| What is parathyroid? | Usually 4 parathyroid glands posterior to the thyroid, some have 3,4,5 or more glands.
Identified based on their location as right or left, superior or inferior.
Could be seen all the way from larynx to aortic arch
Their role is secreting PTH responsible for maintaining extracellular Ca concentrations, secretion is regulated by Ca concentration |
| What are actions of PTH? | Stimulates osteoclasts to increase calcium (bone resorption), promotes renal tubular phosphate excretion and calcium reabsorption, increases 1a-hydroxylation of 25-hydroxy vitamin D in renal cells, increases dihydoxy vitamin D promotes Ca absorption in gut thereby increasing Ca levels. |
| What is hyperparathyroid? | Excessive PTH (84-aa polypeptide), subdivided into primary/secondary or tertiary. |
| What is primary hyperparathyroid? | Most common cause of hypercalcemia in outpatient, hypercalcemia secondary to overproduction of PTH by one or more parathyroid glands, overall incidence is 1%, age 52-56 yrs and female:male 3:1 |
| How is pathophysiology of primary hyperparathyroid? | Calcium sensors for negative feedback are blocked causing unregulated production of PTH even w/Ca elevation, so we get increased PTH, bone resorption, renal reabsorption and vitamin D hydroxylation. |
| What is the differential dx in case of Primary hyperparathyroid? | If we have hypercalcemia and elevated PTH we should exclude: chronic renal disease, thiazide diuretic use , lithium use, familial hypocalciuric hypercalcemia (FHH) |
| What are etiologies causing primary hyperparathyroid? | Single adenoma (85%), multiple glands (adenoma or hyperplasia- 15%), parathyroid carcinoma (<1%)
Cause of adenoma/hyperplasia is unknown. |
| What is familial hyperparathyroidism? | These include: MEN1/2a, hyperparathyroid-jaw tumor (HPT-JT) syndrome, familial isolated hyperparathyroidism (FIHPT), familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism. |
| What is MEN 1? | auto dominant inactivation of MENIN gene on chromosome 11, high penetrance for PHPT which is usually initial presentation of the disease, 90-95% of pt w/MEN 1 develop PHPT often at younger age than usual, multiple gland disease in this case so we need subtotal/total parathyroidectomy w/autotransplantation, pt can also have pituitary lesions. |
| What is MEN 2A? | Auto dominant activation of RET proto-oncogene, 20-30% have PHPT which is mild here, single gland disease or MGD doesn't require surgical approach but they get pheo/MTC which is life threatening, so rule out pheo before parathyroidectomy. |
| What is HPT-JT syndrome? | Auto dominant inactivation of HRPT2, PHPT most common feature and have high risk of parathyroid cancer, at early age SGD or MGD, also develop fibro-osseous tumors of mandible or maxilla and may have renal pathology |
| What are rare causes of PHPT? | Neonatal severe PHPT (homozygous inactivation of Ca sensors, fatal if not treated immediately w/total parathyroidectomy)
Parathyroid cancer (<1%, difficult to dx preop no definitive cytology, severe hypercalcemia need hospitalization and marked elevation of PTH, rarely palpable neck, 5-year survival 86%) |
| How is clinical presentation of PHPT? | Historically (long-standing disease, nephrolithiasis, brown tumors, osteitis fibrosa cystica, muscle atrophy)
Now (seen much earlier by hypercalcemia, up to 80% dx subclinically, and very few were overt)
Symptoms (non specific [fatigue, weakness, depression, bony pain, memory loss, decreased concentration]
common manifestations [nephrolithiasis-20%, subtle change in bone densitometry -altered by high bone turn over results in osteopenia,porosis, various cardiovascular conditions- HTN, valvular calcification, LVH, mortality]) |
| How is dx of PHPT? | Biochemically elevated Ca and PTH, should be adjusted for albumin, some pt may present normocalcemic w/in continuoum of the disease, also PTH may be normal inappropriately to high Ca, Vitamin D seen for deficiency may lead to elevated PTH, so before dx we need to replete vitamin D.
Other labs (Ph, creatinine clearance, 24-hour urine calcium, family hx sus of FHH - urine caclium <100 and clearance <0.01, bone densitometry recommended) |
| What are indications for surgery in PHPT? | All symptomatic individuals should get surgery, if asymptomatic surgery if (age <50, Ca >1mg/dl of the upper limit, BMD<-2.5, GFR<60ml/min see nephrolithiasis) |
| What imaging is done in PHPT? | Preop localization of abnormal glands using minimally invasive surgery (MIP), US or scintigraphy, when used together we have higher accuracy for localization, 4D-CT may be useful (some centers in North America use them) |
| What is intraoperative PTH? | Since PTH has half life of 5 min, in order to check the validity of surgery we see IOPTH, observing if there is any missed MGD and to evaluate post op PTH and calcium levels. |
| What is secondary hyperparathyroid? | Secondary to a chronic stimulus, typically chronic renal failure, another cause if vitamin D deficiency.
In CKD response to hyperphosphatemia, hypocalcemia, impaired vitamin D production, particularely hyperPh most important as it directly stimulates PTH synthesis and causes hyperplasia promoting secondary hyperPT
Seen in pt w/CKD undergoing dialysis (they get bone disease and non skeletal issues like valvular calcification, soft tissue calcification, compromised immune system, neurobehavioral changes and altered erythropoiesis
In pt w/vitamin D deficiency manifestations of vitamin D deficiency appear, some have bone pain |
| What are labs seen in secondary hyperparathyroidism? | Low-normal calcium, elevated PTH, phosphate level varies according to etiology (renal insufficiency/ low vitamin D) |
| What are surgical measures taken for secondary hyperparathyroid? | For bone pain/fracture, pruritis, calciphylaxis, extraskeletal nonvascular calcification, w/elevated pararthyroid hormone.
Procedure of choice is total parathyroid w/autotransplant / 3.5 gland parathyrodiectomy |
| What is tertiary hyperparathyroidectomy? | Excessive secretion of PTH after long-standing secondary hyperparathyroid, results in hypercalcemia, after successful renal transplant hyperparathyroid persists, autonomous hypersecretion causing hypercalcemia (hypertrophied glands cannot get back to normal after renal transplant)
Dangerous since phosphorus is high, so high phosphorus w/calcium leads to diffuse calcinosis |
| What is FHH? | Loss-of-function mutation of one allele of Ca Receptors, causes hypercalcemia, hypophosphatemia, and hypermagnesemia.
PTH w/in normal or slight elevation, distinguished from PHPT by 24-hour urine calcium excretion, asymptomatic usually and no parathyroidectomy indicated. |
| What is hypercalcemia of malignanacy? | Tumor release of PTH-related peptide, less commonly caused by local osteolytic lesions and rarely overproduction of dihydroxycholecalciferol.
Most common cause of hypercalcemia in hospitalizaed pt, low or undectable intact PTH level, easily distinguished from HPT, only a few cases of ectopic true production of PTH are reported. |
| What is hypoparathyroid? | Condition of deficiency in PTH, primary hypoparathyroidism is state of inadequate PTH activity, syndrome from iatrogenic cause or rare disease, secondary hypoparathyroidism is state in which PTH low in response to primary process causing hypercalcemia. |
| How is pathophysiology of hypoparathyroidism? | PTH absence causes no Ca reabsoption/resorption/ absorption so causes hypocalcemia w/ S&S of neuromuscular irritability (paresthesia, hyperirritability, fatigue, anxiety, mood swings, seizures, hoarseness, wheeze and dyspnea, muscle cramps/biliary colic, hypomagnesemia, hypokalemia and alkalosis (hyperventilation) worsen signs and symptoms of hypocalcemia. |
| What are PE findings in case of hypoparathyroidism? | Increased neuromuscular irritability (chvostek sign (facial twitch, gently tapping ipsilateral facial nerve as it courses anterior to ear), Trousseau sign (carpal spasm induced by BP cuff around arm to a pressure 20mmHg above obliteration of radial pulse for 3-5 min)
Muscle cramps, tetany sometimes life-threat bronchospasm.
Chronic hypocalcemia can cause ocular cataracts, abnormal dentition and dry puffy skin, severe hypocalcemia cause QT prolongation on EKG. |
| What are causes of hypoparathyroidism? | Iatrogenic (most common cause is excision of all parathyroid glands via surgery treating thyroid/largeal/ neck malignancy, extensive irradiation to face/neck/mediastinum also could cause it)
Autoimmune (type 1 polyglandular syndrome (HAM syndrome) destroys parathyroid and adrenals, develop by age 10 years, may exist alone or in familial forms, average of development of hypocalcemia is 7 years range 6 months to 20 years)
Congenital causes (numerous causes for agenesis/ hypoplasia thus at birth symptomatic hypocalcemia)
Causes related to metal overload/ion deficiency (hemochromatosis/ thalassemia, Wilson, Aluminium deposits w/in parathyroid in end-stage renal disease, hypermagnesemia and hypomagnesemia)
Infiltration of parathyroid glands (metastasis, granulomatous disease, amyloidosis, syphilis, progressive systemic scleosis)
Neonatal causes (mother w/hypercalcemia supress baby PTH become atrophic glands w/in first 3 weeks of birth we see hypopara but self-limited |
| What is the differential dx of hypoparathyroidism? | Hypocalcemia, pseudohypoparathyroidism (hypocalcemia, hyperphosphatemia, increased PTH, insensitivity to PTH), Albright hereditary osteodystrophy (AHO) short stature, round face, short metacarpals, obesity, dental hypoplasia, soft tissue calcification |
| What is workup done for hypoparathyroidism? | PTH (Primary hypoPTH low PTH and low Ca, pseudohypoPTH elevated PTH due to resistance to PTH by receptors, secondary hypoPTH low PTH and high Ca)
Be careful that calcium may be protein bound, so hypoalbuminemia drops total Ca and elevated proteins elevate Ca all w/normal ionized Ca maybe.
So see albumin (every 1g/dl fall albumin, Ca fall 0.8mg/dl)
Alkalosis causes more albumin binding causing decrease in ionized Ca in serum and trigger hypocalcemia
Other tests may include (vitamin D 25 hydroxy, serum Mg, serum Ph) |
| How is tx of hypoparathyroid? | Hypocalcemia correction admin Ca and vitamin D, recombinant human PTH indicated as adjucnt to Ca and Vitamin D to control hypocalcemia in pt w/ hypoparathyroidism |
