DSA07 - Parathyroid Pathology

3rd and 4th pharyngeal pouches

Where do the Parathyroid Glands originate from?

Chief (darker) = secrete PTH;

Oxyphil (lighter) = unknown function (lots of mitochondria)

What are the 2 types of cells that make up the Parathyroid?

1) Increase free/ionized serum Ca2+

2) Decrease Net serum PO43-

3) Increase 1-alpha-hydroxylase --> activate Vitamin D

What are the functions of PTH?

Stimulates OSTEOBLASTS to express and secrete cytokines (RANK-L and M-CSF) --> Osteoclast precursors convert to ACTIVE OSTEOCLASTS ==> BONE RESORPTION ==> More Ca and PO4

How does PTH increase free/ionized serum Ca2+ via BONE?

Monocytes

From which cells are Osteoclasts derived from?

-Increases Ca reabsorption in the DISTAL Convoluted Tubule

-Decreases PO4 reabsorption in PROXIMAL Convoluted Tubule

How does PTH increase free/ionized serum Ca2+ and decreases PO4 via KIDNEYS?

ACTIVATES the enzyme (converts 25 OH D3 to 1,25-(OH)2D3 (ACTIVE VIT D) in the Proximal Convoluted Tubule)

How does PTH Increase 1-alpha-hydroxylase to activate Vitamin D?

More Serum Ca & PO4 (via reabsorption)

What does more active Vitamin D lead to?

Primary Parathyroid Adenoma

Define Condition:

Single gland that is larger than the others (others smaller or normal size d/t feedback inhibition of increased serum Ca)

-Hx: More Common than Hyperplasia

-Path: Overactive gland, regardless of Ca level (PRIMARY)

> Cyclin D1 gene rearrangement (next to PTH gene) --> PROLIFERATES CHIEF CELLS

> MEN1 mutation = 1/3 sporadic tumors

-Sx/PE:

> STONES (Hypercalcemia)

> Polyuria ("THRONE")

> BONE Pain

> Constipation/Muscle Weakness (GROANS)

> AMS (PSYCH OVERTONES)

-Dx:

Histo

> Nests and sheets of predominantly chief cells + fibrous capsule

> Rim of normal tissue

Labs

> Increased PTH

> Increased Serum Ca

-Prog: (UnTx)

HPT

> Osteoporosis (Low Bone Mass)

> Dissecting Osteitis (More osteoclasts tunnel into center of trabecula)

> BROWN "TUMOR" Bone Loss (MicroFx and Hemorrhage --> Macrophages cause ingrowth of reparative fibrous tissue --> osteoclasts, hemosiderin laden macrophages ==> Mimic tumor)

> Osteitis Fibrosa Cystica (Brown Tumor --> Cystic Degeneration + Peritrabecular Fibrosis)

Hypercalcemia

> Nephrolithiasis + Nephrocalcinosis

> Metastatic calcification

Primary Parathyroid Hyperplasia

Define Condition:

ALL 4 glands enlarged (may be asymmetrical)

-Hx: Less Common than Adenoma

-Sx/PE:

> STONES (Hypercalcemia)

> Polyuria ("THRONE")

> BONE Pain

> Constipation/Muscle Weakness (GROANS)

> AMS (PSYCH OVERTONES)

-Dx:

Histo

> CHIEF CELL Hyperplasia

> NO RIM of normal tissue

Labs

> Increased PTH

> Increased Serum Ca

-Prog: (UnTx)

HPT

> Osteoporosis (Low Bone Mass)

> Dissecting Osteitis (More osteoclasts tunnel into center of trabecula)

> BROWN "TUMOR" Bone Loss (MicroFx and Hemorrhage --> Macrophages cause ingrowth of reparative fibrous tissue --> osteoclasts, hemosiderin laden macrophages ==> Mimic tumor)

> Osteitis Fibrosa Cystica (Brown Tumor --> Cystic Degeneration + Peritrabecular Fibrosis)

Hypercalcemia

> Nephrolithiasis + Nephrocalcinosis

> Metastatic calcification

Secondary Hyperparathyroidism

Define Condition:

Elevated PTH d/t HYPOCALCEMIA

-Hx:

> Chronic Renal Failure

> Vit D deficiency

-Path: Failing GFR --> renal phosphate retention --> Elevated serum phosphate complexes with calcium, which lowers the serum calcium concentration --> Elevated serum phosphate decreases the conversion of vitamin D into its active form, which also contributes to the hypocalcemia

-Prog: (UnTx)

> Bone resorption --> Weak Bones and Bone Pain

> Osteitis fibrosa cystica (Brown Tumor --> Cystic Degeneration + Peritrabecular Fibrosis)

Tertiary Hyperparathyroidism

Define Condition:

D/t chronic renal failure

-Path: PTH glands in chronic secondary become AUTONOMOUS --> More PTH regardless of Ca --> More Serum Ca

-Prog: (UnTx)

> Bone resorption --> Weak Bones and Bone Pain

> Osteitis fibrosa cystica (Brown Tumor --> Cystic Degeneration + Peritrabecular Fibrosis)

Familial Hypocalciuric Hypercalcemia (FHH)

Define Condition:

Rare, AUTOSOMAL DOMINANT Genetic Disorder

-Path: Defective G-coupled Ca-sensing receptors (CASRs) in PTHs and Kidneys --> Abnormal CASRs less sensitive to Ca in blood ==> Overproduce PTH, but kidneys DON'T SENSE CA --> MORE CA REABSORPTION ==> HYPOCALCIURIA and Hypercalcemia

-Dx:

Labs

> Serum = HIGH CA

> Urine = LOW CA

-Prog: BENIGN (Usually Asx & No Tx)

Hypoparathyroidism

Define Condition:

Underproduction of PTH --> Low Serum Ca

-Hx/Path: Parathyroid destruction/damage

> Surgical Ablation (MC = Accidental removal/damage of PTHs during thyroid/neck surgery)

> Autoimmune HypoPTH = Autoimmune Polyendocrine Syndrome (APS) Type I

>> Mutations in Autoimmune Regulator (AIRE) gene

>> Autosomal RECESSIVE

>> Triad

>>> HypoPTH

>>> Addison disease (Adrenal Insufficiency)

>>> Chronic mucocutaneous candidiasis

> DiGeorge Syndrome ("CATCH-22)

>> Deletion of c/s 22q11 --> 3rd and 4th pharyngeal pouches develop

>> 3rd pouch --> Thymus + 2 Inferior PTHs

>> 4th pouch --> 2 superior PTHs

>> Cardiac Abns (TOF)

>> Abn Facies

>> Thymic aplasia/hypoplasia --> recurrent Infex

>> Cleft Palate

>> HypoPTH

-Sx/PE: Hypocalcemia

> Up findings --> NM irritability ==> Muscle tetany, spasms, hyperreflexia, tingling

> Chvostek Sign = Tap facial nerve (tap Cheek) ==> Contraction of facial muscles

> Trousseau Sign = Occlusion of brachial artery w/ BP cuff (cut off Triceps) ==> Carpal Spasm

Paraneoplastic PTHrP

Define Condition:

MCC of Hypercalcemia of Malignancy

-Path: Solid Tumors (TCC, SCC of Lung) secrete PTHrP --> act on PTH receptors --> More Serum Ca

-Dx:

Labs

> PTH = LOW

> Ca = HIGH

Osteolytic Metastases

Define Condition:

-Path: Solid tumors (prostate, lung, renal, breast cancer) and multiple myeloma metastasize to bone -> release osteoclast activating factors -> ↑osteoclast activity -> ↑ serum Ca2+

-Dx:

Labs

> PTH = LOW

> Ca = HIGH

Pseudohypoparathyroidism (PHP) - AKA Albright Hereditary Osteodystrophy

Define Condition:

Bones & Kidneys UNRESPONSIVE to PTH d/t defect in PTH receptor

-Sx/PE:

> Short Stature

> Shortened 4th and 5th digits

> Round Face

-Dx:

Labs

> Ca = LOW

> PO4 = HIGH

> PTH = HIGH