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