{"id":4422514,"date":"2025-01-11T22:25:41","date_gmt":"2025-01-12T04:25:41","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/primary-hyperparathyroidism\/"},"modified":"2025-01-13T06:37:46","modified_gmt":"2025-01-13T12:37:46","slug":"primary-hyperparathyroidism","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/primary-hyperparathyroidism\/","title":{"rendered":"Primary Hyperparathyroidism"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">PATHOPHYSIOLOGY OF PRIMARY HYPERPARATHYROIDISM<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Incidence and Demographics<\/strong>\n<ul class=\"wp-block-list\">\n<li>Annual incidence: ~4 per 100,000<\/li>\n\n\n\n<li>More common in women (2:1 ratio)<\/li>\n\n\n\n<li>Typically diagnosed after age 45<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Underlying Pathology<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Single parathyroid adenoma<\/strong> (~89%)<\/li>\n\n\n\n<li><strong>Multiple (\u201cdouble\u201d) parathyroid adenomas<\/strong> (~4%)<\/li>\n\n\n\n<li><strong>Multigland parathyroid hyperplasia<\/strong> (~6%)<\/li>\n\n\n\n<li><strong>Parathyroid carcinoma<\/strong> (~1%)<\/li>\n\n\n\n<li>Correctly identifying each pathologic form is crucial for determining the surgical approach.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Parathyroid Adenomas<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Gross &amp; Histology<\/strong>\n<ul class=\"wp-block-list\">\n<li>Usually <strong>encapsulated<\/strong>, arising from <strong>chief cells<\/strong> (some from oxyphilic cells).<\/li>\n\n\n\n<li>Typically located in the <strong>neck<\/strong>, but ectopic sites can occur in <strong>anterior\/posterior mediastinum<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clonal Mutations<\/strong>\n<ul class=\"wp-block-list\">\n<li>Arise from <strong>somatic mutations<\/strong> in growth regulatory genes.<\/li>\n\n\n\n<li>~30% show <strong>cyclin D1 (CCND1)<\/strong> overexpression.<\/li>\n\n\n\n<li><strong>MEN1 gene<\/strong> (tumor suppressor) mutations found in ~15% of sporadic adenomas.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Parathyroid Hyperplasia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>General<\/strong>\n<ul class=\"wp-block-list\">\n<li>May involve <strong>all four glands<\/strong> (\u201cmultigland disease\u201d).<\/li>\n\n\n\n<li>Typically <strong>chief cell hyperplasia<\/strong> (rarely clear cell hyperplasia).<\/li>\n\n\n\n<li>Pathologically: less fat within hyperplastic glands, and they appear enlarged.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Sporadic<\/strong> or part of <strong>familial<\/strong> syndromes:\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/multiple-endocrine-neoplasia\/\"  data-wpil-monitor-id=\"254\">Multiple Endocrine Neoplasia<\/a> (MEN) type 1<\/strong>\n<ul class=\"wp-block-list\">\n<li>HPT occurs in almost all MEN 1 patients; hypercalcemia evident by 3rd decade.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>MEN 2A<\/strong>\n<ul class=\"wp-block-list\">\n<li>Only \u223c10% develop hyperparathyroidism, usually later in life.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>HPT\u2013jaw tumor syndrome<\/strong>\n<ul class=\"wp-block-list\">\n<li>Often multiple, cystic adenomas; associated jaw tumor is typically fibrous.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Familial Isolated Hyperparathyroidism<\/strong><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Parathyroid Carcinoma<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Incidence<\/strong>: ~1% in primary HPT.<\/li>\n\n\n\n<li><strong>Diagnosis<\/strong>: confirmed by <strong>local tissue invasion<\/strong> or <strong>metastases<\/strong> (lymph nodes or distant).<\/li>\n\n\n\n<li><strong>Germline inactivating mutations<\/strong> in <strong>CDC73\/HRPT2<\/strong> gene:\n<ul class=\"wp-block-list\">\n<li>Associated with <strong>HPT\u2013jaw tumor syndrome<\/strong> and increased risk of parathyroid carcinoma.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">NORMAL CALCIUM\u2013PTH HOMEOSTASIS<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Calcium-Sensing Mechanism<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Serum ionized <\/strong><a href=\"https:\/\/myendoconsult.com\/learn\/calcium-regulation\/\"  data-wpil-monitor-id=\"255\">calcium tightly regulated<\/a> (8.9\u201310.1 mg\/dL total Ca\u00b2\u207a).<\/li>\n\n\n\n<li><strong>Hypocalcemia<\/strong> \u2192 stimulates <a href=\"https:\/\/myendoconsult.com\/learn\/parathyroid-hormone-pth-lab-assessment\/\"  data-wpil-monitor-id=\"252\">parathyroid <strong>PTH<\/strong><\/a> secretion.<\/li>\n\n\n\n<li><strong>Hypercalcemia<\/strong> \u2192 suppresses PTH secretion.<\/li>\n\n\n\n<li><strong>Calcium-sensing receptor<\/strong> (CaSR) in parathyroid glands modulates PTH release.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Actions of PTH<\/strong>\n<ol class=\"wp-block-list\">\n<li><strong>Bone<\/strong>: Stimulates osteoclasts (indirectly via osteoblast signals) \u2192 release of Ca\u00b2\u207a &amp; phosphate.<\/li>\n\n\n\n<li><strong>Kidney<\/strong>:\n<ul class=\"wp-block-list\">\n<li>\u2193Renal <a href=\"https:\/\/myendoconsult.com\/learn\/fractional-excretion-of-calcium-calculator\/\"  data-wpil-monitor-id=\"253\">calcium excretion<\/a> by promoting distal tubular reabsorption of Ca\u00b2\u207a.<\/li>\n\n\n\n<li>\u2191Phosphate excretion by inhibiting proximal <a href=\"https:\/\/myendoconsult.com\/learn\/tubular-reabsorption-of-phosphate\/\"  data-wpil-monitor-id=\"256\">tubular phosphate reabsorption<\/a>.<\/li>\n\n\n\n<li>\u2191Renal 1\u03b1-hydroxylation \u2192 more 1,25(OH)\u2082 vitamin D (calcitriol).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>GI Tract<\/strong>: Enhanced calcium absorption indirectly via <strong>calcitriol<\/strong>.<\/li>\n<\/ol>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">PRIMARY HYPERPARATHYROIDISM: DISRUPTED REGULATION<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Elevated Set Point<\/strong>\n<ul class=\"wp-block-list\">\n<li>In primary HPT, <strong>feedback suppression<\/strong> of PTH by calcium is abnormal.<\/li>\n\n\n\n<li>The \u201cset point\u201d (threshold for PTH suppression) is raised ~15\u201330% above normal.<\/li>\n\n\n\n<li><strong>PTH not fully autonomous<\/strong>; can be partially suppressed by very high Ca\u00b2\u207a.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Consequences<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Excess PTH<\/strong> \u2192 chronic <strong>hypercalcemia<\/strong> via:\n<ol class=\"wp-block-list\">\n<li>\u2191Bone resorption of Ca\u00b2\u207a &amp; phosphate.<\/li>\n\n\n\n<li>\u2191Intestinal Ca\u00b2\u207a absorption (via more calcitriol).<\/li>\n\n\n\n<li>\u2191Renal Ca\u00b2\u207a reabsorption.<\/li>\n<\/ol>\n<\/li>\n\n\n\n<li>Concurrently, PTH <strong>inhibits phosphate reabsorption<\/strong> \u2192 <strong>hypophosphatemia<\/strong>.<\/li>\n\n\n\n<li>Excess urinary excretion of Ca\u00b2\u207a and phosphate \u2192 predisposes to <strong>calcium phosphate<\/strong> or <strong>calcium oxalate<\/strong> stones.<\/li>\n\n\n\n<li><strong>Nephrocalcinosis<\/strong> can occur from calcium deposits in kidney tissue.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Bone Disease<\/strong>\n<ul class=\"wp-block-list\">\n<li>~25% with primary HPT have notable skeletal involvement.<\/li>\n\n\n\n<li>Marked <strong>osteoclast<\/strong> activity plus a compensatory rise in <strong>osteoblast<\/strong> activity.<\/li>\n\n\n\n<li>Bone mineral = hydroxyapatite (Ca\u2081\u2080(PO\u2084)\u2086(OH)\u2082) with minor carbonate, Mg\u00b2\u207a, Na\u207a, K\u207a.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">CLINICAL MANIFESTATIONS &amp; LABORATORY FINDINGS<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Asymptomatic &amp; Mild Forms<\/strong>\n<ul class=\"wp-block-list\">\n<li>~80% are <strong>asymptomatic<\/strong>, discovered incidentally on routine labs revealing hypercalcemia.<\/li>\n\n\n\n<li>Subtle manifestations: fatigue, mild depression, musculoskeletal aches.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Classic Symptoms<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>\u201cBones, Stones, Abdominal Moans, and Groans\u201d<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Stones<\/strong>: Nephrolithiasis (20% of primary HPT) from hypercalciuria &amp; calcium oxalate\/phosphate stones.<\/li>\n\n\n\n<li><strong>Bone<\/strong>: Osteopenia\/osteoporosis most common; severe forms include subperiosteal bone resorption, salt-and-pepper skull, brown tumors, osteitis fibrosa cystica.<\/li>\n\n\n\n<li><strong>Abdominal<\/strong>: Anorexia, nausea, constipation, peptic ulcer, pancreatitis.<\/li>\n\n\n\n<li><strong>Neuro<\/strong>: Confusion, depression, potential coma if very severe (\u201cparathyroid crisis\u201d).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Physical Examination<\/strong>\n<ul class=\"wp-block-list\">\n<li>Typically no specific findings unless a large parathyroid tumor is palpable (suggestive of carcinoma).<\/li>\n\n\n\n<li><strong>Band keratopathy<\/strong>: Calcium deposits in corneal limbus on slit-lamp exam.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Abnormalities<\/strong>\n<ol class=\"wp-block-list\">\n<li><strong>Elevated serum total &amp; ionized calcium<\/strong>.<\/li>\n\n\n\n<li><strong>Decreased serum phosphate<\/strong> (due to PTH-mediated renal phosphate loss).<\/li>\n\n\n\n<li><strong>High or inappropriately <a href=\"https:\/\/myendoconsult.com\/learn\/normal-pth-levels-by-age\/\"  data-wpil-monitor-id=\"257\">normal PTH<\/a><\/strong> (given hypercalcemia).<\/li>\n\n\n\n<li><strong>Increased 1,25(OH)\u2082 vitamin D<\/strong> (calcitriol) from PTH-induced 1\u03b1-hydroxylation.<\/li>\n\n\n\n<li><strong>Hypercalciuria<\/strong> (high filtered load of Ca\u00b2\u207a).<\/li>\n\n\n\n<li>Possible mild <strong>elevated serum creatinine<\/strong> in chronic disease or nephrocalcinosis.<\/li>\n\n\n\n<li>May see <strong>normocytic, normochromic anemia<\/strong> in severe cases.<\/li>\n<\/ol>\n<\/li>\n\n\n\n<li><strong>Vitamin D Deficiency<\/strong>\n<ul class=\"wp-block-list\">\n<li>Often coexists; can mask severity of hypercalcemia.<\/li>\n\n\n\n<li>Correcting deficiency can worsen hypercalcemia\/hypercalciuria.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">MANAGEMENT<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definitive Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Surgical removal<\/strong> of the overactive gland(s).<\/li>\n\n\n\n<li>For <strong>single adenoma<\/strong>, resection of that adenoma.<\/li>\n\n\n\n<li>For <strong>hyperplasia<\/strong> (e.g., MEN 1), often 3\u00bd gland resection is performed.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Parathyroid Crisis<\/strong> (Calcium >15 mg\/dL)\n<ul class=\"wp-block-list\">\n<li>Urgent IV saline rehydration + medications to reduce bone resorption (e.g., bisphosphonates).<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>PATHOPHYSIOLOGY OF PRIMARY HYPERPARATHYROIDISM Parathyroid Adenomas Parathyroid Hyperplasia Parathyroid Carcinoma NORMAL CALCIUM\u2013PTH HOMEOSTASIS PRIMARY HYPERPARATHYROIDISM: DISRUPTED REGULATION CLINICAL MANIFESTATIONS &amp; LABORATORY FINDINGS MANAGEMENT<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[687],"class_list":["post-4422514","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-parathyroid-gland","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422514","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":3,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422514\/revisions"}],"predecessor-version":[{"id":4422518,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422514\/revisions\/4422518"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422514"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422514"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}