Parathyroid gland

DONE BY : MARAH AL-HIARY

Objectives :

1)Emberyology

2)Anatomy

3)Physiology

4)Hyperparathyrodisim:

- primary

- secondary

- tertary

- Embryology:

o Endodermal origin

o Superior parathyroid glands are derived from the 4th pharyngeal pouch.

o Inferior parathyroid glands are derived from the 3rd pharyngeal pouch.

* Long descent pathway; thus there is an increased incidence of an ectopic gland:

1) If undescended: cranial to the super lobe of thyroid

2) Excessive descent: mediastinum (1% of population)

3) Other sites: thymus is the most common ectopic site.

Anatomy:

o Number of glands:

85% of the population has 4 glands.

5% of the population has 5 glands.

10% of the population has 3 glands.

o Site:

-postero-lateral aspect of the thyroid gland.

* Histologically, parathyroid glands are composed of chief cells and oxyphil cells arranged in

trabeculae, within a stroma composed primarily of adipose cells.

* Superior glands:

found on the junction between the upper third and lower two thirds at the posterior aspect of the thyroid lobe.

Superior to the inferior thyroid artery (1 cm above it).

Posterior to the recurrent laryngeal nerve: the upper parathyroids are used as a landmark for the recurrent laryngeal nerve.

The superior glands are the most functional; during surgery, do not remove them until you find the other glands.

* Inferior glands:

Found inferio-lateral or posterior to the inferior pole of the thyroid gland.

Anterior to the recurrent laryngeal nerve.

o Blood supply: in 80% of the population, it comes from the inferior thyroid artery.

o Notes:

Calcium is the most abundant cation in human beings and has several

functions:

1) Contraction and secretion of most glands and muscles

2) Neuromuscular junction conduction

3) Secondary messenger

4) Coenzyme for many metabolic pathways

5) Blood coagulation

6) Mental activity

Calcium is absorbed in the duodenum and proximal jejunum.

**Bone is the largest calcium reservoir in the body.

The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized

calcium levels range from 4.4 to 5.2 mg/dL (1.1 to 1.3 mmol/L).

*Calcium in serum:

1) 40% bound to albumin

2) 50% free

3) 10% is bound to phosphate and citrate

DiGeorge’s syndrome??

PTH is made of 84 amino acids.

PTH levels are controlled by: calcium serum levels and number of chief cells.

PTH functions to regulate calcium levels via its actions on three target organs, the bone, kidney, and gut. PTH increases the resorption of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation. At the kidney, calcium is primarily absorbed in concert with sodium in the proximal convoluted tubule, but fine adjustments occur more distally. PTH acts to limit calcium excretion at the distal convoluted tubule via an active transport mechanism. PTH also inhibits phosphate reabsorption (at the proximal convoluted tubule) and bicarbonate reabsorption. also its increase vitamin D synthesis , in the gut its increase ca absorption.

Normal PTH value is about 80:

-in primary hyperparathyroidsim it ranges between 100-140.

-in secondary hyperparathyroidism it ranges between 400-500.

-in tertiary hyperparathyroidism it is above 1000.

Hyperparathyroidism :

o Primary: increased secretion of PTH by the parathyroid gland

manifested as an increase in calcium and decrease in

phosphate.

o Secondary: increased serum PTH secondary to calcium wasting.

o Tertiary: persistent hyperparathyroidism after correction of

secondary hyperparathyroidism resulting in autonomous PTH

secretion not responsive to the negative feedback.

Primary hyperparathyroidism:

* Causes:

1) Adenoma (most common): 1 gland; 85%

2) Hyperplasia: 4 glands; 10%

3) Carcinoma: 1 gland; 1%

* Risk factors:

1) Family history

2) MENI, MENIIa

3) Radiation

* Common in postmenopausal women.

* Mostly sporadic.

o Clinical presentation:

o Clinical presentation:

“Stones, Bones, Groans, and psychiatric moans”

1) Stones: kidney stones/ nephrolithiasis

2) Bones: Bone pain/ pathological fractures/ osteoporosis/ subperiosteal bone

resorption

3) Groans: abdominal pain/ weakness/ pancreatitis/ constipation/ gout

4) Psychiatric moans: depression/ anorexia/ weight loss/ anxiety/ emotional

disturbances.

*30-40% of patents asymptomatic.

o X-ray findings: subperiosteal bone resorption usually in the hands and scalp .

o In adenoma, only 5% of patients have more than 1 gland involved.

o In patients with primary hyperparathyroidism due to hyperplasia, always rule out MEN syndromes.

* Parathyroid carcinoma:

* Parathyroid carcinoma:

-may have a palpable neck mass

-Serum Ca2+ >15

- Increased PTH

- Paralysis of recurrent laryngeal nerve leading to a change in voice

- Hypercalcemic crisis

- Tumor marker: hCG

o Investigations:

* Lab studies :

calcium / Phosphate

PTH

Creatinine

Alkaline phosphatase

24-hour urine collection

Cl-

* imaging studies :

US

Systamibi scan (99mTc)

SPECT

PTH-level radioimmunoassay

CT / MRI

KUB for kidney stones

o Treatment:

Initial medical treatment for hypercalcemia consists of IV fluids and bisphosphanates. Do

not use furosemide, unless the patient is overloaded.

Adenoma: surgically remove the adenoma (send for a frozen section) and biopsy all

abnormally enlarged glands

Hyperplasia: neck exploration removing all parathyroid glands and leaving at least half of

parathyroid tissue placed in the forearm muscles. We leave 30mg in order to retain the

parathyroid function. Moreover, if hyperparathyroidism re-occurs, we can remove some tissue

from the forearm (easier access)

If carcinoma: remove the carcinoma, the ipsilateral thyroid lobe, and all enlarged lymph

nodes. Modified neck dissection is indicated if lymph nodes are positive.

o Complications of surgery:

1) Postoperative hypocalcemia: Transient: if severe (<7.5) you should treat rule of 10 for calcium gluconate (10 %/10ml/over 10min)

Persistent: if hypocalcemia persists for more than 6-8 weeks; treat with calcium gluconate.

* Signs and symptoms:

-Perioral numbmess

-Parasthesia and tetany o Chovstek’s sign ??

o Trouesseaus sign ??

2) Recurrent laryngeal nerve injury Unilateral: voice change

Bilateral: airway obstruction

3) Neck hematoma

4) Superior laryngeal nerve injury

Familial hypocalciuric hypercalcemia:

*Familial hypocalciuric hypercalcemia: (FHH)

o Mild increase in calcium, increased to normal PTH.

asymptomatic.

o Decrease urine calcium.

o Autosomal dominant mutation in calcium sensing receptors leading to loss of feedback inhibition.

o Labs: 24-hours urine collection, renal Ca:Cr clearance ratio (if < 0.01 it is diagnostic of FHH).

o Surgery is not indicated for these cases.

* Hungry bone syndrome: severe hypocalcemia seen after surgical correction of hyperparathyroidism

as chronically calcium deprived bone absorbs calcium aggressively post-surgically.

Secondary hyperparathyroidism:

*Secondary hyperparathyroidism:

* Causes:

1) Renal failure ??

2) Vitamin D deficiency (Ricket’s, osteomalacia).

3) Decrease GI absorption of calcium.

* Labs:

1) Decreased calcium

2) Increased PTH

* Treatment:

1) Correct calcium and phosphate

2) Correct the underlying cause

3) No role for parathyroid surgery

Tertiary hyperparathyroidism :

* Tertiary hyperparathyroidism :

o Persistent hyperparathyroidism after correction of secondary

hyperparathyroidism.

o Results from autonomous PTH secretion not responsive to negative

feedback.

o Treatment:

1) Correct calcium and phosphate.

2) Surgical removal of the parathyroids wand implanting some tissue in the

forearm, if refractory to medical treatment.

* Bone disorders seen in hyperparathyroidism:

1)Renal osteodystrophy

2) Osteporosis

3) Osteomalacia

4) Ostitis fibrosa cystica

5) Brown tumors

* Indications of surgery in asymptomatic hyperparathyroidism:

1) Age <50

2) Patients who cannot get appropriate follow up

3) Serum Ca >1mg above normal range

4) Urine Ca >400mg (obsolete criterion)

5) 30% decrease in creatinine clearance / GFR Less than 60 cc/min

6) BY DEXA scan T score less than -2.5 at lumber spine/ total hip/ femoral

neck /distal 1/3 of the radius.

Notes:

Differential diagnosis of hypercalcemia :

1)Hyperparathyroidism

2)Malignancy—hematologic (multiple myeloma), solid tumors(due to PTHrP)

3)Endocrine diseases—hyperthyroidism, Addisonian crisis,VIPoma

4)Granulomatous diseases—sarcoidosis, tuberculosis,berylliosis, histoplasmosis

Milk-alkali syndrome

5)Drugs—thiazide diuretics, lithium, vitamin A or D intoxication

6)Familial hypocalciuric hypercalcemia

7)Paget’s disease

8)Immobilization

Notes:

o The most common cause of hypercalcemia in hospitalized patients is cancer.

o Most common cause of hypercalcemia is outpatients is hyperparathyroidism.

*Postoperative Care and Follow-Up Patients who have undergone parathyroidectomy are

advised to undergo calcium level checks 2 weeks postoperatively, at 6 months, and then

annually.Recurrences are rare (<1%), except in patients with familial HPT. Recurrence rates of

15% at 2 years and 67% at 8 years have been reported for MEN1 patients.

Thank you