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Parathyroid gland and its related illnesses • • • • • • • Parathyroid gland 4 small glands located on the dorsal side of the thyroid gland Yellow brown Ovoid or lentiform shape Measure 3-10 mm x 2-6 mm x 1-4 mm Weigh 50 mg each Produces parathyroid hormone Responsible for monitoring plasma Ca2+ Parathyroid gland • • • • • Parathyroid hormone A peptide hormone that increases plasma Ca2+ Released by chief cells Chief cells contain receptors for Ca2+ A decrease in plasma Ca2+ levels mediates the release of PTH Conversely, hypercalcemia inhibits PTH release Parathyroid hormone PTH causes increase in plasma Ca2+ by: • • • Mobilization of Ca2+ from bone Enhancing renal reabsorption Increasing intestinal absorption (indirect) Calcium metabolism • • • Bone: main effect- stimulates osteoclasts -> bone breaks down -> Ca released Intestines: increases uptake of Ca from intestine Kidney: stimulates reabsorption of Ca from the Ca in kidney tubules Calcium metabolism Causes of hyperparathyroidism • Parathyroid-related -Primary hyperparathyroidism -Lithium therapy -Familial hypocalciuric hypercalcemia • Malignancy-related -Solid tumor with metastases (breast) -Solid tumor with humoral mediation of hypercalcemia (lung, kidney) -Hematologic malignancies (multiple myeloma, lymphoma, leukemia) • Vitamin D-related -Vitamin D intoxication -↑ 1,25(OH)2D; sarcoidosis and other granulomatous diseases -Idiopathic hypercalcemia of infancy • Associated with high bone turnover -Hyperthyroidism -Immobilization -Thiazides -Vitamin A intoxication • • • • • Associated with renal failure -Severe secondary hyperparathyroidism -Aluminum intoxication -Milk-alkali Primary hyperparathyroidism Estimated incidence is 1 case per 1000 men and 2-3 cases per 1000 women – Incidence increases above age 40 – Most patients with sporadic primary hyperparathyroidism are postmenopausal women with an average age of 55 years >80% of cases are caused by a solitary parathyroid adenoma Approximately 10% are caused by double adenoma Specific symptoms – – – – – – • Clinical features of hyperparathyroidism Osteitis fibrosa cystica Nephrolithiasis Pathologic fractures Neuromuscular disease Life-threatening hypercalcemia Peptic Ulcer Disease Non specific symptoms – Fatigue – Subjective muscle weakness – Depression – Increased thirst – Polyuria – Constipation – Musculoskeletal aches and pains Osteitis fibrosa cystica Asociated syndromes with hyperparathyroidism MEN I MEN IIA Familial Hypocalciuric Hypercalcemia Hyperparathyroidism-jaw tumor syndrome Fibro-osseous jaw tumors Renal cysts Solid renal tumors Familial isolated hyperparathyroidism MEN I – – 1 in 30,000 persons Features: Hyperparathyroidism (95%) – Most common and earliest endocrine manifestation Gastrinoma (45%) Pituitary tumor (25%) Facial angiofibroma (85%) Collagenoma (70%) Hyperparathyroidism in MEN I – – – – Early onset Multiple glands affected Post-op hypoparathyroidism more common (more extensive surgery) Successful subtotal parathyroidectomy followed by recurrent HPT in 10 years in 50% of cases MEN II Features: – MTC(95%) – Pheochromocytoma(50%) – HPT(20%) RET mutation (98%) 1 in 30,000-50,000 people Usually single adenoma but may have multi-gland hyperplasia Familial Hypocalciuric Hypercalcemia • • • • • • • • • • Benign condition Autosomal dominant inherited disorder Clinical features: – hypocalciuria (usually < 50 mg/24 h) – variable hypermagnesemia – normal or minimally elevated levels of PTH These patients do not normalize their hypercalcemia after subtotal parathyroid removal and should not be subjected to surgery Excellent prognosis Diagnosed with family history and urinary calcium clearance determination Secondary hyperparathyroidism Decreased GFR leads to reduced inorganic phosphate excretion and consequent phosphate retention Retained phosphate has a direct stimulatory effect on PTH synthesis and on cellular mass of the parathyroid glands Retained phosphate also causes excessive production and secretion of PTH through lowering of ionized Ca2+ and by suppression of calcitriol production Secondary hyperparathyroidism Reduced calcitriol production results both from decreased synthesis due to reduced kidney mass and from hyperphosphatemia – calcitriol is known to have a direct suppressive effect on PTH transcription and therefore reduced calcitriol in CKD causes elevated levels of PTH – • • Reduced calcitriol leads to impaired Ca2+ absorption from the GI tract, thereby leading to hypocalcemia, which then increases PTH secretion and production Tertiary hyperparathyroidism Develops in patients with long-standing secondary hyperparathyroidism, which stimulates the growth of an autonomous adenoma A clue to the diagnosis of tertiary hyperparathyroidism is intractable hypercalcemia and/or an inability to control osteomalacia despite vitamin D therapy Investigations in hyperparathyroidism • Primary HPT – Increased serum calcium – Phosphorus in low normal range – Urinary calcium elevated • Secondary HPT (renal etiology) – Low or normal serum calcium – High phosphorus • • • Tertiary HPT (renal etiology) – High calcium and phosphorus Investigations in hyperparathyroidism Intact PTH and chemistry panel – PTH – Calcium – Phosphate – Creatinine 24-hour urine calcium excretion – Used to rule out familial hypocalciuric hypercalcemia – Values below 100mg/24 hours or a calcium creatinine clearance ratio of <0.01 are suggestive of FHH Investigations in hyperparathyroidism • • • Wrist, spine and hip dexa Consider KUB, IVP or CT Proper drug history Hypoparathyroidism • • • • • Lack of production of parathyroid hormone makes calcium levels in the blood low and phosphorus levels high This is a very rare condition, and almost always occurs because of damage or removal of parathyroid glands at the time of parathyroid or thyroid surgery Causes of hypoparathyroidism Deficient Parathyroid Hormone (PTH) secretion (>99% of all cases) Inability to make an active form of parathyroid hormone (extremely rare) Inability of the kidneys & bones to respond to the parathyroid hormone being produced by normal parathyroids (extremely rare) Causes of hypoparathyroidism • Isolated – Autosomal dominant • PTH gene mutation • CASR activating mutation • GCM2 mutation (dominant negative) – – • Autosomal recessive • PTH gene mutation • GCM2 mutation X-linked Congenital multi-system syndromes – DiGeorge & Velocardiofacial (22q11) – Barakat/HDR – Kenny-Caffey and Sanjad-Sakati Causes of hypoparathyroidism • Metabolic disease – Mitochondrial neuromyopathies – Long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency – Heavy-metal storage disorders • Autoimmune disease – Autoimmune polyendocrine syndrome type I (APS-1 or APECED) • Parathyroid resistance syndromes – Pseudohypoparathyroidism – Blomstrand chondrodysplasia and related PTH receptor defects – Hypomagnesemia • Muscle Cramps (spasms) Dry Skin Cataracts Seizures Pain in face, legs, feet Abnormal teeth formation Weakened tooth enamel • • • • • • • • • • Calcium Phosphorous PTH Magnesium Clinical features of hypoparathyroidism Investigations in hypoparathyroidism