DISEASE OF PARATHYROID GLANDSDr. Mohammed Hajhamad,

MB.ChB. (MUST - Egypt), M.S (UKM - Malaysia)

Department of Surgery

International Medical School

Management and Science University

1

HISTORY

1849 Sir Richard Owen provided 1st accurate

description of normal parathyroid glands after

examining Indian Rhinoceros

2

HISTORY

1879 Anton Wölfer described tetany in a patient

after total thyroidectomy

Ivar Sandström a Swedish medical student

grossly and microscopically described parathyroid

glands

3

HISTORY

Calcium measurement possible in 1909 and

association with parathyroids established

1925 1st successful parathyroidectomy on 38 yr old

man with severe bone pain secondary to osteitis

fibrosa cystica

4

PARATHYROIDS

The parathyroid glands are

usually embedded between the

posterior border of the thyroid

gland and its fibrous capsule.

At times, the parathyroids may

be intrathyroidal.

They measure 6 x4x2 mm in

maximum diameter and weigh

25-40 mg each.

Number of glands can vary from

4-6

5

PARATHYROID GLAND, PHYSIOLOGY

Calcium & Phosphate Metabolism

Distribution & Balance of Ca & PO4

Hormones involved

Parathyroid Hormone

Calcitonin

Vit. D

6

PARATHYROID HORMONE (PTH)

A peptide hormone that increases plasma Ca2+.

by:

Mobilization of Ca2+ from bone

Enhancing renal reabsorption

Increasing intestinal absorption (indirect)

7

PARATHYROID HORMONE RAISES BLOOD CA

BY ACTING ON 3 ORGANS:

Bone: main effect- stimulates osteoclasts bone

breaks down Ca released

Intestines: increases uptake of Ca from intestine

Kidney: stimulates reabsorption of Ca at kidney

tubules.

8

PARATHYROID HORMONE

Actions (to increase plasma calcium):

increasing osteoclastic resorption of bone.

increasing intestinal absorption of calcium.

increasing synthesis of 1,25-(OH)2D3.

increasing renal tubular reabsorption of calcium.

increasing excretion of phosphate.

9

PTH FUNCTION

10

CALCITONIN

a thyroid hormone

produced by C-cells

physiological effects are antagonist to those of PTH

rapid acting, short term regulator of plasma Ca levels

11

CALCITONIN LOWERS BLOOD CA

o Stimulates osteoblasts, inhibits osteoclasts

o Causes removal of Ca from plasma to calcify new bone

o Lowers plasma Ca (opposes PTH)

12

VIT. D

Derived from irradiation of 7-dehydrocholesterol in

skin by UV rays

Causes Ca absorption from intestinal tract

Active form of this hormone is 1,25-

dihydroxycholecalciferol (calcitriol)

13

ACTIVE VITAMIN D (CALCITROL) IS MADE IN 3

STEPS BY DIFFERENT ORGANS

The skin uses ultraviolet sunlight to make vitamin D3 (cholecalciferol) from cholesterol

The vitamin D3 is converted to 25-Hydroxycholecalciferol in the liver

Stimulated by PTH

The 25-Hydroxycholecalciferol is made into calcitriol (1, 25-Dihydroxycholecalciferol) in the kidney

Stimulated by PTH

The main effect of calcitriol is to increase intestinal absorption of Ca

14

HYPERPARATHYROIDISM

Affects approximately 100,000 patients a year

Primary hyperparathyroidism occurs in 0.1 to 0.3%

of the general population and is more common in

women (1:500) than in men (1:2000).

Primary hyperparathyroidism is characterized by

increased parathyroid cell proliferation and PTH

secretion which is independent of calcium levels.

15

HYPERPARATHYROIDISM

Etiology unknown, but radiation exposure, and

lithium implicated, associated with MEN1, and

MEN 2A

Enlargement of a single gland or parathyroid

adenoma in approximately 80% of cases,

multiple adenomas or hyperplasia in 15 to 20%

of patients and parathyroid carcinoma in 1% of

patients 16

CLINICAL FEATURES

Kidney stones, painful bones, abdominal groans, psychic

moans, and fatigue overtones.

Kidney stones calcium phosphate and oxalate

Osteopenia, osteoporosis, and osteitis fibrosa cystica, is

found in approximately 15% of patients with PHPT.

Increased bone turnover .

Peptic ulcer disease, pancreatitis

Psychiatric manifestations such as florid psychosis,

obtubdation, coma, depression, anxiety, fatigue 17

HYPERPARATHYROIDISM

Hypercalcemia can be from other sources. Intact

PTH measurement and elevated PTH level very

sensitive for hyperparathyroidism

18

IMAGING

In the early stages there is demineralisation, with

subperiosteal erosions and terminal resorption in

the phalanges.

A 'pepper-pot' appearance :lateral X-rays of the

skull.

Reduced bone mineral density, resulting in either

osteopenia or osteoporosis. And is assessed by

DEXA

In nephrocalcinosis, scattered opacities within the

renal outline.

There may be soft tissue calcification in arterial

walls, soft tissues of the hands and the cornea.19

IMAGES

Source: http://uwmsk.org/residentprojects/hpth.html20

PRE-OPERATIVE LOCALIZATION

The predictive value of ultrasonography,

CT scan and / or Magnetic resonance imaging

Thallium-technetium dual isotope scintigraphy

21

22

SURGERY

Bilateral neck exploration is “gold standard”

With pre-operative imaging techniques can have

minimally invasive focused surgery towards

adenoma

Can have 99-Tc Sestamibi timed within 3 hours of

surgery to intra-operatively localize parathyroid

adenoma using hand held geiger probe

Can have sequential Sestamibi scan and repeat

technetium injection 10 minutes prior to surgery

In this setting intra-operative PTH level testing

questionable23

PARATHYROID CARCINOMA

1% of cases of primary hyperparathyroidism

15% of patients have lymph node

metastases and 33% have distant

metastases at presentation.

24

PARATHYROID CARCINOMA

Bilateral neck exploration, with en bloc

excision of the tumor and the ipsilateral

thyroid lobe.

Modified radical neck dissection is

recommended in the presence of lymph

node metastases

25

SECONDARY HYPERPARATHYROIDISM

In pts with chronic renal failure

Deficiency of 1,25-dihydroxy vitamin D as a result

of loss of renal tissue, low calcium intake,

decreased calcium absorption, high phosphate

level and abnormal parathyroid cell response

Normally treated medically

26

SECONDARY HYPERPARATHYROIDISM

Surgical treatment is indicated and

recommended for patients with

Bone pain,

Pruritus, and a calcium-phosphate product >=70,

Ca greater than 11 mg/dl with markedly elevated PTH

Calciphylaxis

Progressive renal osteodystrophy,

Soft-tissue calcification

27

TERTIARY HYPERPARATHYROIDISM

Long standing renal failure after renal transplant

autonomous parathyroid gland function and tertiary HPT.

Can cause problems similar to primary hyperparathyroidism

Operative intervention

symptomatic disease

autonomous PTH secretion persists for more than 1 year

after a successful transplant

subtotal or total parathyroidectomy with autotransplantation

28

POST OPERATIVE COMPLICATIONS

Hypocalcemia (Chvostek’s and Trousseau’s

sign)

Vocal cord paralysis after RLN injury

29

HYPOPARATHYROIDISM

Deficient secretion of PTH which manifests itself

biochemically by hypocalcemia, hyperphospatemia

diminished or absent circulating iPTH and clinically

the symptoms of neuromuscular hyperactivity.

30

HYPOPARATHYROIDISM

Surgical hypoparathyroidism – the commonest

After anterior neck exploration for thyroidectomy,

abnormal parathyroid gland removal, excision of a neck

lesion.

It could be due to the removal of the parathyroid glands

or due to interruption of blood supply to the glands.

Causes:

31

HYPOPARATHYROIDISM

Idiopathic hypoparathyroidism

A form occuring at an early age (genetic origin) with

autosomal recessive mode of transmission “multiple

endocrine deficiency –autoimmune-candidiasis

(MEDAC) syndrome”

“Juvenile familial endocrinopathy”

“Hypoparathyroidism – Addisson’s disease –

mucocutaneous candidiasis (HAM) syndrome”

Causes:

32

HYPOPARATHYROIDISM

Idiopathic hypoparathyroidism Circulating antibodies for the parathyroid glands and the

adrenals are frequently present.

Other associated disease: Pernicious anemia

Ovarian failure

Autoimmune thyroiditis

Diabetes mellitus

Causes:

33

HYPOPARATHYROIDISM

Functional hypoparathyroidism In patients who has chronic hypomagesaemia of various

causes.

Magnesium is necessary for the PTH release from the glands and also for the peripheral action of the PTH.

Causes:

34

MAJOR CAUSES OF CHRONIC HYPOCALCEMIA OTHER

THAN HYPOPARATHYROIDISM

Dietary deficiency of vitamin D or calcium

Decreased intestinal absorption of vitamin D or calcium due to primary small bowel disease, short bowel syndrome, and post-gastrectomysyndrome.

Drugs that cause rickets or osteomalacia such as phenytoin, phenobarbital, cholestyramine, and laxative.

35

MAJOR CAUSES OF CHRONIC HYPOCALCEMIA OTHER

THAN PARATHYROPRIVAL HYPOPARATHYROIDISM

States of tissue resistance to vitamin D

Excessive intake of inorganic phosphate compunds

Psudohypoparathyroidism

Severe hypomagnesemia

Chronic renal failure

36

HYPOPARATHYROIDISM

A. Neuromuscular

The rate of decrease in serum calcium is the major

determinant for the development of neuromuscular

complications.

Clinical Features:

37

HYPOPARATHYROIDISM

A. Neuromuscular Parathesia (sensation of numbness or tingling on the skin)

Tetany

Hyperventilation

Adrenergic symptoms

Convulsion (More common in young people and it can take the form of either generalized tetany followed by prolonged tonic spasms or the typical epileptiform seizures.

Signs of latent tetany Chvostek sign (nilateral spasm of the oris muscle is initiated by

a slight tap over the facial)

Trousseau sign

Extrapyramidal signs (due to basal ganglia calcification) Involuntary movements, Tremors and rigidity

Clinical Features:

38

HYPOPARATHYROIDISM

B. Other clinical manifestation

1. Posterio lenticular cataract

2. Cardiac manifestation:

3. Prolonged QT interval in the ECG

4. Resistance to digitalis

5. Hypotension

6. Refractory heart failure with cardiomegally can

occur.

39

HYPOPARATHYROIDISM

B. Other clinical manifestation

3. Dental Manifestation

Abnormal enamel formation with delayed or absent

dental eruption and defective dental root formation.

4. Malabsorption syndrome

Presumably secondary to decreased calcium level

and may lead to steatorrhoea with long standing

untreated disease.

40

HYPOPARATHYROIDISM

In the absence of renal failure the presence of

hypocalcaemia with hyperphosphataemia is virtually

diagnostic of hypoparathyroidism.

Undetectable serum iPTH confirms the diagnosis or

it can be detectable if the assay is very sensitive.

Diagnosis:

41

HYPOPARATHYROIDISM

The mainstay of treatment is a combination of oral

calcium with pharmacological doses of vitamin D or

its potent analogues.

Phosphate restriction in diet may also be useful with

or without aluminum hydroxide gel to lower serum

phosphate level.

Treatment:

42

EMERGENCY TREATMENT FOR HYPOCALCAEMIC

Calcium should be given parenterally (IV) till adequate

serum calcium level is obtained and then vitamin D

supplementation with oral calcium should be initiated.

Tetany:

43

EMERGENCY TREATMENT FOR HYPOCALCAEMIC

In patients with hypoparathyroidism and severe

bone disease who undergo successful

parathyroidectomy hypocalcaemia may be

severe and parenteral calcium infusion with later

supplementation with oral calcium and vitamin D.

Hungry bone syndrome:

44

CLINICAL SCENARIO-

PARATHYROID GLAND45

CASE # 01

A 43-year-old male is admitted to the emergency

room for severe pain in his left flank, radiating to the

groin. The pain is intermittent and initiated after

running a marathon on a hot summer day. The

patient is asked for a urine specimen and blood is

detected in the urine. He is hydrated and additional

diagnostic procedures are done. Laboratory values

show an increased plasma calcium of 12 mg/dL,

and increased plasma intact PTH values of 130

pg/mL.

46

CASE # 02

A 73-year-old woman is admitted to the hospital

following a bout of severe vomiting and generalized

weakness. Initial laboratory values reveal increased

plasma calcium levels. The referring physician tells

you that she has breast cancer and her bone scan

indicates metastasis to bone.

47

CASE # 03

A postmenopausal patient is referred for

asymptomatic hypercalcemia and history of

repeated episodes of urolithiasis (kidney stones).

Blood laboratory values reveal increases in intact

PTH, 1,25(OH)2D, and markers of bone resorption.

Neck ultrasound revealed a mass below the right

lobe of the thyroid gland.

48

CASE # 04

A 35-year-old woman undergoes a thyroidectomy

for papillary serous thyroid cancer. The surgeon

suspects that the parathyroid glands have been

removed. Which of the following findings is most

likely to be seen in the patient 1 week

postoperatively?

A. Coma

B. Constipation

C. Esophagitis

D. Muscle spasms and tetany

49

YOUR BRAIN

BEFORE AFTER

50