Parathyroid Glands
Transcript of Parathyroid Glands
Parathyroid Parathyroid GlandsGlandsScott NguyenScott Nguyen
Dr. LopchinskyDr. Lopchinsky
EmbryologyEmbryology
Branchial arches and Pharyngeal Branchial arches and Pharyngeal pouches form in the 4pouches form in the 4thth week week
Superior Parathyroids - the 4Superior Parathyroids - the 4thth Pharyngeal pouch w/ thyroidPharyngeal pouch w/ thyroid
Inferior Parathyroids – 3Inferior Parathyroids – 3rdrd Pharyngeal pouchPharyngeal pouch
w/ thymusw/ thymus
AnatomyAnatomy Arterial supply usually Arterial supply usually
from inferior thyroid artfrom inferior thyroid art Superior glands usually Superior glands usually
imbedded in fat on imbedded in fat on posterior surface of posterior surface of middle or upper portion middle or upper portion of thyroid lobeof thyroid lobe
Lower glands near the Lower glands near the lower pole of thyroid lower pole of thyroid glandgland
In 1-5% pts, inferior In 1-5% pts, inferior gland in deep gland in deep mediastinummediastinum
HistologyHistology
50/50 parenchymal 50/50 parenchymal cells, stromal fatcells, stromal fat
Chief cells – Chief cells – secrete PTHsecrete PTH
Waterclear cells Waterclear cells Oxyphil cellsOxyphil cells
Parathyroid HormoneParathyroid Hormone Synthesized in chief cells as large Synthesized in chief cells as large
precursor – pre-proparathyroid precursor – pre-proparathyroid hormonehormone
Cleaved intracellularly into Cleaved intracellularly into proparathyroid hormone then to final 84 proparathyroid hormone then to final 84 AA PTHAA PTH
PTH then metabolized by liver into PTH then metabolized by liver into hormonally active N-term and inactive hormonally active N-term and inactive C-termC-term
PTH functionPTH function
HyperparathyroidismHyperparathyroidism
Primary Hyperparathyroidism Primary Hyperparathyroidism Normal feedback of Ca disturbed, causing Normal feedback of Ca disturbed, causing
increased production of PTHincreased production of PTH Secondary HyperparathyroidismSecondary Hyperparathyroidism
Defect in mineral homeostasis leading to a Defect in mineral homeostasis leading to a compensatory increase in parathyroid compensatory increase in parathyroid gland functiongland function
Tertiary HyperparathyroidismTertiary Hyperparathyroidism After prolonged compensatory stimulation, After prolonged compensatory stimulation,
hyperplastic gland develops autonomous hyperplastic gland develops autonomous functionfunction
Primary Primary HyperparathyroidismHyperparathyroidism
EpidemiologyEpidemiology 25/100,000 25/100,000 50,000 new cases yearly50,000 new cases yearly F > MF > M Incidence increases w/ ageIncidence increases w/ age Most in > 50 years oldMost in > 50 years old
EtiologyEtiology
Unknown causeUnknown cause Single gland adenomatous diseaseSingle gland adenomatous disease Multiglandular disease – exogenous Multiglandular disease – exogenous
stimulusstimulus Overexpression of PRAD1 oncogene Overexpression of PRAD1 oncogene
– controlls cell cycle– controlls cell cycle Ionizing radiation exposureIonizing radiation exposure
Clinical PresentationClinical Presentation
NephrolithiasisNephrolithiasis
Bone DiseaseBone Disease
Peptic Ulcer DiseasePeptic Ulcer Disease
Psychiatric disordersPsychiatric disorders
Muscle weaknessMuscle weakness
ConstipationConstipation
PolyuriaPolyuria
PancreatitisPancreatitis
MyalgiaMyalgia
ArthralgiaArthralgia
3030
22
1212
1515
7070
3232
2828
11
5454
5454
Hypercalcemia - DDxHypercalcemia - DDx
Hyperparathyroidism (most common)Hyperparathyroidism (most common) Malignancy (most common in hospitalized)Malignancy (most common in hospitalized)
Lytic metastases to bone Lytic metastases to bone PTHrP producer PTHrP producer
Sarcoidosis / granulomatous diseaseSarcoidosis / granulomatous disease Vit D intoxicationVit D intoxication ThiazidesThiazides HyperthyroidismHyperthyroidism Familial hypocalciuric hypercalcemiaFamilial hypocalciuric hypercalcemia
Renal ComplicationsRenal Complications
Generally the most severe clinical Generally the most severe clinical manifestationsmanifestations
Many have frequency, polyuria, polydipsiaMany have frequency, polyuria, polydipsia Usually present w/ nephrolithiasis (20-30%)Usually present w/ nephrolithiasis (20-30%) Calcium phosphate or Calcium oxalateCalcium phosphate or Calcium oxalate Nephrocalcinosis (in 5-10%) – calcification Nephrocalcinosis (in 5-10%) – calcification
w/in parenchyma of kidneysw/in parenchyma of kidneys Severe renal damageSevere renal damage
Hypertension secondary to renal Hypertension secondary to renal impairmentimpairment
Bone DiseaseBone Disease
Osteitis fibrosa cysticaOsteitis fibrosa cystica In early descripts of disease, many In early descripts of disease, many
had severe bone disease (50-90%), had severe bone disease (50-90%), but now 5-15%but now 5-15%
Subperiosteal resorption – Subperiosteal resorption – pathognomonic of pathognomonic of hyperparathyroidismhyperparathyroidism
Gastrointestinal Gastrointestinal ManifestationsManifestations
Peptic Ulcer disease Peptic Ulcer disease Pancreatitis Pancreatitis Cholelithiasis – 25-35%Cholelithiasis – 25-35%
Emotional DisturbancesEmotional Disturbances
Hypercalcemia of any cause – assoc Hypercalcemia of any cause – assoc w/ neurologic or psychiatric w/ neurologic or psychiatric disturbancesdisturbances Depression, anxiety, psychosis, comaDepression, anxiety, psychosis, coma
Severe disturbances not usually Severe disturbances not usually correctable by parathyroidectomycorrectable by parathyroidectomy
Articular and Soft TissueArticular and Soft Tissue
Chondrocalcinosis and Pseudogout Chondrocalcinosis and Pseudogout 3-7%3-7%
Deposits of Calcium pyrophosphate Deposits of Calcium pyrophosphate in articular cartilages and menisciin articular cartilages and menisci
Vascular and Cardiac calcificationsVascular and Cardiac calcifications
Neuromuscular Neuromuscular complicationscomplications
Muscular weakness, fatigueMuscular weakness, fatigue More commonly in proximal musclesMore commonly in proximal muscles Sensory abnormalities also possibleSensory abnormalities also possible
Laboratory DiagnosisLaboratory Diagnosis Elevated Serum Ca and PTHElevated Serum Ca and PTH
Must measure Ionized Ca (subtle cases of Must measure Ionized Ca (subtle cases of hyperPTH will have normal Serum Ca)hyperPTH will have normal Serum Ca)
50% will have hypophosphatemia 50% will have hypophosphatemia Elevated Alkaline Phosphatase in 10-Elevated Alkaline Phosphatase in 10-40%40%
Hyperchloremic metabolic acidosis Hyperchloremic metabolic acidosis Low Mg in 5-10%Low Mg in 5-10% High Urinary Ca in almost all casesHigh Urinary Ca in almost all cases
Hyperparathyroid crisisHyperparathyroid crisis
Most pts w/ hyperparathyroidism Most pts w/ hyperparathyroidism chronically ill w/ renal and skeletal chronically ill w/ renal and skeletal abnormalitiesabnormalities
Rarely can become acutely illRarely can become acutely ill Rapidly developing weakness, N/V, Rapidly developing weakness, N/V,
weight loss, fatigue, drowsiness, weight loss, fatigue, drowsiness, confusion, Azotemiaconfusion, Azotemia
Uncontrolled PTH production, hyperCa, Uncontrolled PTH production, hyperCa, polyuria, dehydration, reduced renal polyuria, dehydration, reduced renal function, worsening hyperCafunction, worsening hyperCa
Hyperparathyroid CrisisHyperparathyroid Crisis
Definitive therapy - resection Definitive therapy - resection Must reverse hyperCa firstMust reverse hyperCa first
Diuresis - Saline hydration then Lasix to Diuresis - Saline hydration then Lasix to excrete Caexcrete Ca
Calcitonin - rapid affect, inhibits bone Calcitonin - rapid affect, inhibits bone resorptionresorption
Steroids - take up to a weekSteroids - take up to a week Mithramycin - rapidly inhibiting bone Mithramycin - rapidly inhibiting bone
resorptionresorption
TreatmentTreatment
Only Curative treatment - Only Curative treatment - ParathyroidectomyParathyroidectomy
Who should have surgery? Who should have surgery? Many found incidentally, assxMany found incidentally, assx
Who should have Who should have surgery?surgery?
NIH Consensus statement 1991NIH Consensus statement 1991 All symptomaticAll symptomatic If AssymptomaticIf Assymptomatic
Markedly elevated serum CaMarkedly elevated serum Ca H/o episode life-threatening hypercalcemiaH/o episode life-threatening hypercalcemia Reduce renal functionReduce renal function Kidney stone on RadiographKidney stone on Radiograph Markedly elevated urinary Ca excretionMarkedly elevated urinary Ca excretion Substantially reduce bone massSubstantially reduce bone mass
Standard Neck Standard Neck ExplorationExploration
ParathyroidectomyParathyroidectomy
Must find all four glandsMust find all four glands Intraoperative frozen section, PTH Intraoperative frozen section, PTH
measurement usefulmeasurement useful If single gland enlarged, removal usually If single gland enlarged, removal usually
curativecurative If multiple glands enlarged, removed. If multiple glands enlarged, removed.
Normal just biopsiedNormal just biopsied If all 4 enlarged (generalized parathyroid If all 4 enlarged (generalized parathyroid
hyperplasia) - subtotal (3 1/2 removed)hyperplasia) - subtotal (3 1/2 removed) Can reimplant into forearm muscleCan reimplant into forearm muscle
Superior parathyroidSuperior parathyroid easier to findeasier to find more consistent more consistent
positionposition just on dorsal surface just on dorsal surface
of upper thyroidof upper thyroid careful for superior careful for superior
thyroid artery and thyroid artery and superior laryngeal superior laryngeal nervenerve
Inferior glandInferior gland less consistent less consistent
locationlocation may be near thymus may be near thymus
or inside thyroidor inside thyroid careful for recurrent careful for recurrent
laryngeal nerve betw laryngeal nerve betw trachea / esophagustrachea / esophagus
inferior thyroid inferior thyroid arteryartery
Success of SurgerySuccess of Surgery
95% of cases cured at initial neck 95% of cases cured at initial neck explorationexploration
If failed intial procedure, can try to If failed intial procedure, can try to localize w/ Radionuclide, detect w/ localize w/ Radionuclide, detect w/ gamma probegamma probe Sestamibi concentrates in parathyroid tissueSestamibi concentrates in parathyroid tissue Increasingly used in initial operationIncreasingly used in initial operation limits dissectionlimits dissection Limits operative timeLimits operative time
May need mediastinoscopyMay need mediastinoscopy