of endocrine tumors are also discussed.

In corticotroph PitNET, ATRX mutations correlate with aggressive biological behavior and distant metastasis [43]. Densely granulated biochemically functioning corticotroph tumors harbor USP8 [44], USP48, and less frequently BRAF p.V600E mutations [22]. The role of these changes and their potential therapeutic implications are still controversial [24].

The distinctive molecular signature of lactotroph PitNET includes epigenomic alterations such as high expression of MYC targets and dopamine receptor D2 (DRD2) [23]. However, the SF3B1 p.R625H hotspot mutation has been recently discovered in some lactotroph tumors characterized by high prolactin levels and short progression-free survival [45]. Furthermore, somatic SDHA mutations and SDHD loss of heterozygosity have been reported in rare spontaneous PRL-producing macrotumors [16, 46].

The molecular pathogenesis of metastatic PitNETs is still unclear, due to the rarity of these tumors. ATRX [19, 47] and PTEN [43] mutations have all been reported in some metastatic PitNETs.

Based on clinical outcome, malignant tumors of follicular cells are broadly divided into three groups: those that have a favorable prognosis, anaplastic (undifferentiated) thyroid carcinoma characterized by a very poor prognosis, and a third group of tumors that have intermediate prognosis. While tumors in the first group are histologically well differentiated with clearly defined papillary or follicular architecture or are composed of clearly recognizable oncocytic cells, tumors with very poor prognosis are undifferentiated (i.e., anaplastic). Tumors in the group with intermediate prognosis are often poorly differentiated but may also retain conventional histologic differentiation (papillary, follicular, oncocytic). Under the microscope, they have in common with the prognostically favorable tumor group at least some degree of histologic differentiation, while they share with anaplastic carcinoma high-grade features, i.e., the presence of high mitotic activity and/or tumor necrosis. This classification scheme for thyroid carcinoma of follicular cells based on prognosis is clinically relevant and has been endorsed by the latest 5th edition of the World Health Organization (WHO) scheme (Table 3). The group of tumors that are well differentiated is in turn histologically divided into three subgroups. The first subgroup is composed of tumors that are follicular patterned, which include follicular adenoma and follicular carcinoma (follicular carcinoma when there is the invasion of tumor capsule or of blood vessels), as well as tumors of the encapsulated follicular variant papillary carcinoma family: encapsulated follicular variant papillary carcinoma when there is the invasion of tumor capsule or of blood vessels, and NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) when no invasion can be identified [49]. These tumors have a RAS-like molecular signature following the 2014 TCGA molecular classification scheme [50] as discussed in the next paragraph. The second subgroup is that of conventional (i.e., not encapsulated follicular variant type) papillary carcinoma, characterized by the well-known alterations of nuclear morphology (nuclear clearing, irregular contours of the nuclear membrane, grooves, and pseudoinclusions) [49]. These tumors are characterized by infiltrative growth and typically make papillae, although sometimes they can have less typical features, such as infiltrative follicular or solid/trabecular growth, or other less common features that characterize the numerous papillary carcinoma subtypes [51]. These tumors have a BRAF p.V600E-like molecular signature following the 2014 TCGA molecular classification scheme [50], as discussed in the next paragraph. The third subgroup is that in which tumor cells are oncocytic and lack the nuclear alterations of papillary carcinoma. These tumors are characterized by homoplasmic mtDNA mutations [52] associated with dramatic DNA copy-number alterations with widespread loss of heterozygosity [53], as discussed in the next paragraph.

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