Monday, September 06, 2004

Surgery of Parathyroid

THE PARATHYROID GLANDS
The four parathyroid glands are located posterior to the thyroid gland. They produce parathyroid hormone (PTH), which is the primary regulator of calcium physiology. PTH acts directly on bone, where it induces calcium resorption, and on the kidney, where it stimulates calcium reabsorption and Reabsorption of phosphates by the renal tubules. Serum PTH levels are tightly regulated by a negative feedback loop. Calcium, acting through the calcium-sensing receptor, and vitamin D, acting through its nuclear receptor, inhibit PTH synthesis and release.

Surgical Anatomy

These endocrine glands, usually two pairs- superior and inferior, but exact no. of parathyroid may vary .(88% 4 glands,6% 5 glands and in remaining 6% 3 Glands)


Position and embryology: The superior parathyroid, on each side, develops from the fourth pouch (hence called parathyroid IV). Superior parathyroid glands fairly constant in position closely embedded in thyroid postero Lateral border of thyroid Gland immediately above entry of inf. thyroid artery.Rarely it might vary above and within substance of thyroid gland along the of thyroid gland.
Paradoxically , the inferior parathyroid develop from the third pharyngeal pouch (Parathyroid III). The inferior parathyroids develop together with the –thymus and, since the thymus descends low down, the glands come down to a lower level than their counterparts developing from the fourth pouch . They are usually situated at the lower pole of thyroid gland.and may be found any where in this situation downwards to the upper pole Thymus.5% found in upper anterior Mediastinum
di- George Syndrome –( Congenital absence of parathyroid gland,Thymus and pharyngeal derivatives ) is a rare congenital anamoly

The glands are oval in shape, about the size of small peas ,the inferior glands being larger than the superiors. Their color varies from red or pink to yellow depending on the amount of fat deposition as age advances. They have, however, a distinctly different colour from the thyroid and this factor is of great help in their identification either at thyroidectomy or at parathyroidectomy. Small fat lobules usually bruised on operation table may look like parathyroid but Sink it in water parathyroid will sink – fat lobule will float ( Sink test)

Histology
The gland contains rich sinusoidal capillary net work with islands of secretary cells.
Microscopically, the parathyroids contain three types of cells :-
A. Basophilic or chief cells ( Principle cells) They have Small, vasicular nuclei and poorly staining cytoplasm
B. Eosinophilic cells (their number increases as age advances)
C. Water – clear cells. Usually found in hyperplastic parathyroid or neoplastic tumour

Surgical Physiology : - The hormone of the parathyroid is parathromone, which is polypeptide. It regulates the calcium and phosphorous metabolism of the body, maintaining a balanced ratio between the two. The normal level of serum calcium is 9 tp 11 mg per 100 ml and that of serum phosphorus is 3 to 4.5 mg per 100 ml (4,5 to 5.5 and 1.8 to 2.7 mEq. per liter respectively). The product between calcium and phosphorus in mg i.e. Ca x P is about 40 in a normal subject.

The control on the calcium and the phosphorus metabolism is maintained by the effect of parathormone on two organs, viz, bone and kidney. As to the exact mode of control, there are two views :-
1. Parathormone stimulates osteoclasts to bone destruction; thus mobilizing calcium and phosphate from bone to blood. This theory fails to explain why the serum phosphorus level should be low when the calcium level rises in hyperparathyroidism.
2. Parathormone controls Reabsorption of phosphates by the renal tubules. Since there is a reciprocal relationship between phosphorus and calcium, any change in the serum phosphate level brings in a compensatory change in the calcium level by mobilization from the bone. This view is more commonly accepted.
In addition Parathormone augments absorption of Ca from gut and controle GIT limb of Calcium metabolism

One important point about the serum calcium is to how it is held in solution in the blood plasma. From this point of view, the calcium may be divided into three parts: -
(a)About one-third is held adsorbed on plasma proteins; this is non-ionised and is physiologically inactive.
(b) A small part is in close attachment with organic acids; this also is non-ionised and, hence, physiologically inactive.
© The remainder is held in solution by Parathormone. It is only this part which is ionized and is physiologically active i.e. dynamic. The rise or fall of serum calcium, as seen in hyper and hypo-parathyroidism respectively, is only with respect to this part.


HYPERPARATHYROIDISM ( HPT)


It is clinical syndrome where in there is an excess of parathormone secretionthat is acting on all the target organs of Parathormone
Aetiology
Primary Hyperthyroidism
A)Primary Hyperplasia
a) Chief Cell Hyperplasia alone or part of MEA IIA and IIB
b) Water Clear Cell Hyperplasia(WCCH)
Hyperplasia involving all the parathyroids –
these account for about 20% of the cases
B) Neoplasia :
a)Adenoma which might exist alone or as part of Multiple endocrine adenoma syndrome(MEN II A Medullary carcinoma of thyroid, Parathyroid Adenoma or Hyperplasia and Pheochromocytoma )
Solitary adenoma in a parathyroid, obviously hormone-secreting- these account for 80% of the cases
b) Carcinoma in a parathyroid – extremely rare.

Secondary Hyperthyroidism
a)Chronic renal failure with Renal osteodystrophy
b) Malabsorption syndrome
In both the cases Serum Ca is low leading to Compensatory parathyroid Hyperplasia of all 4 glands.

Tertiary Hyperthyroidism
: Persistant HPT after Renal Transplantation in Renal osteodystrophy exists in about
20% of cases of Renal osteodystrophy



Biochemical Changes of HPT
(1)Elevation of the Serum Calcium Level – In the majority of cases there is considerable rise in the level of serum calcium. There are two views to explain this rise:-
(a)That parathormone directly mobilizes calcium from the bone by stimulating the osteoclasts to bone destruction.
(b) That parathormone diminishes tubular Reabsorption of phosphate in the kidney so that there is increased phosphate excretion in the urine. The serum phosphate level, therefore, falls. Since there is a reciprocal relationship between the phosphate and calcium levels in the serum, the serum calcium level is elevated.
The serum calcium level often rises to 12 to 16 mg (sometimes 20mg) from the normal level of 9 to 11 mg per 100 ml.
As has already been stated, this elevation is only in respect to that part of the serum calcium which is held in solution by parathormone and is ionized and physiologically active; i.e. dynamic. The actual level, to which the serum calcium rises, depends on four factors: -
(a) Rate of mobilization from the bones.
(b) Rate of absorption from the gut (i.e. food)
© Rate of excretion by the kidneys.
(d) Rate of Excretion from the gut.

(2) Increased Excretion of Calcium in the Urine – There are two routes of excretion of calcium from the body viz. the stool and the urine. In a normal individual most of the calcium is eliminated in the stool and only 10 to 30% in the urine. In hyperparathyroidism this ratio is reversed and the urine is supersaturated with calcium. This calcium is excreted: -
(a) as calcium phosphate, if the urine is alkaline.
(b) as calcium oxalate if the urine is acid.

3. Increased Excretion of Phosphorus in the Urine : As has been stated, this is the prime factor in the biochemical disturbances. However, when gross renal damage sets in, in the late stage of the disease (see below), the phosphorus excretion may fall.
4. Diminished Level of Serum Phosphorus : As phosphorus is excreted in high quantities in the urine, its level in the serum falls ( normal 3 to 4.5 mg/100ml)
5. Elevation of Serum Alkaline Phosphatase Level: - As in all bone dystrophies, there is an elevation in the level of serum alkaline phosphatase (normal 3 to 13 KA units/100ml)


Clinical Features:
The clinical features of HPT can be described in one statement bones, stones, abdominal groans and psychic moans
A. The Bone Lesions – In early case vague bony pain and joint pains may be presenting features (D/D Rheumatism ) Lesions in bones, i.e. parathyroid, osteodystrophy, is the most well recognized manifestation of hyperparathyroidism but it is not invariable. In at least some cases, the bones may be spared by increased utilization of dietary calcium. The changes may involve the entire skeleton and are as follows:
(1)Generalized demineralization with subperiosteal bone resorption (voRecklinghausen’s disease of bone)
(2) In some areas there may be complete replacement of osseous structure by fibrous tissue ( i.e. osteitis fibrosa) in which there is an abundance of osteoclast giant cells ( the so-called brown tumour of hyperparathyroidism_. Such areas of fibrous replacement may become cystic (osteitis fibrosa cystica). Some bones are commonly affected viz. the metaphysis of long bones, mandible, maxilla, and phalanges.
(3) Softening of bones may lead to deformities.
(4) Pathological fractures may occur through the cystic areas.

(B) Stones (The Kidney Lesions)
The increased urinary output of calcium may lead to the following changes:
(1)Formation of urinary calculi (hyperparathyroidism should be excluded especially in cases of multiple and recurrent calculi)
(2) Nephrocalcinosis: Radiologically seen as streaks of calcification in the line of renal tubules. Calcific foci block the renal tubules and cause fibrosis and obliteration of the corresponding nephrons.
(3) Widespread obliteration of nephrons, resulting in renal damage, may cause polyuria, hypertension and renal failure. Renal failure is often the cause of death in these cases.

C) The Abdominal Groans
(1) Dyspeptic cases :Anorexia, nausea and vomiting may be the presenting features.
(2) Peptic ulcer may occur in 15% of cases. The pain is worsened by alkalis. Recurrent bleeding may occur. The ulcer may not be demonstrable radiologically.
(3) Acute, subacute or chronic pancreatitis may occur in some cases
4) Persistent Irritable GIT may be seen in some cases

D)Psychic Moans :
Uncommon presentation , present with lethargy, Tiredness, Listlessness or irrational behavior and some may be wrongly Labeled as Neurotic

E) Hypercalcemic Syndrome
These patients present with minor mental changes, Lethargy,polydypsia, polyurea
and Dehydration,

F) Acute Hypercalcemic Syndrome is rapidly deteriorating clinical condition where in patients present initially with nausea, vomiting followed by abdominal pain and land up in oliguria and deteriorate fast to be in Coma

G) Asymptomatic: some of the patients may be detected during biochemical check up/.




Special Investigations:
(A)Biochemistry:
(1)Elevation of serum calcium
(2) Increased urinary excretion of calcium.
(3) Increased urinary excretion of phosphorus
(4) Diminished serum phosphorus
(5) Elevation of serum alkaline phosphatase.
(6) Elevation of serum parathormone (upper limit of normal is 0.5 microgram per litre of serum). The hormone is always detectable in hyperparathyroidism patients while it may be undetectable in many normal subjects.
(7) Sulkowitch Test: The patient is given a diet containing 125 mg of calcium daily, for three successive days. In hyperparathyroidism more than 200mg of calcium is excreted in the urine daily ( in a normal subject this level will be less than 100 mg).

B. X-Ray of the Bones:
(1) Generalized decalcification, often with cyst formation.
(2) Subperiosteal resorption, best seen in the middle phalanges. There is often an associated Reabsorption of the tufts of the terminal phalanges.
(3) Pathological fractures.
(4) The skull may have a ‘ground glass’ appearance due to decreased density.

C. X-Ray of the Kidneys may show stones or nephrocalcinosis.
D.Metastatic Calcification in soft tissues may be occasionally seen
Localization of Parathyroid Pathology:
Preoperative:MinimumInvasive
n Ultra Sound :operator dependant
n Computed tomography – usefull for localization outside neck
n Barium swallow, and Cine oesophagogram can partly help
n Neck massage PTH, urinary cyclic AMP
n Technetium Tc 99m Sestamibi radionuclide 91% to100% accuracy
n Thallium Technicium isotope Substraction scanning: useful for Adenoma but not for Hyperplasia
n MRI : 64% detection rate
Low signal is obtained on T1 weighted images,
T2 weighed images give contrast resolution
Preoperative:Invasive:
n Selective venous sampling of PTH
n Selective Angiography
n Arterial injection of selenomethionine 15
n Needle aspiration
Intra operative:
n Methylene blue
n 0-Toludine blue,
n Urinary Cyclic AMP
n Intraoperative assessment of PTH
n Intraoperative gamma probes for nuclear mapping




.

Parathyroidectomy:
Indications
1) Primary HPT
Hyperplasia – 3.1/2 gland is removed
Adenoma --- one
Carcinoma – Local Radical Diss.
2) Secondary HPT
– If bone decalcifation
- Severe pain.
3) Tertiary HPT
4) Re operative.

History
n Felix Mandl in Vienna, Austria performed the first successful Parathyroidectomy in 1925.
n Endoscopic Parathyroidectomy was pioneered by Dr Michel Gagner at the Cleveland Clinic in 1996
Surgical techniques

n Open Parathyroidectomy
n Minimally invasive Radioguided Parathyoidectomy
n Endoscopic Parathyroidectomy
The actual type of surgery depends on the pathology, and may be as follows: -
(1)If there is a parathyroid adenoma, it should be excised. However, after excising the tumour, all the other three parathyroids are to be explored and examined. This is because multiple adenoma may occur, involving more than one parathyroid. The operation is performed with a colar incision, as for subtotal thyroidectomy. While the parathyroids may be found in their normal positions behind the thyroid lobes, they may be located in abnormal situations as well, e;g.
(a)embedded in the substance of the thyroid.
(b) in the tracheo-oesophageal groove.

(2) If no adenoma is detectable and all or several parathyroids are found to be larger than normal, parathyroid hyperplasia is the diagnosis ( had there been a hidden adenoma, the parathyroids would be smaller in size due to disuse atrophy). In such cases, three or three and a half of the parathyroid glands are removed.

(3) When the parathyroids appear normal or smaller in size, adenoma in am ectopic parathyroid is the likely pathology. In these cases, after careful search of the thyroid lobes and the tracheo-oesophageal grooves, the Mediastinum has to be explored. For this purpose, a sternal split is done. An ectopic parathyroid may be located:
(a)retrosternal
(b) on the pericardium
© in relation to the thymus ( a thymectomy may have to be done).

4. If some of the parathyroids ( particularly the inferior glands) are not traceable in the neck, the Mediastinum has to be explored, as above, in order to find out the glands.

Auto Transplantation of Parathyroid
Indications
– Primary Thyroid hyperplasia
– Secondary HPT
– Re operative HPT
– Total Thyroidectomy for Ca Thyroid
This technique is useful to avoid Hypoparathyroidism I cases of hyperplasia Where after the surgery if hypo functioning is seen it can be avoided by auto transplantation

Deferred parathyroid Autotransplantation
n Immediately placed in to sterile saline or tissue culture
n Sliced into 1x1x3mm silvers.
n 3ml Glass vials will accommodate 10 silvers 1 to 1.5 ml
– 10% DMSO dimethyl sulfoxide
– 10% autologus serum
– 80% Tissue culture media
n Frozen after immersion at rate of 1degree centigrade per minute
n Till you reach -80degree Centigrade
n -190 o C Vapour phase Liquid nitrogen freezer
n Linde BF 4/6 biological freezing system
n Thawing rapidly to 57oC
n Implant in Thigh subcutaneously



HYPOPARATHYROIDISM
Causes:

(1)Post Operative: These account for the majority of the cases. They occur after thyroidectomies, but only in about one percent of the cases. The features appear in one to five days after the operation, but if the symptoms are mild, the condition may remain unrecognized for weeks (see complications of thyroidectomy, Chapter 30).

(2) Insidious: These occur spontaneously in some people. The condition is characterized by weakness, opacity of the lenses, brittlessness of the nails, loss of dental enamel, loss of hair, and a low serum calcium level.

(3) Idiopathic: This occurs in children, usually in the active stages of rickets.

(4) Secondary: These cases occur secondary to alkalosis and may be found in:
(a) Long continued vomiting- Pyloric stenosis, high intestinal obstruction.
(b) Prolonged administration of alkalis – peptic ulcer.

Clinical Features: The features of tetany set in when the blood calcium level comes down to the ‘tetany level’ which is usually below 6 mg /100ml of serum. It takes a few days for this level to be reached, so post-operative tetany (the commonest form) takes about 2 to 5 days to appear. The milder forms may be missed clinically for longer periods. The earlier the features appear, the delayed is the recovery.

The clinical features are all motor, resulting from muscular irritability:
(1)Widespread fibrillation of the muscle fibers may give the patient a sensation of tingling and numbness of the lips, nose and extremities, there may be a typical circum-oral pallor.
(2) The muscles of the forearms and legs go into spasm, resulting in what is called the ‘carpo-pedal spasm’. The characteristic features are: -
(a)The foot assumes an equines position 9i.e. plantar-flexion)
(b) The hand assumes the ‘obstetrical position’ – the fingers are extended except at the metacarpophalangeal joints (which are flexed), and the thumb is adducted.

(3) In latent cases, muscle spasms which are not ordinarily seen, may be induced as follows:-
(a)Trousseau’s Sign: - A sphygmomanometer cuff is applied round the arm and the pressure is raised to above the systolic level- the hand assumes the ‘obstetrical position’.
(b) Chvostek’s sign:- Tapping the facial nerve, just in front of the ear, with a percussion hammer, provokes twitching of the facial muscles.


(4) In severe cases, the spasms may be more pronounced e.g.

(a)Generalized fits
(b) Spasm of the muscles of respiration – dyspnoea.
© Spasm of intra-ocular muscles- blurring of vision.

(5) The insidious cases may present with weakness, cataracts, brittle nails, lack of dental enamel and loss of hair.

Special Investigations:
(1)Estimation of Serum Calcium- This is always low, usually below 6 mg. per 100 ml in frank cases of tetany.
(2) Erb’s Sign- A hyper excitability of the muscles can be seen on galvanic stimulation.

Treatment: .