Brown tumor is seen with:
Ans: A (Hyperparathyroidism) Ref: Robbins Pathologic Basis of Disease, 8th edition.Explanation:Primary HyperparathyroidismMost common endocrine disorder causing hypercalcemia.The frequency of the various parathy roid lesions underlying the hyper!unction is as follows:Adenoma: 85% to 95%Primary hyperplasia (diffuse or nodular): 5% to 10%Parathyroid carcinoma: ~ 1%Primary hyperparathyroidism is usually a disease of adultsMore common in women than in men by a ratio of nearly 4:1.Most common Cause is a solitary parathyroid adenoma arising in the sporadic (nonfamitial) settingFamilial syndromes are second commonest cause >> The genetic syndromes associated with familial primary hyperparathyroidism include the following:Multiple endocrine neoplasia-1 (MFN-1):Inactivation of MEN! gene on chromosome 1 Iqla (Tumor suppressor gene jMultiple endocrine neoplasia-2 (MEN-2):Activating mutations in the tyrosine kinase receptor. RET, on chromosome lOq.Familial hypocalciuric hypercalcemiaAutosomal dominant disorderEnhanced parathyroid function due to decreased sensitivity to extracellular calcium.Inactivating mutations in the parathyroid calcium-sensing receptor gene (CASR) on chromosome 3qMorphologyParathyroid adenomasThese are almost always solitaryThe typical parathyroid adenoma averages 0.5 to 5.0 cm: well-circumscribed, soft, tan to reddish-brown nodule: and has a delicate capsule.In contrast to primary hyperplasia, the glands outside the adenoma are usually normal in size or somewhat shrunken because of feedback inhibition by elevated levels of serum calcium.Microscopically, parathyroid adenomas are mostly composed oi fairly uniform, polygonal chief cells with small, centrally placed nucleiAt least a few nests of larger oxyphil cells are present as well:Rarely, entire adenomas may be composed of this cell type (oxyphil adenomas).Primary hyperplasiaIt may occur sporadically or as a component of MEN syndrome.Classically all four glands are involvedThe combined weight of all glands rarely exceeds 1.0 gm and is often less.Microscopically, (he most common pattern seen is that of chief cell hyperplasia, which may involve the glands in a diffuse or multinodular pattern.The constituent cells contain abundant water- clear cells (' water-clear cell hyperplasia").Parathyroid carcinomasMay be circumscribed lesions that are difficult to distinguish from adenomasThese tumors enlarge one parathyroid gland and consist of gray-white, irregular masses that sometimes exceed 10 gm in weight.The cells are usually uniform and resemble normal parathyroid cells.They are arrayed in nodular or trabecular patterns with a dense, fibrous capsule enclosing the mass.Diagnosis of carcinoma based on cytologic detail is unreliableInvasion of surrounding tissues and metastasis are the only reliable criteria.Morphologic changes in other organs deserving special mention include skeletal and renal lesions.Skeletal changesIncreased numbers of osteoclasts, which erode bone matrix and b, particularly in the metaphyses of long tubular bones.Bone resorption is accompanied by increased osteoblastic activity and the formation of new- bony trabeculae.In severe cases, the cortex is grossly thinned, and the marrow contains increased amounts of fibrous tissue accompanied by foci of hemorrhage and cyst formation (osteitis fibrosa cystica)Aggregates of osteoclasts, reactive giant cells, and hemorrhagic debris occasionally form masses that may be mistaken for neoplasms (Brown tumors of hyperparathyroidism).PTH-induced hypercalcemia favors, formation of urinary tract stones (nephrolithiasis) as well as calcification of the renal inters!itium and tubules (nephrocalcinosis).Metastatic calcification secondary to hypercalcemia may also be seen in other sites, including the stomach, lungs, myoebardium. and blood vessels.Clinical CoursePrimary' hyperparathyroidism may he:Asymptomatic and identified after a routine chemistry profileAssociated with the Classic clinical manifestations of primary hyperparathyroidism.Asymptomatic Hyperparathy roidismPrimary hyperparathyroidism is the most common cause of asymptomatic hypercalcemiaMost common manifestation of primary hyperparathyroidism is hypercalcemia.Malignancy is the most frequent cause of clinically apparent hypercalcemia in adultsIn individuals with primary hyperparathyroid ism. serum PTH levels are inappropriately elevated for the level of serum calcium, whereas PTH levels are low to undetectable in hypercalcemia caused by of nonparathyroid diseasesOther laboratory alterations referable to PTH excess include hypophosphatemia and increased urinary excretion of both calcium and phosphate.Secondary renal disease may lead to phosphate retention with normalization of serum phosphates.Causes of HypercalcemiaRaised (PTH]Decreased HyperparathyroidismHypercalcemia of malignancyPrimary (Adenoma > hyperplasia)Vitamin D toxicitySecondaryImmobilizationTertiaryThiazide diureticsFamilial hypocalcsuric hypercalcemiaGranulomatous disease (sarcoidosis)Symptomatic Primary HyperparathyroidismThe signs and symptoms of hyperparathyroidism reflect the combined effects of increased PTH secretion and hypercalcemia.Classical description of symptoms in Primary hy perparathy roi d i smPainful bonesRenal stonesAbdominal groansPsychic moansThe constellation of symptoms includes:Bone disease and bone pain secondary to fractures of bones weakened by osteoporosis or osteitis fibrosa cystica.Nephrolithiasis (renal stones) in 20% of newly diagnosedpatients, with attenoant pain and obstructive uropathy. Chronic renal insufficiency and abnormalities in renal function lead to polyuria and secondary polydipsia.Gastrointestinal disturbances, including constipation,nausea, peptic ulcers, pancreatitis, and gallstones.Central nervous system alterations, including depression,lethargy, and eventually seizures.Neuromuscular abnormalities, including weakness andfatigue.Cardiac manifestations including aortic or mitral valve calcifications (or both).SECONDARY HYPERPARATHYROIDISMIt is caused by any condition that gives rise to chronic hypocalcemia, which in turn leads to compensatory overactivity of the parathyroid glands.CausesRenal failure is by far ihe most common cause of secondary hyperparathyroidismInadequate dietary intake of calciumSteatorrheaVitamin D deficiencyThe eliopathogenesis is complex and not fully understood.Chronic renal insufficiency is associated with decreased phosphate excretion, which in turn results in hyperphosphatemia.The elevated serum phosphate levels directly depress serum calcium levels and thereby stimulate parathyroid gland activity.In addition, loss of renal substance reduces the availability of a-1-hydroxylase necessary for the synthesis of the active form of vitamin D, which in turn reduces intestinal absorption of calcium Because vitamin D has suppressive effects on parathyroid growth and PTH secretion, its relative deficiency compounds the hyperparathyroidism in renal failure.
Hyperparathyroid ism
Hypoparathvroidism
Hypothyroidism
Hyperthyroidism
Thyroid and Parathyroid