{"id":4422532,"date":"2025-01-11T22:55:36","date_gmt":"2025-01-12T04:55:36","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/pseudohypoparathyroidism\/"},"modified":"2025-01-13T06:28:59","modified_gmt":"2025-01-13T12:28:59","slug":"pseudohypoparathyroidism","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/pseudohypoparathyroidism\/","title":{"rendered":"Pseudohypoparathyroidism"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">PATHOPHYSIOLOGY OF PSEUDOHYPOPARATHYROIDISM<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definition<\/strong>\n<ul class=\"wp-block-list\">\n<li>Pseudohypoparathyroidism (PHP) = <strong>end-organ resistance<\/strong> to <a href=\"https:\/\/myendoconsult.com\/learn\/parathyroid-hormone-pth-lab-assessment\/\"  data-wpil-monitor-id=\"263\">parathyroid hormone<\/a> (PTH).<\/li>\n\n\n\n<li>Laboratory fi ndings: <strong>hypocalcemia<\/strong>, <strong>hyperphosphatemia<\/strong>, and <strong>increased blood PTH<\/strong> (secondary hyperparathyroidism).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Main Types<\/strong>\n<ol class=\"wp-block-list\">\n<li><strong>PHP Type 1<\/strong><\/li>\n\n\n\n<li><strong>PHP Type 2<\/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<h3 class=\"wp-block-heading\">PSEUDOHYPOPARATHYROIDISM TYPE 1<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Overview<\/strong>\n<ul class=\"wp-block-list\">\n<li>Characterized by <strong>decreased renal cAMP production<\/strong> in response to exogenous PTH.<\/li>\n\n\n\n<li>Caused by mutations in the <strong>GNAS<\/strong> gene (encodes the \u03b1-subunit of the stimulatory G protein, Gs\u03b1).<\/li>\n\n\n\n<li>Result: <strong>lack of adenyl cyclase activation<\/strong> when PTH binds its receptor \u2192 <strong>PTH effect is lost<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Maternal Imprinting<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>GNAS expression<\/strong> in kidney, pituitary, gonads, thyroid is primarily from the <strong>maternal<\/strong> allele.<\/li>\n\n\n\n<li>Tissue-specific imprinting leads to <strong>three<\/strong> PHP-1 subtypes.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">1. PHP Type 1a (Albright Hereditary Osteodystrophy)<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inheritance<\/strong>: Autosomal dominant, <strong>maternally<\/strong> transmitted GNAS inactivating mutation.<\/li>\n\n\n\n<li><strong>Biochemical<\/strong>: Hypocalcemia, hyperphosphatemia, <strong>high PTH<\/strong> (secondary hyperparathyroidism).<\/li>\n\n\n\n<li><strong>Physical Phenotype<\/strong> (Albright hereditary osteodystrophy):\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/myendoconsult.com\/learn\/evaluation-of-short-stature\/\"  data-wpil-monitor-id=\"265\">Short stature<\/a>, rounded face, short neck, obesity.<\/li>\n\n\n\n<li>Ocular abnormalities.<\/li>\n\n\n\n<li><strong>Shortened fourth and fi fth metacarpals<\/strong> (\u201cknuckle, knuckle, dimple, dimple\u201d).<\/li>\n\n\n\n<li>Dental hypoplasia, subcutaneous calcifications.<\/li>\n\n\n\n<li>Developmental delay, mental retardation, flattened nasal bridge.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Additional Hormone Resistance<\/strong>\n<ul class=\"wp-block-list\">\n<li>Often have resistance to <strong>other<\/strong> G-protein\u2013coupled hormones (e.g., TSH, gonadotropins).<\/li>\n\n\n\n<li>Clinical manifestations: hypothyroidism, delayed puberty, oligomenorrhea, infertility, growth hormone deficiency.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Bone Changes<\/strong>\n<ul class=\"wp-block-list\">\n<li>PTH can be functional at the bone \u2192 potential for osteoclast overactivity, subperiosteal resorption, and osteitis fi brosa cystica changes.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">2. Pseudopseudohypoparathyroidism<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Inheritance<\/strong>: Paternally transmitted GNAS mutation.<\/li>\n\n\n\n<li><strong>Phenotype<\/strong>: Albright hereditary osteodystrophy <strong>without<\/strong> PTH resistance.<\/li>\n\n\n\n<li><strong>Laboratory<\/strong>: Normal serum calcium, phosphate, and PTH.<\/li>\n\n\n\n<li><strong>Notable Finding<\/strong>: May show <strong>excess dermal ossification<\/strong> (progressive osseous heteroplasia).<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">3. PHP Type 1b<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cause<\/strong>: Maternal transmission of mutations in GNAS <strong>regulatory elements<\/strong>.<\/li>\n\n\n\n<li><strong>Phenotype<\/strong>: <strong>No<\/strong> Albright hereditary osteodystrophy features.<\/li>\n\n\n\n<li><strong>Main Feature<\/strong>: <strong>Renal<\/strong> PTH resistance \u2192 hypocalcemia, hyperphosphatemia, increased serum PTH.<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">4. PHP Type 1c<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Defect<\/strong>: Mutation affects <strong>coupling<\/strong> of G protein to the PTH receptor; adenyl cyclase itself is intact.<\/li>\n\n\n\n<li><strong>Clinical<\/strong>: Albright hereditary osteodystrophy features + biochemical abnormalities (hypocalcemia, hyperphosphatemia, high PTH).<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">PSEUDOHYPOPARATHYROIDISM TYPE 2<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Overview<\/strong>\n<ul class=\"wp-block-list\">\n<li>Same laboratory fi ndings as PHP type 1: <strong>hypocalcemia<\/strong>, <strong>hyperphosphatemia<\/strong>, <strong>high PTH<\/strong>.<\/li>\n\n\n\n<li><strong>No<\/strong> Albright hereditary osteodystrophy phenotype.<\/li>\n\n\n\n<li><strong>Normal<\/strong> cAMP response to exogenous PTH.<\/li>\n\n\n\n<li>But no phosphaturia after PTH \u2192 suggests a defect <strong>beyond<\/strong> cAMP (e.g., at cAMP-dependent protein kinase A).<\/li>\n\n\n\n<li><strong>Acquired<\/strong> (not familial), onset can be from infancy to older age.<\/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 OF PHP TYPE 1A<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Synonym<\/strong>: Albright hereditary osteodystrophy.<\/li>\n\n\n\n<li><strong>Inheritance<\/strong>: Autosomal dominant, maternal GNAS mutation.<\/li>\n\n\n\n<li><strong>Onset<\/strong>: Hypocalcemia usually noticed between ages 3 and 8 due to secondary hyperparathyroidism.<\/li>\n\n\n\n<li><strong>Key Phenotype<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Short stature<\/strong>, round face, short neck, obesity, flattened nasal bridge.<\/li>\n\n\n\n<li><strong>Short 4th and 5th metacarpals\/metatarsals<\/strong>, causing the \u201cknuckle, knuckle, dimple, dimple\u201d sign.<\/li>\n\n\n\n<li>Ocular issues (microphthalmia, strabismus, hypertelorism, etc.).<\/li>\n\n\n\n<li>Dental hypoplasia.<\/li>\n\n\n\n<li>Developmental delay or mental retardation.<\/li>\n\n\n\n<li>Subcutaneous ossifications (osteoma cutis).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormonal Resistance Beyond PTH<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>TSH<\/strong> \u2192 hypothyroidism.<\/li>\n\n\n\n<li><strong>Gonadotropins<\/strong> \u2192 delayed puberty, oligomenorrhea, infertility.<\/li>\n\n\n\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/mechanism-of-action-of-growth-hormone\/\"  data-wpil-monitor-id=\"264\">Growth hormone<\/a><\/strong> \u2192 short stature, poor growth.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Bone<\/strong>\n<ul class=\"wp-block-list\">\n<li>Some skeletons show changes of secondary hyperparathyroidism (bone resorption, cystic lesions).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Variant: Pseudopseudohypoparathyroidism<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Paternal<\/strong> GNAS mutation \u2192 physical features of Albright hereditary osteodystrophy <strong>without<\/strong> PTH resistance.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>PATHOPHYSIOLOGY OF PSEUDOHYPOPARATHYROIDISM PSEUDOHYPOPARATHYROIDISM TYPE 1 1. PHP Type 1a (Albright Hereditary Osteodystrophy) 2. Pseudopseudohypoparathyroidism 3. PHP Type 1b 4. PHP Type 1c PSEUDOHYPOPARATHYROIDISM TYPE 2 CLINICAL MANIFESTATIONS OF PHP TYPE 1A<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[687],"class_list":["post-4422532","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\/4422532","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\/4422532\/revisions"}],"predecessor-version":[{"id":4422536,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422532\/revisions\/4422536"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422532"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422532"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}